Adrenal Hormones

Overview

Regions of the adrenal gland

The adrenal glands Adrenal Glands The adrenal glands are a pair of retroperitoneal endocrine glands located above the kidneys. The outer parenchyma is called the adrenal cortex and has 3 distinct zones, each with its own secretory products. Beneath the cortex lies the adrenal medulla, which secretes catecholamines involved in the fight-or-flight response. Adrenal Glands: Anatomy have 2 primary areas with separate functions and regulatory mechanisms.

• Adrenal medulla Adrenal Medulla The inner portion of the adrenal gland. Derived from ectoderm, adrenal medulla consists mainly of chromaffin cells that produces and stores a number of neurotransmitters, mainly adrenaline (epinephrine) and norepinephrine. The activity of the adrenal medulla is regulated by the sympathetic nervous system. Adrenal Glands: Anatomy:
  • Inner portion
  • Secretes catecholamines
  • Functions in conjunction with the sympathetic nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. Nervous System: Anatomy, Structure, and Classification
• Adrenal cortex Adrenal Cortex The outer layer of the adrenal gland. It is derived from mesoderm and comprised of three zones (outer zona glomerulosa, middle zona fasciculata, and inner zona reticularis) with each producing various steroids preferentially, such as aldosterone; hydrocortisone; dehydroepiandrosterone; and androstenedione. Adrenal cortex function is regulated by pituitary adrenocorticotropin. Adrenal Glands: Anatomy:
  • Outer portion
  • All cortical hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types are synthesized from cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism
  • Has 3 different zones:
    • Zona glomerulosa Zona Glomerulosa The narrow subcapsular outer zone of the adrenal cortex. This zone produces a series of enzymes that convert pregnenolone to aldosterone. The final steps involve three successive oxidations by cytochrome p-450 cyp11b2. Adrenal Glands: Anatomy: secretes mineralocorticoids Mineralocorticoids Mineralocorticoids are a drug class within the corticosteroid family and fludrocortisone is the primary medication within this class. Fludrocortisone is a fluorinated analog of cortisone. The fluorine moiety protects the drug from isoenzyme inactivation in the kidney, allowing it to exert its mineralocorticoid effect. Mineralocorticoids
    • Zona fasciculata Zona Fasciculata The wide middle zone of the adrenal cortex. This zone produces a series of enzymes that convert pregnenolone to cortisol (hydrocortisone) via 17-alpha-hydroxyprogesterone. Adrenal Glands: Anatomy: secretes glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids
    • Zona reticularis Zona Reticularis The inner zone of the adrenal cortex. This zone produces the enzymes that convert pregnenolone, a 21-carbon steroid, to 19-carbon steroids (dehydroepiandrosterone; and androstenedione) via 17-alpha-hydroxypregnenolone. Adrenal Glands: Anatomy: secretes androgens Androgens Androgens are naturally occurring steroid hormones responsible for development and maintenance of the male sex characteristics, including penile, scrotal, and clitoral growth, development of sexual hair, deepening of the voice, and musculoskeletal growth. Androgens and Antiandrogens
  • Part of the hypothalamic-pituitary-adrenal (HPA) axis

Hypothalamic-pituitary-adrenal (HPA) axis

Hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types secreted by the adrenal cortex Adrenal Cortex The outer layer of the adrenal gland. It is derived from mesoderm and comprised of three zones (outer zona glomerulosa, middle zona fasciculata, and inner zona reticularis) with each producing various steroids preferentially, such as aldosterone; hydrocortisone; dehydroepiandrosterone; and androstenedione. Adrenal cortex function is regulated by pituitary adrenocorticotropin. Adrenal Glands: Anatomy (not the medulla) are controlled by, and help regulate, the HPA axis.

• The hypothalamus Hypothalamus The hypothalamus is a collection of various nuclei within the diencephalon in the center of the brain. The hypothalamus plays a vital role in endocrine regulation as the primary regulator of the pituitary gland, and it is the major point of integration between the central nervous and endocrine systems. Hypothalamus (paraventricular nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles) secretes corticotropin-releasing hormone Corticotropin-releasing hormone A peptide of about 41 amino acids that stimulates the release of adrenocorticotropic hormone. Crh is synthesized by neurons in the paraventricular nucleus of the hypothalamus. After being released into the pituitary portal circulation, crh stimulates the release of acth from the pituitary gland. Crh can also be synthesized in other tissues, such as placenta; adrenal medulla; and testis. Hypothalamic and Pituitary Hormones (CRH).
• CRH stimulates the anterior pituitary Pituitary A small, unpaired gland situated in the sella turcica. It is connected to the hypothalamus by a short stalk which is called the infundibulum. Hormones: Overview and Types to release adrenocorticotropic hormone (ACTH).
• ACTH stimulates the adrenal cortex Adrenal Cortex The outer layer of the adrenal gland. It is derived from mesoderm and comprised of three zones (outer zona glomerulosa, middle zona fasciculata, and inner zona reticularis) with each producing various steroids preferentially, such as aldosterone; hydrocortisone; dehydroepiandrosterone; and androstenedione. Adrenal cortex function is regulated by pituitary adrenocorticotropin. Adrenal Glands: Anatomy to synthesize and release all of the cortical hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types:
  • Mineralocorticoids Mineralocorticoids Mineralocorticoids are a drug class within the corticosteroid family and fludrocortisone is the primary medication within this class. Fludrocortisone is a fluorinated analog of cortisone. The fluorine moiety protects the drug from isoenzyme inactivation in the kidney, allowing it to exert its mineralocorticoid effect. Mineralocorticoids
  • Glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids
  • Androgens Androgens Androgens are naturally occurring steroid hormones responsible for development and maintenance of the male sex characteristics, including penile, scrotal, and clitoral growth, development of sexual hair, deepening of the voice, and musculoskeletal growth. Androgens and Antiandrogens 
• Negative inhibition within the HPA axis:
  • ACTH inhibits further CRH release.
  • Cortisol Cortisol Glucocorticoids (the primary glucocorticoid) inhibits both CRH and ACTH.
• Other factors that can stimulate the HPA axis:
  • Stresses:
    • Physical (e.g., exercise)
    • Mental (e.g., fear)
    • Biochemical (e.g., low blood sugar Low blood sugar Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dl (≤ 3. 9 mmol/l) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia)
  • Biologic rhythms:
    • Circadian rhythms
    • Rhythms associated with growth and development

Adrenal Cortex Hormones: Mineralocorticoids

Mineralocorticoid overview

• Primary hormone: aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia
• Secreted from the zona glomerulosa Zona Glomerulosa The narrow subcapsular outer zone of the adrenal cortex. This zone produces a series of enzymes that convert pregnenolone to aldosterone. The final steps involve three successive oxidations by cytochrome p-450 cyp11b2. Adrenal Glands: Anatomy within the adrenal cortex Adrenal Cortex The outer layer of the adrenal gland. It is derived from mesoderm and comprised of three zones (outer zona glomerulosa, middle zona fasciculata, and inner zona reticularis) with each producing various steroids preferentially, such as aldosterone; hydrocortisone; dehydroepiandrosterone; and androstenedione. Adrenal cortex function is regulated by pituitary adrenocorticotropin. Adrenal Glands: Anatomy
• Synthesized by aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia synthase
• Regulation:
  • Partially under the control of ACTH
  • Renin-angiotensin-aldosterone system (see below)
  • Serum K⁺ levels
• Effects:
  • ↑ Blood pressure (↑ water reabsorption from the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy)
  • ↑ Serum Na⁺ (↓ urinary excretion of Na⁺)
  • ↓ Serum K⁺ (↑ urinary excretion of K⁺)
  • ↑ Serum pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance (↑ urinary excretion of H⁺)

The renin-angiotensin-aldosterone system (RAAS)

The RAAS is one of the primary regulators of blood pressure, total body water Total body water Body Fluid Compartments, serum sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia levels, and pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance balance in the body.

• Angiotensinogen: secreted by hepatocytes Hepatocytes The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. Liver: Anatomy
• Renin Renin A highly specific (leu-leu) endopeptidase that generates angiotensin I from its precursor angiotensinogen, leading to a cascade of reactions which elevate blood pressure and increase sodium retention by the kidney in the renin-angiotensin system. Renal Sodium and Water Regulation:
  • Secreted by the juxtaglomerular (JG) cells within the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy (part of the afferent Afferent Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology arterioles Arterioles The smallest divisions of the arteries located between the muscular arteries and the capillaries. Arteries: Histology) 
  • Converts angiotensinogen to angiotensin I 
• ACE:
  • Secreted by pulmonary vascular endothelium Endothelium A layer of epithelium that lines the heart, blood vessels (vascular endothelium), lymph vessels (lymphatic endothelium), and the serous cavities of the body. Arteries: Histology (and other tissues)
  • Converts angiotensin I to angiotensin II Angiotensin II An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the c-terminal by angiotensin converting enzyme. The amino acid in position 5 varies in different species. To block vasoconstriction and hypertension effect of angiotensin II, patients are often treated with ace inhibitors or with angiotensin II type 1 receptor blockers. Renal Sodium and Water Regulation
• Angiotensin II Angiotensin II An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the c-terminal by angiotensin converting enzyme. The amino acid in position 5 varies in different species. To block vasoconstriction and hypertension effect of angiotensin II, patients are often treated with ace inhibitors or with angiotensin II type 1 receptor blockers. Renal Sodium and Water Regulation:
  • Stimulates the zona glomerulosa Zona Glomerulosa The narrow subcapsular outer zone of the adrenal cortex. This zone produces a series of enzymes that convert pregnenolone to aldosterone. The final steps involve three successive oxidations by cytochrome p-450 cyp11b2. Adrenal Glands: Anatomy in the adrenal cortex Adrenal Cortex The outer layer of the adrenal gland. It is derived from mesoderm and comprised of three zones (outer zona glomerulosa, middle zona fasciculata, and inner zona reticularis) with each producing various steroids preferentially, such as aldosterone; hydrocortisone; dehydroepiandrosterone; and androstenedione. Adrenal cortex function is regulated by pituitary adrenocorticotropin. Adrenal Glands: Anatomy to release aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia 
  • Induces systemic vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure
  • Stimulates Na⁺ and water reabsorption in the renal tubules
• Aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia:
  • Stimulates production of the following proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis within the principal cells Principal cells Tubular System in the distal renal tubules:
    • Na⁺/K⁺-ATPase on the basolateral side
    • Epithelial sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia channels Channels The Cell: Cell Membrane (ENaCs) on the lumen side: allows ↑ Na⁺ reabsorption from the lumen into the principal cells Principal cells Tubular System
    • Renal outer medullary potassium channel Renal outer medullary potassium channel Renal Potassium Regulation (ROMK) on the lumen side: allows excretion of K⁺ into the urine
  • Stimulates Na⁺ reabsorption from the renal tubules
    • Water follows the Na⁺ → results in ↑ water reabsorption
    • Creates a negative electrical gradient Electrical gradient Renal Potassium Regulation across the lumen, promoting the secretion Secretion Coagulation Studies of K⁺ and H⁺ into the urine
• Factors that normally trigger Trigger The type of signal that initiates the inspiratory phase by the ventilator Invasive Mechanical Ventilation the RAAS (and thus ↑ aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia):
  • ↓ Renal perfusion:
    • ↓ Blood pressure
    • ↓ Effective blood volume (e.g., venous congestion due to cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis)
  • ↑ Serum potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia (K⁺)
  • ↓ Sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia delivery to the kidney
  • ↑ Sympathetic tone

Adrenal Cortex Hormones: Glucocorticoids and Androgens

Glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids

• Hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types:
  • Cortisol Cortisol Glucocorticoids 
  • Corticosterone
• Secreted primarily from the zona fasciculata Zona Fasciculata The wide middle zone of the adrenal cortex. This zone produces a series of enzymes that convert pregnenolone to cortisol (hydrocortisone) via 17-alpha-hydroxyprogesterone. Adrenal Glands: Anatomy
• Effects: respond to immediate stressors
  • ↑ Immediately available energy through:
    • Fat and protein catabolism → ↑ blood amino acid Amino acid Amino acids (AAs) are composed of a central carbon atom attached to a carboxyl group, an amino group, a hydrogen atom, and a side chain (R group). Basics of Amino Acids and lipid levels
    • Gluconeogenesis Gluconeogenesis Gluconeogenesis is the process of making glucose from noncarbohydrate precursors. This metabolic pathway is more than just a reversal of glycolysis. Gluconeogenesis provides the body with glucose not obtained from food, such as during a fasting period. The production of glucose is critical for organs and cells that cannot use fat for fuel. Gluconeogenesis
    • Appetite stimulation
  • ↑ RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology
  • ↑ Serum calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes from bone resorption Bone resorption Bone loss due to osteoclastic activity. Bones: Remodeling and Healing (leads to ↓ bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types mineral density over time)
  • Antiinflammatory effects:
    • ↓ Inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation
    • ↓ Blood vessel permeability
    • Long-term exposure suppresses the immune system Immune system The body’s defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components. Primary Lymphatic Organs.
• Regulated by the HPA axis

Androgens Androgens Androgens are naturally occurring steroid hormones responsible for development and maintenance of the male sex characteristics, including penile, scrotal, and clitoral growth, development of sexual hair, deepening of the voice, and musculoskeletal growth. Androgens and Antiandrogens

• Hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types:
  • DHEA DHEA A major C19 steroid produced by the adrenal cortex. It is also produced in small quantities in the testis and the ovary. Dehydroepiandrosterone (dhea) can be converted to testosterone; androstenedione; estradiol; and estrone. Androgens and Antiandrogens
  • Androstenedione Androstenedione A delta-4 C19 steroid that is produced not only in the testis, but also in the ovary and the adrenal cortex. Depending on the tissue type, androstenedione can serve as a precursor to testosterone as well as estrone and estradiol. Androgens and Antiandrogens 
• Secreted primarily from the zona reticularis Zona Reticularis The inner zone of the adrenal cortex. This zone produces the enzymes that convert pregnenolone, a 21-carbon steroid, to 19-carbon steroids (dehydroepiandrosterone; and androstenedione) via 17-alpha-hydroxypregnenolone. Adrenal Glands: Anatomy
• Adrenal androgens Androgens Androgens are naturally occurring steroid hormones responsible for development and maintenance of the male sex characteristics, including penile, scrotal, and clitoral growth, development of sexual hair, deepening of the voice, and musculoskeletal growth. Androgens and Antiandrogens can be converted to testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens and estrogens in peripheral tissue (primary source of estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy in postmenopausal women).
• Effects:
  • Important for secondary sex characteristics Secondary sex characteristics Gonadal Hormones
  • Stimulates axillary, pubic, and male-pattern facial hair

Hormones Secreted by the Adrenal Medulla

Hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types and their regulation

• The adrenal medulla Adrenal Medulla The inner portion of the adrenal gland. Derived from ectoderm, adrenal medulla consists mainly of chromaffin cells that produces and stores a number of neurotransmitters, mainly adrenaline (epinephrine) and norepinephrine. The activity of the adrenal medulla is regulated by the sympathetic nervous system. Adrenal Glands: Anatomy secretes catecholamines:
  • Epinephrine Epinephrine The active sympathomimetic hormone from the adrenal medulla. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. Sympathomimetic Drugs (80%)
  • Norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS (20%)
• Synthesized from dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS within chromaffin cells (modified sympathetic neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology)
• Controlled by the sympathetic nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. Nervous System: Anatomy, Structure, and Classification (rather than the hypothalamus Hypothalamus The hypothalamus is a collection of various nuclei within the diencephalon in the center of the brain. The hypothalamus plays a vital role in endocrine regulation as the primary regulator of the pituitary gland, and it is the major point of integration between the central nervous and endocrine systems. Hypothalamus/ pituitary Pituitary A small, unpaired gland situated in the sella turcica. It is connected to the hypothalamus by a short stalk which is called the infundibulum. Hormones: Overview and Types):
  • Preganglionic nerve fibers Nerve Fibers Slender processes of neurons, including the axons and their glial envelopes (myelin sheath). Nerve fibers conduct nerve impulses to and from the central nervous system. Nervous System: Histology synapse Synapse The junction between 2 neurons is called a synapse. The synapse allows a neuron to pass an electrical or chemical signal to another neuron or target effector cell. Synapses and Neurotransmission with the chromaffin cells.
  • Acetylcholine Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS from the preganglionic nerve fibers Nerve Fibers Slender processes of neurons, including the axons and their glial envelopes (myelin sheath). Nerve fibers conduct nerve impulses to and from the central nervous system. Nervous System: Histology stimulates the nicotinic type 2 Type 2 Spinal Muscular Atrophy receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors on the chromaffin cells.
  • Chromaffin cells release the catecholamines directly into the blood.
  • Catecholamines stimulate α- and β-adrenergic receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors throughout the body.

Effects

The primary purpose of the medullary catecholamines is to supplement the effects of the sympathetic nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. Nervous System: Anatomy, Structure, and Classification. Because these substances are released directly into the bloodstream as hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types, their effects last longer than when catecholamines are released as neurotransmitters. These effects include characteristics of the fight-or-flight response:

• ↑ Blood pressure
• ↑ HR
• ↑ Circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment to skeletal muscles Skeletal muscles A subtype of striated muscle, attached by tendons to the skeleton. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles. Muscle Tissue: Histology
• ↑ Respirations and bronchodilation
• ↑ Blood glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance levels by:
  • Stimulating glycogenolysis Glycogenolysis The release of glucose from glycogen by glycogen phosphorylase (phosphorolysis). The released glucose-1-phosphate is then converted to glucose-6-phosphate by phosphoglucomutase before entering glycolysis. Glycogenolysis is stimulated by glucagon or epinephrine via the activation of phosphorylase kinase. Glycogen Metabolism 
  • Stimulating gluconeogenesis Gluconeogenesis Gluconeogenesis is the process of making glucose from noncarbohydrate precursors. This metabolic pathway is more than just a reversal of glycolysis. Gluconeogenesis provides the body with glucose not obtained from food, such as during a fasting period. The production of glucose is critical for organs and cells that cannot use fat for fuel. Gluconeogenesis 
  • Epinephrine Epinephrine The active sympathomimetic hormone from the adrenal medulla. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. Sympathomimetic Drugs inhibits insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin release
• ↓ Digestion Digestion Digestion refers to the process of the mechanical and chemical breakdown of food into smaller particles, which can then be absorbed and utilized by the body. Digestion and Absorption

Clinical Relevance

There are a number of clinical conditions that result from abnormalities of the adrenal hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types. Some of the most clinically important include:

• Pheochromocytoma Pheochromocytoma Pheochromocytoma is a catecholamine-secreting tumor derived from chromaffin cells. The majority of tumors originate in the adrenal medulla, but they may also arise from sympathetic ganglia (also referred to as paraganglioma). Symptoms are associated with excessive catecholamine production and commonly include hypertension, tachycardia, headache, and sweating. Pheochromocytoma: rare catecholamine-secreting tumors arising from the chromaffin cells of the adrenal medulla Adrenal Medulla The inner portion of the adrenal gland. Derived from ectoderm, adrenal medulla consists mainly of chromaffin cells that produces and stores a number of neurotransmitters, mainly adrenaline (epinephrine) and norepinephrine. The activity of the adrenal medulla is regulated by the sympathetic nervous system. Adrenal Glands: Anatomy. The presentation of pheochromocytoma Pheochromocytoma Pheochromocytoma is a catecholamine-secreting tumor derived from chromaffin cells. The majority of tumors originate in the adrenal medulla, but they may also arise from sympathetic ganglia (also referred to as paraganglioma). Symptoms are associated with excessive catecholamine production and commonly include hypertension, tachycardia, headache, and sweating. Pheochromocytoma is typically with treatment-resistant hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, episodic headaches, sweating, and tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children. Diagnosis is made via laboratory assessment showing elevated serum catecholamines and adrenal imaging studies. These tumors are benign Benign Fibroadenoma 90% of the time, and surgical resection is the only curative treatment.
• Adrenal insufficiency Adrenal Insufficiency Conditions in which the production of adrenal corticosteroids falls below the requirement of the body. Adrenal insufficiency can be caused by defects in the adrenal glands, the pituitary gland, or the hypothalamus. Adrenal Insufficiency and Addison Disease: refers to the inadequate production of glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids, mineralocorticoids Mineralocorticoids Mineralocorticoids are a drug class within the corticosteroid family and fludrocortisone is the primary medication within this class. Fludrocortisone is a fluorinated analog of cortisone. The fluorine moiety protects the drug from isoenzyme inactivation in the kidney, allowing it to exert its mineralocorticoid effect. Mineralocorticoids, and adrenal androgens Androgens Androgens are naturally occurring steroid hormones responsible for development and maintenance of the male sex characteristics, including penile, scrotal, and clitoral growth, development of sexual hair, deepening of the voice, and musculoskeletal growth. Androgens and Antiandrogens. Diagnosis is made by measuring cortisol Cortisol Glucocorticoids levels and ACTH levels and with ACTH stimulation testing. Management involves glucocorticoid and mineralocorticoid replacement therapy.
  • Addison’s disease Addison’s Disease Adrenal insufficiency (AI) is the inadequate production of adrenocortical hormones: glucocorticoids, mineralocorticoids, and adrenal androgens. Primary AI, also called Addison’s disease, is caused by autoimmune disease, infections, and malignancy, among others. Adrenal Insufficiency and Addison Disease ( primary adrenal insufficiency Primary adrenal insufficiency An adrenal disease characterized by the progressive destruction of the adrenal cortex, resulting in insufficient production of aldosterone and hydrocortisone. Clinical symptoms include anorexia; nausea; weight loss; muscle weakness; and hyperpigmentation of the skin due to increase in circulating levels of acth precursor hormone which stimulates melanocytes. Adrenal Insufficiency and Addison Disease): Etiologies include autoimmune disease, infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease, and malignancy Malignancy Hemothorax, among others. 
  • Secondary and tertiary adrenal insufficiency Tertiary adrenal insufficiency Deficiency in the hypothalamic secretion of corticotropin-releasing hormone (CRH). Adrenal Insufficiency and Addison Disease: due to the decreased production of ACTH within the pituitary Pituitary A small, unpaired gland situated in the sella turcica. It is connected to the hypothalamus by a short stalk which is called the infundibulum. Hormones: Overview and Types (secondary) or decreased production of CRH from the hypothalamus Hypothalamus The hypothalamus is a collection of various nuclei within the diencephalon in the center of the brain. The hypothalamus plays a vital role in endocrine regulation as the primary regulator of the pituitary gland, and it is the major point of integration between the central nervous and endocrine systems. Hypothalamus (tertiary). Secondary insufficiency can also occur because of prolonged glucocorticoid therapy. 
• Congenital Congenital Chorioretinitis adrenal hyperplasia Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. Cellular Adaptation ( CAH CAH Congenital adrenal hyperplasia (CAH) consists of a group of autosomal recessive disorders that cause a deficiency of an enzyme needed in cortisol, aldosterone, and androgen synthesis. The most common subform of cah is 21-hydroxylase deficiency, followed by 11β-hydroxylase deficiency. Congenital Adrenal Hyperplasia): group of autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritance disorders that cause a deficiency of an enzyme (most commonly 21-hydroxylase) needed in cortisol Cortisol Glucocorticoids, aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia, and androgen synthesis Synthesis Polymerase Chain Reaction (PCR). Clinical manifestations include ambiguous genitalia Ambiguous Genitalia Primary Amenorrhea in genotypic females, salt wasting, and hypoglycemia Hypoglycemia Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia. A less severe form, known as nonclassical CAH CAH Congenital adrenal hyperplasia (CAH) consists of a group of autosomal recessive disorders that cause a deficiency of an enzyme needed in cortisol, aldosterone, and androgen synthesis. The most common subform of cah is 21-hydroxylase deficiency, followed by 11β-hydroxylase deficiency. Congenital Adrenal Hyperplasia, also exists; this form typically presents in puberty Puberty Puberty is a complex series of physical, psychosocial, and cognitive transitions usually experienced by adolescents (11-19 years of age). Puberty is marked by a growth in stature and the development of secondary sexual characteristics, achievement of fertility, and changes in most body systems. Puberty. Lifelong glucocorticoid replacement is needed. 
• Cushing syndrome Cushing syndrome A condition caused by prolonged exposure to excess levels of cortisol (hydrocortisone) or other glucocorticoids from endogenous or exogenous sources. It is characterized by upper body obesity; osteoporosis; hypertension; diabetes mellitus; hirsutism; amenorrhea; and excess body fluid. Endogenous Cushing syndrome or spontaneous hypercortisolism is divided into two groups, those due to an excess of adrenocorticotropin and those that are acth-independent. Paraneoplastic Syndromes: condition resulting from chronic exposure to excess glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids. Etiologies include chronic glucocorticoid intake or increased adrenal secretion Secretion Coagulation Studies of cortisol Cortisol Glucocorticoids due to problems either in the adrenal glands Adrenal Glands The adrenal glands are a pair of retroperitoneal endocrine glands located above the kidneys. The outer parenchyma is called the adrenal cortex and has 3 distinct zones, each with its own secretory products. Beneath the cortex lies the adrenal medulla, which secretes catecholamines involved in the fight-or-flight response. Adrenal Glands: Anatomy directly, or to increased pituitary Pituitary A small, unpaired gland situated in the sella turcica. It is connected to the hypothalamus by a short stalk which is called the infundibulum. Hormones: Overview and Types or ectopic secretion Secretion Coagulation Studies of ACTH. Typical clinical features include central obesity Central Obesity Cushing Syndrome, thin, bruisable skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions, abdominal striae, secondary hypertension Secondary hypertension Hypertension, hyperglycemia Hyperglycemia Abnormally high blood glucose level. Diabetes Mellitus, and proximal muscle weakness Proximal Muscle Weakness Lambert-Eaton Myasthenic Syndrome. Diagnosis involves urinary and/or salivary cortisol Cortisol Glucocorticoids testing along with a low-dose dexamethasone Dexamethasone An anti-inflammatory 9-fluoro-glucocorticoid. Antiemetics suppression Suppression Defense Mechanisms test, measurement of ACTH levels, and possibly imaging. 
• Hyperaldosteronism Hyperaldosteronism Hyperaldosteronism is defined as the increased secretion of aldosterone from the zona glomerulosa of the adrenal cortex. Hyperaldosteronism may be primary (resulting from autonomous secretion), or secondary (resulting from physiological secretion due to stimulation of the RAAS). Classically, hyperaldosteronism presents with hypertension, hypokalemia, and metabolic alkalosis. Hyperaldosteronism: increased secretion Secretion Coagulation Studies of aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia from the adrenal cortex Adrenal Cortex The outer layer of the adrenal gland. It is derived from mesoderm and comprised of three zones (outer zona glomerulosa, middle zona fasciculata, and inner zona reticularis) with each producing various steroids preferentially, such as aldosterone; hydrocortisone; dehydroepiandrosterone; and androstenedione. Adrenal cortex function is regulated by pituitary adrenocorticotropin. Adrenal Glands: Anatomy. Hyperaldosteronism Hyperaldosteronism Hyperaldosteronism is defined as the increased secretion of aldosterone from the zona glomerulosa of the adrenal cortex. Hyperaldosteronism may be primary (resulting from autonomous secretion), or secondary (resulting from physiological secretion due to stimulation of the RAAS). Classically, hyperaldosteronism presents with hypertension, hypokalemia, and metabolic alkalosis. Hyperaldosteronism may be primary (resulting from autonomous secretion Secretion Coagulation Studies (known as Conn syndrome Conn Syndrome Hyperaldosteronism)) or secondary (resulting from physiologic secretion Secretion Coagulation Studies caused by increased stimulation of the RAAS). Hyperaldosteronism Hyperaldosteronism Hyperaldosteronism is defined as the increased secretion of aldosterone from the zona glomerulosa of the adrenal cortex. Hyperaldosteronism may be primary (resulting from autonomous secretion), or secondary (resulting from physiological secretion due to stimulation of the RAAS). Classically, hyperaldosteronism presents with hypertension, hypokalemia, and metabolic alkalosis. Hyperaldosteronism presents with hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, hypokalemia Hypokalemia Hypokalemia is defined as plasma potassium (K+) concentration < 3.5 mEq/L. Homeostatic mechanisms maintain plasma concentration between 3.5-5.2 mEq/L despite marked variation in dietary intake. Hypokalemia can be due to renal losses, GI losses, transcellular shifts, or poor dietary intake. Hypokalemia, and metabolic alkalosis Alkalosis A pathological condition that removes acid or adds base to the body fluids. Respiratory Alkalosis. Diagnosis involves measuring plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia and renin Renin A highly specific (leu-leu) endopeptidase that generates angiotensin I from its precursor angiotensinogen, leading to a cascade of reactions which elevate blood pressure and increase sodium retention by the kidney in the renin-angiotensin system. Renal Sodium and Water Regulation activity levels, along with imaging to look for hormone-secreting tumors. Management involves the use of aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors antagonists and surgical excision of any aldosterone-secreting tumors.
• Hypoaldosteronism Hypoaldosteronism Hypoaldosteronism is a hormonal disorder characterized by low levels of aldosterone. These low levels can be caused by decreased aldosterone production or a peripheral resistance to aldosterone. When hypoaldosteronism occurs as a result of an acquired decrease in renin production, the condition is more commonly referred to as renal tubular acidosis (RTA) type 4. Hypoaldosteronism: condition resulting from low levels of aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia. Hypoaldosteronism Hypoaldosteronism Hypoaldosteronism is a hormonal disorder characterized by low levels of aldosterone. These low levels can be caused by decreased aldosterone production or a peripheral resistance to aldosterone. When hypoaldosteronism occurs as a result of an acquired decrease in renin production, the condition is more commonly referred to as renal tubular acidosis (RTA) type 4. Hypoaldosteronism can be caused by decreased aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia production or by a peripheral resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing to aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia. When the condition occurs as a result of an acquired decrease in renin Renin A highly specific (leu-leu) endopeptidase that generates angiotensin I from its precursor angiotensinogen, leading to a cascade of reactions which elevate blood pressure and increase sodium retention by the kidney in the renin-angiotensin system. Renal Sodium and Water Regulation production from the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy, the condition is referred to as renal tubular acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis ( RTA RTA Renal tubular acidosis (RTA) is an imbalance in physiologic pH caused by the kidney’s inability to acidify urine to maintain blood pH at physiologic levels. Renal tubular acidosis exist in multiple types, including distal RTA (type 1), proximal RTA (type 2), and hyperkalemic RTA (type 4). Renal Tubular Acidosis) type 4 Type 4 Spinal Muscular Atrophy. Most individuals are asymptomatic and diagnosed when routine lab evaluation demonstrates hyperkalemia Hyperkalemia Hyperkalemia is defined as a serum potassium (K+) concentration >5.2 mEq/L. Homeostatic mechanisms maintain the serum K+ concentration between 3.5 and 5.2 mEq/L, despite marked variation in dietary intake. Hyperkalemia can be due to a variety of causes, which include transcellular shifts, tissue breakdown, inadequate renal excretion, and drugs. Hyperkalemia and a mild hyperchloremic metabolic acidosis Hyperchloremic Metabolic Acidosis Potassium-sparing Diuretics, prompting further workup.