Adrenal Gland Functions and Diseases Lecture (Dr. Lopez) Flashcards
The Adrenal Gland
- TWO Adrenal Glands
- Each located at the SUPERIOR POLES of the Two Kidneys
- ENDOCRINE and NEUROENDOCRINE Gland
The Adrenal is TWO Endocrine Glands that derive from Distinct Embryological Origin
- ADRENAL MEDULLA is of ECTODERMAL Origin
- ADRENAL CORTEX is of EPIDERMAL Origin
Adrenal Cortex Hormones (Gland)
1) ALDOSTERONE (Steroid)
a) PRIMARY TARGET:
- Kidney
b) MAIN EFFECT:
- Na+ and K+ Homeostasis
2) CORTISOL(Steroid)
a) PRIMARY TARGET:
- Many Tissues
b) MAIN EFFECT:
- Stress Response
3) ANDROGENS (Steroid)
a) PRIMARY TARGET:
- Many Tissues
b) MAIN EFFECT:
- Stress Response
Adrenal Medulla (Neuron)
1) EPINEPHRINE (Amino Acid Derived)
a) PRIMARY TARGET:
- Many Tissues
b) MAIN EFFECT:
- “Fight or Flight” Response
2) NOREPINEPHRINE (Amimo Acid Derived)
a) PRIMARY TARGET:
- Many Tissues
b) MAIN EFFECT:
- “Fight or Flight” Response
Hormone Secretion by the Adrenal Gland
1) Zona Glomerulusa:
- ALDOSTERONE (Mineralocorticoid)
2) Zone Fascicultata:
- CORTISOL (Glucocorticoids)
- ANDROGENS
3) Zona Reticulares:
- CORTISOL (Glucocorticoids)
- ANDROGENS
4) Adrenal Medulla:
- EPINEPHRINE and NOREPINEPHRINE (Catecholamines)
Pathways for the Synthesis of Steroid hormone by the Adrenal Cortex
KEY ENZYMES:
1) 3 Beta- Hydroxysteroid Dehydrogenase
2) 17 Alpha- Hydroxylase
3) 21 Beta- Hydroxylase
4) 11 Beta Hydroxylase
5) 17,20 Lyase
The Steroidogenic Acute Regulatory Protein (StAR)
- StAR, is a Transport Protein that regulates CHOLESTEROL transfer within the MITOCHONDRIA, which is the RATE-LIMITING step in the Production of Steroid Hormones (DESMOLASE!!!!!)
Steroid Hormones
- LIPOPHILIC; Easily Across Membrane
- Cytoplasmic or Nuclear Receptors
a) Genomic effect to ACTIVATE or REPRESS Genes for Protein Synthesis (SLOWER ACTING) - Cell Membrane Receptors
a) Non-Genomic Responses
Adrenocorticotropic Hormone (ACTH)
- ACTH stimulates Synthesis and Secretion of Adrenal Cortical Hormones:
1) Glucocorticoids (Cortisol)
2) Mineralocorticoids (Aldosterone)
3) Androgens
***** CRH (Hypo) —-> ACTH (Ant Pit)—–>
Adrenocorticotropic Hormone (ACTH) Cont
- Produced in the ANTERIOR PITUITARY
- Derived from POST-TRANLSAITON processing of POMC (Pro-Opiomelanocortin)
- Is a Peptide
***Leads to MELANIN SYNTHESIS from the Alpha-MSH!!!!!!
HPA Axis
- The Hypothalamic, Pituitary, Adrenal (HPA) Axis is under Negative FEEDBACK Control by CORTISOL!!!!!!
Cortisol Effects
1) Immune System
- Immune SUPPRESSION
2) Liver:
- Gluconeogenesis
3) Muscle:
- Protein Catabolism
4) Adipose Tissue:
- Lipolysis
Circadian Rhythm of Cortisol
- The Secretory rates of Cortisol are HIGH Early in the Morning but LOW in the Evening
Exogenous Glucocorticoids have the same Negative Feedback Effect as Cortisol
- Exogenous Administration may SHUT DOWN ACTH Production and Adrenal Cells that produce CORTISOL (Atrophy!)
- Examples of Synthetic Glucocorticoids:
a) Cortisone
b) Prednisone
c) Methylprednisone
d) Dexamethasone
Hyper and HypoCortisolism
HYPERCORTISOLISM: 1) Cushing Syndrome: - ACTH Decrease - CORTISOL Increase - CRH Decrease (Caused by ADRENAL TUMOR)
2) Cushing’s Disease:
- CORTISOL Increase
- ACTH INCREASE
- CRH Decrease
( Pituitary Tumor)
HYPOCORTISOLISM: 1) Addison's Disease - CRH Increase - ACTH Increase - CORTISOL Decrease ( Autoimmune Disease of the Adrenal Gland)
2) Secondary Adrenal Insufficiency
- CRH Decrease
- ACTH Decrease
- CORTISOL Decrease
(Glucocorticoid Drugs SUPPRESSING Hypothalamus and Pituitary)
HYPERCORTISOLISM
HYPERCORTISOLISM (Cushing’s Syndrome)
- ADRENAL Tumor that AUTONOMOUSLY Secretes Cortisol (PRIMARY: Adrenal Excess)
- Drug Induced Hypercortisolism
- PITUITARY Tumor that AUTONOMOUSLY Secretes ACTH (SECONDARY: Pituitary Excess)
- **Ex: Cushing’s Disease
HYPOCORTISOLISM
HYPOCORTISOLISM
- HYPOSECRETION of all ADRENAL STEROID Hormones
- ***Ex: ADDISON’S DISEASE (PRIMARY Adrenocortical Insufficiency)
- Secondary Adrenocortical Insufficiecny (ACTH Deficiency)
- **Ex: Chronic Exogenous Glucocorticoid Treatment
Use Cosyntropin (Synthetic ACTH) Stimulation Test to Detect Adrenal Gland INSUFFICIENCY
- Tests that measure the level of Hormones are used to Diagnose Pathologies
- **Ex: COSYNTROPIN Stimualtion Test (CST)
Regulation of Aldosterone Secretion
1) A DECREASE in BP —>
2) Kidney produces more RENIN —>
3) Renin converts Angiotensin into ANGIOTENSIN I —>
4) Angiotensin I converts to ANGTIOTENSIN II by ACE!!! —>
5) Angiotensin II leads to ALDOSTERONE Production —>
6) Aldosterone leads to Water/ Na+ REABSORPTION —–>
7) Water Retention leads to an INCREASE in BP
***The Primary action of Aldosterone is RENAL SODIUM REABSORPTION
The Primary action of Aldosterone is RENAL SODIUM REABSORPTION
1) Aldosterone combine sixth Cytoplasmic Receptor in Distal Convoluted Tubule or Collecting Duct
2) Hormone- Receptor complex initiates Transcription in the Nucleus
3) Translation and Protein Synthesis makes new protein Channels and Pumps
4) Aldosterone- Induced Protein modulate EXISTING Channels and Pumps
5) Results in INCREASED Na+ Reabsorption and K+ Secretion
Aldosterone Pathologies
1) HYPERALDOSTERONISM:
a) PRIMARY Hyperaldosteronism:
- Excessive Release of Aldosterone from the Adrenal Cortex
* * EX: CONN’S SYNDROME: Adenoma in the Adrenal Cortex
b) SECONDARY Hyperaldosteronism: Excessive RENIN Secretion by the JUXTAGLOMERULAR Cells in the Kidney
2) HYPOALDOSTERONISM:
- Destruction of the Adrenal Cortex
- Defects in Aldosterone Synthesis
- Inadequate Stimulation of Aldosterone Secretion
Overview of Hormones produced by the Adrenal Medulla
- The Adrenal Medulla produces CATECHOLAMINES: Primarily EPINEPHRINE (80%) and small amounts of NOREPINEPHRINE (20%)
- Adrenomedullary Catecholamines are Secreted into the blood and act as Hormones
- EPINEPHRINE
a) Responder to STRESS such as Hypoglycemia/ Exercise
b) Influences Energy Metabolism and Cardiac Output
Synthesis of Catecholamines
- Under Control of the CRH - ACTH - Cortisol Axis
a) ACTH Stimulates Synthesis of DOPA
b) CORTISOL increases Pheynlethanolamin - N - Methyl Transferase (PNMT) Enzyme (NOREPI —-> EPI)
- Release is triggered by CNS Control
***Norepinephrine and Epinephrine are Synthesized in DIFFERENT Cellular Compartments
Norepinephrine and Epinephrine are Synthesized in DIFFERENT Cellular Compartments
- RATE LIMITING STEP is the Hydroxylation of Tyrosine by TYROSINE HYDROXYLASE, producing DOPA
- DOPA is converted to DA by the Cytoplasmic Enzyme, Aromatic Amino Acid Decarboxylase (AADC) and is then transported into the Secretory Vesicle (CHROMAFFIN GRANULE)
- Within the Chromatin Granule, DA is converted to NE by Enzyme, Dopamine Beta- Hydroxylase (DBH)
Norepinephrine and Epinephrine are Synthesized in DIFFERENT Cellular Compartments Cont.
- In most Adrenomedulalry Cells, essentially all of the NE diffuses out of the Chromaffin Granule by FACILITATED TRANSPORT and is METHYLATED by the Cytoplasmic Enzyme, PHENYLETHANOLAMINE - N - METHYL TRANSFERASE (PNMT), to form Epinpehrine
- Epinephrine is the transported back into Granule by VESICULAR MONAMINE TRANSPORTERS (VMATs)
- Multiple molecules of Epinephrine, and to a lesser extent Norepinephrine, are stored in the Chromaffin Granule complexed with ATP, Ca2+, and protein called CHROMOGRANINS
a) CHROMAGRANINS: Miltimolecular Complexes, thought to Decrease the Osmotic Burden of Strong Individual molecules of Epinephrine within Chromaffin Granules
b) Circulating Chromogranins can be used as a marker of Sympathetic Paraganglion-derived tumors (Paragangliomas)
Degradation of Catecholamines
*** Action of Catecholamines is brief is about 10 seconds
COMT: Catecholamine- O - Methyltrasferase
MOA: Monoamine Oxidase
***Catecholamines, Metanephrines, and Vanillylmandelic Acid (VMA) can be measured to determine Total Catecholamine production
Catecholamine Receptors
Epinephrine has HIGHER affinity for Beta 2 Receptors*
- The ALPHA Receptors, BETA 3 Receptors respond better to Norepinephrine than Epinephrine
- BETA 1 Receptors respond equally to Norepinephrine and Epinephrine
- Epinephrine is MORE POTENT than Norepinephrine for the BETA 2 Receptors
Pheochromocytoma
PHEOCHROMOCYTOMA: Tumor of the CHROMAFFIN TISSUE
a) Produces Excess CATECHOLAMINES
b) Symptoms SPORADIC
1) Hypertension (Reported that 1% of patents with Hypertension have a Pheochromocytoma)
2) Orthostatic Hypotension (Volume Depletion)
3) HEADACHES
4) SWEATING
5) Anxiety
6) PALPITATIONS
7) Chest Pain
8) Flushing
