Adrenal Gland Physiology Flashcards
Zona glomerulosa
Produce mineralcorticoids (aldosterone) Regulate mineral/electrolyte balance
Zona fasciculata
Glucocorticoids (cortisol)
Regulate glucose metabolism
Zona reticularis
Androgens
Stimulate masculinization
dehydroepiandrosterone
Medulla
Stress hormones
Sympathetic ANS
epi and norepi
HPA axis
Hypothalamus -corticotropin releasing hormone->
Anterior pituitary -Adrenocorticotropic hormone
Adrenal cortex- cortisol
Mineralcorticoids
Aldosterone
Stimulated mainly by signals from the kidneys but also hypothalamic (CRH) and pituitary (ACTH)
Glucocorticoids and androgens
Cortisol and dehydroepiandrosterone
Stimulated mainly by signals from the hypothalamus (CRH) and pituitary (ACTH)
Catecholamines
Epi
Stimulated by signals from the sympathetic nervous system
Andrenal cortex hormone synthesis
Produces steroid hormones- derived from cholesterol
In the first step- cholesterol is used to form pregnenolone
This step is common to all arden-cortical hormones
Occurs in the mitochondrion
This step is regulated by ACTH- limits the rate of synthesis of all adrenocortical hormones
Mineralocorticoid overview
These are corticosteroids that influence salt and water balances (electrolyte and fluid balance)
Aldosterone is the primary mineralocorticoid
Acts on distal tubules in kidneys to provide:
-active reabsorption of Na
-active secretion of K
-active secretion of protons
-passive reabsorption of water
Adrenal cortex aldosteron
Closely linked to a renin (enzyme) and angiotensin (hormone, which create RAAS.
Primary regulators: decrease in blood volume or BP will activate RAAS. Also an increase in K in blood
Leads to zona glomerulosa enhanced secretion of aldosterone which leads to increase blood volume and BP
Main stimulants are low blood Na or high blood K or low blood volume and pressure
Major function- regulate NA and K through the distal tubules in kidneys
-active reabsorption of Na, active secretion of K and passive reabsorption of water
Negative feedback primarily via restoration of electrolyte balance
Weakly binds to plasma transport proteins.
-bound 10% to transcortin and 50% to albumin
-40$ is free or bioactive
Action on target tissue
-via cytoplasm or nuclear receptors- mineralocorticoid-receptor complex on DNA
half life iin circulation 20 minutes
metabolized in liver
-sulfates and glucuronides reduce bioactivity and increase water solubility
-secreted in urine
Steroid hormones bind to intracellular receptors
- most hydrophobic steroids are bound to plasma protein carriers. Only unbound hormones can diffuse into target cell
- Steroid hormon receptors are in the cytoplasm or nucleus
- The receptor-hormone complex binds to DNA and activates or represses one or more genes
- Activated genes create new mRNA that moves back to the cytoplasm
- Translation produces new proteins for cell processes
- Some steroid hormones also bind to membrane receptors that use second messenger systems to create rapid cell response
Glucocorticoids overview
These are corticosteroids that have broad effects but are primarily involved in metabolic (carbohydrate) and immunologic (antiinflammatory) responses
Cortisol- the most important glucocorticoids- considered stress hormoen
Circadian or diurnal rhythm- higher blood concentrations in morning than afternoon/evening
Regulation is via hypothalamic (CRH)- pituitary (ACTH) adrenal (cortisol) axis in response to low blood glucose and other stressors
Adrenal cortex: Cortisol
Stress is a biological response to external or internal stimuli or a bodys reaction to change to maintain homeostasis
- hypoglycemis
- physical trauma
- inflammation
- pathogenic
- disease
Glucocorticoids, stress and diurnal rhythm can influence the axis
Metabolic enhancer: Stimulated in response to low blood sugar or glucose
- Increases glucose via countering insulin and inhibiting glucose uptake and storage in muscle and adipose tissue, except brain
- Simulates liver enzymes to increase gluconeogenesis and glucogenolysis
- mobilize aas and FFAs to serve as substrates for gluconeogenesis
Cortisol actions on carbohydrate metabolism
Stimulates synthesis of enzymes involves in gluconeogenesis
Antagonizes insulins effects to inhibit gluconeogenesis in liver
Decrease glucose utilization be cells
Potentiates the action of glucagon and epic on glucose metabolism
Can cause diabetes mellitus
-increased gluconeogenesis + reduction in glucose utilization
Cortisol actions on protein metabolism
Stimulate catabolism of protein in muscle
Cause mobilization of aa from the extra hepatic tissues
-mainly from muscle
-serves as substrate for enzyme manufacturing
Cortisol actions on fat metabolism
Increase mobilization of FAs from adipose tissue
-shift the metabolism from glucose to fat utilization
-enhance the oxidation of FFAs in cells- reduced glucose transport into fat cells
Can cause obesity- depletion peripheral fat while increasing visceral (abdominal) fat
Cortisol actions on immune system
Immune system suppressant:
Immunosuppresive and anti-inflammatory effects
-decrease formation of prostaglandins and leukotrienes production
-reduce secretion of histamine by mast cells
-decreases phagocytosis and surpasses antibody formation
Down regulates a variety of pro-inflammatory factors
Up-regulates a variety of anti-inflammatory factors- inhibits inflammation
Inhibits secondary functions not necessary for survival
Cortisol
Cortisol transported in plasma by binding proteins
-bound 75% to transcortin and 15% to albumin
-10% free or bioactive
Half life in circulation 66 minutes
Metabolized in liver
-sulfates and fllucuronides reduce bioactivity and increase water solubility
Secreted in urine
Androgens overview
Hormones that interact with male sex hormone receptors
DHEA converted to DHEA-sulfate
DHEA concertes to androstenedione released into the blood stream and taken up by testis or ovaries to produce testosterone and estogerns
Adrenal medulla: Catecholamines
Chromaffin cells-neuroendocrine cells -modified post-ganglionic sympathetic neurons
-lack dendrites and axons
–stimulated by acetylcholine from pre-ganglionic sympathetic neurons that binds with nicotinic receptors on the chromatin cells
Produce and secrete epic (80%) norepinephrine (20%) and dopamine
Short term stress response
increased HR
increased BP
liver converts glycogen to glucose and releases to blood
Dilation of bronchioles
Changes in blood flow patterns leading to decreased digestive system activity and reduced urin output
Increased metabolic rate
Long term stress response
Mineralocorticoids
Retention of Na and water by kidneys
Increased Blood volume and BP
Glucocoricoids
Proteins and fats converted to glucose or broken down for energy
Increased blood glucose
suppression of immune system
Catecholamines
Acetylcholin release from pregangionic nerve fibers initiates the synthesis
The synthesis inside of the cells begins with conversion of tyrosine to DOPA by the enzyme tyrosine hydrozylase
End products of tyrosine metabolism include DOPA, dopamine, epic, and norepi
-DOPA concerted to dopamin in the cytosol
-dopamine is concerted tonorepi within the chromatin granules –dopamine beta-hydroxylate
-in cells that secrete epinephrin, NE returns to cytosol where is converted to epic– EPI moves to granules for storage before release
Fight or flight
EPI and NE
increases energy availability and overall metabolism
Bind to adrenoceptors which are cell surface GPCR on target tissues
Two major types of adrenergic receptors:
alpha, a1 and a2
Beta, B1 and B2
Adrenergic receptors
Alpha
a1= smooth muscle contraction, mydriasis
a2= mixed smooth muscle effects
Beta
B1= increased cardiac chronotropic (Increase HR) and inotropic (increase contractibility) effects
B2= bronchodilation
Medulla: catecholamines
Half-life in circulation about 2 minutes for NE and less for EPI
Liver and kidney metabolism
-degraded primarily by methylation by catechol-o-methyltransferases
Ecreted in urine
Disorders of adrenal gland
Hyperadrenocorticism- cushings
Hypoadrenocorticism- addisons
Hyperaldosteronism- conns syndrome
Adrenal dysfunction: In primary hyperadrenocorticism there is an overproduction of cortisol caused by a tumor…
In zona fasciculata
Hyperadrenocorticism is an overproduction of cortisol. What part of HPA axis or adrenal cortex is responsible for secondary hyperadrenocortiscism
Anterior pituitatry
Adrenal cortex dysfunction: hyperadrenocorticism
Overproduction of cortisol
-primary= adrenal gland tumor (20%)
-secondary= pituitary gland tumor (80-85%). Tumor secretes ACTH which stimulates overproduction of cortisol
-cushings disease=pituitary-dependent hyperadrenocorticism
Common in dogs, rare in cats
Increased rate of lipolysis results in redistribution of fat into the liver and abdomen -classic potbelly
Adrenal cortex dysfunction: hypoadrenocorticism
Deficiency of cortisol and or aldosterone= addisons disease
Most common in young to middle age dogs and occasionally horses
Deficiency can be result in dysfunctional adrenal gland (primary) or pituitary gland (secondary)
Primary : endogenous plasma ACTH are increased due to lack of negative feedback. Reduced response to exogenous ACTH
Secondary: Endogenous ACTH are typically decreased
Mya or may not be a reduced response exogenous ACTH
Adrenal cortex dysfunction: Hyperaldosteronism
Overproduction of aldosterone= Conn’s syndrome
Diagnosed in older cats and occasionally dogs
Hypersecreting adrenal tumor or bilateral adrenal hyperplasia
Classic electrolyte changes: decrease in blood K, increase Blood Na and pH
Diagnosis: increased plasma aldosterone, low to undetectable plasma renin, increased plasma aldosterone-to-plasme renin concentration
Ultrasonographic imaging: unilateral or bilateral or adrenal hyperplasia or enlargement
Treatment: K supplementation
Surgical removal of adrenal tumor- tumors of adrenal gland usually benign
Excessive production of aldosterone- the most common form of adrenal disease in cats
caused by hyperplasia or neoplasia of zona glomerulosa
Adrenal cortex dysfunction: Hypoaldosteronism
Very rare
Pheochromocytoma
Neoplasm of adrenal medullary chromatin cells -catecholamine-secreting tumor Signs can be absent/sporatic Hypertension -blindness Collapse Tachypnea Arrithmia
