Lec 24- The adrenal gland Flashcards
2 different tissues of the adrenal gland
1)Adrenal cortex
-Surrounds the medulla
-Secretes steroids: glucocorticoids and mineralocorticoids (and adrogens)
2) Adrenal medulla
-Chromaffin tissue
-Secretes adrenaline and NA
These glands are above the kidney
Glucocorticoids
-Produced by cells of zona fasciculata- Controlled by the pituitary ACTH (Adrenocorticotropic hormone)
ROLES
1)INTERMEDIARY METABOLISM (has enough energy to keep cells living and respond to change)
-Carbohydrate; lipid; protein
-Anabolic effect on the liver; catabolic effect on skeletal muscle and adipose tissue
2)PERMISSIVE ACTION (when other systems need a specific level of glucocorticoid to work)
-Required for functioning of sympathoadrenal system (when dealing with stress so body can cope with rise of adrenaline)
-Necessary for catecholamine synthesis, uptake and action
3)Enable the body to respond to stress and not be damaged
HPA axis
Hypothalamus (Constantly monitoring body) –CRH (corticotropin releasing hormone) –> Anterior pituitary –ACTH (adrenocorticotropic hormone)—>
Adrenal cortex –> corticoid
-This is an example of homeostatic mechanism
What do endogenous glucocorticoids do
- Permissive action: usually when an organism is resting state
- They permit or help action of other hormones
- Respond to threats
- Need at rest and in stress
What do glucocorticoids do
Enable body to respond to stress
-direct effect and permissive effects both important
Metabolic actions
-Increased availability of glucose (energy)- (increase lipolysis; proteolysis; gluconeogenesis)
Regulatory actions of glucocorticoids
Negative feedback on HPA
Reduced vasodilation, reduced fluid exudation
Effects on cells of immune system to REDUCE inflammatory response and immune response
-Reduce unwanted inflammation
-Reduce bodies ability to heal
-Reduce body’s ability to respond to infection
How do glucocorticoids act
In most target tissue
-Bind to specific cytoplasmic receptors
-Translocation of bound complex to nucleus
-Bind to steroid response elements on DNA
-Either repress or induce transcription of specific genes (depends on tissue)
Therefore
-Some actions of glucocorticoids take time to develop as rely on gene transcription
Why are glucocorticoid drugs anti-inflammatory
- Decreased production of prostanoids through reduced expression of COX2
- Decreased generation of many cytokines including (IL-1,2,3,4,5,8; TNF-a)
- Reduction in conc of complement components
- Decreased generation of induce NO by NOS
- Decreased histamine release from basophils and mast cells
- Decrease in IgG
- Increased synthesis of Anti-inflammatory factors e.g. IL-10
Cushings’ syndrome
-Hormonal disorder caused by prolonged exposure of tissues to high levels of cortisol: HYPERcorticolism SYMPTOMS -upper body obesity (Fat neck) -roudn face -Thinning arms and legs -Fra
Cushings’ symptoms
SYMPTOMS
- upper body obesity (Fat neck)
- roudn face
- Thinning arms and legs
- Fragile skin which bruises easily
- Brittle bones (Reduced osteoblast increased osteoclast)
- Weak muscles
- High BP
- High blood sugar
- Irritable/ anxiety/ depression
Causes of Cushings’
-Iatorogenic (drug induced) effects- because we give them chronic glucocorticoid
-Pituitary adenoma: common; benign; women 5:1 men; secretes excess ACTH
-Ectopic (not in pituitary) ACTH (tumour): Malignant or benign; 50% lung, men 3:1 women
-Adrenal tumours: non-malignant adenomas; onset >40 years; uncommon; rapid onset of symptoms: women>Men
+secrete excess cortisol and other adrenal hormones (mineralocorticoids) this will mean its easier to spot as only one that release mineralocorticoids
Diagnosis- hypercorticoaemia
-Patient history; physical examination; biochemical tests; scan for tumours
-24 hour free cortisol (urines): level >50-100 mcg/day => Cushings’
-Dexamethasone suppression test:
+Distinguishes between pituitary and ectopic ACTH-secreting tumours
+Only pituitary ACTH suppressed by dexamethasone (this acts like endogenous corticoid therefore switches off corticoid production, if you still get corticoid production its not in pituitary)
DST (dexamethasone suppression test)
Normal pituitary -Normal cortisol levels -Dex --> ACTH? --> cortisol? Pituitary adenoma -High cortisol, high ACTH -Dex--> ACTH --> cortisol Ectopic adenoma -ACTH and cortisol increased -Dex --> no effect
Management for Cushing (look into this more)
Depends on cause
-Normalisation of cortisol levels or actions
-If caused by exogenous corticoid then reduce dosing gradually- fast removal can lead to deficit in glucocorticoid
-Often surgical: Tumor removal;
-Radiotherapy- to reduce tumor size
-Medicines to reduce the effect of cortisol on your body
+Ketoconazole: inhibits 17a-hydroxylase which inhibits aldosterone and cortisol synthesis: also inhibits adrenal C17-20lyase enzymes resulting in androgen synthesis inhibition and may have a direct effect on corticotropic tumor cells in patients with cushings syndrome
+Metyrapone is a competative inhibitor of 11beta-hydroxylation in adrenal cortex resulting in inhibition of cortisol= increase in ACTH which leads to increase release of cortisol precursors (differential diagnosis)
Addisons disease
-Chronic adrenal insufficiency
+Affects 1 in 100k people
+Can occur in all again groups and affects men and women equally
-Hypocorticolism
+What are the symptoms
+Complete after doing the previous directed study
-Insidious worsening of symptoms
+Often undiagnosed, sometimes until an addisonian crisis occurs
