Test 5 Flashcards
What are hormones?
Chemical regulators of cellular function
Where are hormones synthesized?
Endocrine glands
What happens after hormones are produced?
They are put into circulation (released)
How do hormones act on target tissues?
Through what?
Through specific receptors
What are the three types of hormones?
Amino acid based hormones
Eicosanoids
Steroidal hormones
What kind of hormones are insulin, GH, and catechols?
Amino acid based hormones
These are AAs, peptides, proteins, and catecholamines
What kind of hormones are prostaglandins?
Eicosanoids
Locally acting and locally secreted
What kind of hormones are adrenocortical and gonadal hormones?
Steroids
What are steroids deratives of?
Cholesterol
What kind of steroid hormones are cortisol and aldosterone?
Adrenocortical hormones
What kind of steroid hormones are estrogen and testosterone?
Gonadal hormones
What kind of receptors do steroidal hormones act on?
Intracellular/nuclear hormones
They are lipid soluble so pass through membrane
Which acts faster, plasma membrane receptors or intracellular receptors?
Plasma membrane receptors
They do not have to do with gene transcription which is slow
What kind of responses would steroid hormones produce when binding to a receptor?
Gene suppression or activation
Also thyroid hormones as well
How does a steroid get to the intracellular receptor?
Pass through plasma membrane into the cytosol and bind to intracellular receptor to form the hormone receptor complex
How do steroids affect gene transcription activity?
The hormone receptor complex interacts with DNA and affects gene transcriptional activity to cause transcription of mRNA and Synthesis or translation of protein
Are steroidal hormones packaged?
No they are synthesized and immediately released
Where are the enzymes that produce steroids located?
Mitochondria and smooth ER
How do hormones get transported throughout the body?
Bound to binding globulins to get transported by the blood
What binding globulin carries cortisol?
Corticosteroid binding globulin
What globulin carries estradiol and testosterone?
Sex steroid Binding globulin
What converts steroids to active form if they are not already activated?
The target cell
What are the three main roles of steroidal hormones in physiological function?
Carbohydrate regulation
Mineral balance
Reproductive steroids
Glucocorticoids
Mineralocorticoids
Gonadal steroids
What kind of steroid helps with inflammation response, stress response, bone metabolism, behavior and mood?
Glucocorticoids
What is the hypothalamus made up of?
Neurosecretory hormone secreting cells of the posterior pituitary via the infudibular stalk
What does the hypothalamus do?
Release releasing and inhibiting factors that act on cells in the anterior pituitary via the hypopheseal portal system
What is the pituitary made up of?
Cells that produce hormones that are released into the blood stream
Anterior and posterior sections have different functions
What is the posterior pituitary comprised of?
The endings of axons from cell bodies in the hypothalamus that are released into the posterior pituitary
What are the principal hormones of the posterior pituitary?
ADH/ vasopressin
Oxytocin
What does ADH do?
Regulate fluid levels (increase water reabsorption in the kidneys)
This would increase blood pressure- also called vasopressin
What does oxytocin do?
Cause milk ejection and uterine contraction
How are the hypothalamus and pituitary gland connected?
Via blood vessels that converge at the median eminence at the base of the hypothalamus
Hypophyseal portal system
What is released from the hypothalamus?
Releasing factors
Inhibiting hormones
What do releasing hormones do?
Cause release of hormones by the anterior pituitary
What do inhibiting hormones do?
Inhibit secretion of hormones by the anterior pituitary
DA
Somatostatin
What are the Anterior pituitary hormones?
ACTH
GH
Prolactin
TSH
FSH
LH
What does ACTH do?
Stimulates cortisol secretion by adrenal cortex
What is CRF/CRH?
Corticotropic releasing factor/hormone
What does CRF do?
Regulates ACTH secretion from Anterior pituitary which causes release of cortisol into the blood
What stimulates release of ACTH?
CRF or CRH release
What inhibits CRH?
ACTH and cortisol
What inhibits ACTH?`
Cortisol
What is hyposecretion?
Too little of the hormone produced
Less than normal response
Hypothyroidism
What is hypersecretion?
Excess hormone produced
exaggeration of normal effect
Hyperthyroidism
What is the primary pathology of hormone secreting glands?
Damage to hormone secreting glands
Tumor or death cells
Addison’s
CAH
What kind of disease is Addison’s Disease?
An autoimmune
What kind of disease is adrenal hyperplasia?
Autosomal abnormality
What is the secondary pathology caused for hypersecretion?
Damage to the control systems and mechanisms
Caused by pituitary adenomas
What happens/side effects are caused by Hyperpituitarism?
Adenomas
Visual field changes
Increased intraocular pressure
Pushes the optic neuronal tracks
Effects ACTH, GH, and prolactin
What causes hypopituitarism?
Destruction of the pituitary
What is the most common cause of destruction of the anterior pituitary?
Panhypopituitarism
Loss of AcTH, TSH and is life threatening
Non secretory pituitary adenomas
What are the layers of the adrenal cortex?
Zona glomerulosa- outer
Zona fasciculata- middle
Zona reticularis- inner
What is produced by the adrenal cortex?
Steroid hormones
What does the zona reticularis produce?
Gonadal steroids
Adrogens to be converted to estrogens in females
What does the zona glomerulosa produce?
Mineralocorticoids
Ion
H2O balance
Aldosterone
What does the zone fasciculata produce?
Glucocorticoids
Glucose metabolism
Cortisol
What does cortisol do for the body?
Helps with blood glucose levels unders stress
Increase gluconeogenesis also in the liver
Decrease the immune response
What is cortisol stimulated by?
CRH and ACTH
When is cortisol produced?
Under what body condition
Stress
Low plasma glucose concentration
What are the actions of glucocorticoids mediated by?
What receptor
Glucocorticoid receptor
What super family is the human Glucocorticoid receptor under?
Transcription factor proteins
Steroid, thyroid, retonic acid nuclear receptor superfamily
What do these transcription factors do?
Regulate the expression of glucocorticoid responsive element GRE either positively or negatively
What happens when the GR is activated?
Receptors translocate to the nucleus to alter gene transcription by binding to specific response elements
What are glucocorticosteroids blocked by?
11 Beta HSD
Inactivates them
What is the inactive form of cortisol?
Cortisone
From studies of GR knock out in mice, what is GR necessary for?
Lung development for producing surfactant
Regulation of liver, adrenal glands, brain, and HPA axis
What kind of regulatory hormone are glucocorticoids?
In terms of biological effects on carbs, proteins and lipids
Significant counter-regulatory hormone to insulin
What do glucocorticoids do for the carbohydrates, proteins, and lipid metabolism?
Mobiize amino acids for hepatic gluconeogenesis
Increase blood glucose concentration
Increase lipolysis in adipose tissue
Inparts insulin resistance cells and increasing permissiveness
What do glucocorticoids do for the skin?
Regulate epithelial integrity and immune function
What are Glucocorticoids used for to treat the skin?
Inflammation caused by eczema, hives, allergies, and psoriasis
Side effects- skin atrophy, and delayed wound healing
What do glucocorticoids do for circulation?
Maintains body fluid volumes and vascular integrity
Sensitizes arterioles to action of NE
Decrease capillary permeability
Maintain normal renal function
Minaralocorticoid effects from cortisol
What does cortisol do for blood pressure?
It increases blood pressure by sodium retention and volume expansion
Intrinsic mineralcorticoid activity
Increase vascular smooth muscle sensitivity
Decrease NO
Increases RAAS
What does cortisol do for calcium metabolism?
Inhibits osteoblastic function
Decreases the ability to add new bone
Causes osteoporosis and osteopenia
What is Addison’s disease caused by?
Cortisol insufficiency
What is primary Addison’s disease caused by?
Cortisol insufficiency due to the loss of ability to make cortisol in adrenal gland
Increases ACTH levels and there is no feedback
Increase in MSH
Hyper pigmentation
What is secondary Addison’s disease caused by?
Decrease in ACTH
Decrease CRH
Loss of function in hypothalamus
Rapid withdraw from steroids
What might cause Addisonian Crisis?
Adrenal insufficiency
Weakness
Fatigue
Hypotenion
GI probs
Hypoglycemia
Increase in K decrease in NA
What might cause Addisonian Crisis?
Adrenal insufficiency
Weakness
Fatigue
Hypotenion
GI probs
Hypoglycemia
Increase in K decrease in NA
What causes Cushing’s Syndrome?
Hypersecretion of ACTH and Cortisol
What causes an increase cortisol release
Tumor
What causes an increase in ACTH release?
Tumor in lungs, pituitary gland, kidneys, and pancreas
What causes ectoptic release by neoplasias?
Lung cancer
What causes Iatrogenic Cushing’s Syndrome?
Exogenous Glucocorticosteroid Administration
What does excess release of GCs cause?
Osteoporosis
Cataracts
Skin thinning/ cutaneous striae
Decrease proteins and myopathies
Connective tissue breakdown
Blood changes
CNS effects
How does Cushing’s disease affects lipid distribution?
Causes an increase in weight
Trunkal obesity
Moon facies
Buffalo hump
What happens to the skin in Cushing’s Disease?
Fragility
Easy bruising “cutaneous striae”
What does Cushing’s disease do when an infection occurs?
Masks them through anti inflammatory actions
What does cushing’s syndrone cause metabolically?
Water and salt retention
Increased glucose concentration
Increased osteoclasts and decreased osteoblasts
Hypertension
Hyperglycemia “steroidal diabetes”
Bone atrophy muscle too
What are glucocorticoids mainly used for?
Their anti-inflammatory effects
What does glucocorticoid use do to the production of eosinophils and prostaglandins?
Inhibit them
What enzyme do glucocorticoids inhibit to stop the production of prostaglandins?
Phospholipase A2
What are the ways glucocorticoids cause decrease in inflammation?
Inhibit phospholipase A2
Decrease permeability of capillary membranes
Decrease swelling
Decrease histamine effect
How do glucocorticoids suppress the immune system?
Decrease Tcell and antibody production
Decrease eosinophils and lymphocytes
Inhibit macrophage and neutrophil function
Decrease immunity
When would inhaled glucocorticosteroids be prescribed ?
What disease state
Asthma
Chronic respiratory inflammation
How do inhaled glucocorticosteroids inhibit the inflammatory response of asthma?
Inhibit NF-kV and activator protein 1 activity which is a transcription factor
Decrease production and secretion of cytokines, chemokines,cell adhesion
What are glucocorticoid agonists used for?
Adrenal insufficiency
Inflammatory disorders
Autoimmune disorders
Addison’s
Asthma/skin
RA, IBS, MS
When are glucocorticoid antagonists used?
Cushing’s disease or syndrome
What is the primary naturally occuring steroid in the body?
Hydrocortisone
Taken orally
What is the prodrug for prednisolone?
Prednisone
When is prednisolone usually chosen?
Chosen for anti-inflammatory
Little sodium retention
What kind of glucocorticosteroid is Triamcinolone?
Flurinated glucocorticosteroid
No sodium retaining effect
Triamcinolone has a serious adverse effect, what is it and what is a good part of triamcinolone at lower doses?
Bad- causes muscle wasting
Good- low sodium retention
What two drugs are usually chosen over prednisolone because they are longer acting?
Dexamethasone
Betamethasone
When would you use glucocorticoid for replacement therapy?
Acute adrenal insufficiency
Chronic adrenal insufficiency (addison’s)
Congential adrenal hyperplasia (autosomal)
What is the main problem with using glucocorticoids for non endocrine disorders?
They have good effects but the same amount of side effects
What kind of steroid is aldosterone?
Mineralocorticoid
No place in routine therapy
too much first pass metabolism
used for sodium retention
What is used instead of aldosterone in practice?
Fludrocortisone
Large sodium retention
long acting flourinated
Replace aldosterone where adrenal cortex is destroyed (addisons)
What does long term use of corticosteroids do?
Cause long term suppression of the HPA axis so they need to be tappered off
What is addisonian crisis?
Acute adrenocortical insufficiency
Emergency
What is the most common cause of Adrenal crisis?
HPA axis suppression / abrupt with drawal
What can treat Addison’s?
Hydrocortisone
Prednisone
What is the goal in treating addisons disease?
Establish an effective dose while mimicking normal diurnal adrenal rhythm (cortisol is highest in the morning)
Why is hydrocortisone used the most to treat addison’s disease?
Because it has both mineralocorticoid and glucocorticoid activity and in addison’s disease aldosterone is lost too
What happens in cushing’s syndrome?
Too much cortisol either exogenously or endogeneously
What is their too much of in ectopic or lung tumors?
ACTH
What kind of tumors cause too much cortisol?
Adrenal tumors
Adrenal hyperplasia
WHat is the most common way to diagnose chushings?
The 24 hours urinary free- cortisol test
Collect urine over 24 hours and test cortisol levels
IF high then yes
What are the three main forms of treatment for cushings?
Surgery of tumor
Radiation Therapy
Medications
What medications are used to treat cushings?
Steroidogenic inhibitors
What do steroidogenic inhibitors do?
Uses medications that inhibit enzymes required for synthesis of corticosterone and cortisol
Inhibition of 11 beta hydroxylase
What is Metyrapone used for?
Cushings disease
What does metyrapone do?
Inhibits 11 beta hydroxylase in the adrenal gland
What does Osilodrostat do?
Inhibition of 11 beta hydroxylase
For those who cannot have surgery or it did not work
What does ketoconazole do?
Normally for fungal infections
Inhibits the P450 enzyme system which then inhibits the 11 Beta hydroxylase
What does Mitotane do?
Inhibits 11 hydroxylation and pregenolone synthesis from cholesterol in. thecortex
Could have life threatening side effects since it is an anti neoplastic agent
What is Pasireotide?
Somatostatin analog that is universillay an inhibitor
what does Pasireotide do?
Acts via somatostatin receptors to inhibit secretion of corticotropin from pituitary adenomas with Cushings disease
Somatostatin receptor type 5?
what does Pasireotide do?
Acts via somatostatin receptors to inhibit secretion of corticotropin from pituitary adenomas with Cushings disease
Somatostatin receptor type 5?
What is the main side effect of Pasireotide?
Hyperglycemia
What kind of effect do topical steroids have?
Topical anti inflammatory effect
What are the main topical steroids?
Hydrocortisone
Prenisolone and methylpred
Dexa and Betamethasone
Triamcinolone
Fluocinonide
How war topical steroids ranked?
In classes from 1 to 7 based on potency with 1 being the most potent
What do ointments treat?
Dry thick lesions
What kind of effect do creams have?
Anti inflammatory with a little bit of drying
Good for sensitive areas
What kind of agent are lotions and gels?
Occlusive and they have alcohol so drying as well
Good on hair
What potency should you use on the face?
Decrease side effects by lowering the potency
What are side effects related to?
Frequency
Potency
Duration of use
Anatomical site of application
what is Asthma?
Chronic inflammatory disease of airways (bronchials) increase in responsiveness allergens
WHat are the features of asthma?
Inflammation of bronchial walls and inflammation cell infiltration
Reversible airflow obstruction
Increase in mucous
When do asthma attacks normally occurr?
At night
What are the immune responses you see with asthma?
Inflammatory cell infiltration
Mast cell activation
Edema
Denudation of airway epithelium
Collagen deposition beneath the basement membrane
What causes Atopy?
Too much IgE
Inflammation response
What kind of response is the early phase of airway inflammation?
Bronchospasm Response
release of inflammation mediators from mast cells macrophages and epithelials
What kind of inflammation happens in the secondary dip for asthma attacks?
Chemotactic inflammation
What are the primary mediators?
Histamine
What are the secondary mediators?
Leukotrienes
Prostaglandins
What does the mediator soup cause?
Bronchoconstriction
Microvascular Leakage
Mucus Hypersecretion
Airways Hyperresponsiveness
What kind of steroids are used as quick relief medications for asthma?
Systemic steroids
Oral or IV
Gain control of moderate to severe acute exacerbations
What are the two main systemic steroids?
Prednisone and prednisolone
Acutely speed resolution of airflow obstruction
What is used for controller medications for asthma?
Inhaled Glucocorticoids
What must be taken with LABAs?
Inhaled Glucocorticoids
MOmetasone
Fluticasone
What do inhaled glucocorticoids do?
Decrease Bronchial Hyperreactivity
Decrease dependency on SABAs for sympathetic relief
Increase pulmonary function
Increase quality of life
What is the mechanism of action of inhaled corticosteroids?
Suppress cytokine production
Decrease eosinophil function
Inhibits macrophages and release of cytokine inflammation
Stablizes endothelial membranes
What are the respiratory corticosteroid inhalation products?
Budesonide
Ciclesonide
Beclomethasone Dipropionate
Mometasone
Why is Flonase good for inhalation?
It is rapidly metabolized by the liver (3A4) so it has little systemic side effects if swallowed
What are the main side effects of inhaled corticosteroids?
Deposition in mouth and throat that may increase oral candidiasis
Stop this by rinsing after use
Why do you not use ICS for COPD?
The side effects outweigh the benefits
What cell types are found in asthma?
Mast cells
Eosinophils
CD4+ T cells
Macrophages
What cell types are found in COPD?
Neutrophils
CD8+
T cells
Many macrophages
What effects are different between COPD and Asthma?
Asthma only effects bronchials and then COPD effects bronchials and alveoli
