Endocrine Flashcards
Endocrine system basics
Series of messenger systems with hormonal feedback loops
Hormones regulate distant target organs
Hormones
Regulate metabolism, growth, development, tissue function, sexual function, reproduction, sleep and mood, etc…
Control center of the endocrine system
Hypothalamus
Endocrine
Chemical signals secreted into the blood and transported to target tissues
Exocrine
Secrete substances into ductal system leading to an epithelial surface (internal or external)
Sweat glands, salivary glands, etc…
Paracrine
Cell to cell communication via chemical signals (short distance!)
Within a neuron, AP from cell body to axon terminal, triggers NT release, downstream cell is then influenced by paracrine NT and undergoes change/continues AP
Autocrine
Chemical signals which act upon the cell which created them (super super short)
Cell recognizing a change in its environment and telling itself to change/adapt to the new environment
Endocrine vs Paracrine vs Autocrine vs Exocrine
Hypothalamus
Located in the diencephalon and plays a crucial role in homeostasis and hormone production/release
Regulates body temp
Maintain physiological cycles
Controlling appetite
Managing sexual behavior
Regulating emotional responses
Regulates metabolism
How does the hypothalamus regulate the body
Feedback loops
Can increase or decrease production of releasing or inhibiting hormones based on circulating levels or changes in physiologic need
Pituitary gland
Base of the brain under the hypothalamus
Can produce and release hormones as indicated by the hypothalamus (stimulated with inhibiting or releasing hormones)
Connection of hypothalamus to pituitary gland
Anterior: Vascular portal system
Posterior: Neurons
Parts of the pituitary
Anterior and posterior
Anterior pituitary
Produces and releases many of the hormones within the endocrine system
How the anterior pituitary is connected to the hypothalamus
Hypothalamo-hypophseal portal system
Hormones synthesized by the anterior pituitary
Growth hormone (GH)
Thyroid- stimulating hormone (TSH)
Adrenocorticotropic hormone (ACTH)
Follicle-stimulating hormone (FSH)
Luteinizing hormone (LH)
Prolactin (PRL)
Chart of anterior pituitary hormones from hypothalamus to effects
Posterior pituitary
Doesn’t make hormones, able to store hormones made by the hypothalamus in vesicles and then releases when needed, can releases a large amount very quickly, don’t need to synthesize the hormone
Advantage of posterior pituitary
When secreting ADH and oxytocin, usually you want them very quickly (bleeding out or labor) and want a lot. Since they are already made and just stored, when stimulated a lot can be released at once into the body
Hormones secreted by the posterior pituitary
Antidiuretic hormone
Oxytocin
Posterior pituitary chart hypothalamus to effects
How posterior pituitary is connected to the hypothalamus
Infundibulum/pituitary stalk which is comprised of axons
Pineal gland
Releases melatonin which controls circadian rhythms
Thyroid overview
Releases T3/T4 and regulates metabolism
Also releases calcitonin which acts to lower calcium levels in the blood
Parathyroid overview
Releases parathyroid hormone (PTH) which acts to increases serum calcium and decreases serum phosphorus levels in the blood
Pancreas
Releases insulin which lowers blood sugar
Releases glucagon which raises blood sugar
Insulin
Lowers blood sugar
Glucagon
Raises blood sugar
Exo pancreas
Digestion
Endo pancreas
Insulin and glucagon release
Adrenal cortex releases
Aldosterone and cortisol
Aldosterone
Released by the adrenal cortex and helps to regulate blood volume
Cortisol
Released by the adrenal cortex and has catabolic and anti-inflammatory effects
Adrenal medulla
Releases catecholamines
Ovaries
Releases estrogen for XX characteristics
Testes
Releases testosterone hormone for XY characteristics
Chart of Hypothalamus - Pituitary axis
Types of hormones
Peptide
Steroid
Tyrosine derivaties
Peptide hormones
Bind to receptors on the cell for 2nd messenger, unable to get into the cell since H20 soluble
Pit/hypo make
Insulin/glucagon
PTH (parathyroid hormone)
Steroid hormones
Precursor is cholesterol, lipid based
Fat soluble so can go through the plasma bind in cell or nucleus
Ex: Aldosterone, cortisol, estrogen, testosterone
Tyrosine derivatives
Amino acid base
T3/T4
Catecholamines
Prolactin inhibiting factor
Hormone receptor types
Cell membrane receptors
Cell cytoplasm receptors
Cell nuclear receptors
Types of hormones that bind to cell membrane receptors
Proteins, peptides, catacholamines
Types of hormones that bind to cell cytoplasm receptors
Steroid hormones
Types of hormones that bind to cell nuclear receptors
Thyroid hormones
Down regulation of receptors
Decrease in number because of overstimulation
Decrease the tissue sensitivity
Up regulation of receptors
Increase in number often due to hormone deficit
Increases sensitivity of tissue to hormone
Protein bound hormones
Steroid
T3/T4
Proteins that dissolve in plasma and are H20 soluble
Peptide hormones
Thyroid axis
TRH in hypothalamus to anterior pituitary to release TSH which then goes systemically to increase release of T3/T4
ADH axis
Osmoreceptors detect salt concentration
When osmolarity is high ADH is increase (sucks in water)
PTH released when serum calcium is low
Osmoreceptors
Measure internal salt concentration
Location of pituitary and impact with growth
Sits on the “turkish saddle” and right below optic chiasm
If there is tumor growth it presses on the optic chiasm and results in bitemporal hemianopsia
Primary endocrine disorder
Due to the downstream organ
Thyroid or adrenal gland has an issue with their hormone secretion
Secondary endocrine disorder
Due to problems with the pituitary (anterior)
Tertiary endocrine disorder
Problem with the hypothalamus
Thyroid
Located on the front of the trachea and is the largest purely endocrine gland in the body
Right and letf lobe with parathyroid glands on each “peak”
Thyroid hormones main controls
Metabolism
Growth and development
Cellular and body functions
Mood
Metabolize cholesterol
Two thyroid hormones
Triiodothyronine (T3, 3 iodine’s)
Thyroxine/tetraiodothyronine (T4, 4 iodine’s)
Hypothalamic - Pituitary - Thyroid Axis
Hypothalamus releases TRH (thyrotropin releasing hormone) into the pituitary, which then releases TSH (thyroid stimulating hormone) to the thyroid, which then secretes T3 and T4 and works as a negative feedback loop
Iodine
Trace element absorbed by the small intestine
Integral part of T3 and T4
Hypothyroidism
Underactive thyroid gland, decrease in T3 and T4
Bradycardia
Cold intolerance
Constipation
Fatigue
Weight gain
Myxedema coma
Hyperthyroidism
Increase in thyroid gland function, increase in T3/T4
Weight loss
Exophthalmos
Heat intolerance
Diarrhea
Tremors
Muscle weakness
Thyroid storm
Cells of the thyroid
Two primary cells
Follicular cells and parafollicular cells (C cells)
Parafollicular cells
Neuroendocrine cells that make calcitonin, which lowers calcium concentrations
Calcitonin
Lowers serum calcium concentrations (decrease for less muscle contraction, increase for more)
Secreted by parafollicular cells in the thyroid
Follicular cells
Synthesize thyroid hormones
Arranged in follicles with colloid center (storage center)
Produces thyroglobulin which stores hormones until needed
Contain receptor that TSH acts on
Thyroglobulin
Produced by follicular cells
Stores T3/4 until needed by combing with them
Production of thyroid hormone
Iodine trapped by thyroid and combined with tyrosine via TPO to make MIT and DIT which then combine to make T3/T4 (DIT + DIT = T4… MIT + DIT = T3)
Combines with thyroglobulin in colloid for storage
Thyroglobulin complex broken down once back in the follicle and then secreted into the blood
Thyroid peroxidase enzyme (TPO)
Combines iodine and tyrosine to make MIT and DIT which then combines to make T3/T4
How follicle cells trap iodine
Extracellular Na/iodine symporter uses gradient to move into the cell
(Na takes iodine with it into the colloid)
Thyroid stimulating hormone (TSH)
Up regulates sodium - iodide symporter
Stimulates proteolysis of iodinated thyroglobulin to T4 and T3 and secretes across membrane into circulation
How T3 and T4 travel systemically
Bound to thyroxine binding globulin protein and in inactive state
Need to be unbound to be active
Then converted from T4 to T3 in tissues to act
The body can only use T3 or T4
T3
So must be converted to T3 in the organ by removing a molecule of iodine
T4 binding to intranuclear receptor
Activates genes for increasing metabolic rate and thermogenesis
Increase O2 and energy consumption
Physiological functions of T3
Increase metabolic rate
Lipolysis or lipid synthesis
Stimulate metabolism of carbs
Anabolism of proteins (or catabolism in high doses)
Increase potency of catecholamines
Cardiovascular effects of T4
Converted to T3 in tissues
Increases metabolism, causes skin arterial dilation to “blow off” excess heat
Decreases afterload and increases CO
Increased expression of Beta 1 receptors to increase HR, SV, and CO
MAP stays the same
Thyroid hormones in children
Brain development in peri-natal period
Act synergistically with growth hormone to stimulate bone growth
Grave’s disease
Hyperthyroidism
B cells create antibodies that bind to TSHR to secrete T3 and T4
No negative feedback loop
Hashimoto’s thyroiditis
B cell antibodies attack TPO enzyme which is what makes T3 and T4 from MIT/DIT
Can be fatal or cause heart failure
Hypothyroidism
Hypothalamus Anterior Pituitary Target organ chart
Growth hormone target site
Whole body is the target but mainly musculoskeletal
Growth hormone releasing hormone causes
Target organ to release insulin like IGF-2 which acts to induce growth
Feedback for GHRH
IGF-1 acts as negative feedback
Hypothalamus Pituitary Growth hormone axis
Causes of growth hormone releasing hormone secretion
Hypoglycemia
Starvation
Trauma/stress/excitement
Exercise
Sex hormones
Deep sleep
Inhibitors of growth hormone releasing hormone
Hyperglycemia
Elevated growth hormone (from negative feedback)
GHIH (somatostatin)
Age
Obesity
Metabolic effects of GH
Shifts metabolism to burning fat instead of sugars, so starts lipolysis which provides fatty acids and glycerol for energy metabolism
Impacts of GH on the body
Metabolizes fat (lipolysis)
Gluconeogenesis (produce glucose form non-carbs)
Increase serum cholesterol (for fat breakdown)
Antagonizes insulin’s action (increase serum glucose)
Hypoglycemia and GHRH
Decrease in glucose stimulates growth hormone
Hyperglycemia and GHRH
Increase in glucose inhibits growth hormone
Gluconeogenesis
Production of glucose from non-carbohydrate substrates
Stimulated by GH
GH impact on serum cholesterol
Increases cholesterol
Which increases fat breakdown
GH on the ehart
Increases sodium and water retention
Increases BP
Negative feedback loops of GH
GH negatively feeds back to the hypothalamus
IGF-1 negatively feeds back to the pituitary
Effects of IGF-1
Bone/cartilage grows and thickens
- Osteoblast activation
- Increased bone length prior to adulthood
- Increased bone thickness
GH and IGF-1 cascade chart
GH pathologies
Pituitary dwarfism
Gigantism
Acromegaly
Pituitary dwarfism
Normal body proportions but decreased rate of development
IGF-1 deficiency
Giantism
Pre-adolescent elevated GH
Often develops diabetes becomes tumor is blind to hyperglycemia
Acromegaly
Post-adolescent GH elevation
Growth of bone thickness but not length because epiphyseal plate has closed
Prolactin
Under hypothalamic inhibition via dopamine
Increased levels of prolactin doesn’t necessarily decrease PRH release from the hypothalamus
Prolactin actions
Increase milk production
Decreases GnRH
Decreases LH/FSH
Prolactin is a ________ feedback loop
Positive
As more milk production, stimulates more milk production
When suckling stops dopamine increases and inhibits prolactin
Dopamine and prolactin
Dopamine is always on and you need to inhibit it to turn on prolactin
Hyperprolactinemia
XY: Infertility and decreased sex drive
XX: Infertility and decreased sex drive
Most common anterior pituitary tumor
Prolactinoma
Prolactinoma
Hyperprolactinemia symptoms plus
- Headache
- Bitemporal hemianopsia
Posterior pituitary releases
ADH and oxytocin
ADH main function
Regulate sodium concentration within the blood via osmoreceptors
When highly concentrated, more ADH to dilate
Where does ADH act
Distal convoluted tubule of the kidneys which reabsorbs water back into the blood via aquaporins
ADH axis chart
Aquaporins
On the collecting duct and only permeable to water
Allows the kidneys to reabsorb water
Things that increase ADH
Nicotine
Opiates
Nausea
Increased osmolarity
Decreased IV volume
Things that decrease ADH
Alcohol
Cortisol
Things that stimulate thirst
ADH secretion
Angiotensin II
Increased osmolality
Decreased IV volume
Diabetes insipidus
ADH deficit or defect
Can’t reabsorb water from the collecting duct which means peeing more water and causes dehydration
Causes of DI
Neurologic/Central: Low or abnormal ADH from head injury, hypothalamic destruction, post pituitary destruction
Nephrogenic: Normal or high ADH from abnormal ADH receptor in kidney
SIADH
Inappropriate ADH secretion, means too much ADH that is secondary to another disease process elsewhere in the body
Retaining too much water
Treatment for SIADH
Withhold water but not food
Oxytocin
Causes uterine contractions and milk ejection
Oxytocin feedback loop
Positive feedback loop
Secretion of oxytocin causes
Vaginal stretch - Labor or intercourse
Suckling infant
Inhibition of oxytocin
Lack of secretory stimuli
Layers of the adrenal gland way to remember
GFR
Salt
Sugar
Sex
Layers of the adrenal gland
Cortex: zona glomerulosa, zona fasciculata, zona reticularis
Medulla
Hormones made in the Zona glomerulosa
Mineralocorticoids - aldosterone
Mineralocorticoids - adrenal
Mineral base that influences salts and absorption
Aldosterone
Glucocorticoids - adrenal
Glucose, increase in glucose
Cortisol
Androgens - adrenal
Sex hormones
Estrogen and testosterone
Aldosterone main effects
Increase sodium and water retention, prevent hyperkalemia
Activates sodium potassium exchangers in kidneys so it absorbs Na (water follows Na) and kicks K into the urine
Chemoreceptors - aldosterone
Release aldosterone in response to elevated levels of K
Secondary actions of aldosterone
Vasoconstriction
Vascular stiffness
Cardiac inflammation
Renin - angiotensin - aldosterone - system (RAAS)
Baroreceptors detect decrease in BV and BP and trigger release of renin
This cleaves angiotensinogen into angiotensin I
This is converted into angiotensin II in the lungs via ACE
Angiotensin II then leads to cardiac and vascular effects (vasoconstriction leads to increase in BV and BP)
AngII
Potent vasoconstrictor which increases BP
Triggers aldosterone
ACTH secretion that causes thirst sensation
Stimuli to release aldosterone
Increased K+ in the body
Ang II
Decreased arterial blood volume
Hormones made in zona fasciculata
Glucocorticoids - cortisol
Cortisol feedback loop
Cortisol is the primary negative feedback to the hypothalamus for CRH regulation
Cortisol axis
Hypothalamus releases CRH to pituitary
Pituitary releases ACTH to the adrenal cortex
Adrenal gland releases cortisol
Glucocorticoids involved in
Glucose metabolism
Cortisol effects
Gluconeogenesis - increases blood glucose
Inhibits tissue building and promotes catabolism of stored nutrients - increase cholesterol
Impair wound healing
Increased blood pressure
CNS stimulant
Bone reabsorption for increased serum calcium
Anabolism
Set of metabolic pathways that construct molecules from smaller units
Catabolsim
Breaking down molecules into smaller units
Short term cortisol stimulation
Nerve impulses from sympathetic fibers that trigger the adrenal medulla to secrete catecholamines
Cushing’s syndrome
Adrenal cortex overproduces cortisol
Cushing’s disease
Pituitay produces increased ACTH, usually a tumor
Zona reticularis
Produces sex hormones like angrogen
Regulated by ACTH
Hypothalamic - pituitary - gonadal axis
Hypothalamus - GnRH - Anterior pit - LH, FSH - Gonads - Sex hormones
General function of cortex of adrenal gland
Hormonal/endocrine
Regulated and slow
General function of medulla of adrenal gland
Autonomic nervous system, fast
Receives sympathetic input and releases catecholamines
Functions of the pancreas
Exocrine to help in digestion
Endocrine to help regulate blood sugar (via insulin and glucagon)
Endocrine pancreas
Regulates blood sugar in the whole body via insulin and glucagon
Exocrine pancreas
Ductal network, releasing lipase and amylase to help in digestion
Anatomy of the pancreas
95% is exocrine tissue that produces pancreatic enzymes for digestion
Remaining is endocrine cells called islets of Langerhans
Islets of Langerhans
Produce hormones that regulate blood sugar
Alpha and beta cells
Alpha vs beta islet of langerhans
Alpha produces glucagon (25%)
Beta produces insulin (60%)
Glycolysis
Breakdown of glucose into ATP and pyruvate
Gluconeogenesis
Making glucose from things that aren’t carbs
Building up sugars
Occurs mainly in the liver
Glycogen
Stored in the form of glucose
Glycogen molecule may contain 30,000 glucose units
Stored in the liver and skeletal muscle
Glycogenolysis
Breakdown of glycogen to release glucose for energy production
Glycogenesis
Formation of glycogen from glucose
Insulin derived from
Prohormone molecule called proinsulin which is a peptide hormone
Structure of insulin
Protein that is composed of two chains
A chain and B chain linked by sulfur atoms
How to activate insulin
Cleave the c-peptide chain that is attached to the A and B chains
C-peptide
This is cleaved off of insulin to make it active
Can measure the amount in the blood and can determine cause of hypoglycemia
Insulin
Peptide hormone that promotes glucose uptake, glycogenesis, lipogenesis, and protein synthesis
Trigger for insulin release
Hyperglycemia - stores glucose as glycogen
Promotes
What increases secretion of insulin
Elevated glucose
Elevated cortisol or glucagon
Rest and digest
What decreases secretion of insulin
Low glucose/fasting
GH
Glucagon
When blood sugar levels are too low this is released by the pancreas to increase blood glucose from stores (glycogen)
Glycogenolysis
Gluconeogenesis
Glycogenolysis vs gluconeogenesis
Lysis is catabolic
Genesis is anabolic
Glycogenolysis: Breakdown of glycogen to free the stored glucose chains
Gluconeogenesis: Forms glucose from non-glucose sources
Hypoglycemia immediate action
Glucagon secretion
Sympathetic stimulation
Hypoglycemia delayed reaction
Growth hormone increases serum glucose by increasing fatty acid metabolism
Cortisol increases serum glucose
Hyperglycemia immediate action
Insulin secretion
Insulin resistance
Increased exposure to insulin decreases (down regulates) the amount of insulin receptors
Transport protein for glucose
Glut4
Glut4
Glucose transport protein that is stimulated by insulin
When insulin binds, glut4 incorporates into the plasma
Incretin
When there is glucose present in the lumen of your small intestine, incretins are released
Incretins enhance the glucose - dependent insulin secretion resulting in stimulation of pancreatic B cells
Types of incretins
GIP and GLP-1
DPP4 enzyme
Responsible for the degradation of incretins such as GLP-1
- Increased levels result in less incretin and less insulin release and higher blood glucose
Parathyroid glands
Regulate the calcium and phosphorus levels in our body via the release of PTH (parathyroid hormone)
Chemoreceptors parathyroid glands
Detect calcium concentration in the blood
When low levels of calcium are detected, chief cells secrete PTH to increase serum calcium levels
Downstream effects of detecting low calcium levels
Parathyroid release PTH onto the kidneys and the bones
Kidneys increase vitamin D to increase Ca and Pi absorption in the gut
Kidney’s cause increase in Ca reabsorption from the urine and Pi excretion into the urine
Bones have increased osteoclast activity and creases Ca release into the blood
Hydroxyapatite
Ion salt formed between calcium and phosphorus
Can deposit in the vasculature and tendons
Also found in the kidney stones
Ca/P relationship
Calcium has an inverse relationship to phosphorus
Therefore when phosphorus in the blood rises, levels of calcium in the blood fall
Because phosphorous binds to calcium reducing free calcium
Exception to Ca/P relationship
Vitamin D in the gut causes an increase in both Ca and Pi
FLAT PG
Pituitary gland hormones
Follicle stimulating hormone
Leutanizing hormone
ACTH
TSH
Prolactin releasing hormone
Growth hormone
Bone deposition
Depositing or creating new bone matrix by the osteoblasts
Bone reabsorption
Osteoclasts break down the tissue in bones and release minerals to the blood
PTH
Increases amount of Ca by reabsorbing from the urine
Decreases the amount of phosphate by increasing the amount of secretion into the urine
Increase calcium and AP
Increased Ca blocks sodium channels
Makes the threshold potential less negative, so harder to reach threshold
Hypoexcitable
Negative bathmotropic effect
Negative bathmotropic effect
Increase in calcium makes it harder for Na to go into the cell and harder to depolarize
Decreased calcium and AP
Low calcium releases sodium channels so more sodium enters the cell decreasing the threshold potential
Hyperexcitable
Positive bathmotropic effect
Positive bathmotropic effect
Decrease in Ca makes it easier for Na into the cell
Hyperexcitable
PTH regulating serum Ca
Low serum calcium will increase PTH and increase Ca
High serum calcium will decrease PTH and decrease calcium
PTH on organ systems
Increase bone reabsorption
In kidneys decrease phosphate reabsorption and increase Ca reabsorption
In intestines increase calcium reabsorption
1 alpha-hydroxylase
Activates Vitamin D and is increased by PTH and produced in the kidneys
Vitamin D
Increase Ca and Pi absorption in the intestines
Increases kidney reabsorption of Ca from the urine
Calcitonin
Thyroid hormone that is released by C cells
Decreases Ca levels by inhibiting osteoclast activity and increases renal excretion of calcium
