Endocrinology Flashcards
General functions of endocrine system
- regulate cellular metabolism (TH)
- maintain water, electrolyte, and nutrient balance (insulin, aldosterone, ADH)
- promote growth and development (GH,TH)
- control reproduction (estrogen, testerone)
- help the body cope with stress (cortisol)
- regulate digestion and adsorption of food (GI hormones)
hormone imbalance
- hypo/hyper
- weight gain/loss
- increase/decrease BP
- infertility, etc.
endocrine glands
secrete substances into the bloodstream
hormones
chemical messengers of the endocrine system
paracrine agent
in the same tissue
ex: histamine, nitric oxide (NO), cytokines
nervous system
- fast/wired
- APs (electrical) and NTs at synapses (chemical)
- short duration
- local effects
endocrine system
- slow/wireless
- hormones into blood (chemical)
- long duration
- widespread effects
Peptides/Proteins
- amino acids
- range in size from 3 amino acids to full proteins
- more of these than the other two
Amines
- derivatives of tyrosine
- TH
- Epi
- NE
steroids
made from cholesterol
- 85% from liver
- 15% from diet
peptide hormones
- composed of amino acids
- most hormones are proteins/peptides
ex: GH, insulin, ADH, LH, FSH
peptide hormone synthesis
peptide hormones are processed and packaged into secretary vesicles for exocytosis
- transcription –> DNA –> mRNA
- translation
- synthesis –> rough ER
- packaging –> Golgi
- storage –> vesicle
cells that secrete lots of peptides have:
- increased rough ER
- increased Golgi
- increased secretory vesicles
properties of peptides hormones
- hydrophilic
- vesicle storage
- soluble in blood
- extracellular receptors (use 2nd messengers)
- fast effect (modify existing proteins)
- short 1/2 life (rapidly degraded)
vesicle storage
release is controled
soluble in blood
no transport needed
rapidly degraded
because unbound in blood
signaling transduction pathway
- hormone-receptor binding activates a G protein
- G protein activates adenylate cyclase
- adenylate cyclase produces cAMP
- cAMP activates protein kinases
- -> 2 nd messenger - protein kinases phosphorylate enzymes. This activates some enzymes and deactivates others
- activated enzymes catalyze metabolic reactions with a wide range of possible effects on the cell
steroid synthesis occurs in
mitochondria and smooth ER
steroid synthesis depends on
- cell type
- enzymes expressed
ex: ovaries express aromatase
testes do NOT
cells that synthesize steroid hormone have:
- increase mitochondria
- increase smooth ER
- increase specific enzyme
properties of steroid hormones
- hydrophobic
- membrane permeant
- need binding/transport proteins
- intracellular receptors
- slow effect (synthesize proteins)
- long 1/2 life
binding proteins of steroid hormones
- transport hydrophobic / lipophilic substances
- hormones inactive when bound
- creates storage pool
- reduce metabolic clearance rate
cellular response to steroid hormone
- dissociates from transport protein
- diffuses into target cell
- binds to receptor complex
- complex binds to DNA (hormone response elements)
- -> alter gene expression
what two categories why tyrosine break into?
- catecholamines
- thyroid hormones
properties of catecholamines
- hydrophilic
- vesicle storage
- soluble in blood
- extracellular receptors
- fast effect
- short 1/2 life
properties of thyroid hormones
- hydrophobic
- membrane permeant
- needed binding proteins
- intracellular receptors
- slow effect
- long 1/2 life
catecholamines hormones
- DA
- NE
- Epi
Thyroid hormone hormones
- T4
- T3
hormone receptors
- determine which tissues response to an endocrine “broadcast”
- only cells with a receptor for a hormone will respond to that hormone
- even if cells possess the same receptor, cellular response can differ
endocrine glands
- glands NOT anatomically connected
- form a system in a functional sense
- some glands have multiple (non-endocrine) functions
- some glands secrete multiple hormones
infundibulum
connects hypothalamus and pituitary
hypothalamus
master gland
- responds to many stimuli and instructs pituitary what to do to maintain homeostasis
inputs to hypothalamus
- hormone
- general sense (pain, touch, temp, suckling)
- higher centers (emotion)
- special senses
- blood conditions (glucose, osm, temp)
- –> lacks blood brain barrier
pituitary gland
- 2 lobes
- different origins and different mechanisms of action
- size of garbanzo bean
- lies in pocket of sphenoid bone just below hypothalamus
anterior pituitary (adenohypopohysis)
glandular pituitary
anterior pituitary develops from
epithelial tissue in mouth
posterior pituitary (neurohypophysis)
neural pituitary
posterior pituitary develops from
nervous tissue in brain
- neural extension of hypothalamus
posterior pituitary
- hormones are made in cell bodies of hypothalamus and stored in axons in posterior pituitary
- action potential from hypothalamus = hormone release from axon terminal in bloodstream
peptide hormones in posterior pituitary
- ADH
- oxytocin
ADH
- AKA: vasopressin
- released in response to: increase osmolarity
- stimulates water retention by kidneys and vasoconstriction (Increased BP)
ADH result
- increase blood volume
- decrease urine production
= decrease blood osmolarity
oxytocin (OT) causes
- contraction of uterine smooth muscle during birth
- milk secretion from breast tissue upon suckling
anterior pituitary
- no neural connection
- system of blood vessels
advantages of portal system in anterior pituitary
- local route for blood flow (very little in general regulation)
- hypothalamus hormones doesn’t get dilutes so doesn’t need as much
anterior pituitary hormones
- releasing hormones (RH)
- inhibiting hormones
releasing hormones
- ON
- stimulate anterior pituitary to secrete hormones
examples of releasing hormones
- TRH
- GnRH
- CRH
- GHRH
inhibiting hormones
- OFF
- prevent anterior pituitary from secreting hormones
examples of inhibiting hormones
- somatostatin (SS)
- -> AKA: growth hormone inhibiting hormone
- prolactin inhibiting hormone (PIH)
- -> actually dopamine (DA)
prolactin (PRL)
milk production
advantages of three hormone feedback system
- amplification
- only need small amount of starting hormone - multiple feedback pathways
- limits extremes in hormone secretion
hypersecretion
increased amounts of hormones
hyposecretion
decreased amounts of hormones
primary
primary with final gland in axis
secondary
problem with tropic hormone (pituitary)
receptor
either receptor doesn’t respond (desensitized), or nonexistent or permanently turned on
signal transduction
problem with protein in pathway
hypertrophy
gland overstimulated and grows
atrophy
gland shrinks
thyroid gland
largest pure endocrine gland
follicular cells
follicule
- site of TH synthesis
C cells
secrete calaitonin
Ca+2 regulation
T4 (thyroxine)
- 90% of secretion
- -> higher affinity for transport protein
- “storage pool” in blood
- converted to T3 in target cells
T3 (triiodothyronine)
- most active form
- 4x more potent
- R inside target cells have higher affinity for T3
synthesis of TH
- iodide is cotransported with Na+
- diffusion
- iodide is oxidized and attached to rings of tyrosines in thyroglobulin
- the iodinated ring of one MIT or DIT is added to a DIT at another spot
- endocytosis of thyroglobulin containing T3 and T4 molecules
- lysosomal enzymes release T3 and T4 and TG
- T3 and T4 secretion
exception for thyroid hormone
- conjugation of TG allows storage inside colloid until needed
- can be stored
- TSH regulates release
mechanism of TH action
- affects virtually every cell
- can affect transcription of > 100 proteins
- once bound, can control function for many days
major functions of thyroid hormone
- increases basal metabolic rate
- permissive to actions of Epi, NE
- essential for CNS development (fetus) and activity (adults)
- permissive for overall growth and development
- increases epidermal growth / turnover (skin/hair)
TH increases basal metabolic rate
- increase heat production
- rate at which cells burn fuel to maintain basic life functions
- increases number of mitochondria
- increases Na+/K+ ATPase activity
- increase glucose concentration
TH permissive actions of Epi, NE
- increases SNS activity
- increases beta-adrenergic receptor expression –> cells are more responsive to Epi and NE
TH essential for CNS development and activity
- neural growth
- synapse formation
- number of glia
- myelination
TH permissive for overall growth and development
needed for normal production of GH
cretinism
absence of TH in development
- poorly developed CNS
- severe mental retardation
- decreased growth
- caused by dietary lack of iodine
hypothyroidism caused by
- iodine deficiency
- radiation
- autoimmune destruction (very common in females)
hypothyroidism results in
- low metabolism
- fatigue
- weight gain
- decreased HR (decreased beta-AR, decreased Epi/NE effect)
- cold intolerance
myxedema
dry skin, mucus and protein build up under the skin
goiter
- decreased TH leads to increased TSH
- TSH increases size and number of follicular cells
- if goiter due to iodine deficiency highly treatable
goiter pathway
- No Iodine = No TH
- no feedback
- increase TSH secretion
- TSH increases size and number of follicular cells
hyperthyroidism caused by
- tumor
- auto-antibodies that stimulate TSH-R
hyperthyroidism results in
- nervousness
- anxiety
- weight loss
- heat intolerance
- hyperglycemia
- high resting HR
exophthalmos
eye bulge out
- antibodies attack eye muscles
- may also be goiter
- can be treated by removing thyroid / beta-blocker
how many layers does the medulla of the adrenal glands have?
1 layer
what type of tissue it the medulla of the adrenal glands?
nervous tissue
what is the medulla of the adrenal glands controlled by?
sympathetic nervous system
what does the medulla secrete?
epinephrine and norepinephrine
how many layers does the cortex of the adrenal glands contain?
3 layers
what is the inner most layer of the adrenal glands of the cortex?
zona reticularis
what is the middle layer of the adrenal glands of the cortex?
zona faciculata
what is the outer most layer of the adrenal glands of the cortex?
zona glomerulosa
what does the zona reticularis secrete?
estrogen and testosterone
what does the zona faciculata secrete?
cortisol
what does the zona glomerulosa secrete?
aldosterone
what type of tissue is the cortex of the adrenal glands?
glandular tissue
aldosterone
- 90%
- mineralocorticoids
- increase Na+ reabsorption in kidneys
- increase H2O retention (H2O follows Na+)
- increase blood volume = increase BP
adrenal medulla
- catecholamines
- modified sympathetic ganglion that does not give rise to postganglionic fibers = hormones are secreted (neuroendocrine reflex)
functions of adrenal catecholamines
- dilates respiratory airways
- increases HR and BP
- dilates blood vessels to heart and skeletal muscle –> vasodilation
- mobilizes glucose, fatty acids –> hormone effect only
- increases alertness –> hormone effect only
- dilates pupils
- reduces digestive activity
- inhibits bladder emptying
- Epi reinforces SNS effects NE during “fight or “flight” stress response”
androgens
- similar to testosterone but 20% as potent –> plays role in females, fetus and puberty
- also, source of estrogen in men and post menopausal females
stress
anything that disrupts homeostasis
stress examples
- phycological stress
- daily exercise
- trauma
- surgery
- infection
- starvation
- sleep deprivation
functions of cortisol (basal levels)
- fetal/neonatal development of brain, intestines, lungs, glands
- liver glucose production between meals
- anti-inflammatory / anti-immune (prevent hyper-response)
cortisol liver glucose production between meals
- break down of fats and proteins for energy
- mobilizes glucose (gluconeogensis, decrease glucose use)
cortisol anti-inflammatory / anti-immune
without this function autoimmune disorders develop
functions of cortisol in stress
- metabolic effects (glucose sparing)
- support SNS responses
- stimulates erythropoietin (EPO) (replace RBC’s)
- bone resorption
- anti-inflammatory / immunosuppression
- psychological / analgesic
- inhibition of non-essential functions
cortisol in stress metabolic effects
mobilizes glucose, fatty acids, and amino acids
cortisol in stress supports SNS response
- vasoconstriction
- increased HR and RR
- bronchodilation
cortisol in stress stimulates EPO
- in case of bleeding
cortisol in stress bone resorption
- Ca+2 mobilization
- to repair broken bones and blood clotting pathway
cortisol in stress anti-inflammatory / immunosuppression
- decrease antibodies
- decrease leukotrienes and prostaglandins
drugs used as cortisol mimics
- cortisone
- prednisone
- dexamethasone
cortisone
synthetic cortisol
- equipotent
prednisone
4x as potent as cortisol
dexamethasone
30x as potent as cortisol
- used for RA
cortisol in stress psychological / analgesic
- elevates mood (short term)
- endorphins co-released with ACTH inhibit pain
cortisol in stress inhibition of non-essential functions
- reproduction/growth
- LH/FSH decrease
- sex hormones decrease
effects of chronic stress
- weight loss (muscle)
- impaired growth
- —> these two have increased protein catabolism
- high BP (SNS effect)
- polycythemia (increased RBC)
- decrease bond density
- decrease immune response
- decrease fertility
adrenal insufficiency
Addison’s disease
Addison’s disease caused by
- tuberculosis
- tumors
- autoimmune destructions
tuberculosis
destroys adrenal cells
Addison’s disease results in
- low BP (decreased SNS, decreased aldosterone)
- low blood glucose
- anxiety, fatigue
- weight loss
- muscle weakness / pain
- hyperpigmentation of skin
cortisol hypersecretion
Cushing’s syndrome
Cushing’s syndrome caused by
tumors (adrenal/pituitary)
Cushing’s syndrome results in
- osteoporosis
- thin skin
- muscle weakness
- immunosuppression
- high blood glucose (mimics diabetes)
- high BP (increased SNS)
- redistribution of fat
brain
- done by about 5 years (size)
- development into 20’s
total body height
- 2 periods of rapid growth
- -> first 2 years
- -> puberty
what is growth influenced by?
- genetics
- environment
requirements for normal growth
- adequate nutrition (especially protein)
- freedom from chronic illness/disease
- freedom from chronic stress
- normal host of hormones
normal host of hormones promoting growth
- growth hormone (GH)
- insulin - like growth factors (liver)
- –> these two work together for growth
- insulin
- thyroid hormone
- testosterone
- estrogens
- other peptide growth factors
what gland secretes growth hormone?
anterior pituitary
insulin (in fetus)
protein synthesis
thyroid hormone
permissive: allows GH to have growth effects but does not medicate those effect on growth
testosterone
stimulates GH and IGF secretion at puberty, stimulates protein synthesis, closure of epiphyseal plates
estrogens
stimulates GH and IGF secretion at puberty, closure of epiphyseal plates
other peptide growth factors
> 60
- stimulate differentiation and cell division
increased IGF does what?
- increased cell division
- increased protein synthesis
- increased bone growth
- increased blood glucose
functions of growth hormone
- postnatal growth (espically bones)
- –> increased osteoblasts
- protein synthesis (muscle)
- secretion of IGF-1
- fetal development
- cell division
- mobilize glucose and fatty acids
end result of growth hormone
- protein synthesis
- catabolize fat for energy
- prevent glucose storage
what does insulin promote?
growth during fetal / childhood development
with age:
- decreased GH
- decreased muscle formation
- increased fat formation
dwarfism
- GH / IGF-1 / GF deficiency or receptor insensitivity
- decreased done growth
- decreased muscle development
hypersecretion of GH
caused by slow growing pituitary tumor
gigantism
excess GH before epiphyseal plates close
- will be excessively tall
acromegaly
excess GH after epiphyseal plates close
acromegaly results in
- bone thickening –> hands, feet, head
- enlarged organs (heart)
- hyperglycemia (mimic diabetes)
absorptive state
after meal:
- anabolic processes exceed catabolism
- increased insulin
- most glucose used for fuel
- glucose stored by glycogenesis
- gluconeogensis is suppressed
post absorptive state
between meals:
- catabolic processes increase
- glucagon
- glucose is released by glycogenolysis
- gluconeogensis stimulated
- fatty acids oxidized for fuel
beta cells
- contain 1% of insulin
- secreted during and immediately following a meal (during absorptive state)
- increased absorption of glucose in most cells
alpha cells
- contain 1% of glucagon
- secreted between meals (during post absorptive state)
effects of insulin
- facilitates the entry of glucose into muscle, adipose and most other tissues
- stimulates liver to store glucose as glycogen
effects of glucagon
- causes liver to convert stored glycogen into glucose and release into bloodstream
- stimulates gluconeogenesis
diabetes mellitus - type 1
type 1 / insulin-dependent / juvenile onset
- 5%
diabetes type 1 caused by
destruction of beta cells (autoimmune) –> no insulin secretion
diabetes type 1 results in
hyperglycemia “starvation in the midst of plenty”
diabetes type 1 effects
- extreme hyperglycemia
- increased fat catabolism
- atherosclerosis
- increased urine volume = osmotic diuresis
extreme hyperglycemia
nerve damage and blindness
increased fat catabolism
ketoacidosis (coma)
atherosclerosis
- hypertension
- kidney damage / vessel damage
- amputations
diabetes mellitus - type 2
type 2 / non - insulin dependent / adult - onset
- 95%
diabetes type 2 caused by
- desensitized insulin receptors on target cells
- often associated with obesity and inactivity
diabetes type 2 effects
- hyperglycemia
- other symptoms like type 1, but usually milder
- insulin secretion normal to elevated
diabetes type 2 treated with
diet and exercise
too high Ca+2 homeostasis
cardiac arrhythmia / decrease neuromuscular excitability
too low Ca+2 homeostasis
increased excitability of neurons and muscles
- tremors in muscles
where is majority of Ca+2 stored?
in the bones
what is the parathyroid hormone?
peptide
what does the parathyroid hormone do?
secreted when Ca+2 levels fall
hyperparathyroid
- weaker bones / bone pain
- constipation
- gall / kidney stones
- muscle weakness / fatigue
calcitonin
secreted when increased Ca+2
where is calcitonin found?
from parafollicular cells (c-cells) in thyroid gland
calcitonin effects
- increased Ca+2 storage in bone
- decreased blood Ca+2
- increased osteoblast
- decreased osteoclast
parathyroid hormone pathway
- decrease plasma calcium
- increase parathyroid hormone secretion
1. increase bone resorption- -> increase osteoclasts
- -> decrease osteoblasts
- increase calcium reabsorption in the kidneys and decrease urinary excretion of calcium
- increase calcium absorption into blood & increase active vitamin D
25-OH D
calcidol
calcitrol
active form of vitamin D
parathyroid hormone within vitamin D pathway
increases active vitamin D
calcitonin role in children
bones in kids are highly active and release increase Ca+2 (about 5g/day)
calcitonin role in adults
- doesn’t have much of an effect on adult
- kidney correct increased Ca+2 in adults
- adults need PTH but don’t need calcitonin
- only about 0.3 g/day
androgen/estrogen/progesterone
growth/reproduction
GI tract
sections/motility
lepin (adipose)
appetite
ANP (heart)
blood pressure
EPO (kidney)
RBC production
