Physiology Flashcards
Message transmission: Synaptic
across synaptic cleft
Is synaptic local or general?
Local
The specificity of synaptic depends on?
anatomic location and receptors
Message Transmission: Paracrine & Autocrine
By diffusion in interstitial fluid
Is Paracrine & Autocrine local or general?
locally diffuse
The specificity of Paracrine & Autocrine depends on?
receptors
Message transmission: Endocrine
by circulating body fluids
Is Endocrine local or general?
general
The specificity of Endocrine depends on?
receptors
Message transmission: neuro-endocrine
by circulating body fluids
Is neuro-endocrine local or general?
general
The specificity of neuro-endocrine depends on?
receptors
What are the 2 major control systems?
1) Endocrine
2) Nervous System
Hormone
“to set in motion, to excite”
- a chemical substance released in small quantities from certain glands (endocrine) that travels through the circulatory system to elicit a typical physiological response in other cells and tissues, called target cells/tissues
- includes “neurohormones”
- NOT CO2, intracellular messengers like cyclic AMP
3 general categories of hormones?
1) Steroids & Steroid-Like
2) Amino acid derivatives (catecholamines & thyroid hormones)
3) Peptides & Proteins
Where are steroids & steroid-like hormones from?
cholesterol
Where are Amino acid derivative hormones from?
tyrosine
Androgens
“steroids”
- testosterone
- dihydrotestosterone
- weaker androgens (androstenedione, DHEA, DHEA-S)
Ductless glands
-secret into ECF (into blood)
Estrogens
“steroids”
- estradiol-17beta (E2)
- weaker estrogens (estrone, estriol)
Progestagens
“steroids”
-progesterone
Mineralocorticoids
“steroids”
- aldosterone
- deoxycorticosterone
Glucocorticoids
“steroids”
cortisol
“steroid like” Vitamin D
“steroids”
-cholecalciferol & its derivatives
Catecholamines
“amino acid derivatives”
- norepinephrine
- epinephrine
- dopamine (DA, PIH)
Thyroid Hormones
“amino acid derivatives”
- thyroxine (T4)
- tri-iodothyronine (T3)
Hormones using intracellular receptors?
-steroids (TH)
Hormones using surface receptors?
-cachacolomines, proteins, peptides
Functions of second messengers?
1) amplify signals (from 1 to 1,000,000 molecules)
2) disperse signals (to many places in cell)
Permissiveness
- an increase in response to the hormone
ex: thyroid hormone increase response of fat cells to epinephrine
Transport of hormones in blood
- free (unbound) hormone in plasma (H)
- Bound to large proteins (hormone binding proteins, “BP”, hormone binding globulins “BG”)
- “total” hormone conc. in plasma = free + bound
- Active form of hormone
- on target cells
- on feedback sensors
How to measure hormone?
-usually by competitive binding assays (radioimmunoassays, readireceptor assays, measure ability to bind to an antibody or to a “receptor” not always biological activity)
Circadian Diurnal Rhythm
-one major secretory period/day
Circadian Ultradian Rhythm
- multiple times a day
- pulsatile secretion (a type of ultradian rhythm)
The 3 ways that blood levels of a hormone can be altered?
1) increase/decrease secretion rate
2) increase/decrease conc. of plasma hormone binding protein for that particular hormone
3) increase/decrease degradation rate (clearance)
Causes of endocrine disease?
- over/underproduction of a hormone
- alterations in receptors (# or affinity)
- post-receptor events in target cells
- altered metabolism of the hormone
Synthesis of Peptides/Proteins & Catecholamines
nearly continuous, mild regulation
Storage of Peptides/Proteins & Catecholamines
granules
Secretion of Peptides/Proteins & Catecholamines
regulated (& taken from these stores)
Transport of Peptides/Proteins & Catecholamines
mostly free
Half lives of Peptides/Proteins/Catecholamines
Peptides: few minutes
Proteins: minutes
Catecholamines: few minutes in plasma
Do Peptides/Proteins/Catecholamines need to be activated?
no
Receptor binding of Peptides/Proteins?
surface (on plasma membrane)
Actions on cells of Peptides/Proteins?
Mechanism?
Rapidity?
Duration?
- second messangers
- fast (sec/min); some slower (few hours)
- brief (few min); some longer
Degradation of Peptides/Proteins?
much( to AA in kid, liver, target tissues)
Excretion of Peptides/Proteins?
little, some exceptions
Receptor binding of Catecholamines?
Surface (alpha, beta)
Actions on cells of Catecholamines?
Mechanism?
Rapidity?
Duration??
- second messanger
- fast (sec)
- brief (min)
Degradation of Catecholamines?
much by MAO, COMT
Excretion of Catecholamines?
VMA, Metanephrine, & nor-metanephrine
Synthesis of Steroid Hormones?
little, until stim; regulated
Storage of Steroid Hormones?
little
Secretion of Steroid Hormones?
as synthesized
Transport of Steroid Hormones?
mostly bound,
half life: hours-days
Activation of Steroid Hormones?
Degradation of Steroid Hormones?
- testosterone to DHT; vit D to 1,25(OH)2
- liver, elsewhere
Actions of Steroid Hormones on cells:
Mechanism
Rapidity
Duration
- gene activation
- slow (hr)
- lone (hr-day)
Excretion of Steroid Hormones?
urine (mainly)
Thyroid hormones?
synthesis: partially - precursor (thyroglobulin)
storage: in precursor form (thyroglobulin)
secretion: slow, ~continuous
transport: mostly bound >99%
T1/2 days 6-T4 1-T3
activated: thyroxine (T4) to T3
binding to receptors: nuclear
mechanism: gene activation
rapidity: slow (hr)
duration: long (days)
degradation: liver, products recycled
excretion: very little (enterohepatic circulation)
Positive Feedback
endocrine system’s response to a stimulus reinforces that stimulus
Negative Feedback
endocrine system’s response to a stimulus is to reduce (negate, oppose, minimize) that stimulus
Pituitary
- at base of brain in bony pocket (sella turcica)
- connects to bottom of brain by stalk of tissue (the infundibulum) containing nerves and special veins (long portal veins)
- anterior
- posterior
Hypothalamus
- has many regulatory functions, including control over many endocrine glands and their hormones
1) various nuclei-clusters of nerve cell bodies that synthesize on of the hypothalamic releasing hormones that regulate secretion of hormones from the anterior pituitary gland, tow posterior pituitary gland hormones (ADH/OT)
2) bottom portion = median eminence, axon terminals of neurons containing the hypothalamic releasing hormones that regulate the anterior pituitary gland, these RHs are secreted into first capillaries of a portal system.
Posterior Pituitary
Neurohypophysis
axoplasmic flow through center of axon
-takes a week
Hypothalamo-pituitary portal system
from hypothalamus to the anterior pituitary
Hormones from posterior pituitary?
- oxytocin (OT)
- vasopressin (VP; ADH; antidiuretic hormone)
Neural Extension of Hypothalamus
1) Nerve axons come mainly from 2 nuclei in hypothalamus: supraoptic nucleus (SON) and paraventricular nucleus (PVN)
2) Axons terminate near capillaries in the posterior pituitary: store and release their hormones here
Pars nervosa of posterior lobe: structure
- neurosecretory nerve fibers from PV & SON (hypothalamohypophyseal T)
- associated cells - pituicytes
Pars nervosa of posterior lobe: Function
release 2 hormones
OT & VP
Oxytocin
- stimulates contraction of smooth muscles in pregnant uterus
- contraction of myoepithelial cells in mammary gland
Vasopressin
- regulates retention of water (increase water channels in walls of kidney), increase water reabsorption
- increase contraction of arterial smooth muscle; increase blood pressure
Structure, Synthesis, Secretion of ADH & OT
- nonapeptides with S-S bridge
- synthesized as much larger molecules
- stored in granules with (neurophysins I & II)
- secreted-when action potentials reach nerve terminals, analogous to neurotransmitter release, secreted together with their respective neurophysins
Control of Secretion: Oxytocin
- dilation of cervix
- suckling
Control of Secretion: ADH
-decrease ECF plasma volume, acts via volume receptors
decrease PV by 5-10% for ADH secretion
-increase osmolarity, very sensitive, increase osm 1-2% to increase ADH)
location of osmoreceptors: hypothalamus
Effect of stalk section on nerve tracts to posterior pituitary?
1) pee a lot
2) drank lots of water
- then capillaries grew in and problem was fixed
- transient diabetes incipideous
Intermediate Lobe of Pituitary
-may secrete MSH
Pituitary blood supply
-hypophyseal portal veins
Anterior Lobe of Hormones
-GH
-PRL
-ACTH
-FSH
-LH
-TSH
“trophic hormones” except prolactin
Chemical nature/cell type of anterior lope hormones?
- peptide: ACTH-is a split from pro-opiomelanocortin (POMC)
- 39 amino acids; straight chain
- COOH terminal has most of antigenic activity
- only 20 needed for biological activity
- ACTH1-24
- alpha-MSH structure is located within the ACTH molecule
- varied cell staining
MSH activity
Melanocyte Stimulating Hormone
- melanophores in skin in granules (amphibians)
- synthesis of melanin in humans, darkens skin
- structure of MSH lies within ACTH molecule, so excess ACTH causes hyperpigmentation
Glycoproteins Hormone
TSH, FSH, LH
cell staining: basophils; occupy (15-20% pituitary volume)
Subunit structure: dimers of alpha and beta
alpha subunit is very similar in al three
What subunit do you measure in a test assay?
beta
Proteins
GH, PRL cell staining: acidophils % volume of pituitary: 75% somatotrophs-50% volume lactotrophs-15-25%
Somatotrophs
- increase by T3
- decrease by somatostatin, exogenous GH Rx
Lactotrophs
- increase in pregnancy (estrogen effect)
- have increase blood flow
Anatomy of Thyroid Gland
- located in anterior neck
- shape like a bow tie
- left branch, right branch, isthmus
- seen & palpated during regular exam
- utilizes trace element iodine
- generates hormones thyroxine & triiodothyronine & calcintonin
Key steps in Thyroid Hormone Synthesis
1) Iodine uptake by Na+/I+ symporter
2) Thyroglobulin synthesis and release into follicular lumen
3) Iodination of tyrosine residues in thyroglobulin
4) Endocytosis of iodinated thyroglobulin into follicular cells
5) Generation and secretion of T3 & T4
6) Iodide recycling
What decreases uptake of I- in step 1 of Thyroid Hormone synthesis.=?
ClO4-
TcO4-
SCN
Thyroglobulin
- large protein with few tyrosine residues
- packed into secretory vesicles and released into apical lumen
- inside surface of vesicle is thyroid peroxidase and thyroglobulin is on the outside
Ratio of T4 to T3 release?
90% T4
10% T3
Are T3 and T4 bound?
T4 - 99.98% bound
T3 - 99.5% bound
What changes TBG of thyroid hormone?
Increase - hepatitis, pregnancy, heroin abuse
Decrease - steroid use
***the total amount of bound T4 & T3 stay the same
Deiodinase Enzymes: Type 1
5’/3’
T4 to T3
- responsible for all free T3
- in Liver, Kidney, Tyroid
- falls in starvation
Deiodinase Enzymens: Type 2
5’/3’
T4 to T3
- in Pituitary, CNS, Placenta
- does NOT fall in starvation
Effect of Thyroid Hormone on: Basal Metabolic Rate
Hyperthyroid: increase
Hypothyroid: decrease
Effect of Thyroid Hormone on: Carbohydrate Metabolism
Hyperthyroid: increase
Hypothyroid: decrease
when blood glucose does not change
Effect of Thyroid Hormone on: Protein Metabolism
Hyperthyroid: increase (increase muscle wasting)
Hypothyroid: decrease
Effect of Thyroid Hormone on: Lipid Metabolism
Hyperthyroid: increase (decrease serum cholesterol)
Hypothyroid: decrease (increase serum cholesterol)
Effect of Thyroid Hormone on: Thermogenesis
Hyperthyroid: increase
Hypothyroid: decrease
How does TSH increase thyroid hormone secretion?
1) Increase activity of NIS
2) Stimulates the iodination of thyroglobulin in the follicular lumen
3) Stimulates conjugation of iodinated tyrosines to generate T4 & T3
4) Increases endocytosis of iodinated thyroglobulin into follicular cells
5) Stimulates proteolysis of iodinated thyroglobulin in lysondosomes
6) Increases secretion of T4 & T3 into circulation
7) Exerts growth factor effects on thyroid cells, increasing size & #
