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What is the anatomy of the semicircular canals?
Lateral- horizontal movements (shaking head “no”)
Anterior- forward and backward movements (nodding)
Posterior- head tilt (toward shoulders)
Perilymph- similar to extracellular fluid, high in Na+
Endolymph- similar to intracellular fluid, high in K+
Embedded in gelatinous cupula
Kinocilium- the 1 longest cilium
(vestibular) Stereocilia- 40-70 smaller cilia
Describe the physiology of the semicircular canals (describe what happens in the endolymph, and the movement of the stereocilia)
As the head rotates, the endolymph moves in the opposite direction, which deflects the cupular and bends the hair cell stereocilia
The movement direction of the stereocilia determines increased (towards the kinocilia) or decreased (away from) nerve impulses
When we bend hair cells toward the kinocilium, there is an increase in action potential frequency
When the hair cells bend away from the kinocilium, there is a decrease in action potential frequency
Stereocilia move towards the kinocilia opens cation channels
Endolymph (K+ rich) enters the cell
This causes depolarization, opens voltage-gated calcium channels, triggering the release of glutamate
Stereocilia moving away from the kinocilia closes the cation channels
What happens to the other ear when you are turning in one direction?
The canal that depolarizes is on the same side that you are turning and the canal on the other side is hyperpolarizing
What happens when you turn left? Right? Tilting left? Right? Bending down? Up?
Turning head to the left
Left lateral canal is depolarizing
Right lateral canal is hyperpolarizing
Turning head to the right
Left lateral canal is hyperpolarizing
Right lateral canal is depolarizing
Tilting head to the left
Left posterior canal is depolarizing
Right posterior canal is hyperpolarizing
Tilting head to the right
Left posterior canal is hyperpolarizing
Right posterior canal is depolarizing
Bending head down
Left anterior canal is depolarizing
Right anterior canal is depolarizing
Bending head up
Left anterior canal is hyperpolarizing
Right anterior canal is hyperpolarizing
What are the otolith organs?
Provide info about head position relative to gravity (static tilt)
Detect changes in the rate of linear motion
Utricle and Saccule are between semicircular canals and cochlea
Describe the utricle (what happens when you tilt your head? what happens in horizontal linear motion?)
Hairs of the receptor hair cells protrude into gelatinous layer
Movement of this layer displaces hairs and results in potentials
Otoliths or otoconia (CaCO3 crystals) in gelatinous layer give it more inertia
Activation of Utricle by Head tilt
Tilt head- utricle hairs are bent in the direction of the tilt due to gravity exerted on gelatinous layer
Activation of Utricle by Horizontal linear motion
Horizontal linear motion- initial lag from inertia, hairs bend towards the back, hairs unbend at a constant pace, then hairs bend forward when you stop walking
Describe the saccule
Responds selectively to head tilting away from horizontal position and to vertically directed linear motion (like jumping or getting out of bed)
How do we maintain our sense of balance?
Vestibular info is integrated with input from the eyes, skin, joints, and muscles
Balance and posture
Control external eye muscles so that the eyes remain fixed on a point despite head movement
Perceive motion and orientation
What is Benign Paroxysmal Positional Vertigo?
Otoliths which are normally in the utricle become dislodged and end up in the semicircular canals
If calcium carbonate particles roll along hair cells going back and forth, it mimics motion → moves endolymph or rolls directly on hair cells leading to opening of ion channels
Treatment: Physical therapy
EPLEY maneuver
What type of receptors are taste receptors?
Chemoreceptors are packaged in taste buds in mouth and through, majority on the upper tongue surface
Describe the structure of the taste bud (what is the taste pore? can they be renewed? how is it turned to receptor potentials? how do they attach?)
~50 long, spindle-shaped taste receptor cells packaged with supporting cells in an arrangement like slices of an orange
Taste pore = where the food or drink enters
Taste receptor cells can be regenerated and constantly renewed via basal cells
Modified epithelial cells with microvilli that increase surface area
Contains integral membrane protein receptors that transduce chemicals into receptor potentials
Takes stimuli and converting it into action potentials
Basal cells divide and differentiate to replace taste receptor cells
Only chemicals in solution can attach to receptor cells
Oral cavity generates enzymes to help with digestion and helps bring chemicals into solution
How do we discriminate taste?
Binding of a tastant with a receptor cell alters the cell’s ionic channels to produce a depolarizing receptor potential
Voltage-gated calcium channels leading to release of neurotransmitter
Action potentials are initiated within terminal endings of afferent nerve fibers
Each taste receptor cell responds to only one tastant
Each taste has a distinct signal transduction mechanism
How do we discriminate salty?
Stimulated by sodium influx through channels in the receptor cell membrane → cell depolarizes → triggers voltage-gated calcium channels to open → neurotransmitter release → AP to afferent nerve
How do we discriminate sweet?
Glucose activates G protein (gustducin) and cAMP pathway to close K+ channels
How do we discriminate sour?
Stimulated by acids containing H+
H+ blocks passive K+ out of the cell → cell depolarizes
How do we discriminate bitter?
Associated with many poisonous substances, e.g. alkaloids like strychnine, arsenic
Activate gustducin second-messenger pathways
How do we discriminate umami?
Amino acids (glutamate, others) binds GPCR and acts via gustducin second-messenger pathways
Which taste receptors are ion channels and which receptors activate GPCR?
Ion= salty, sour
GPCR= sweet, bitter, umami
How do we perceive taste?
Afferent endings of cranial nerves terminate on taste buds in various regions
Signals are conveyed to primary gustatory cortex where taste is perceived
Taste signals sent to hypothalamus and limbic system add effective dimensions
Structure of the olfactory mucosa (what cells do they contain? how do odorants reach receptors?)
Contains olfactory receptor cells (detect odors), supporting cells (secrete mucus), and basal cells (olfactory cell precursors)
Cilia have the receptors for binding odorants
Odorants reach receptors by diffusion in normal breathing
Enhanced by sniffing, wafting, etc to reach olfactory bulb
To be detected, odorants must be volatile, water soluble, and dissolved
Briefly describe olfactory signaling
Odorant activates G protein, Golf, triggering cAMP intracellular reactions
Na+ and Ca2+ influx causes depolarizing potential
Does each cell respond to one odorant? or many?
Each of the cells responds to more than one different odorant
Some cells respond preferentially to a single odorant
How do we process scent in the olfactory bulb?
Afferent fibers from receptors synapse in the olfactory bulb
Lined with glomeruli where receptors synapse with mitral cells
Glomeruli file the odors
Mitral cells refine and relay signals to the brain
Odors elicit different patterns in several cortical areas
Olfactory receptors →cells they synapse on is the mitral cells (the place it occurs in is the glomeruli)
Factors that affect sense of smell
Being human- dogs have 4B while humans have 5M
Hunger- being hungry increases sensitivity
Sex- females greater olfactory sensitivities than males, sense of smell in pregnancy increases
Smoking- decreased sensitivity with smoking
Age- decreases with age
State of the olfactory mucosa- the sense of smell decreases when the mucosa is congested
Describe the smell disorders
Head trauma- brain injury, concussion
Neurological Disorders- Parkinson’s disease
Aging- smell function naturally declines with age
Genetics- predisposition to smell disorders
What is a hormone?
Chemical molecules that are released into the bloodstream by glands–which affects the activity of cells and tissues
What are the two types of hydrophilic hormones? Describe their major form in plasma, receptor location, signaling mechanism, and rate of metabolism
Peptide hormones and amines (catecholamines, indolamines)
Major form in plasma: free
Receptor location: plasma membrane
Signaling mechanism: GPCRs (cAMP, IP3, DAG, calcium), enzyme activation (tyrosine kinase, JAKs), alters activity of pre-existing intracellular proteins
Rate of metabolism: faster (minutes), less sustained (e.g. insulin via injection)
What are the two types of lipophilic hormones? Describe their major form in plasma, receptor location, signaling mechanism, and rate of metabolism
Steroid hormones and thyroid hormones (amine)
Major form in plasma: bound
Receptor location: intracellular
Signaling mechanism: directly alters gene transcription, causes formation of new intracellular proteins
Rate of metabolism: slow (hours/days), more sustained (e.g. birth control orally)
They are only active when unbound
Describe the processing of hydrophilic peptide hormones
Preprohormones are synthesized in the RER
Preprohormone → prohormone → hormone
Pruned to active hormones
Packed in secretory vesicles in Golgi, stored in cytoplasm
Secreted out of cell and picked up by the blood
Rate of secretion controlled by regulating the release of stored hormone
Describe the processing of lipophilic steroid hormones
Cholesterol is the precursor
Specific enzymes, hormones, and organs
Once formed, they immediately enter the blood
Some need processing in peripheral tissues to be action
Rate of secretion controlled by synthesis
Possible fates of a hormone following its secretion
Excreted in urine or feces
Inactivated by metabolism
Target cells → bind to receptor and produce a cellular response
Activated by metabolism
All of these influence the effective plasma concentration
What are the three factors that regulate secretion rates of hormones? Briefly describe each.
Negative-feedback control to counteract a change in input
Your body wants to keep [hormones] relatively stable → for example, increase in plasma glucose concentration leads to increase in insulin → when plasma insulin increases, the inhibits further production of insulin
Neuroendocrine reflexes
Neural component and endocrine component
E.g. sympathetic innervation in the nervous system activates adrenal medulla which will lead to hormone secretion (epinephrine)
Diumal rhythm
Some hormones have normal fluctuations throughout the day
E.g. cortisol: highest in the morning and decrease over the course of the day
What happens when you have too little hormone activity?
Hyposecretion (most common)
Increased removal from blood
Abnormal tissue responsiveness
Normal range of some hormone, but there is a problem with the tissue response → non-functional receptors
What happens when you have too much hormone secretion?
Hypersecretion (most common)
Decreased removal from blood
Reduced plasma protein binding
How are two ways that hormone receptors regulate?
Upregulation
Can lead to too much hormone activity
Target cells start gaining receptors
Downregulation
Can lead to too little hormone activity
Target cells start losing receptors
How are three ways that hormones affect hormones? Briefly describe each
Permissiveness
The presence of a second hormone will allow the first hormone to do its job better
E.g. if epinephrine is there by itself, there is low levels of fatty acid release → if thyroid hormone is also present, epinephrine is able to do its job better → thyroid hormone upregulates the epinephrine receptors in cells
Synergism
The combo of two hormones makes the effects much greater than the sum of its effects individually
E.g. : FSH and testosterone together makes greater effect together, than apart
Antagonism
One hormone inhibits the effect of another hormone
E.g. hormonal changes in pregnancy: increase in progesterone during pregnancy which blocks the uterine receptors for estrogen since estrogen helps with contractions
What are the central endocrine glands?
hypothalamus, posterior pituitary, and anterior pituitary
Describe the posterior pituitary (hormones, relationship with hypothalamus)
Hormones
Oxytocin (love hormone)
Helps with orgasm, bonding, helps with uterine contractions for birth, lactation, maternal behavior, social cognition, synaptic plasticity
Vasopressin (antidiuretic hormone)
Helps with water retention, helps kidney reabsorb fluid, causes blood vessels to constrict leading to increased arterial pressure
Posterior pituitary only stores these, NOT synthesize
Hypothalamus and posterior pituitary act as a unit
Neurons in hypothalamus produce vasopressin and oxytocin in the paraventricular and supraoptic nuclei → hormone travels down axon; stored in neuronal terminals in the posterior pituitary → upon neuron excitation, stored hormone is released into blood
Describe anterior pituitary and its hormones
Anterior pituitary- glandular epithelial tissue (adenohypophysis) → it has unique vascular link with the hypothalamus
Hormones
Anterior pituitary synthesizes the hormones it releases
TSH, ACTH, FSH, LH act via GPCR’s and cAMP
GH, prolactin act via JAK/STAT pathway
5 types of cells that produce the 6 hormone groups: thyrotropes, corticotropes, lactotropes, somatotropes, and gonadotropes
“tropic”= regulates another hormone
Thyrotrope:Produces TSH
Corticotropes: Produces ACTH
Lactotrope: Produces prolactin (acts directly on non-endocrine tissue)
Somatotropes: Produces growth hormone
Gonadotropes: Produces hormones for the gonads
Describe the hypothalamic hormones in the anterior pituitary
Hypothalamic hypophysiotropic hormones stimulate or inhibit secretion from anterior pituitary
Called the hypothalamic-hypophyseal portal system
Major hypophysiotropic hormones
Hypothalamus secretes hormones and regulates the anterior pituitary → anterior pituitary hormones act on other endocrine glands to secrete more hormones (EXCEPT PROLACTIN)
Somatostatin= growth hormone inhibiting hormone
Dopamine= prolactin inhibiting hormone
Describe the portal system for the anterior pituitary
Regulatory hormones supplied directly to anterior pituitary
At the hypothalamus, there are neurons that will secrete those releasing or inhibiting hormones → travel down axon → be stored in terminals until stimulated for release → there is a capillary network that connects hypothalamus to anterior pituitary → release of hormones to capillary network allows hormones to go directly to anterior pituitary → cells of the anterior pituitary then synthesize hormones into the bloodstream → enters systemic circulation
All of the blood that end up in the anterior pituitary first end up in the hypothalamus
Why is it important to have direct connection and bypass systemic circulation from the hypothalamus to the anterior pituitary?
It’s faster acting
Hormones will be diluted in general circulation
What. is the endocrine axis?
There are three hormone network:
Hypothalamic hypophysiotropic hormone (Hormone 1)
Anterior pituitary tropic hormone (Hormone 2)
Target endocrine gland hormone (Hormone 3)
KNOW THE CHART OF PITUITARY VS. ANTERIOR
KNOW THE CHART OF PITUITARY VS. ANTERIOR
What is the body’s master circadian clock?
suprachiasmatic nucleus
Describe the pineal gland (what does it interact with, environmental cues)
Communicates with pineal gland to regulate the hormone melatonin (indoleamine)
Synchronizing biological clock with environmental cues
SCN helps control natural circadian rhythm
Our brain during light needs to recognize that it is light and tells pineal gland not to make melatonin
Ganglion cells contain melanoxin which reacts to light and tells the SCN that it is light which inhibits pineal gland from making melatonin
SCN also synthesizes clock proteins that are synthesized throughout the day and then degraded – takes around 25 hours
What happens when it’s out of sync?
Jet lag
What is the biggest self-prescribed supplement?
Melatonin
What. is growth?
Growth of long bones
What factors affect growth?
Genetics
Adequate Diet
Freedom from chronic disease and stress
Normal levels of growth influencing hormones
Describe growth in children
Fetal growth- placenta hormones, genetics, environmental factors
Postnatal growth- growth hormone, neoplacental hormones, genetics, nutrition
Growth hormone is the most abundant hormone produced by anterior pituitary even in adults. What does this tell us?
Growth hormone has metabolic effects
Glucose is shunted to brain and mobilized fatty acids used for muscles
Maintains homeostasis in prolonged fasting or when glucose stores are exceeded
Increases hunger
Increases fat mobilization
Describe soft tissue growth vs bone growth
Indirect influence by stimulating insulin-like growth factor I binding to tyrosine kinase in target cells
Soft tissue growth
Cellular hypertrophy through protein synthesis (GH and IGF1)
Cellular hyperplasia through increased division and decreased cell death (GH and IGF1)
Bone growth
Chondrocyte proliferation and hypertrophy lengthens bones (GH and IGF1)
Action of osteoblasts and osteoclasts thicken bones (GH and IGF1)
Sex hormones close growth plate
How is protein synthesis related to growth hormones?
Direct via GH (JAK) and indirect via IGF 1
Increased amino acid uptake from blood (GH and IGF1) → increased ribosome and protein synthesis (GH and IGF1) → Decreased protein breakdown (GH)
What are the three ways to regulate growth hormone?
Negative feedback loops
Hypothalamus-pituitary-liver axis
GH releasing hormone
Stimulatory and dominant
Increases cAMP
GH inhibiting hormone
Inhibitory
Decreases cAMP
Describe growth hormone deficiency
Onset in Childhood
Defects in pituitary (lack of GH), hypothalamus (lack of GHRH), GH receptors (not deficient in GH but can’t respond), or lacking IGF1
Onset in adulthood
Tumors, infections, inflammation, injury, surgery, radiation, vascular issues
Describe growth hormone excess
Gigantism
Excess GH
Acromegaly
Excess GH (everything is wider)
Describe growth hormone effect on blood glucose, fatty acids, amino acids, muscle protein, major stimuli, and primary role in metabolism
Effect on Blood Glucose: Increase blood glucose → brain uses glucose by decreasing glucose uptake by muscles (shunted to brain) → increase gluconeogenesis
Effect on Blood Fatty Acids: Increase blood fatty acids → increase lipolysis
Effect on Blood Amino Acids: Decrease blood amino acids → increase uptake in muscles to build protein
Effect on Muscle Protein: increase muscle protein → increase protein synthesis → decrease protein degradation
Major Stimuli: hypoglycemia, exercise, stress, deep sleep
Primary Role in Metabolism: promote growth, mobilize fuel in stress sparing glucose for the brain