Block 4 Shut the door Flashcards
homeostasis example pathway
receptors: baroreceptors (peripheral) or temperature (central) > AFF > hypothalamus > EFF > hormones/ANS
homostasis fxn
integrates info for control of ENDOCRINE, ANS, and neural systems concerned with motivation (LIMBIC SYSTEM)
fornix
major projection from hypothalamus > mammillary bodies
pituitary structure
when head trauma…
lies at base of brain in sphenoid bone: sella turcica
infundibulum/stalk to pit can be severed = severs pit from thalamus»_space;> increase in prolactin (because under inhibitory control)
adenohypophysis
neurophypophysis
median eminence
anterior pituitary (more rostral)
posterior pituitary
infundibulum (intersection between hypothalamus and pit gland = impt relay)
posterior pituitary fxn
synthesis and secretion of VASOPRESSIN OR OXYTOCIN
synthesized in MAGNOCELLULUAR hypothalamic neurons in SUPRAOPTIC (SON) and PARAVENTRICULAR (PVN) nuclei (secrete directly into systemic circulation)
>
transported via axons to nerve terminals in posterior pituitary
Supraoptic nucleus (SON) and paraventricular nucleus (PVN) are where?
activated by
in medulla
limbic structures (motivation, emotions) solitary nucleus (medulla) (requires AFF from baroreceptors and gi tract)
nerve terminals in posterior pituitary >
vasopression and oxytocin axonal transported > terminal > vesicles > released by AP activity
Vasopressin/ADH stimulus
- increased BLOOD OSMOLALITY: too much NaCl > hypothalamus > VP > kidney > INC WATER RESORPTION by kidney
- HYPOVOLEMIA: dec blood volume > receptors in heart > hypothalamus > VP > INC WATER RESORPTION
- HYPOTENSION: dec blood pressure > baroreceptor > hypothalamus > VP > VASOCONSTRICTION > inc BP
Oxytocin stimulus
WOMEN
- SUCKLING/nursing > inc OT > “milk ejection reflex” via smooth muscle contraction in breast
- UTERINE SITMULATION > inc OT > uterine contraction > delivery of newborn
* bonding idea, delivered intranasally
anterior pituitary fxn
families
secretions of “families” of hormones into system circulation
1. somatomammotropins
GH
PROLACTIN
- glycoproteins
TSH
FSH
LH - opiomelanocortin peptides
ACTH
B-EP
somatomammotropins
stimulus and effects
GH growth hormone
stimulus: EXERCISE, STRESS, SLEEP
effect: tissue growth, metabolism of fat, carbs, etc.
PROLACTIN
stimulus: SUCKING, STRESS
effect: development of mammary tissue, LACTATION (to be ejected by oxytocin)
glycoprotein
stimulus and effects
TSH thyroid-stimulating hormone
stimulus: COLD TEMPS
effects: increase TH > inc cell metabolism, inc metabolic rate, inc heat production *negative feedback
FSH follicle-stimulating hormone gonadotropin regulated by hypothalamic peptide effects: MEN inc SPERMATOGENESIS WOMEN development of ovarian FOLLICLE
LH luteinizing hormone
gonadotropin regulated by hypothalamic peptide
effects:
MEN *required for SPERATOGENESIS (with FSH), stimulates TESTOSTERONE
WOMEN initiates OVULATION “trigger,” stimulates PROGESTERONE from spent follicle
opiomelanocortin peptides
stimulus and effects
opiate receptor binding, pigment action, adrenal cortex
common precursor: pro-imc: POMC
ACTH adrenocorticotropic hormone
stimulus: STRESS
effects: secretes CORTISOL/glucocorticoid from adrenal cortex
B-EP beta-endorphin
stimulus: STRESS (fight or flight)
effects: opiate-like ANALGESIA
POMC special because
when cleaved makes two biologically active peptides: ACTH and B-EP
test used clinically to asses anterior pituitary function?
stress common stimulus, so induce insulin-induced hypoglycemia
inject small insulin: decrease blood glucose»_space;> increase in ACTH, cortisol, prolactin, b-EP, GH
hypothalamus controls anterior pituitary by _______ neurons,
which secrete _______ to median eminence
parvocellular neurons
hypothalamic releasing hormones
hypothalamic releasing hormone
function/pathway
synthesized in parvocellular neurons > transported via axons to median eminence > released from nerve terminals into hypophyseal portal vein
hypothalamic releasing hormones
excitatory
inhibitory
4 excitatory:
TRH thryotropin-releasing hormone = INC TSH
GnRH gonadotropin-releasing hormone = INC FSH and LH
CRH corticotropin-releasing hormone = INC ACTH and B-EP
GHRH growth hormone-releasing hormone = INC GH
2 inhibitory:
SOMATOSTATIN decrease GH secretion
DOPAMINE decrease PROLACTIN
only pituitary hormone controlled by excitatory and inhibitor HRHs
GH
diabetes insipidus
bitter urine
LOSS OF VASOPRESSIN SECRETION
etiology: head trauma (sever pit stalk), autoimm, idiopathic
POLYURIA excess urine
POLYDYPSIA excess drinking
Tx: desaminovasopression
galactorrhea-amenorrhea
inappropriate lactation
cessation of menstruation
HYPERPROLACTINEMIA increased blood prolactin
etiology: tumor in pituitary = MICROADENOMA that release prolactin > dec LH and FSH > cessation of menstruatio > INFERTILITY
Tx: surgically remove microadenoma, block prolactin with DOPAMINE REC AGONIST
signals from periphery that cause us to stop eating
- hormone CCK from gi tract thru vagus to brainstem
(SHORT-TERM SIGNAL) - LEPTIN from intestines from high fat content to hypothalamus
(LONG-TERM SIGNAL)
short term signals of satiety (decreased food intake)
a. oropharyngeal: TASTE
b. GASTRIC DISTENSION/STRETCH and INTENSTINAL NUTRIENT
c. POST-ABSROPTIVE SATIETY: gi > liver through portal vein; SENSORS FOR GLUCOSE AND FREE FAs in liver
satiety factors in CNS
a. gastric distention
b. CCK
c. ghrelin
a. gastric distenion: MECHANORECEPTORS on VAGAL AFFERENTS > solitary nucleus (NTS)
* add leptin, increased response to gastric stretch
b. cholecystokinin CCK: hormone released from duodenum in response to meals
-inc gallbladder contraction > inc bile release > inc fat digestion
-inc pyloric constriction
-inc gastric contractions
CCK Rec > inc VAGAL AFF response > NTS
c. ghrelin hormone: from stomach
increased by fasting
OREXIGENIC: INC APPETITE
Prader-Willi syndrome
Sx
fetal hypotonia mental retardation hypogonadotropic hypogonadism DEC FSH and LH ghrelin secretion HYPERGHRELINEMIA obesity hyperphagia EXCESSIVE EATING
long-term CNS signals of satiety
LEPTIN: adipocytes release leptin *morbid obesity: higher > normal amounts leptin site of action: 1. solitary nucleus in brainstem 2. hypothalamus
MULTIPLE HYPOTHALAMIC NUCLIE implicated in control of food intake: LHA, PVN, ARC
CNS nuclei of satiety:
LHA lateral hypothalamic area
PVN paraventricular nucleus
ARC arcuate nucleus
activation of LHA > release of “anabolic” NT = OREXIN > increase in eating
activation of PVN > release of “catabolic” NT = CRH (corticotropin releasing hormone) > decrease in eating
ARC: integrates all this info
two populations of neurons:
i. NPY (neuropeptide Y) neurons project both to PVN and LHA to INC EATING
ii. MELANOCORTIN neurons project both to PVN and LHA to DEC EATING
LHA lesion
APHAGIA cessation of eating
1. aphagia due to damage to MEDIAL FOREBRAIN BUNDLE = MESOLIMBIC SYSTEM dopeminergic system
reduced MOTIVATION to eat
reduced MOTOR FUNCTION to eat
- aphagia due to loss of neurons that synthesis “orexigenic” peptide = OREXIN
actions of leptin on ARC
i. leptin acts in ARC to inhibit NPY: DEC FOOD INTAKE
ii. leptin acts in ARC to activate melanocortin neurons: DEC FOOD INTAKE
actions of ghelin on ARC
ghrelin acts in ARC to activate NPY neurons: INC FOOD INTAKE
what type of drug could be promising candidates for treating hyperphagia-induced obesity?
activate melanocrtin receptors
___% treated for mood disorders
over 50%
limbic system related structures
amygdala hippocampus septal nuclei nucleus accumbens medial prefrontal cortex and anterior cingulate cortex ventral segmental area anterior and dorsomedial nuclei of thalamus mamillary nuclei
limbic system pathways:
FORNIX: hippocampus > mammillary body and septal nuclei
MAMMILLO-THALAMIC TRACT: mammillary body > anterior n of thalamus
anterior n of thalamus > cingulate gyrus and prefrontal cortex
STRIA TERMINAULIS: amygdala > septal nucleus
MEDIAL FOREBRAIN BUNDLE: midbrain via hypothalamus > forebrain
all limbic areas receive rich innervation by _____ and _____ axons
monoaminergic and cholinergic axons
a. NE from locus ceruleus (LC) in pons
b. 5HT from raphe nuclei (Ra) midbrain, pons
c. DA from mesolimbic system***
d. ACh from nucleus baseless and septal nucleus
= general arousal, sleep wake cycles
ventral segmental area (VTA) projects to:
DA neurons
nucleus accumbens
medial prefrontal cortex
amygdala
septal nuclei
mesolimbic system (DA)
i. self-stimulation studies: VTA > REWARDING
ii. drug addiction
COCAINE block DA repute: inc DA in synapse
lesion VTA, NAcc
decreased drug seeking behavior
DA receptors permanently blocked
***has effects on our natural reward system (endorphins, natural opioids, nicotine, opioids)
natural rewards
SEX
FOOD
ACh neurons lost in AD in
nucleus basalis**
spetal nucleus
limbic system functions
AMYGDALA and lesion
amygdala fxns
a. role in fear conditioning/type of learning
Pavlovian classical conditioning
lesions to amygdala: prevent fear conditioning
limbic system functions
PREFRONTAL CORTEX and syndrome
prefrontal cortex
“The Case of Phineas Gage” rod through prefrontal while RR working
Prefrontal Lobe Syndrome:
GAAII
a. impaired GOAL directed behavior, no job
b. lack of emotion in decision-making APATHY
c. poor social judgment ANTISOCIAL behavior
d. poor emotional control INCREASED IMPULSIVITY
etiology:
dorsolateral PFC: working memory and executive function
orbital frontal cortex: projections to amygdala
limbic system functions
HIPPOCAMPUS and injury
patient H.M. fell off bike > seizures
*bilateral medial temporal lobectomy = removed hippocampus bilaterally
»>
a. anterograde amnesia (no new memories)
b. temporally graded retrograde amnesia (lost old memories, post surgery, can remember prior to surgery)
c. explicity or declarative memory lost (semantic/facts and episodic/experiences)
d. IMPLICIT MEMORY MOTOR SKILLS NOT LOST
limbic system dysfunction
Urbach-Wiethe disease
AMYGDALA dysfunction
a. impaired recognition of emotion in facial expressions, INABILITY TO JUDGE “LIKE” EMOTIONS (fear vs anger, surprise vs. joy)
b. MEMORY LOSS especially w/ EMOTIONAL CONTENT
limbic system dysfunction
PTSD
AMYGDALA dysfunction
triad of symptoms:
1. re-experiencing phenomena/flashbacks
2. avoidance of situations that parallel initial trauma
3. hyperarousal: hypervigilance and increased anxiety
etiology:
increased amygdala activity in fMRI
increased medial prefrontal cortex activity which usually inhbitis amygdala
Korsakoff’s syndrome triad
- DISORDER of immediate memory > no new memories
- DISORIENTATION > to space and time
- CONFABULATION > fabrication
etiology:
chronic alcoholism and thiamine B1 deficiency
MAMMILLARY BODY DEGENERATION
Kluver-Bucy Syndrome
- oral tendencies: all objects in mouth (Gary Busey has a big mouth)
- changes in emotions (“k” is the most apathetic response)
- hypersexuality (“luver”)
- visual agnosia: physchic blindness (Gary Busey has asymmetric eyes)
Alzheimer’s Dementia AD
etiology:
- loss of CHOLINERGIC input (in nucleus basalis) to HIPPOCAMPUS
- presence of NFTs (intracellular, phosphorylated tau proteins) and beta-amyloid plaques (extracellular)
Sx:
- loss of memory
- mood disorders: anx and dep
- loss of motor fxn: slow
- complete loss of cognitive fxn
___% over 85yo have AD
over 50% over 85yo have AD
according to engeland, treat AD with
donepezil (Aricept)
AChE
Schizophrenia
Sx and incidence
fragmentation of mood, thought, and movement
Sx:
positive: delusions and hallucinations
negative: social withdrawal
1% US population diagnosed
Schizophrenia
neurochemical basis hypotheses
1. "dopamine hypothesis" increase in DA rec activity > amphetamine psychosis Tx: antipsychotic: HALOPERIDOL block DA receptors (SE: parkinsonian) atypical anti-psychotic: CLOZAPINE block DA receptors block 5HT receptors block glutamate repute: increase glutamate in synapse
2. "glutamate hypothesis" PHENCYCLIDINE (PCP) "angel dust" blocks NMDA glutamate receptor Tx: increase glutamate receptor activity
Depression
Sx and incidence
Sx:
lethargy, anhedonia, loss of sleep
15% US population
20% F, 13% M treated
Depression
neurochemical basis hypothesis
“monoamine hypothesis”
decreased NE and/or decreased 5HT receptor activity
Tx: increase NE and DA
- MAOIs
- TCAs: block repute of NE and/or 5HT
- SSRIs: block repute of 5HT
Chronic Traumatic Encephalopathy (CTE)
progressive neurodegenerative disease cause by repeated head trauma
TRIAD Sx:
- cognition: ANTEROGRADE AMNESIA and LOSS EXECUTIVE FXN (prefrontal cortex and hippocampus)
- mood: DEP and APATHY
- behavior: DEC IMPULSE CONTROL and INC AGRESSIVENESS
~age 30-50 yo
risk factors: HEAD TRAUMA
etiology: generalized BRAIN ATROPHY including prefrontal cortex, temporal lobes (amygdala, hippocampus), and parietal lobes
NFTs PRESENT
MCA stroke
weakness and snsory deficits to CONTRLATERAL side
lateral side frontal, parental and temporal
FACE and ARMS
HOMONYMOUS HEMIANOPSIA
“looking at their lesion”
dominant hem: aphasia > problems speaking
nondom hem: contralateral hemineglect
ACA stroke
weakness and sensory contralat SAME
anterior and medial frontal and parietal and temporal
LEGS
PERSONALITY CHANGES
Lenticulostriate stroke
branch of MCA to DEEP STRUX OF BRAIN
hallmark: LACK CORTICAL SIGNS
pure motor: POSTERIOR LIMB OF IC (hemiparesis of legs, arms, face)
pure sensory: LATERAL THALAMUS (numbness of legs, arms, face CONTRALAT)
Vertebral Artery stroke
supplies inferior cerebellum and lateral medulla
VERTIGO, BLURRED VISION, VOMITING, NYSTAGMUS, ATAXIA
WALLENBERG syndrome: numbness on one side of face and opposite side of body*****
Basilar artery stroke
supplies rostral brainstem and occipital lboes
CN PALSIES, GAZE ISSUES, HEMIANOPSIA, MIOSIS
may cause LOSS OF CONSCIOUSNESS
Posterior cerebral artery stroke (PICA)
supplies occipital lobes
HOMONYMOUS HEMIANOPSIA (of contralateral)
MACULAR SPARING
ACROMATOPSIA difficulty naming colors
nondom hem: neglect of affected vision field
intracerebral hemorrhage
HTN
decreased vascular elasticity
subarachnoid hemorrhage
rupture of intracranial aneurysms or trauma
thunderclap sudden HA, “worst headache ever”
N/V, nuchal rigidity, photophobia, change in consciousness
ischemia stroke
atherosclerosis via thrombosis of cerebral vessels OR embolism
> inadequate oxygen delivery to brain > neuronal death as soon as 4 min
sudden onset focal neurologic deficits, no HA
stroke imaging
non-contrast CT
for intracranial bleeding, including SAH, intracerebral bleeding or hematoma
MRI: ischemic stroke and focal cerebral ischemia
when is cerebral angiography indicated?
to evaluate patients with ischemic strokes in vertebrobasilar distribution and subarachnoid/intraparencymal hemorrhage
modifiable risk factors for stroke
HTN DM lipids sympathomimetic abuse smoking EtOH obesity Afib
non modifiable risk factors for stroke
age*most imp
race
ethnicity
heredity
Hispanic Americans, American Indians, Alaska Natives > white Americans
African Americans 2X than white Americans
tPA for stroke
MOA
enchances conversion of plasminogen to plamin by binding to fibrin > INITIATES FIBRINOLYSIS
*helps restore potency to thromboses vessels
considered for patients with ISCHEMIC stroke who can be treated WITHIN 3-4.5 HOURS OF SX ONSET
tPA contraindecations
HBP INTRACRANIAL HEMORRHAGE SAH rapidly resolving symptoms MI, stroke, head injury in past 3 mo GIB past 3 weeks active bleeding anticoagulation therapy
hypothermia is resisted by
heat conservation: VASOCONSTRICTION
heat production: SHIVERING
hypothalamus received input from ____ and ____ temperature receptors
skin (local) and spinal cord (central)
***2 sensory receptors
local skin sensors cause release of ______
core SC temperature sensory send signals to CNS to activate _____
NO = VASODILATOR
SYMPATHETIC NERVE OUTFLOW (adrengergic and cholinergic)
cold skin sensors release _____
NE = VASOCONSTRICTOR
fever involves a pyrogen which stimulates the hypothalamus to produce _____
PGE2 = causes shivering
hypothalamic temperature is special because
does not change in temperature (receives sensors from elsewhere)
sympathetic receptors related to blood pressure regulation
NE interacts with:
Beta-1: stimulate HR, increase stroke volume
Alpha-1: increase total peripheral resistance
=increase BP
blood pressure regulation pathway
stretch receptors on carotid arteries and aortic arch > sense stretch/BP > as BP increases, firing rate incrases > glossopharyngeal IX and vagus X nere to medulla > solitary nucleus > rostral ventrolateral medulla suppressed
baroreceptors inhibit: sympathetic PREganglionic neurons which usually increase BP
baroreceptors
attenuate (decrease) high BP
if blood pressure drops >
less activation of IX and X > less stimulation of NTs > LESS INHIBITION of rostral ventrolateral medulla > GREATER STIMULATION of PREganglionic sympathetics in thoracic cord > INC HR, SV, RESISTANCE using a1 and b1 receptors
orthostatic hypotension
LBP when stand up from sitting or laying down
young people, most common cause: dehydration, not enough fluids
inspiration requires
a PUMP (diaphragm and external intercostals) a PACEMAKER to initiate breathing (Pre-Boetzinger area of ventrolateral medulla)
stimulate _____ to innervate diaphragm
phrenic nerve (C3-5) ACh and nicotinic receptor
inputs to Pre-Boetzinger area
parafacial respiratory center SENSES CO2 (ACTUALLY H+) and DIRECTLY EXCITES ABDOMINALS
BTW, how do you get H+ from CO2?
CA carbonic anhydrase
Ondyne’s curse
lack of CO2 sensors»_space;> HYPOVENTILATION
FATAL
sympathetics control _______ of _______
parasympathetics affect ______ of _______
rate of breathing
dilation of bronchioles
urination is controlled by both
voluntary and involuntary mechanisms
1. external sphincter VOLUNTARY
ACh and NICOTINIC
- internal sphincter INVOLUNTARY
ACh and MUSCARINIC
PARAsympathetic
bladder full > sends AFF signals to
medial prefrontal cortex (usually suppresses voiding)
detected by STRETCH MECHANORECEPTORS
Pontine micturition center activates
the sacral cord to stimulate PREganglionic PARAsympathetic nerves >
relaxation of external voluntary sphincter
contraction of urinary bladder
urination involves dis-inhibitor of the micturition center when bladder is full, controlled by activation of which nerve
pudendal nerve > relax external sphincter
incontinence Tx
ANTIMUSCARINICS
M3 antagonists
HYPOkinetic disorders
DIRECT pathway INHIBITED
INDIRECT pathway ACTIVE
= decreased motor activity
PARKINSON DISEASE = LOSS OF DOPAMINERGIC NEURONS
HYPERkineteic disorders
DIRECT pathway ACTIVE
INDIRECT pathway INHIBITED
= incrased motor activity
HUNTINGTON DISEASE = expanded CAG repeats
parkinson disease Tx
RESTORE dopaminergic activity (not slow progression of disease)
LEVODOPA (prodrug) plus CARBIDOPA (inh AAAD) = sinemet
adverse effects of L-DOPA
“peak dose” dyskinesia
high plasma level, activating DIRECT too much
diphasic sykinesia
at onset and offset of loop effect
“off” period dystonia
when levels all off: no relief
think morning/eve when dose is off
“wearing off” phenomenon
driven by progressive loss of DA neurons
PRIMARY SIDE EFFECTS BECAUSE DA RECEPTORS IN ALL OF BODY
L-DOPA primary adverse effects
- confusion, anxiety, agitation, insomnia, nightmares, depression
- psychotic reactions: schizophrenia-like delusions and hallucinations (because increased DA in limbic system) REVERSIBLE
- orthostatic hypotension
- nausea, vomiting, anorexia
COMT inhibitors
ENTACAPONE
decrease peripheral metabolism of L-DOPA
(like AAAD, but not into DA, will be excreted instead)
smoother response
longer on time
MAOI
SELEGINE
MAO-a: metabolizes NE and 5HT
MAO-b: priary metabolism of dopamine: USEFUL PD TX
can be mono therapy in early stages
smoothes out dosing
Dopaine receptor agonists
PRAMIPEXOLE D3 agonist
ROPINIROLE D2 agonist
direct action on D2 receptors in stiatum
becoming more first line
less SE
muscarinic antagonists
Ach is NT for a small amount of striatal interneurons
TRIHEXYPHENIDYL
Amantadine
antiviral
PD Tx tissue transplantation?
human fetal adrenal medullary tissue into caudate nucleus
PD surgery
pallidotomy: allieviates akinesia
