Block 3 Clinical correlates and Misc. Week 13

How are babies an exception to the mechanics of ingestion?

they can breathe and ingest at the same time

the larynx and epiglottis sits more superiorly than in adults

the epiglottis and soft palate interlock allowing liquid food to pass laterally and bypass entry into the larynx and trachea

what often becomes clogged by allergic inflammation or swelling of nasal lining from the common cold?

ostia

sinuses are connected to the nasal cavity through ostia

what is the danger zone: pterion?

It is a thin area overlying middle meningeal artery 

Hard blow to side of the head may fracture thin bones forming the pterion, rupturing the middle meningeal artery which sits between the skull and the dura mater 

hemorrhage and hematomas

Intracranial hemorrhage/hematoma

blood accumulation in the endocranial (brain) cavity) resulting in life threatening compression of the brain  

where is an Epidural hematoma?

between the skull and dura mater

where is a Subdural hematoma?

between the dura mater and arachnoid mater  

Common when bridging veins and sagittal sinus is torn

where is a Subarachnoid hemorrhage?

between arachnoid mater and pia mater 

Common when cerebral arteries rupture 

what is the danger zone 2 with the triangle of death?

the facial vein has no valves, so blood may drain superiorly into superior and inferior ophthalmic veins and enter the cavernous sinus 

Infection around the nose (ex: pimples or boils) can spread into the cavernous sinus where important arteries and nerves are located 

what is danger zone 3?

space between the alar fascia and prevertebral fascia 

Infections can travel down through the mediastinum to the diaphragm (they hop the highway)

thyroid gland disease

Goiter: enlargement of the thyroid gland, presented as lump on anterior aspect of the neck. 

Often due to iodine deficiency 

Could be associated with: 

Hyperthyroidism: overproduction of thyroid hormones 

Hypothyroidism: underproduction of thyroid hormones. Glands swell to try to produce more hormones 

Could cause breathing/swallowing difficulties or speech loss die to compression of the trachea, larynx, esophagus, or recurrent laryngeal nerve 

what is a goiter?

enlargement of the thyroid gland, presented as lump on anterior aspect of the neck

what is hyperthyroidism?

overproduction of thyroid hormones 

what is hypothyroidism?

underproduction of thyroid hormones

Glands swell to try to produce more hormones

olfactory nerve and tract

fiber type: special sensory

function: olfaction

optic nerve

fiber type: special sensory

functions: vision

oculomotor nerve

fiber type: somatic motor

function: Eye movement (superior, inferior, and medial recti, inferior oblique, and levator palpebrae superioris muscle). Also does visceral motor: constriction of pupil (sphincter pupillae m.) and accommodation (ciliary muscle) 

trochlear nerve

fiber type: somatic sensory

function: Eye movement (superior oblique muscle) 

trigeminal nerve

fiber type: somatic sensory

function: Sensation of most of head and teeth. Somatic sensory: touch for anterior 2.3^rd of tongue. Somatic motor: temporalis, masseter, medial and lateral pterygoids, anterior belly of digastric, tensor veli palatini, tensor tympani 

abducens nerve

fiber type: somatic motor

function: Abducts the eye (lateral rectus muscle) 

facial nerve

fiber type: somatic motor

function: muscles of facial expression

vestibulocochlear nerve

fiber type: special sensory

function: hearing and balance

glossopharyngeal nerve

fiber type: special sensory

function: Taste from posterior 1/3^rd tongue. Somatic motor: stylopharyngeus muscle. Visceral motor; parotid gland (saliva secretion). Visceral sensory: carotid sinus and body 

vagus nerve

fiber type: visceral motor

function: Smooth muscles and glands in thoracic and abdominal visceral organs. Somatic motor: pharynx, larynx, and palate muscles. Somatic sensory: sensation in lower pharynx, larynx, and trachea. Special sensory: taste of epiglottis. Somatic sensory: auricle, external acoustic meatus 

spinal accessory nerve

fiber type: somatic motor

function: motor innervation to sternocleidomastoid and trapezius muscle

hypoglossal nerve

fiber type: somatic motor

function: tongue movement

what number is the olfactory nerve?

CN I

what number is the optic nerve?

CN II

what number is the oculomotor nerve?

CN III

what number is the trochlear nerve?

CN IV

what number is the trigeminal nerve?

CN V

what number is the abducens nerve?

CN VI

what number is the facial nerve?

CN VII

What number is the vestibulocochlear nerve?

CN VIII

what number is the glossopharyngeal nerve?

CN IX

what number is the vagus nerve?

CN X

what number is the spinal accessory nerve?

CN XI

what number is the hypoglossal nerve?

CN XII

Branchial fistula and cyst

Caused by persistent cervical sinus derived from fusion of Pharyngeal clefts 2-4 

Typically, internal fistula opens at the palatine tonsil formed from pouch 2 and external fistula opens on the skin of the neck anterior to the sternocleidomastoid muscle 

what is a thyroid duct cyst?

forms in the midline (not lateral) of the neck rom incomplete closure of the thyroglossal duct. Rupture of this cyst from infection creates a sinus

what is an ectopic thyroid gland?

is the existence of gland tissue along the path of the thyroglossal duct (common) (commonly we see this as a pyramidal lobe) 

Cleft lip & palate

caused by incomplete closure of the maxilla and/or palate 

Results in abnormal facial appearance and defective speech 

Treatment involves surgery and any therapies (like speech therapy) to improve related conditions 

what is Craniosynostosis?

deformity in the cranium due to the premature closure of sutures/fontanelles 

Type of defect depends on which suture closes prematurely 

what is microcephaly?

caused by abnormal development of the brain, rather than premature closure of sutures. Often results in mental deficiency 

what is hydrocephalus?

caused by elevated pressure in ventricles due to CSF buildup (resulting in enlarged brain ventricles) 

what is Treacher Collins syndrome?

Genetic disorder that involves faulty migration of neural crest cells in pharyngeal arches 1 and 2 

Symptoms: hearing loss, downturned eyes, hypoplasia (underdevelopment) of midface, micrognathia (small lower jaw), cleft palate 

Oculomotor palsy examples 

Ptosis; complete lesion; anisocoria; medial rectus palsy 

what is ptosis?

weak or paralyzed levator palpebrae superioris; lesion located in the superior division of the nerve 

what would a complete lesion of the oculomotor nerve present as?

weakness or paralysis of 4 of the 6 extraocular muscles; unopposed muscles pull eye down and out 

what is anisocoria?

weakness or paralysis of sphincter pupillae; the affected eye remains more dilated than contralateral eye (eye doesn’t dilate in response to light changes) 

what is medial rectus palsy?

a lesion located in the inferior division (oculomotor)

Trochlear nerve palsy

Lesion produces weakness/paralysis of the superior oblique 

Unopposed muscles draw the affected eye up and in 

Abducens Palsy 

Lesion produces weakness/paralysis of the lateral rectus muscle 

The unopposed medial rectus muscle pulls the eye toward the nose 

what is special about the abducens nerve?

The abducens lies most medial in the cavernous sinus 

This placement puts the nerve the most at risk for compression related to aneurysms and blood clots

what is trigeminal neuralgia?

Patients complain of acute, intense pain on face 

Can be stimulated by a slight breeze 

Most cases are idiopathic 

Treatment varies from local anesthesia to verve resection 

TMJ disorders 

Problem related to the temporomandibular jaw joint 

Unbalanced muscle firing produces: misaligned teeth, can lead to tooth grinding (bruxism), jaw tenderness, headaches, lock jaw, and ear pain

Bell’s palsy

Lesion to one or more branches of parotid plexus 

Causes partial/ total paralysis of ipsilateral facial muscles 

Most cases are idiopathic 

Symptoms usually to resolve over weeks/months 

Clinical correlates for Vagus nerve / Recurrent laryngeal nerve damage:

result of surgical accidents (like during a thyroid tumor removal) 

Consequences of compression from tumors or aneurysms 

A lesion produces partial or total paralysis of most laryngeal muscles 

Unilateral lesion can result in a hoarse voice 

A bilateral lesion produces muteness and trouble breathing (vocal cords can’t abduct) 

Only muscle left unaffected is the cricothyroid

what nerve gets injured in whiplash, surgery accidents, and childbirth usually?

spinal accessory

can cause shoulder drop or torticollis

what is shoulder drop and what spinal nerve is associated?

trapezius weakness/paralysis; shoulder slopes towards side of lesion

CN XI spinal accessory

what is torticollis and what spinal nerve is associated?

this is a damage during birth; sternocleidomastoid hypertonicity (acquired/ spasmodic) or entrapment (congenital) where the head tilts toward lesion and face turns away 

CN XI spinal accessory

what is Stern’s law and what is the order?

If it has tensor then it is innervated by CN V3 

If it has palate in the name then it is innervated by CN X; unless it has tensor in the name, then that trumps “palate” and its CN V3 

If it has glossus in the name then it is CN XII; unless it has palate in the name, then that trumps “glossus” and it is innervated by CNX

tensor then palate then glossus

Hypoglossal lesions: test and presentation

Hypoglossal lesion test (Genioglossus test) is the simplest way to see if hypoglossal nerve is damaged 

A common test for hypoglossal damage is to have the patient stick out their tongue 

Lesions to hypoglossal present as weakness or paralysis of most tongue muscles 

Weakness/paralyzed genioglossus will present asymmetric activation 

This results in the tongue deviating to the lesion side

Pharmacodynamics

what the drug does to the body and how

Pharmacokinetics

what the body does to the drug and how

what do Physicochemical characteristics of a drug determine?

the ability to move through the body and initiate a cellular effect (this is a structure-activity relationship) 

Determine the drug’s ability to be absorbed, will the drug pass through the physiologic membranes (like lipid bilayers), once it is there will it get to its target (like if it goes to the brain, can it cross the blood-brain barrier), how will it be metabolized and how will it be excreted 

what is intrinsic activity?

will the drug be able to produce the same cellular response that the endogenous ligand could produce naturally in the body

what is the receptor occupancy theory?

Assumes that the portion of occupied receptors is related to the effect of the drug 

what is equilibrium binding?

This is when the number/amount of drug-receptor complexes is the same as the number of drugs and receptors that are separate 

Basically the drug-receptor association rate and dissociation rate are equal 

how do you know if there are spare receptors?

if it is possible to elicit a maximal biologic response at a concentration of agonist that does not result in occupancy of the full complement of available receptors 

what is the two-state receptor occupancy model?

suggests that in the absence of a ligand, a receptor assumes two conformational states- active (Ra) and inactive (Ri). Some receptors in the receptor pool must exist in the Ra form some of the time and produce constitutive (basal) activity. The extent to which an agonist shifts the equilibrium toward the active state is determined by the relative affinity of the drug for the two conformations 

Full agonists

have a much higher affinity for the Ra conformation and stabilize it so that a large percentage of receptors in the pool are in the Ra-D complex which produces the full effect

Partial agonists

bind Ra with slightly greater affinity than Ri so only a submaximal response is produced no matter the dose 

Neutral antagonists

bind Ra and Ri with equal affinity. The equilibrium is not altered. No change in activity is observed 

Inverse agonists

stabilize a large percentage of receptors as Ri-D, which reduces basal activity

The classical receptor occupancy model

suggests that receptors in a receptor pool are inactive unless activated by a ligand  

Agonists

bind receptors and activate the receptor signaling pathway

Antagonists

bind receptors, do not activate signaling, and interfere with the agonist’s ability to activate the receptor

what do agonists have?

affinity and intrinsic activity

what do antagonists have?

affinity, zero intrinsic activity, and they block the agonist from activating the receptor

Competitive antagonists

competes for the same binding site as the agonist and affects the amount of agonist needed to achieve a maximal response.

The dose-response curves are shifted rightward and Emax is not reduced

Irreversible (noncompetitive) active site antagonists

bind irreversibly or with very high affinity to the active site, which prevents the agonist from activating the receptor. The effects are insurmountable 

Negative allosteric modulators

bind an allosteric site, which reduces the affinity and/or efficacy of the agonist

Positive allosteric modulators

enhance the affinity of the receptors for the agonists, enhancing the agonist effect 

Receptor desensitization

a decrease in the coupling efficiency of receptors- the receptor and the cell become unresponsive (insensitive) to the action of the drug, even in the continued presence of the drug 

Receptor downregulation

a decrease in the number of receptors by internalization followed by degradation of the receptor (and ligand)

what is Tachyphylaxis?

an acute, sudden decrease in response after continuous or repeated administration of a drug 

what is an estimate of the safety of a drug?

the therapeutic index (TI)

Median effective dose (ED50)

the dose of a drug required to produce a specifies effect in 50% of the population 

Median lethal dose (LD50)

the dose of a drug that is lethal in 50% of the population 

Median toxic dose (TD50)

the dose of a drug that produces a specified toxic effect in 50% of the population 

what is the therapeutic window?

represents the range of steady state concentrations (dose range) at which the likelihood of efficacy is high and the probability of adverse effects is low 

what are the three primary processes of pharmacokinetics?

input, distribution, and elimination

what is ion trapping?

a process that prevents the reabsorption of drugs and other unwanted substances in the body by altering the pH of urine or other body fluids 

there is a potential for adverse effects and drug interactions based on the fact that?

they can be induced, downregulated, competitive inhibition, noncompetitive inhibition, and have genetic variants 

how is secondary active transport powered?

by energy stored in electrochemical gradients 

how is primary active transport powered?

by ATP hydrolysis (ATPase)

By what mechanism can a hydrophilic drug cross physiologic barriers? 

transport proteins

Parenteral

drugs that are injected

topical

application for local effect (can include oral inhalation- lungs)