12/18/2017

usmle step 1 Middle cerebral artery–supplies lateral aspect of brain, trunk-arm-face area of motor and sensory cortices, Broca’s and Wernicke’s speech areas.

By Live Dr - Mon Dec 01, 1:30 am

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Circle of Willis

Anterior cerebral artery–supplies medial surface of the brain, leg-foot area of motor and

sensory cortices.

Middle cerebral artery–supplies lateral aspect of brain, trunk-arm-face area of motor

and sensory cortices, Broca’s and Wernicke’s speech areas.

Anterior communicating artery–most common circle of Willis aneurysm; may cause

visual-field defects.

Posterior communicating artery–common area of aneurysm; causes CN III palsy.

Lateral striate–divisions of middle cerebral artery; “arteries of stroke”; supply internal

capsule, caudate, putamen, globus pallidus.

In general, stroke of anterior circle . general sensory and motor dysfunction, aphasia;

stroke of posterior circle . cranial nerve deficits (vertigo, visual deficits), coma,

cerebellar deficits (ataxia).

Dural venous sinuses Venous sinuses run in the dura mater where its meningeal and periosteal layers

separate. Cerebral veins . venous sinuses . internal jugular vein.

HIGH-YI E LD SYSTEMS NEUROLOGY AND PSYCHIATRY

Posterior

communicating artery

Posterior inferior

cerebellar artery (PICA)

Middle

cerebral artery

Anterior inferior

cerebellar artery (AICA)

Posterior

cerebral artery

Right anterior

cerebral artery

Optic chiasm

Lateral striate

CN III

Internal carotid artery (ICA)

Anterior

communicating artery

Basilar artery

Vertebral artery

Anterior spinal artery

(Adapted, with permission, from White JS. USMLE Road Map: Gross Anatomy, 1st ed. New York: McGraw-Hill, 2003.)

Sup. sagittal sinus (main

location of CSF return via

arachnoid granulations)

Inf. sagittal sinus

Great cerebral v.

Straight sinus

Confluence

of the sinuses

Sigmoid sinus

Int. jugular v.

Jugular foramen

Inf. petrosal sinus

Sup. petrosal sinus

Cavernous sinus

Sphenoparietal sinus

Sup. ophthalmic v.

Transverse sinus

Occipital sinus

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NEUROLOGY AND PSYCHIATRY-ANATOMY AND PHYSIOLOGY (continued)

Ventricular system

Lateral ventricle . 3rd ventricle via foramen of Monro.

3rd ventricle . 4th ventricle via aqueduct of Sylvius.

4th ventricle . subarachnoid space via:

Foramina of Luschka = lateral.

Foramen of Magendie = medial.

Spinal nerves There are 31 spinal nerves altogether: 8 cervical, 12 31, just like 31 flavors!

thoracic, 5 lumbar, 5 sacral, 1 coccygeal. Vertebral disk herniation usually

occurs between L5 and S1.

Spinal cord lower In adults, spinal cord extends to lower border of To keep the cord alive, keep the

extent L1-L2; subarachnoid space extends to lower spinal needle between L3 and

border of S2. Lumbar puncture is usually L5.

performed in L3-L4 or L4-L5 interspaces, at

level of cauda equina.

Lumbar puncture CSF obtained from lumbar subarachnoid space

between L4 and L5 (at the level of iliac crests).

Structures pierced as follows:

1. Skin/superficial fascia

2. Ligaments (supraspinous, interspinous,

ligamentum flavum)

3. Epidural space

4. Dura mater

5. Subdural space

6. Arachnoid

7. Subarachnoid space–CSF Pia is not pierced.

NEUROLOGY AND PSYCHIATRY HIGH-YI E LD SYSTEMS

Lateral ventricles

Posterior

horn

Aqueduct

of Sylvius

Foramen of Magendie

Foramen of Luschka

Third

ventricle

Fourth

ventricle

Ventricular

foramen

Anterior

horn

Needle in

subarachnoid space

Cauda

equina

L5

L3

L4

L4/5

disk

Spinous

process

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Spinal cord and associated tracts

Spinal tract anatomy and functions

Dorsal column Fasciculus gracilis = legs. Dorsal column is organized as

organization Fasciculus cuneatus = arms. you are, with hands at

sides–arms outside and legs

inside.

HIGH-YI E LD SYSTEMS NEUROLOGY AND PSYCHIATRY

Sacral

Cervical Spinothalamic tract (pain and temperature)

Gray matter

Lateral

corticospinal tract

(voluntary motor)

Legs

Arms

Fasciculus

cuneatus

(upper body,

extremities)

Dorsal

columns

Fasciculus

gracilis

(lower body,

extremities)

(pressure, vibration,

touch, proprioception)

Tract and function 1st-order neuron Synapse 1 2nd-order neuron Synapse 2 3rd-order neuron

Dorsal column-medial Sensory nerve ending Nucleus Decussates in medulla VPL of Sensory cortex

lemniscal pathway . dorsal root ganglion cuneatus or . ascends contralaterally thalamus

(ascending pressure, . enters spinal cord, gracilis in medial lemniscus

vibration, touch, and ascends ipsilaterally in (medulla)

proprioceptive dorsal column

sensation)

Spinothalamic tract Sensory nerve ending Ipsilateral Decussates at anterior VPL of Sensory cortex

(ascending pain and (A-delta and C fibers) gray matter white commissure . thalamus

temperature sensation) . enters spinal cord (spinal cord) ascends contralaterally

Lateral corticospinal Upper motor neuron: Cell body of Lower motor neuron: Neuromuscular

tract (descending 1° motor cortex . anterior horn Leaves spinal cord junction

voluntary movement descends ipsilaterally (spinal cord)

of contralateral limbs) until decussating at

caudal medulla

(pyramidal decussation)

. descends

contralaterally

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NEUROLOGY AND PSYCHIATRY-ANATOMY AND PHYSIOLOGY (continued)

Brachial plexus

Randy

Travis

Drinks

Cold

Beer.

Clavicle fracture is relatively

common–brachial plexus is

protected from injury by

subclavius muscle.

Radial nerve Known as the “great extensor nerve.” Provides Radial nerve innervates the

innervation of the Brachioradialis, Extensors of the BEST!

wrist and fingers, Supinator, and Triceps. To SUPinate is to move as if

carrying a bowl of SOUP.

Thenar-hypothenar Thenar–Opponens pollicis, Abductor pollicis Both groups perform the same

muscles brevis, Flexor pollicis brevis. functions: Oppose, Abduct,

Hypothenar–Opponens digiti minimi, Abductor and Flex (OAF).

digiti minimi, Flexor digiti minimi.

Clinically important Pudendal nerve block–ischial spine.

landmarks Appendix–2/3 of the way from the umbilicus to the anterior superior iliac spine

(McBurney’s point).

Lumbar puncture–iliac crest.

NEUROLOGY AND PSYCHIATRY HIGH-YI E LD SYSTEMS

C5 C6 C7 C8 T1

Rad = radial nerve

Ax = axillary nerve

LT = long thoracic nerve

MC = musculocutaneous nerve

Med = median nerve

Uln = ulnar nerve

LT

1. Waiter´s tip

2. Claw hand

3. Wrist drop

4. Winged scapula

5. Deltoid paralysis

6. Saturday night palsy (wrist drop)

7. Difficulty flexing elbow,

variable sensory loss

8. Decreased thumb function,

Pope´s blessing

9. Intrinsic muscles of hand,

claw hand

1

4

3

5 6

7 8

2

9

MC Med Uln

Ax Rad

Roots

Trunks

Divisions

Upper Middle Lower

Lat. Post. Med. Cords

Branches

Extensors

Flexors

Claw

hand

Winged

scapula

Wrist

drop

Hypothenar

eminence

Thenar

eminence

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Landmark C2 is the posterior half of a skull “cap.” Gallbladder pain referred

dermatomes C3 is a high turtleneck shirt. to the right shoulder via

C4 is a low-collar shirt. the phrenic nerve.

T4 is at the nipple. T4 at the teat pore.

T7 is at the xiphoid process.

T10 is at the umbilicus (important for early T10 at the belly butTEN.

appendicitis pain referral).

L1 is at the inguinal ligament. L1 is IL (Inguinal Ligament).

L4 includes the kneecaps. Down on L4s (all fours).

S2, S3, S4 erection and sensation of penile and “S2, 3, 4 keep the penis off

anal zones. the floor.”

Spindle muscle control

Muscle spindle In parallel with muscle fibers. Muscle stretch . Muscle spindles monitor muscle

intrafusal stretch . stimulates Ia afferent. length (help you pick up a

stimulates a motor neuron . reflex muscle heavy suitcase when you

(extrafusal) contraction. didn’t know how heavy it

Gamma loop CNS stimulates . motor neuron .contracts intrafusal was). Golgi tendon organs

fiber . increased sensitivity of reflex arc. monitor muscle tension (make

you drop a heavy suitcase

you’ve been holding too long).

Clinical reflexes Biceps = C5 nerve root. Reflexes count up in

Triceps = C7 nerve root. order.

Patella = L4 nerve root. S1, 2

Achilles = S1 nerve root. L3, 4

Babinski–dorsiflexion of the big toe and fanning of other C5, 6

toes; sign of UMN lesion, but normal reflex in 1st year C7, 8

of life.

Primitive reflexes 1. Moro reflex–extension of limbs when startled Normally disappear within 1st

2. Rooting reflex–nipple seeking year. May reemerge following

3. Palmar reflex–grasps objects in palm frontal lobe lesion.

4. Babinski reflex–large toe dorsiflexes with

plantar stimulation

HIGH-YI E LD SYSTEMS NEUROLOGY AND PSYCHIATRY

C3

C6

C2

V3

V2

V1

C8

C8

C7

L5

C6

S2

S3

L4

C4

C5

T1

T4

T6

T10

T8

L1

Golgi tendon

organ

Intrafusal

(regulates

length)

Ib

a

Extrafusal

Ia

.

(senses tension and provides

inhibitory feedback to a motor neurons)

C5, 6

L3, 4

C7, 8

S1, 2

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NEUROLOGY AND PSYCHIATRY-ANATOMY AND PHYSIOLOGY (continued)

Brain stem anatomy

CNs that lie medially at brain stem: III, VI, XII. 3(×2) = 6(×2) = 12.

Cranial nerves

Nerve CN Function Type Mnemonic

Olfactory I Smell Sensory Some

Optic II Sight Sensory Say

Oculomotor III Eye movement, pupil constriction, Motor Marry

accommodation, eyelid opening

Trochlear IV Eye movement Motor Money

Trigeminal V Mastication, facial sensation Both But

Abducens VI Eye movement Motor My

Facial VII Facial movement, taste from anterior 2/3 of Both Brother

tongue, lacrimation, salivation (submaxillary

and sublingual glands), eyelid closing

Vestibulocochlear VIII Hearing, balance Sensory Says

Glossopharyngeal IX Taste from posterior 1/3 of tongue, swallowing, Both Big

salivation (parotid gland), monitoring carotid

body and sinus chemo- and baroreceptors

Vagus X Taste from epiglottic region, swallowing, palate Both Brains

elevation, talking, thoracoabdominal viscera,

monitoring aortic arch chemo- and baroreceptors

Accessory XI Head turning, shoulder shrugging Motor Matter

Hypoglossal XII Tongue movement Motor Most

Cranial nerve Located in tegmentum portion of brain stem Lateral nuclei = sensory.

nuclei (between dorsal and ventral portions). Medial nuclei = Motor.

1. Midbrain–nuclei of CN III, IV.

2. Pons–nuclei of CN V, VI, VII, VIII.

3. Medulla–nuclei of CN IX, X, XI, XII.

NEUROLOGY AND PSYCHIATRY HIGH-YI E LD SYSTEMS

Middle cerebellar peduncle

Interpeduncular fossa

Crus cerebri

(cerebral peduncle)

Anterior perforated substance

Pons

CN XII

Pyramid

C1

Olfactory bulb (CN I)

Olfactory tract

CN II

Optic tract

CN III

CN IV (arises dorsally)

CN V

CN VI

CN VII

CN VIII

CN IX

CN X

CN XI

Pyramidal decussation

Optic chiasm

Infundibulum

Tuber cinereum

Mammillary body

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Vagal nuclei

Nucleus Solitarius Visceral Sensory information (e.g., taste, VII, IX, X.

baroreceptors, gut distention).

Nucleus aMbiguus Motor innervation of pharynx, larynx, and upper IX, X, XI.

esophagus (e.g., swallowing, palate elevation).

Dorsal motor nucleus Sends autonomic (parasympathetic) fibers to heart,

lungs, and upper GI.

Cranial nerve and Cribriform plate (CN I). Divisions of CN V exit owing

vessel pathways Middle cranial fossa (CN II-VI)–through sphenoid to Standing Room Only.

bone:

1. Optic canal (CN II, ophthalmic artery, central

retinal vein)

2. Superior orbital fissure (CN III, IV, V1, VI,

ophthalmic vein)

3. Foramen Rotundum (CN V2)

4. Foramen Ovale (CN V3)

5. Foramen spinosum (middle meningeal

artery)

Posterior cranial fossa (CN VII-XII)–through

temporal or occipital bone:

1. Internal auditory meatus (CN VII, VIII)

2. Jugular foramen (CN IX, X, XI, jugular vein)

3. Hypoglossal canal (CN XII)

4. Foramen magnum (spinal roots of CN XI,

brain stem, vertebral arteries)

HIGH-YI E LD SYSTEMS NEUROLOGY AND PSYCHIATRY

344

NEUROLOGY AND PSYCHIATRY-ANATOMY AND PHYSIOLOGY (continued)

Cavernous sinus A collection of venous sinuses on either side of the The nerves that control

pituitary. Blood from eye and superficial cortex extraocular muscles (plus V1

. cavernous sinus . internal jugular vein. and V2) pass through the

CN III, IV, V1, V2, and VI and postganglionic cavernous sinus.

sympathetic fibers en route to the orbit all pass Cavernous sinus syndrome (e.g.,

through the cavernous sinus. Only CN VI is due to mass effect)–

“free-floating.” Cavernous portion of internal ophthalmoplegia, ophthalmic

carotid artery is also here. and mandibular sensory loss.

Mastication 3 muscles close jaw: Masseter, teMporalis, Medial M’s Munch.

muscles pterygoid. 1 opens: lateral pterygoid. All are Lateral Lowers (when

innervated by the trigeminal nerve (V3). speaking of pterygoids with

respect to jaw motion).

Muscles with All muscles with root glossus in their names (except Palat: vagus nerve.

glossus palatoglossus, innervated by vagus nerve) are Glossus: hypoglossal nerve.

innervated by hypoglossal nerve.

Muscles with palat All muscles with root palat in their names (except Palat: vagus nerve (except

tensor veli palatini, innervated by mandibular TENSor, who was too

branch of CN V) are innervated by vagus nerve. TENSE).

NEUROLOGY AND PSYCHIATRY HIGH-YI E LD SYSTEMS

(Adapted, with permission, from Stobo J et al. The Principles and Practice of Medicine, 23rd ed. Stamford, CT: Appleton

& Lange, 1996:277.)

Optic chiasm

Hypothalamus Third ventricle

Pituitary stalk

Diaphragma sellae

Pituitary gland

Oculomotor nerve (III)

Trochlear nerve (IV)

Abducens nerve (VI)

Ophthalmic nerve (V1)

Maxillary nerve (V2)

Internal carotid artery

Cavernous sinus

Sella turcica

Sphenoid bone Sphenoidal

sinus Nasopharynx

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Eye and retina

Extraocular CN VI innervates the Lateral

muscles and nerves Rectus.

CN IV innervates the Superior

Oblique.

CN III innervates the Rest.

The “chemical formula”

LR6SO4R3.

The superior oblique abducts,

introverts, depresses.

Direction of eye

movements by

extraocular muscles

HIGH-YI E LD SYSTEMS NEUROLOGY AND PSYCHIATRY

Sclera

Choroid

Retina

Optic

nerve

Central

artery

and vein

Fovea

Ciliary body

Ciliary

process

Iris

Lens

Vitreous

humor

Anterior

chamber

Canal of

Schlemm

Cornea

(Note: inferior oblique not in plane of diagram)

……..

……..

…………….

…………

……….

……….

….

….

….

….

….

….

….

….

….

….

……..

……..

……..

Superior Superior rectus m.

ophthalmic v.

Ophthalmic a. Superior oblique m.

Medial rectus m.

Levator palpebrae

superioris m.

Maxillary sinus

……

……

Infraorbital n.

……

……

……

……

Inferior

rectus m.

Lateral

rectus m.

Optic n.

SR

IR SO

IO

LR

(temporal)

MR

(nasal)

NEUROLOGY AND PSYCHIATRY-ANATOMY AND PHYSIOLOGY (continued)

Pupillary Light in either retina sends a signal via CN III to pretectal nuclei (dashed lines) in

light reflex midbrain that activate bilateral Edinger-Westphal nuclei; pupils contract bilaterally

(consensual reflex).

Note that the illumination of 1 eye results in bilateral pupillary constriction.

KLM sounds: kuh, Kuh-kuh-kuh tests palate elevation (CN X–vagus). Say it aloud.

la, mi La-la-la tests tongue (CN XII–hypoglossal).

Mi-mi-mi tests lips (CN VII–facial).

Sleep stages

Stage (% of total Description Waveform

sleep time in Awake (eyes open), alert, active mental Beta (highest frequency, lowest

young adults) concentration amplitude)

Awake (eyes closed) Alpha

1 (5%) Light sleep Theta

2 (45%) Deeper sleep Sleep spindles and K complexes

3-4 (25%) Deepest, non-REM sleep; sleepwalking; night Delta (lowest frequency,

terrors, bed-wetting (slow-wave sleep) highest amplitude)

REM (25%) Dreaming, loss of motor tone, possibly a memory Beta

processing function, erections, . brain O2 use At night, BATS Drink Blood.

1. Serotonergic predominance of raphe nucleus key to initiating sleep

2. NE reduces REM sleep

3. Extraocular movements during REM due to activity of PPRF (paramedian pontine

reticular formation/conjugate gaze center)

4. REM sleep having the same EEG pattern as while awake and alert has spawned the

terms “paradoxical sleep” and “desynchronized sleep”

5. Benzodiazepines shorten stage 4 sleep; thus useful for night terrors and sleepwalking

6. Imipramine is used to treat enuresis because it . stage 4 sleep

NEUROLOGY AND PSYCHIATRY HIGH-YI E LD SYSTEMS

(Adapted, with permission, from Simon RP et al. Clinical Neurology, 3rd ed. Stamford, CT: Appleton & Lange,

1996.)

Edinger-Westphal nucleus

Ciliary ganglion

Optic tract

Lateral geniculate nucleus

Oculomotor nerve

Light

Optic

nerve

Pretectal nucleus

Pupillary constrictor muscle

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REM sleep . and variable pulse, REM, . and variable blood REM sleep is like sex:

pressure, penile/clitoral tumescence. Occurs . pulse, penile/

every 90 minutes; duration . through the clitoral tumescence,

night. ACh is the principal neurotransmitter . with age.

involved in REM sleep. REM sleep . with age.

HIGH-YI E LD SYSTEMS NEUROLOGY AND PSYCHIATRY

348

NEUROLOGY AND PSYCHIATRY-PATHOLOGY

Neural tube Associated with low folic acid intake during pregnancy. Elevated a-fetoprotein in amniotic

defects fluid and maternal serum.

Spina bifida occulta–failure of bony spinal canal to close, but no structural herniation.

Usually seen at lower vertebral levels.

Meningocele–meninges herniate through spinal canal defect.

Meningomyelocele–meninges and spinal cord herniate through spinal canal defect.

Brain lesions

Area of lesion Consequence

Broca’s area Motor (nonfluent/expressive) aphasia with good BROca’s is BROken speech.

comprehension Wernicke’s is Wordy but

Wernicke’s area Sensory (fluent/receptive) aphasia with poor makes no sense.

comprehension

Arcuate fasciculus Conduction aphasia; poor repetition with good Connects Wernicke’s to

comprehension, fluent speech Broca’s area.

Amygdala (bilateral) Klüver-Bucy syndrome (hyperorality, hypersexuality,

disinhibited behavior)

Frontal lobe Personality changes and deficits in concentration,

orientation, and judgment; may have reemergence of

primitive reflexes

Right parietal lobe Spatial neglect syndrome (agnosia of the

contralateral side of the world)

Reticular activating Coma

system

Mammillary bodies Wernicke-Korsakoff syndrome

(bilateral)

Basal ganglia May result in tremor at rest, chorea, or athetosis

Cerebellar Intention tremor, limb ataxia Cerebellar hemispheres are

hemisphere laterally located–affect

Cerebellar vermis Truncal ataxia, dysarthria lateral limbs. Vermis is

Subthalamic nucleus Contralateral hemiballismus centrally located–affects

central body.

Chorea Sudden, jerky, purposeless movements. Chorea = dancing (Greek).

Characteristic of basal ganglia lesion (e.g., Think choral dancing or

Huntington’s disease). choreography.

NEUROLOGY AND PSYCHIATRY HIGH-YI E LD SYSTEMS

Subarachnoid

space

Transverse

process

Skin Tuft of hair

Dura

Spinal

cord

Meninges

Normal Spina bifida occulta Meningocele Meningomyelocele

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Athetosis Slow, writhing movements, especially of fingers. Athetos = not fixed (Greek).

Characteristic of basal ganglia lesion. Think snakelike.

Hemiballismus Sudden, wild flailing of 1 arm. Half ballistic (as in throwing a

Characteristic of contralateral subthalamic nucleus baseball).

lesion. Loss of inhibition of thalamus through

globus pallidus.

Aphasia

Broca’s Nonfluent aphasia with intact comprehension. Broca’s is Broken speech;

Broca’s area–inferior frontal gyrus. Wernicke’s is Wordy but

Wernicke’s Fluent aphasia with impaired comprehension. makes no sense.

Wernicke’s area–superior temporal gyrus. Wernicke’s = “What?”

Degenerative diseases

Cerebral cortex Alzheimer’s disease–most common cause of Multi-infarct dementia is the

dementia in the elderly. Associated with senile 2nd most common cause

plaques (extracellular, ß-amyloid core) and of dementia in the elderly.

neurofibrillary tangles (intracellular, abnormally May cause amyloid angiopathy

phosphorylated tau protein). Familial form (10%) .intracranial hemorrhage.

associated with genes on chromosomes 1, 14, 19

(APOE4 allele), and 21 (p-App gene) (see Color

Image 41).

Pick’s disease–dementia, aphasia, parkinsonian

aspects; associated with Pick bodies (intracellular,

aggregated tau protein) and is specific for the

frontal and temporal lobes.

Basal ganglia and Huntington’s disease–autosomal-dominant Chromosome 4–expansion of

brain stem inheritance, chorea, dementia. Atrophy of CAG repeats. CAG–Caudate

caudate nucleus (loss of GABAergic neurons). loses ACh and GABA.

Parkinson’s disease–associated with Lewy bodies TRAP = Tremor (at rest),

and depigmentation of the substantia nigra pars cogwheel Rigidity, Akinesia,

compacta (loss of dopaminergic neurons). Rare and Postural instability (you

cases have been linked to exposure to MPTP, a are TRAPped in your body).

contaminant in illicit street drugs.

Spinocerebellar Olivopontocerebellar atrophy; Friedreich’s ataxia.

Motor neuron Amyotrophic lateral sclerosis (ALS)–associated Commonly known as Lou

with both LMN and UMN signs; no sensory Gehrig’s disease.

deficit.

Werdnig-Hoffmann disease–autosomal-recessive

inheritance; presents at birth as a “floppy baby,”

tongue fasciculations; median age of death 7

months. Associated with degeneration of anterior

horns.

Polio–follows infection with poliovirus; LMN signs.

Associated with degeneration of anterior horns.

HIGH-YI E LD SYSTEMS NEUROLOGY AND PSYCHIATRY

350

NEUROLOGY AND PSYCHIATRY-PATHOLOGY (continued)

Poliomyelitis Caused by poliovirus, which is transmitted by the fecal-oral route. Replicates in the

oropharynx and small intestine before spreading through the bloodstream to the CNS,

where it leads to the destruction of cells in the anterior horn of the spinal cord, leading in

turn to LMN destruction.

Symptoms Malaise, headache, fever, nausea, abdominal pain, sore throat. Signs of LMN lesions–

muscle weakness and atrophy, fasciculations, fibrillation, and hyporeflexia.

Findings CSF with lymphocytic pleocytosis with slight elevation of protein. Virus recovered

from stool or throat.

Demyelinating and 1. Multiple sclerosis (MS)–. prevalence with Classic triad of MS is a

dysmyelinating . distance from the equator; periventricular SIN:

diseases plaques (areas of oligodendrocyte loss and Scanning speech

reactive gliosis) with preservation of axons; . Intention tremor

protein (IgG) in CSF. Many patients have a Nystagmus

relapsing-remitting course. Patients can present Most often affects women in

with optic neuritis (sudden loss of vision), MLF their 20s and 30s; more

syndrome (internuclear ophthalmoplegia), common in whites.

hemiparesis, hemisensory symptoms, or bladder/ Treatment: ß-interferon or

bowel incontinence (see Color Image 47). immunosuppressant therapy.

2. Progressive multifocal leukoencephalopathy

(PML)–associated with JC virus and seen in

2-4% of AIDS patients (reactivation of latent

viral infection).

3. Acute disseminated (postinfectious)

encephalomyelitis.

4. Metachromatic leukodystrophy (a

lysosomal storage disease).

5. Guillain-Barré syndrome (see below).

Guillain-Barré Inflammation and demyelination of peripheral Associated with infections .

syndrome (acute nerves and motor fibers of ventral roots (sensory immune attack of peripheral

idiopathic effect less severe than motor), causing symmetric myelin (e.g., herpesvirus

polyneuritis) ascending muscle weakness beginning in distal or Campylobacter jejuni

lower extremities. Facial diplegia in 50% of cases. infection), inoculations,

Autonomic function may be severely affected and stress, but no definitive

(e.g., cardiac irregularities, hypertension, or link to pathogens.

hypotension). Almost all patients survive; the Respiratory support is critical

majority recover completely after weeks to until recovery. Additional

months. treatment: plasmapheresis,

Findings: elevated CSF protein with normal cell IV immune globulins.

count (“albuminocytologic dissociation”).

Elevated protein . papilledema.

NEUROLOGY AND PSYCHIATRY HIGH-YI E LD SYSTEMS

351

Seizures Partial seizures–1 area of the brain. Epilepsy is a disorder of

1. Simple partial (consciousness intact)– recurrent seizures (febrile

motor, sensory, autonomic, psychic seizures are not epilepsy).

2. Complex partial (impaired consciousness) Partial seizures can secondarily

Generalized seizures–diffuse. generalize.

1. Absence (petit mal)–blank stare Causes of seizures by age:

2. Myoclonic–quick, repetitive jerks Children–genetic, infection,

3. Tonic-clonic (grand mal)–alternating trauma, congenital,

stiffening and movement metabolic.

4. Tonic–stiffening Adults–tumors, trauma,

5. Atonic–“drop” seizures stroke, infection.

Elderly–stroke, tumor, trauma,

metabolic, infection.

Intracranial hemorrhage

Epidural hematoma Rupture of middle meningeal artery, often 2° to CT shows “biconvex disk”

fracture of temporal bone. Lucid interval (see not crossing suture lines.

Color Image 44).

Subdural hematoma Rupture of bridging veins. Venous bleeding (less Crescent-shaped hemorrhage

pressure) with delayed onset of symptoms. Seen that crosses suture lines.

in elderly individuals, alcoholics, blunt trauma,

shaken baby (predisposing factors–brain atrophy,

shaking, whiplash) (see Color Image 43).

Subarachnoid Rupture of an aneurysm (usually berry aneurysm)

hemorrhage or an AVM. Patients complain of “worst headache

of my life.” Bloody or xanthochromic spinal tap.

Parenchymal Caused by hypertension, amyloid angiopathy,

hematoma diabetes mellitus, and tumor.

Berry aneurysms Berry aneurysms occur at the bifurcations in the circle of Willis. Most common site is

bifurcation of the anterior communicating artery. Rupture (most common complication)

leads to hemorrhagic stroke/subarachnoid hemorrhage. Associated with adult polycystic

kidney disease, Ehlers-Danlos syndrome, and Marfan’s syndrome. Other risk factors:

advanced age, hypertension, smoking, race (higher risk in blacks) (see Color Image

46).

HIGH-YI E LD SYSTEMS NEUROLOGY AND PSYCHIATRY

352

NEUROLOGY AND PSYCHIATRY-PATHOLOGY (continued)

Primary Clinical presentation due to mass effects (e.g., seizures, dementia, focal lesions); 1° brain

brain tumors tumors rarely undergo metastasis. The majority of adult 1° tumors are supratentorial,

while the majority of childhood 1° tumors are infratentorial. Note: half of adult brain

tumors are metastases.

Adult peak incidence

A. Glioblastoma Most common 1° brain tumor. Prognosis grave; < 1- “Pseudopalisading” tumor

multiforme year life expectancy. Found in cerebral hemispheres. cells–border central areas

(grade IV Can cross corpus callosum (“butterfly glioma”) (see of necrosis and hemorrhage.

astrocytoma) Color Image 48). Stain astrocytes with GFAP.

B. Meningioma 2nd most common 1° brain tumor. Most often occurs Spindle cells concentrically

in convexities of hemispheres and parasagittal arranged in a whorled pattern;

region. Arises from arachnoid cells external to psammoma bodies (laminated

brain. Resectable. calcifications).

C. Schwannoma 3rd most common 1° brain tumor. Schwann cell Bilateral schwannoma found in

origin; often localized to 8th nerve .acoustic neurofibromatosis type 2.

schwannoma. Resectable.

D. Oligodendro- Relatively rare, slow growing. Most often in Oligodendrocytes = “fried egg”

glioma frontal lobes (see Color Image 49). cells–round nuclei with clear

cytoplasm. Often calcified in

oligodendroglioma.

E. Pituitary Prolactin secreting is most common form. Bitemporal Rathke’s pouch.

adenoma hemianopia (due to pressure on optic chiasm) and

hyper- or hypopituitarism are sequelae.

Childhood peak incidence

F. Pilocytic Diffusely infiltrating glioma. In children, most often Rosenthal fibers-eosinophilic,

(low-grade) found in posterior fossa. Benign; good prognosis. corkscrew fibers.

astrocytoma

G. Medullo- Highly malignant cerebellar tumor. A form of Rosettes or perivascular

blastoma primitive neuroectodermal tumor (PNET). Can pseudorosette pattern of

compress 4th ventricle, causing hydrocephalus. cells. Radiosensitive.

H. Ependymoma Ependymal cell tumors most commonly found in Characteristic perivascular

4th ventricle. Can cause hydrocephalus. Poor pseudorosettes. Rod-shaped

prognosis. blepharoplasts (basal ciliary

bodies) found near nucleus.

I. Hemangio- Most often cerebellar; associated with von Hippel- Foamy cells and high

blastoma Lindau syndrome when found with retinal vascularity are characteristic.

angiomas. Can produce EPO .2°

polycythemia.

J. Craniopharyn- Benign childhood tumor, confused with pituitary Derived from remnants of

gioma adenoma (can also cause bitemporal hemianopia). Rathke’s pouch.

Most common childhood supratentorial tumor. Calcification is common.

NEUROLOGY AND PSYCHIATRY HIGH-YI E LD SYSTEMS

I.

H. C.

J.

G. E.

A.

F.

D.

B.

Supratentorial Infratentorial

353

Motor neuron signs

Sign UMN lesion LMN lesion Lower MN = everything

Weakness + + lowered (less muscle mass,

Atrophy – + . muscle tone, . reflexes,

Fasciculation – + downgoing toes).

Reflexes . . Upper MN = everything up

Tone . . (tone, DTRs, toes).

Babinski + –

Spinal cord lesions

Syringomyelia Enlargement of the central canal of spinal cord. Syrinx (Greek) = tube, as in

Crossing fibers of spinothalamic tract are damaged. syringe.

Bilateral loss of pain and temperature sensation in Often presents in patients with

upper extremities with preservation of touch Arnold-Chiari malformation.

sensation. Most common at C8-T1.

Tabes dorsalis Degeneration of dorsal columns and dorsal roots due to 3° syphilis, resulting in impaired

proprioception and locomotor ataxia. Associated with Charcot’s joints, shooting

(lightning) pain, Argyll Robertson pupils (reactive to accommodation but not to light),

and absence of DTRs.

HIGH-YI E LD SYSTEMS NEUROLOGY AND PSYCHIATRY

Tabes dorsalis (3° syphilis):

degeneration of dorsal roots

and dorsal columns;

impaired proprioception,

locomotor ataxia

Complete occlusion of

ventral artery; spares

dorsal columns and

tract of Lissauer

Syringomyelia: crossing

fibers of corticospinal

tract damaged; bilateral

loss of pain and

temperature sensation

Vitamin B12 neuropathy and

Friedreich´s ataxia:

demyelination of dorsal

columns, lateral corticospinal

tracts, and spinocerebellar

tracts; ataxic gait,

hyperreflexia, impaired

position and vibration sense

Poliomyelitis and Werdnig-

Hoffmann disease: lower

motor neuron lesions only,

due to destruction of

anterior horns; flaccid

paralysis

Multiple sclerosis: mostly

white matter of cervical

region; random and

asymmetric lesions, due

to demyelination; scanning

speech, intention tremor,

nystagmus

ALS: combined upper

and lower motor neuron

deficits with no sensory

deficit; both upper and

lower motor neuron signs

Syrinx

Chiari

malformation

Dorsal column

354

NEUROLOGY AND PSYCHIATRY-PATHOLOGY (continued)

Brown-Séquard Hemisection of spinal cord. Findings:

syndrome 1. Ipsilateral UMN signs (corticospinal tract) below

lesion–not shown

2. Ipsilateral loss of tactile, vibration, proprioception

sense (dorsal column) below lesion

3. Contralateral pain and temperature loss

(spinothalamic tract) below lesion

4. Ipsilateral loss of all sensation at level of lesion

5. LMN signs at level of lesion

If lesion occurs above T1, presents with Horner’s syndrome.

Horner’s syndrome Sympathectomy of face: PAM is horny.

1. Ptosis (slight drooping of eyelid)

2. Anhidrosis (absence of sweating) and

flushing (rubor) of affected side of face

3. Miosis (pupil constriction)

Associated with lesion of spinal cord above T1

(e.g., Pancoast’s tumor, hemisection, latestage

syringomyelia).

The 3-neuron oculosympathetic pathway above projects from the hypothalamus to the

intermediolateral column of the spinal cord, then to the superior cervical (sympathetic)

ganglion, and finally to the pupil, the smooth muscle of the eyelids, and the sweat

glands of the forehead and face. Interruption of these pathways results in Horner’s

syndrome.

NEUROLOGY AND PSYCHIATRY HIGH-YI E LD SYSTEMS

Lesion

4

3 2

(Adapted, with permission, from Simon RP et al. Clinical Neurology, 4th ed. Stamford,

CT: Appleton & Lange, 1999:146.)

C2

T1

First neuron

Spinal cord

Third neuron

Superior cervical ganglion

To sweat glands of forehead

To smooth muscle of eyelid

To pupil

To sweat glands of face

Long ciliary nerve

Ophthalmic division

of trigeminal nerve

Hypothalamus

Internal carotid artery

External carotid artery

Second neuron

355

Upper extremity nerve injury

Nerve Site of injury/deficit in motion Deficit in sensation/course

Radial Shaft of humerus–loss of triceps brachii (triceps Posterior brachial cutaneous.

reflex), brachioradialis (brachioradialis reflex), Posterior antebrachial

and extensor carpi radialis longus (. wrist cutaneous. Passes through

drop). supinator.

Median Supracondyle of humerus–no loss of power in Loss of sensation over the

any of the arm muscles; loss of forearm pronation, lateral palm and thumb and

wrist flexion, finger flexion, and several thumb the radial 21/2 fingers. Passes

movements; eventually, thenar atrophy. through pronator teres.

Ulnar Medial epicondyle–impaired wrist flexion and Loss of sensation over the

adduction, and impaired adduction of thumb medial palm and ulnar 11/2

and the ulnar 2 fingers (. claw hand). fingers. Passes through flexor

Axillary Surgical neck of humerus or anterior shoulder carpi ulnaris.

dislocation–loss of deltoid action.

Musculocutaneous Loss of function of coracobrachialis, biceps, and Passes through coracobrachialis.

brachialis muscles (biceps reflex).

Erb-Duchenne Traction or tear of the upper trunk of the brachial “Waiter’s tip” owing to

palsy plexus (C5 and C6 roots); follows blow to shoulder appearance of arm.

or trauma during delivery.

Findings: limb hangs by side (paralysis of abductors),

medially rotated (paralysis of lateral rotators),

forearm is pronated (loss of biceps).

Lower extremity nerve injury

Nerve Deficit in motion

Common peroneal Loss of dorsiflexion (. foot drop). Deep peroneal PED = Peroneal Everts and

(L4-S2) nerve innervates anterior compartment; Dorsiflexes; if injured, foot

superficial peroneal nerve innervates lateral dropPED.

compartment.

Tibial (L4-S3) Loss of plantar flexion. Tibial nerve innervates TIP = Tibial Inverts and

posterior compartment. Plantarflexes; if injured,

can’t stand on TIPtoes.

Femoral (L2-L4) Loss of knee extension/knee jerk.

Obturator (L2-L4) Loss of hip adduction.

HIGH-YI E LD SYSTEMS NEUROLOGY AND PSYCHIATRY

SP

DP

T

356 NEUROLOGY AND PSYCHIATRY HIGH-YI E LD SYSTEMS

NEUROLOGY AND PSYCHIATRY-PATHOLOGY (continued)

Thoracic outlet An embryologic defect; can compress subclavian artery and inferior trunk of brachial

syndrome plexus (C8, T1), resulting in thoracic outlet syndrome:

(Klumpke’s 1. Atrophy of the thenar and hypothenar eminences

palsy) 2. Atrophy of the interosseous muscles

3. Sensory deficits on the medial side of the forearm and hand

4. Disappearance of the radial pulse upon moving the head toward the opposite side

Cranial nerve and CN XII lesion (LMN)–tongue deviates toward side of lesion (lick your wounds).

cerebellar lesions CN V motor lesion–jaw deviates toward side of lesion.

Unilateral lesion of cerebellum–patient tends to fall toward side of lesion.

CN X lesion–uvula deviates away from side of lesion.

CN XI lesion–weakness turning head to contralateral side of lesion. Shoulder droop on

side of lesion.

Facial lesions

UMN lesion Lesion of motor cortex or connection ALexander Bell with STD:

between cortex and facial nucleus. AIDS, Lyme, Sarcoid,

Contralateral paralysis of lower face only. Tumors, Diabetes.

LMN lesion Ipsilateral paralysis of upper and lower face.

Bell’s palsy Complete destruction of the facial nucleus itself

or its branchial efferent fibers (facial nerve

proper).

Peripheral ipsilateral facial paralysis with inability

to close eye on involved side.

Can occur idiopathically; gradual recovery

in most cases.

Seen as a complication in AIDS, Lyme

disease, Sarcoidosis, Tumors, Diabetes.

Upper

division

Lower

division

Face area

of motor

cortex

Corticobulbar

tract

(UMN

lesion =

central

facial)

Facial

nucleus

LMN

lesion

CN VII

(LMN

lesion =

Bell´s

palsy)

357

Herniation syndromes

1. Cingulate herniation Can compress anterior

under falx cerebri cerebral artery.

2. Downward transtentorial Coma and death result

(central) herniation when these herniations

3. Uncal herniation compress the brain stem.

4. Cerebellar tonsillar Uncus = medial temporal

herniation into the lobe.

foramen magnum

Uncal herniation

Clinical signs Cause

Ipsilateral dilated Stretching of CN III

pupil/ptosis

Contralateral Compression of ipsilateral posterior cerebral artery

homonymous

hemianopia

Ipsilateral paresis Compression of contralateral crus cerebri (Kernohan’s notch)

Duret Caudal displacement of brain stem

hemorrhages–

paramedian artery

rupture

Visual field defects

1. Right anopia

2. Bitemporal hemianopia

3. Left homonymous

hemianopia

4. Left upper quadrantic

anopsia (right temporal lesion)

5. Left lower quadrantic

anopia (right parietal lesion)

6. Left hemianopia with

macular sparing

HIGH-YI E LD SYSTEMS NEUROLOGY AND PSYCHIATRY

Defect in visual field of

1

2

3

4

5

6

4

Optic

chiasm

Optic

nerve

Optic tract

Meyer´s

loop

(temporal

lobe)

Calcarine

fissure

Visual

cortex

1

5

3

2

Dorsal

optic

radiation

(parietal

lobe)

Lt. Rt.

6

Lateral

geniculate

body

Lt. eye Rt. eye

Lateral

ventricles

Falx cerebri

Tentorium

cerebelli

Brain stem Cerebellar

tonsil

Uncus

Supratentorial

mass

1

2 3

4

(Adapted, with permission, from Simon RP et al. Clinical Neurology, 4th ed.

Stamford, CT: Appleton & Lange, 1999:314.)

358

NEUROLOGY AND PSYCHIATRY-PATHOLOGY (continued)

Internuclear Lesion in the medial longitudinal fasciculus (MLF). MLF =MS.

ophthalmoplegia Results in medial rectus palsy on attempted lateral When looking left, the left nucleus

(MLF syndrome) gaze. Nystagmus in abducting eye. Convergence is of CN VI fires, which contracts

normal. MLF syndrome is seen in many patients the left lateral rectus and

with multiple sclerosis. stimulates the contralateral

(right) nucleus of CN III via the

right MLF to contract the right

medial rectus.

Neurotransmitter Anxiety–. NE, . GABA, . serotonin (5-HT).

changes with Depression–. NE and . serotonin (5-HT).

disease Alzheimer’s dementia–. ACh.

Huntington’s disease–. GABA, . ACh.

Schizophrenia–. dopamine.

Parkinson’s disease–. dopamine.

Orientation Is the patient aware of him- or herself as a person? Order of loss: 1st–time;

Does the patient know his or her own name? 2nd–place; last–person.

Anosognosia–unaware that one is ill.

Autotopagnosia–unable to locate one’s own body

parts.

Depersonalization–body seems unreal or dissociated.

Amnesia types Anterograde amnesia is the inability to remember Antero = after.

things that occurred after a CNS insult (no new

memory).

Korsakoff’s amnesia is a classic anterograde amnesia

that is caused by thiamine deficiency (bilateral

destruction of the mammillary bodies), is seen in

alcoholics, and is associated with confabulations.

Retrograde amnesia is inability to remember things Retro = before.

that occurred before a CNS insult.

Substance Maladaptive pattern of substance use defined as 3 or more of the following signs in 1 year:

dependence 1. Tolerance

2. Withdrawal

3. Substance taken in larger amounts or over longer time than desired

4. Persistent desire or attempts to cut down

5. Significant energy spent obtaining, using, or recovering from substance

6. Important social, occupational, or recreational activities reduced because of

substance use

7. Continued use in spite of knowing the problems that it causes

NEUROLOGY AND PSYCHIATRY HIGH-YI E LD SYSTEMS

Medial recti

Right

MLF

Medial

rectus

subnucleus

of CN III

Lateral

recti

Nucleus

of CN VI

L R

Left

MLF

359

Substance abuse Maladaptive pattern leading to clinically significant impairment or distress. Symptoms

have not met criteria for substance dependence. 1 or more of the following in 1 year:

1. Recurrent use resulting in failure to fulfill major obligations at work, school, or home

2. Recurrent use in physically hazardous situations

3. Recurrent substance-related legal problems

4. Continued use in spite of persistent problems caused by use

Signs and symptoms of substance abuse

Drug Intoxication Withdrawal

Alcohol Disinhibition, emotional lability, slurred Tremor, tachycardia, hypertension, malaise,

speech, ataxia, coma, blackouts. Serum nausea, seizures, delirium tremens (DTs),

.-glutamyltransferase (GGT)–sensitive tremulousness, agitation, hallucinations

indicator of alcohol use.

Opioids CNS depression, nausea and vomiting, Anxiety, insomnia, anorexia, sweating,

constipation, pupillary constriction dilated pupils, piloerection (“cold turkey”),

(pinpoint pupils), seizures (overdose is life- fever, rhinorrhea, nausea, stomach cramps,

threatening). diarrhea (“flulike” symptoms), yawning

Amphetamines Psychomotor agitation, impaired judgment, Post-use “crash,” including depression, lethargy,

pupillary dilation, hypertension, tachycardia, headache, stomach cramps, hunger,

euphoria, prolonged wakefulness and hypersomnolence

attention, cardiac arrhythmias, delusions,

hallucinations, fever.

Cocaine Euphoria, psychomotor agitation, impaired Post-use “crash,” including severe depression

judgment, tachycardia, pupillary dilation, and suicidality, hypersomnolence, fatigue,

hypertension, hallucinations (including malaise, severe psychological craving

tactile), paranoid ideations, angina, sudden

cardiac death.

PCP Belligerence, impulsiveness, fever, Recurrence of intoxication symptoms due to

psychomotor agitation, vertical and reabsorption in GI tract; sudden onset of

horizontal nystagmus, tachycardia, ataxia, severe, random, homicidal violence

homicidality, psychosis, delirium.

LSD Marked anxiety or depression, delusions, visual

hallucinations, flashbacks, pupil dilation.

Marijuana Euphoria, anxiety, paranoid delusions,

perception of slowed time, impaired

judgment, social withdrawal, . appetite,

dry mouth, hallucinations.

Barbiturates Low safety margin, respiratory depression. Anxiety, seizures, delirium, life-threatening

cardiovascular collapse

Benzodiazepines Greater safety margin. Amnesia, ataxia, Rebound anxiety, seizures, tremor, insomnia

somnolence, minor respiratory depression.

Addictive effects with alcohol.

Caffeine Restlessness, insomnia, increased diuresis, Headache, lethargy, depression, weight gain

muscle twitching, cardiac arrhythmias.

Nicotine Restlessness, insomnia, anxiety, arrhythmias. Irritability, headache, anxiety, weight gain,

craving

HIGH-YI E LD SYSTEMS NEUROLOGY AND PSYCHIATRY

360

NEUROLOGY AND PSYCHIATRY-PATHOLOGY (continued)

Alcoholism Physiologic tolerance and dependence with symptoms of withdrawal (tremor,

tachycardia, hypertension, malaise, nausea, delirium tremens) when intake is

interrupted. Continued drinking despite medical and social contraindications and life

disruptions.

Treatment: disulfiram to condition the patient to abstain from alcohol use. Supportive

treatment of other systemic manifestations. Alcoholics Anonymous and other peer

support groups are helpful in sustaining abstinence.

Delirium tremens Life-threatening alcohol withdrawal syndrome that peaks 2-5 days after last drink.

In order of appearance–autonomic system hyperactivity (tachycardia, tremors, anxiety),

psychotic symptoms (hallucinations, delusions), confusion.

Treat with benzodiazepines.

Complications Alcoholic hepatitis and cirrhosis, pancreatitis, dilated cardiomyopathy, peripheral

of alcoholism neuropathy, cerebellar degeneration,Wernicke-Korsakoff syndrome, testicular atrophy

and hyperestrinism, and Mallory-Weiss syndrome.

Alcoholic cirrhosis Long-term alcohol use leads to micronodular cirrhosis with accompanying symptoms of

jaundice, hypoalbuminemia, coagulation factor deficiencies, and portal hypertension,

leading to peripheral edema and ascites, encephalopathy, neurologic manifestations

(e.g., asterixis, flapping tremor of the hands), and esophageal varices.

Wernicke-Korsakoff Caused by vitamin B1 (thiamine) deficiency; common in malnourished alcoholics.

syndrome Classically may present with triad of confusion, ophthalmoplegia, and ataxia (Wernicke’s

encephalopathy). May progress to memory loss, confabulation, personality change

(Korsakoff’s psychosis; irreversible). Associated with periventricular hemorrhage/necrosis,

especially in mammillary bodies.

Treatment: IV vitamin B1 (thiamine).

Mallory-Weiss Longitudinal lacerations at the gastroesophageal junction caused by excessive vomiting.

syndrome Associated with pain in contrast to esophageal varices.

NEUROLOGY AND PSYCHIATRY HIGH-YI E LD SYSTEMS

Forms adducts with

proteins and nucleic

acids

Increased NADH/NAD:

Increases lactate/pyruvate

Inhibits gluconeogenesis

Inhibits fatty acid oxidation

Inhibits glycerophosphate

dehydrogenase, leading

to elevated

glycerophosphate

Converted to acetate

Converted to acetyl-CoA

Fatty liver

Increased

fatty acid synthesis

Interpolates into

membranes

Increased

membrane fluidity

Toxic effects,

particularly in the brain

Acetaldehyde

Alcohol dehydrogenase

MEOS

Ethanol

361

Heroin addiction Approximately 500,000 U.S. addicts. Heroin is Naloxone (Narcan) and

Schedule I (not prescribable). Look for track naltrexone competitively

marks (needle sticks in veins). inhibit opioids.

Users at risk for hepatitis, abscesses, overdose, Methadone (long-acting oral

hemorrhoids, AIDS, and right-sided endocarditis. opiate) for heroin

detoxification or long-term

maintenance.

Delirium Rapid . in attention span and level of arousal– DeliRIUM = changes in

disorganized thinking, hallucinations, illusions, sensoRIUM.

misperceptions, disturbance in sleep-wake cycle, Most common psychiatric

cognitive dysfunction. illness on medical and surgical

Key to diagnosis: waxing and waning level of floors. Often reversible.

consciousness; develops rapidly. Check for drugs with

Often due to substance use/abuse or medical illness. anticholinergic effects.

Dementia Gradual . in cognition–memory deficits, aphasia, DeMEMtia characterized by

apraxia, agnosia, loss of abstract thought, MEMory loss. Commonly

behavioral/personality changes, impaired irreversible.

judgment.

Key to diagnosis: rule out delirium–patient is alert,

no change in level of consciousness. More often

gradual onset. In elderly patients, depression

may present like dementia.

Major depressive Characterized by at least 5 of the following for 2 weeks,

episode including either depressed mood or anhedonia:

1. Sleep disturbance SIG E CAPS.

2. Loss of Interest (anhedonia)

3. Guilt or feelings of worthlessness

4. Loss of Energy

5. Loss of Concentration

6. Change in Appetite/weight

7. Psychomotor retardation or agitation

8. Suicidal ideations

9. Depressed mood

Lifetime prevalence of major depressive episode–5-12% male, 10-25% female.

Major depressive disorder, recurrent–requires 2 or more episodes with a symptom-free

interval of 2 months.

Dysthymia is a milder form of depression lasting at least 2 years.

Sleep patterns of Patients with depression typically have the following changes in their sleep stages:

depressed patients 1. . slow-wave sleep

2. . REM latency

3. Early-morning awakening (important screening question)

HIGH-YI E LD SYSTEMS NEUROLOGY AND PSYCHIATRY

362

NEUROLOGY AND PSYCHIATRY-PATHOLOGY (continued)

Risk factors for Sex (male), Age (teenager or elderly), Depression, SAD PERSONS.

suicide completion Previous attempt, Ethanol or drug use, loss of

Rational thinking, Sickness (medical illness, 3 or

more prescription medications), Organized plan,

No spouse (divorced, widowed, or single,

especially if childless), Social support lacking.

Women try more often; men succeed more often.

Electroconvulsive Treatment option for major depressive disorder refractory to other treatment. ECT is

therapy painless and produces a seizure. The major adverse effects of ECT are disorientation

and anterograde and retrograde amnesia. Complications can result from anesthesia.

Manic episode Distinct period of abnormally and persistently

elevated, expansive, or irritable mood lasting at

least 1 week.

During mood disturbance, 3 or more of the

following are present:

1. Distractibility DIG FAST.

2. Irresponsibility–seeks pleasure without

regard to consequences

3. Grandiosity–inflated self-esteem

4. Flight of ideas–racing thoughts

5. . in goal-directed Activity/psychomotor

Agitation

6. . need for Sleep

7. Talkativeness or pressured speech

Hypomanic Like manic episode except mood disturbance not severe enough to cause marked

episode impairment in social and/or occupational functioning or to necessitate hospitalization;

there are no psychotic features.

Bipolar disorder 6 separate criteria sets exist for bipolar disorders with combinations of manic (bipolar I),

hypomanic (bipolar II), and depressed episodes. 1 manic or hypomanic episode

defines bipolar disorder. Lithium is drug of choice.

Cyclothymic disorder is a milder form lasting at least 2 years.

Malingering Patient consciously fakes or claims to have a disorder in order to attain a specific gain

(e.g., avoiding work, obtaining drugs).

Factitious disorder Consciously creates symptoms in order to assume “sick role” and to get medical attention.

Munchausen’s syndrome is manifested by a chronic history of multiple hospital

admissions and willingness to receive invasive procedures. Munchausen’s syndrome

by proxy is seen when illness in a child is caused by the parent. Motivation is

unconscious. Is a form of child abuse and must be reported.

NEUROLOGY AND PSYCHIATRY HIGH-YI E LD SYSTEMS

363

Somatoform Both illness production and motivation are unconscious drives. More common in women.

disorders Several types:

1. Conversion–motor or sensory symptoms (e.g., paralysis, pseudoseizure) that suggest

neurologic or physical disorder, but tests and physical exam are negative; often

follows an acute stressor; patient may be unconcerned about symptoms

2. Somatoform pain disorder–prolonged pain that is not explained completely by illness

3. Hypochondriasis–preoccupation with and fear of having a serious illness in spite of

medical reassurance

4. Somatization disorder–variety of complaints in multiple organ systems with no

identifiable underlying physical findings

5. Body dysmorphic disorder–preoccupation with minor or imagined physical flaws;

patients often seek cosmetic surgery

6. Pseudocyesis–false belief of being pregnant associated with objective physical signs

of pregnancy

Gain: 1°, 2°, 3° 1° gain–what the symptom does for the patient’s internal psychic economy.

2° gain–what the symptom gets the patient (sympathy, attention).

3° gain–what the caretaker gets (like an MD on an interesting case).

Panic disorder Recurrent periods of intense fear and discomfort PANICS.

peaking in 10 minutes with 4 of the following:

Palpitations, Paresthesias, Abdominal distress,

Nausea, Intense fear of dying or losing control,

lIght-headedness, Chest pain, Chills, Choking,

disConnectedness, Sweating, Shaking, Shortness

of breath.

Panic is described in context of occurrence (e.g.,

panic disorder with agoraphobia). High incidence

during Step 1 exam.

Specific phobia Fear that is excessive or unreasonable, cued by presence or anticipation of a specific

object or situation. Exposure provokes anxiety response. Person recognizes fear is

excessive (insight). Fear interferes with normal routine. Treatment options

include systematic desensitization. Examples include:

1. Gamophobia (gam = gamete)–fear of marriage

2. Algophobia (alg = pain)–fear of pain

3. Acrophobia (acro = height)–fear of heights

4. Agoraphobia (agora = open market)–fear of open places

Post-traumatic Person experienced or witnessed event that involved actual or threatened death or serious

stress disorder injury. Response involves intense fear, helplessness, or horror. Traumatic event is

persistently reexperienced as nightmares or flashbacks; person persistently avoids

stimuli associated with the trauma and experiences persistent symptoms of increased

arousal. Disturbance lasts > 1 month and causes distress or social/occupational

impairment. PTSD often follows acute stress disorder, which lasts up to 2-4 weeks.

HIGH-YI E LD SYSTEMS NEUROLOGY AND PSYCHIATRY

364

NEUROLOGY AND PSYCHIATRY-PATHOLOGY (continued)

Other anxiety Adjustment disorder–emotional symptoms (anxiety, depression) causing impairment

disorders following an identifiable psychosocial stressor (e.g., divorce, moving) and lasting

< 6 months.

Generalized anxiety disorder–uncontrollable anxiety for at least 6 months that is

unrelated to a specific person, situation, or event. Sleep disturbance, fatigue, and

difficulty concentrating are common.

Childhood and Autistic disorder–patients have severe communication problems and difficulty forming

early-onset relationships. Characterized by repetitive behavior, unusual abilities (savants), and

disorders usually below-normal intelligence. Treatment: . communication and social skills.

Asperger disorder–a milder form of autism involving problems with social

relationships and repetitive behavior. Children are of normal intelligence and lack

social or cognitive deficits.

Rett disorder–X-linked disorder seen only in girls (affected males die in utero).

Characterized by loss of development and mental retardation appearing at

approximately age 4. Stereotyped hand-wringing.

Attention-deficit hyperactivity disorder (ADHD)–limited attention span and

hyperactivity. Children are emotionally labile, impulsive, and prone to accidents.

Normal intelligence. Treatment: methylphenidate (Ritalin).

Conduct disorder–continued behavior violating social norms. At > 18 years of age,

diagnosed as antisocial personality disorder.

Oppositional defiant disorder-child is noncompliant in the absence of

criminality.

Tourette’s syndrome–motor/vocal tics and involuntary profanity. Onset < 18 years.

Treatment: haloperidol.

Separation anxiety disorder–fear of loss of attachment figure leading to factitious

physical complaints to avoid going to school. Common onset age 7-8.

Eating Anorexia nervosa–abnormal eating habits (excessive dieting), body image distortion,

disorders and . exercise. Severe weight loss, amenorrhea, anemia, and electrolyte disturbances

can follow. Seen primarily in adolescent girls. Commonly coexists with depression.

Bulimia nervosa–binge eating followed by self-induced vomiting or use of laxatives.

Body weight is normal. Parotitis, enamel erosion, electrolyte disturbances, alkalosis,

dorsal hand calluses from inducing vomiting.

Hallucination Hallucinations are perceptions in the absence of external stimuli.

vs. illusion Illusions are misinterpretations of actual external stimuli.

vs. delusion Delusions are false beliefs not shared with other members of culture/subculture that are

firmly maintained in spite of obvious proof to the contrary.

Delusion vs. loose A delusion is a disorder in the content of thought (the actual idea).

association A loose association is a disorder in the form of thought (the way ideas are tied together).

NEUROLOGY AND PSYCHIATRY HIGH-YI E LD SYSTEMS

365

Hallucination types Visual and auditory hallucinations are common in schizophrenia.

Olfactory hallucination often occurs as an aura of a psychomotor epilepsy.

Gustatory hallucination is rare.

Tactile hallucination (e.g., formication–the sensation of ants crawling on one’s skin) is

common in DTs. Also seen in cocaine abusers (“cocaine bugs”).

HypnaGOgic hallucination occurs while GOing to sleep.

Hypnopompic hallucination occurs while waking from sleep.

Sleep apnea Person stops breathing for at least 10 seconds Treatment: weight loss, CPAP,

repeatedly during sleep. surgery.

Central sleep apnea–no respiratory effort.

Obstructive sleep apnea–respiratory effort against

airway obstruction.

Associated with obesity, loud snoring, systemic/

pulmonary hypertension, arrhythmias, and

possibly sudden death.

Individuals may become chronically tired.

Narcolepsy Disordered regulation of sleep-wake cycles. May include hypnagogic (just before sleep)

or hypnopompic (just before awakening) hallucinations. The person’s nocturnal and

narcoleptic sleep episodes start off with REM sleep. Cataplexy (loss of all muscle tone

following a strong emotional stimulus) in some patients. Strong genetic component.

Treat with stimulants (e.g., amphetamines).

Schizophrenia Periods of psychosis and disturbed behavior with 5 subtypes:

a decline in functioning lasting > 6 months 1. Disorganized

(1-6 months–schizophreniform disorder; < 1 2. Catatonic

month–brief psychotic disorder, usually stress 3. Paranoid

related). 4. Undifferentiated

Diagnosis requires 2 or more of the following (1-4 5. Residual

are “positive symptoms”): Schizoaffective disorder–a

1. Delusions combination of schizophrenia

2. Hallucinations–often auditory and a mood disorder.

3. Disorganized thought (loose associations)

4. Disorganized or catatonic behavior

5. “Negative symptoms”–flat affect, social

withdrawal, lack of motivation, lack of

speech or thought

Genetic factors outweigh environmental factors

in the etiology of schizophrenia.

Lifetime prevalence–1.5% (males = females,

blacks = whites). Presents earlier in men.

HIGH-YI E LD SYSTEMS NEUROLOGY AND PSYCHIATRY

366

NEUROLOGY AND PSYCHIATRY-PATHOLOGY (continued)

Personality Personality trait–an enduring pattern of perceiving, relating to, and thinking about the

environment and oneself that is exhibited in a wide range of important social and

personal contexts.

Personality disorder–when these patterns become inflexible and maladaptive, causing

impairment in social or occupational functioning or subjective distress; person is usually

not aware of problem. Disordered patterns must be stable by early adulthood; not

usually diagnosed in children.

Cluster A Odd or eccentric; cannot develop meaningful social “Weird.”

personality relationships. No psychosis; genetic association

disorders with schizophrenia.

Types:

1. Paranoid–distrust and suspiciousness;

projection is main defense mechanism

2. Schizoid–voluntary social withdrawal, limited

emotional expression

3. Schizotypal–interpersonal awkwardness, odd

beliefs or magical thinking, eccentric appearance

Cluster B Dramatic, emotional, or erratic; genetic association “Wild.”

personality with mood disorders and substance abuse.

disorders Types:

1. Antisocial–disregard for and violation of rights

of others, criminality; males > females; conduct

disorder if < 18 years

2. Borderline–unstable mood and interpersonal

relationships, impulsiveness, sense of emptiness;

females > males

3. Histrionic–excessive emotionality, attention

seeking, sexually provocative

4. Narcissistic–grandiosity, sense of entitlement;

may react to criticism with rage; may demand

“top” physician/best health care

Cluster C Anxious or fearful; genetic association with anxiety “Worried.”

personality disorders.

disorders Types:

1. Avoidant–sensitive to rejection, socially

inhibited, timid, feelings of inadequacy

2. Obsessive-compulsive–preoccupation with

order, perfectionism, and control

3. Dependent–submissive and clinging,

excessive need to be taken care of, low

self-confidence

NEUROLOGY AND PSYCHIATRY HIGH-YI E LD SYSTEMS

367

NEUROLOGY AND PSYCHIATRY-PHARMACOLOGY

Parkinson’s disease Parkinsonism is due to loss of dopaminergic neurons and excess cholinergic activity.

drugs

Strategy Agents

Agonize dopamine Bromocriptine (ergot alkaloid and partial BALSA:

receptors dopamine agonist), pramipexole, ropinirole Bromocriptine

Increase dopamine Amantadine (may . dopamine release) Amantadine

L-dopa/carbidopa (converted to dopamine in Levodopa (with carbidopa)

CNS) Selegiline (and COMT

Prevent dopamine Selegiline (selective MAO type B inhibitor); inhibitors)

breakdown entacapone, tolcapone (COMT inhibitors) Antimuscarinics

Curb excess Benztropine (Antimuscarinic; improves tremor

cholinergic activity and rigidity but has little effect on

bradykinesia)

L-dopa (levodopa)/carbidopa

Mechanism . level of dopamine in brain. Unlike dopamine, L-dopa can cross blood-brain barrier

and is converted by dopa decarboxylase in the CNS to dopamine.

Clinical use Parkinsonism.

Toxicity Arrhythmias from peripheral conversion to dopamine. Carbidopa, a peripheral

decarboxylase inhibitor, is given with L-dopa in order to . the bioavailability of

L-dopa in the brain and to limit peripheral side effects. Long-term use can .

dyskinesia following administration, akinesia between doses.

Selegiline

Mechanism Selectively inhibits MAO-B, thereby . the availability of dopamine.

Clinical use Adjunctive agent to L-dopa in treatment of Parkinson’s disease.

Toxicity May enhance adverse effects of L-dopa.

Sumatriptan

Mechanism 5-HT1D agonist. Causes vasoconstriction. Half-life < 2 hours.

Clinical use Acute migraine, cluster headache attacks.

Toxicity Coronary vasospasm, mild tingling (contraindicated in patients with CAD or

Prinzmetal’s angina).

HIGH-YI E LD SYSTEMS NEUROLOGY AND PSYCHIATRY

368

NEUROLOGY AND PSYCHIATRY-PHARMACOLOGY (continued)

Epilepsy drugs

Epilepsy drug toxicities

Benzodiazepines Sedation, tolerance, dependence.

Carbamazepine Diplopia, ataxia, blood dyscrasias (agranulocytosis, aplastic anemia), liver toxicity,

teratogenesis, induction of cytochrome P-450.

Ethosuximide GI distress, lethargy, headache, urticaria, Stevens-Johnson syndrome.

Phenobarbital Sedation, tolerance, dependence, induction of cytochrome P-450.

Phenytoin Nystagmus, diplopia, ataxia, sedation, gingival hyperplasia, hirsutism, megaloblastic

anemia, teratogenesis, SLE-like syndrome, induction of cytochrome P-450.

Valproic acid GI distress, rare but fatal hepatotoxicity (measure LFTs), neural tube defects

in fetus (spina bifida), tremor, weight gain.

Lamotrigine Stevens-Johnson syndrome.

Gabapentin Sedation, ataxia.

Topiramate Sedation, mental dulling, kidney stones, weight loss.

NEUROLOGY AND PSYCHIATRY HIGH-YI E LD SYSTEMS

PARTIAL GENERALIZED

Simple Complex Tonic-Clonic Absence Status Mechanism Notes

Phenytoin . . 1st line 1st line

for

prophylaxis . Na+ channel inactivation

Carbamazepine . . 1st line . Na+ channel inactivation 1st line for

trigeminal

neuralgia

Lamotrigine . . . Blocks voltage-gated Na+

channels

Gabapentin . . . . GABA release Also used for

peripheral

neuropathy

Topiramate . . . Blocks Na+ channels,

. GABA action

Phenobarbital . . . . GABAA action 1st line in

pregnant

women,

children

Valproic acid . . 1st line . . Na+ channel inactivation, Also used for

. GABA concentration myoclonic

seizures

Ethosuximide 1st line Blocks thalamic T-type Ca+

channels

Benzodiazepines 1st line . GABAA action Also used for

(diazepam or for acute seizures of

lorazepam) eclampsia (1st

line to prevent

seizures of

eclampsia is

MgSO4)

369

Phenytoin

Mechanism Use-dependent blockade of Na+ channels; inhibition of glutamate release from

excitatory presynaptic neuron.

Clinical use Tonic-clonic seizures. Also a class IB antiarrhythmic.

Toxicity Nystagmus, ataxia, diplopia, sedation, SLE-like syndrome, induction of cytochrome

P-450. Chronic use produces gingival hyperplasia in children, peripheral neuropathy,

hirsutism, megaloblastic anemia (. vitamin B12), and malignant hyperthermia (rare);

teratogenic (fetal hydantoin syndrome).

Barbiturates Phenobarbital, pentobarbital, thiopental, secobarbital.

Mechanism Facilitate GABAA action by . duration of Cl- BarbiDURATe (increased

channel opening, thus . neuron firing. DURATion).

Clinical use Sedative for anxiety, seizures, insomnia, induction Contraindicated in porphyria.

of anesthesia (thiopental).

Toxicity Dependence, additive CNS depression effects with

alcohol, respiratory or cardiovascular depression

(can lead to death), drug interactions owing to

induction of liver microsomal enzymes

(cytochrome P-450).

Treat overdose with symptom management (assist

respiration, . BP).

Benzodiazepines Diazepam, lorazepam, triazolam, temazepam, oxazepam, midazolam, chlordiazepoxide,

alprazolam.

Mechanism Facilitate GABAA action by . frequency of FREnzodiazepines (increased

Cl- channel opening. Most have long half-lives FREquency).

and active metabolites. Short acting = TOM Thumb =

Clinical use Anxiety, spasticity, status epilepticus (lorazepam and Triazolam, Oxazepam,

diazepam), detoxification (especially alcohol Midazolam.

withdrawal-DTs), night terrors, sleepwalking.

Toxicity Dependence, additive CNS depression effects with

alcohol. Less risk of respiratory depression and coma

than with barbiturates.

Treat overdose with flumazenil (competitive antagonist

at GABA receptor).

HIGH-YI E LD SYSTEMS NEUROLOGY AND PSYCHIATRY

370

NEUROLOGY AND PSYCHIATRY-PHARMACOLOGY (continued)

Antipsychotics Thioridazine, haloperidol, fluphenazine, chlorpromazine.

(neuroleptics)

Mechanism Most antipsychotics block dopamine D2 receptors Evolution of EPS side effects:

(excess dopamine effects connected with 4 h acute dystonia

schizophrenia). 4 d akinesia

Clinical use Schizophrenia, psychosis, acute mania, Tourette 4 wk akathisia

syndrome 4 mo tardive dyskinesia

Toxicity Extrapyramidal system (EPS) side effects, endocrine (often irreversible)

side effects (e.g., dopamine receptor antagonism .

hyperprolactinemia . gynecomastia), and side

effects arising from blocking muscarinic (dry

mouth, constipation), a (hypotension), and

histamine (sedation) receptors.

Neuroleptic malignant syndrome–rigidity,

myoglobinuria, autonomic instability, hyperpyrexia

(treat with dantrolene and dopamine agonists).

Tardive dyskinesia–stereotypic oral-facial movements

probably due to dopamine receptor sensitization;

results of long-term antipsychotic use.

Atypical Clozapine, olanzapine, risperidone. It’s not atypical for old closets

antipsychotics to RISPER.

Mechanism Block 5-HT2 and dopamine receptors.

Clinical use Treatment of schizophrenia; useful for positive and

negative symptoms. Olanzapine is also used for

OCD, anxiety disorder, depression, mania, Tourette

syndrome.

Toxicity Fewer extrapyramidal and anticholinergic side effects

than other antipsychotics. Clozapine may cause

agranulocytosis (requires weekly WBC monitoring).

Lithium

Mechanism Not established; possibly related to inhibition of LMNOP:

phosphoinositol cascade. Lithium side effects–

Clinical use Mood stabilizer for bipolar affective disorder; blocks Movement (tremor)

relapse and acute manic events. Nephrogenic diabetes

Toxicity Tremor, hypothyroidism, polyuria (ADH antagonist insipidus

causing nephrogenic diabetes insipidus), HypOthyroidism

teratogenesis. Narrow therapeutic window requiring Pregnancy problems

close monitoring of serum levels.

NEUROLOGY AND PSYCHIATRY HIGH-YI E LD SYSTEMS

371

Antidepressants

1. SSRIs

2. Tricyclic

antidepressants

3. Heterocyclic

antidepressants

4. MAOIs

SSRIs Fluoxetine, sertraline, paroxetine, citalopram.

Mechanism Serotonin-specific reuptake inhibitors. It normally takes 2-3 weeks

Clinical use Endogenous depression, OCD. for antidepressants to have

Toxicity Fewer than TCAs. GI distress, sexual dysfunction an effect.

(anorgasmia). “Serotonin syndrome” with

MAO inhibitors–hyperthermia, muscle

rigidity, cardiovascular collapse.

Tricyclic Imipramine, amitriptyline, desipramine, nortriptyline, clomipramine, doxepin.

antidepressants

Mechanism Block reuptake of NE and serotonin.

Clinical use Major depression, bedwetting (imipramine), OCD (clomipramine).

Side effects Sedation, a-blocking effects, atropine-like (anticholinergic) side effects (tachycardia,

urinary retention). 3° TCAs (amitriptyline) have more anticholinergic effects

than do 2° TCAs (nortriptyline). Desipramine is the least sedating.

Toxicity Tri-C’s: Convulsions, Coma, Cardiotoxicity (arrhythmias); also respiratory depression,

hyperpyrexia. Confusion and hallucinations in elderly due to anticholinergic side

effects (use nortriptyline).

HIGH-YI E LD SYSTEMS NEUROLOGY AND PSYCHIATRY

(Adapted, with permission, from Katzung BG, Trevor AJ. USMLE Road Map: Pharmacology, 1st ed. New York: McGraw-Hill, 2003:80.)

Metabolites

Serotonergic

neuron

Noradrenergic

neuron

NE reuptake

NE

receptor

5-HT

receptor

Postsynaptic

neuron

a2

receptor

MAO

Fluoxetine,

trazodone

Metabolites

5-HT reuptake

MAO

Tricyclics,

maprotiline

MAO inhibitors

Mirtazapine

372

NEUROLOGY AND PSYCHIATRY-PHARMACOLOGY (continued)

Heterocyclic 2nd- and 3rd-generation antidepressants with varied

antidepressants and mixed mechanisms of action. Treat major

depression.

Bupropion Also used for smoking cessation. Mechanism not well You need BUtane in your

known. Toxicity: stimulant effects (tachycardia, VEINs to MURder for a

insomnia), headache, seizure in bulimic patients. MAP of AlcaTRAZ.

Does not cause sexual side effects.

Venlafaxine Also used in generalized anxiety disorder. Inhibits

serotonin, NE, and dopamine reuptake. Toxicity:

stimulant effects, sedation, nausea, constipation, .

BP.

Mirtazapine a2 antagonist (. release of NE and serotonin) and

potent 5-HT2 and 5-HT3 receptor antagonist.

Toxicity: sedation, . appetite, weight gain, dry mouth.

Maprotiline Blocks NE reuptake. Toxicity: sedation, orthostatic

hypotension.

Trazodone Primarily inhibit serotonin reuptake. Toxicity:

sedation, nausea, priapism, postural hypotension.

Monoamine Phenelzine, tranylcypromine.

oxidase (MAO)

inhibitors

Mechanism Nonselective MAO inhibition ..levels of amine neurotransmitters.

Clinical use Atypical depression (i.e., with psychotic or phobic features), anxiety, hypochondriasis.

Toxicity Hypertensive crisis with tyramine ingestion (in many foods) and meperidine; CNS

stimulation. Contraindication with SSRIs or ß-agonists (to prevent serotonin

syndrome).

Anesthetics- CNS drugs must be lipid soluble (cross the blood-brain barrier) or be actively

general principles transported.

Drugs with . solubility in blood = rapid induction and recovery times.

Drugs with . solubility in lipids = . potency = 1

MAC

where MAC = minimal anesthetic concentration.

Examples: N2O has low blood and lipid solubility, and thus fast induction and low

potency. Halothane, in contrast, has . lipid and blood solubility, and thus high

potency and slow induction.

Inhaled anesthetics Halothane, enflurane, isoflurane, sevoflurane, methoxyflurane, nitrous oxide.

Mechanism Mechanism unknown. The lower the solubility in blood, the quicker the anesthetic

induction and the quicker the recovery.

Effects Myocardial depression, respiratory depression, nausea/emesis, . cerebral blood flow

(. cerebral metabolic demand).

Toxicity Hepatotoxicity (halothane), nephrotoxicity (methoxyflurane), proconvulsant

(enflurane), malignant hyperthermia (rare).

NEUROLOGY AND PSYCHIATRY HIGH-YI E LD SYSTEMS

373

Intravenous anesthetics

Barbiturates Thiopental–high potency, high lipid solubility, rapid B. B. King on OPIATES

entry into brain. Used for induction of anesthesia PROPOses FOOLishly.

and short surgical procedures. Effect terminated by

redistribution from brain. . cerebral blood flow.

Benzodiazepines Midazolam most common drug used for endoscopy;

used adjunctively with gaseous anesthetics and

narcotics. May cause severe postoperative

respiratory depression, . BP (treat with flumazenil),

and amnesia.

Arylcyclohexamines PCP analogs that act as dissociative anesthetics.

(Ketamine) Cardiovascular stimulants. Cause disorientation,

hallucination, and bad dreams. . cerebral blood flow.

Opiates Morphine, fentanyl used with other CNS depressants

during general anesthesia.

Propofol Used for rapid anesthesia induction and short

procedures. Less postoperative nausea than

thiopental.

Local anesthetics Esters–procaine, cocaine, tetracaine; amides–lIdocaIne, mepIvacaIne, bupIvacaIne

(amIdes have 2 I’s in name).

Mechanism Block Na+ channels by binding to specific receptors on inner portion of channel.

3° amine local anesthetics penetrate membrane in uncharged form, then bind to ion

channels as charged form.

Principle 1. In infected (acidic) tissue, anesthetics are charged and cannot penetrate membrane

effectively. Therefore, more anesthetic is needed in these cases.

2. Order of nerve blockade–small-diameter fibers > large diameter. Myelinated fibers >

unmyelinated fibers. Overall, size factor predominates over myelination such that very

small unmyelinated pain fibers > small myelinated autonomic fibers > large myelinated

autonomic fibers. Order of loss–pain (lose first) > temperature > touch > pressure (lose

last).

3. Given with vasoconstrictors (usually epinephrine) to enhance local action–.

bleeding, . anesthesia by . systemic concentration.

Clinical use Minor surgical procedures, spinal anesthesia. If allergic to esters, give amides.

Toxicity CNS excitation, severe cardiovascular toxicity (bupivacaine), hypertension,

hypotension, and arrhythmias (cocaine).

Neuromuscular Used for muscle paralysis in surgery or mechanical ventilation. Selective for motor

blocking drugs (vs. autonomic) nicotinic receptor.

Depolarizing Succinylcholine.

Reversal of blockade:

Phase I (prolonged depolarization)–no antidote. Block potentiated by cholinesterase

inhibitors.

Phase II (repolarized but blocked)–antidote consists of cholinesterase inhibitors (e.g.,

neostigmine).

Nondepolarizing Tubocurarine, atracurium, mivacurium, pancuronium, vecuronium, rapacuronium.

Competitive–compete with ACh for receptors.

Reversal of blockade–neostigmine, edrophonium, and other cholinesterase inhibitors.

HIGH-YI E LD SYSTEMS NEUROLOGY AND PSYCHIATRY

374

NEUROLOGY AND PSYCHIATRY-PHARMACOLOGY (continued)

Dantrolene Used in the treatment of malignant hyperthermia, which is caused by the concomitant

use of inhalation anesthetics (except N2O) and succinylcholine. Also used to treat

neuroleptic malignant syndrome (a toxicity of antipsychotic drugs).

Mechanism: prevents the release of Ca2+ from the sarcoplasmic reticulum of skeletal

muscle.

NEUROLOGY AND PSYCHIATRY HIGH-YI E LD SYSTEMS

Anatomy

Physiology

Pathology

Pharmacology

H I G H -Y I E L D S Y S T E M S

Renal

375

“But I know all about love already. I know precious little about kidneys.”

–Aldous Huxley, Antic Hay

“This too shall pass. Just like a kidney stone.”

–Hunter Madsen

376

RENAL-ANATOMY

Retroperitoneal structures 1. Duodenum (2nd, 3rd, 4th

parts)

2. Descending colon

3. Ascending colon

4. Kidney and ureters

5. Pancreas (except tail)

6. Aorta

7. IVC

Adrenal glands and rectum (not

shown in diagram)

Kidney anatomy and glomerular structure

Ureters: course Ureters pass under uterine artery and under ductus Water (ureters) under the

deferens (retroperitoneal). bridge (artery, ductus

deferens).

RENAL HIGH-YI E LD SYSTEMS

Perirenal

space

Transversalis fascia

Peritoneum

1

3 2

7 6

5

4

(Adapted, with permission, from McPhee S et al. Pathophysiology of Disease: An Introduction to Clinical Medicine,

3rd ed. New York: McGraw-Hill, 2000:384.)

Cortex

Medullary

pyramids

(papillae)

Glomerulus

Bowman´s

capsule

Afferent

arteriole

Interlobar

artery and vein

Medulla

Collecting

ducts

Vasa

recta

Renal artery

and vein

Proximal

and distal

convoluted

tubules

Efferent arteriole

Afferent arteriole–blood flow to the glomerulus

Macula

densa

Basement membrane

Mesangial cells

Podocytes

(visceral layer)

Bowman´s capsule

Efferent arteriole–blood flow

out of glomerulus

Interlobular

artery and

Pelvis vein

Ureter

377

RENAL-PHYSIOLOGY

Fluid compartments

TBW – ECF = ICF.

ECF – PV = interstitial volume.

60-40-20 rule (% of body weight):

60% total body water

40% ICF

20% ECF

Plasma volume measured by

radiolabeled albumin.

Extracellular volume measured

by inulin.

Renal clearance Cx = UxV/Px = volume of plasma from which the Be familiar with calculations.

substance is cleared completely per unit time. Cx = clearance of X.

If Cx < GFR, then there is net tubular reabsorption of X. Ux = urine concentration of X.

If Cx > GFR, then there is net tubular secretion of X. Px = plasma concentration of X.

If Cx = GFR, then there is no net secretion or V = urine flow rate.

reabsorption.

Glomerular Responsible for filtration of plasma according to The charge barrier is lost in

filtration barrier size and net charge. nephrotic syndrome,

Composed of: resulting in albuminuria,

1. Fenestrated capillary endothelium (size barrier) hypoproteinemia,

2. Fused basement membrane with heparan sulfate generalized edema, and

(negative charge barrier) hyperlipidemia.

3. Epithelial layer consisting of podocyte foot

processes

Glomerular Inulin can be used to calculate GFR because it is Creatinine clearance is an

filtration rate freely filtered and is neither reabsorbed nor approximate measure of GFR.

secreted.

GFR = Uinulin × V/Pinulin = Cinulin

= Kf [(PGC – PBS) – (pGC – pBS)].

(GC = glomerular capillary; BS = Bowman’s space.)

pBS normally equals zero.

Effective renal ERPF can be estimated using PAH because it is both filtered and actively secreted in the

plasma flow proximal tubule. All PAH entering the kidney is excreted.

ERPF = UPAH × V/PPAH = CPAH.

RBF = RPF/1- Hct.

ERPF underestimates true RPF by ~10%.

HIGH-YI E LD SYSTEMS RENAL

Total

body

weight

(kg)

nonwater

mass

40%

60% total body

water (L)

1/3 extracellular

fluid

2/3 intracellular

fluid

1/4 plasma vol.

3/4 interstitial vol.

378

RENAL-PHYSIOLOGY (continued)

Filtration fraction FF = GFR/RPF.

Changes in renal function

Effect RPF GFR FF (GFR/RPF)

Afferent arteriole constriction . . NC

Efferent arteriole constriction . . .

. plasma protein concentration NC . .

. plasma protein concentration NC . .

Constriction of ureter NC . .

Free water Given urine flow rate, urine osmolarity, and plasma osmolarity, be able to calculate free

clearance water clearance:

CH2O = V – Cosm.

V = urine flow rate; Cosm = UosmV/Posm.

Glucose clearance Glucose at a normal level is completely reabsorbed Glucosuria is an important

in proximal tubule. At plasma glucose of 200 clinical clue to diabetes

mg/dL, glucosuria begins (threshold). At 350 mellitus.

mg/dL, transport mechanism is saturated (Tm).

Amino acid Reabsorption by at least 3 distinct carrier systems, with competitive inhibition within

clearance each group. 2° active transport occurs in proximal tubule and is saturable.

RENAL HIGH-YI E LD SYSTEMS

Prostaglandins

dilate afferent

arteriole. (. RPF,

. GFR, so FF

remains constant)

NSAIDs

Angiotensin II

preferentially

constricts efferent

arteriole. (. RPF,

. GFR, so FF

increases)

Blood

– ACE

inhibitor

379

Nephron physiology

B. Thin descending loop of Henle–passively reabsorbs

water via medullary hypertonicity (impermeable to

sodium).

A. Early proximal convoluted tubule–“workhorse C. Thick ascending loop of Henle–actively reabsorbs Na+,

of the nephron.” Reabsorbs all of the glucose and K+, and Cl- and indirectly induces the reabsorption of

amino acids and most of the bicarbonate, sodium, Mg2+ and Ca2+. Impermeable to H2O.

and water. Secretes ammonia, which acts as a buffer

for secreted H+.

D. Early distal convoluted tubule–actively reabsorbs E. Collecting tubules–reabsorb Na+ in exchange for

Na+, Cl-. Reabsorption of Ca2+ is under the secreting K+ or H+ (regulated by aldosterone).

control of PTH. Reabsorption of water is regulated by ADH

(vasopressin). Osmolarity of medulla can reach

1200 mOsm.

HIGH-YI E LD SYSTEMS RENAL

ATP

Lumen-

urine

Proximal

convoluted

tubule

Interstitium-

blood

CA CA

Base-

Na+

K+

Cl-

Na+

Na

Glucose

+

HCO3 H+ + HCO3

+ H+

H2CO3

H2O + CO2

H2CO3

CO2

+ H2O

+

– –

Lumen-

urine

Thick

ascending

limb

Interstitium-

blood

Na+ Na+

K+

K+

K+

K+

Cl-

2Cl-

(+)

potential

Mg2+, Ca2+

ATP

Cl-

Lumen-

urine

Collecting

tubule

Interstitium-

blood

Na+

K+

Cl-

Na+

K+

R

V2

Principal cell Aldosterone

Water

channel

molecules

H2O ADH

Intercalated cell

H+

HCO3

ATP

ATP

Ca2+ –

Ca2+

Lumen-

urine

Distal

convoluted

tubule

Interstitium-

blood

Na+

Na+

Cl-

Na+

K+

R PTH

ATP

380

RENAL-PHYSIOLOGY (continued)

Relative concentrations along renal tubule

* Neither secreted nor reabsorbed; concentration increases as water is reabsorbed.

Renin-angiotensin system

Mechanism Renin is released by the kidneys upon sensing . BP and cleaves angiotensinogen to

angiotensin I (a decapeptide). Angiotensin I is then cleaved by angiotensin-converting

enzyme (ACE), primarily in the lung capillaries and elsewhere, to angiotensin II (an

octapeptide).

Actions of 1. Potent vasoconstriction

angiotensin II 2. Release of aldosterone from the adrenal cortex

3. Release of ADH from posterior pituitary

4. Stimulates hypothalamus ..thirst

Overall, angiotensin II serves to . intravascular volume and . BP.

ANP released from atria may act as a “check” on the renin-angiotensin system (e.g., in

heart failure).

RENAL HIGH-YI E LD SYSTEMS

3.0

2.0

1.4

1.2

1.0

0.8

0.6

0.4

0.2

0

Amino acids

Glucose

Secretion

Reabsorption

Percent distance along proximal tubule

[Tubular fluid]

[Plasma]

25 50 75 100

Inulin*

Cl-

K+

OSM

Pi

HCO3

TF

P

PAH

TF

P

NA+

=

(Adapted, with permission, from Ganong WF. Review of Medical Physiology, 22nd ed. New York: McGraw-Hill, 2005.)

JUXTAGLOMERULAR

APPARATUS (JGA)

Angiotensinogen

Angiotensin I

Angiotensin II

ADRENAL

CORTEX

ACE

Aldosterone

Increased renal arterial

mean pressure, decreased

discharge of renal nerves

Increased

extracellular

fluid volume

Decreased Na+

(and water) excretion

BP

Renin

(Adapted, with permission, from Ganong WF. Review of Medical Physiology, 20th ed. New York: McGraw-Hill,

2001.)

381

Juxtaglomerular JGA–JG cells (modified smooth muscle of afferent JGA defends glomerular

apparatus (JGA) arteriole) and macula densa (Na+ sensor, part of filtration rate via the reninthe

distal convoluted tubule). JG cells secrete angiotensin system.

renin (leading to . angiotensin II and aldosterone Juxta = close by.

levels) in response to . renal blood pressure, . Na+

delivery to distal tubule, and . sympathetic tone.

Kidney endocrine Endocrine functions of the kidney: NSAIDs can cause acute

functions 1. Endothelial cells of peritubular capillaries renal failure in high

secrete erythropoietin in response to hypoxia vascoconstrictive states by

2. Conversion of 25-OH vitamin D to 1,25-(OH)2 inhibiting the renal

vitamin D by 1a-hydroxylase, which is production of prostaglandins,

activated by PTH which keep the afferent

3. JG cells secrete renin in response to . renal arterioles vasodilated to

arterial pressure and . renal sympathetic maintain GFR.

discharge (ß1 effect)

4. Secretion of prostaglandins that vasodilate

the afferent arterioles to . GFR

Hormones acting on kidney

HIGH-YI E LD SYSTEMS RENAL

Aldosterone

Secreted in response to . blood volume (via AT II)

and . plasma [K+]

Causes . Na+ reabsorption, . K+ secretion, . H+ secretion

Atrial natriuretic factor (ANF)

Secreted in response to . atrial pressure

Causes . GFR and . Na+ excretion

Vasopressin/ADH

Secreted in response to

. plasma osmolarity and

. blood volume

Binds to receptors on

principal cells, causing

. number of water channels

and . H2O reabsorption

Parathyroid hormone (PTH)

Secreted in response to

. plasma [Ca2+]

Causes . [Ca2+] reabsorption (DCT),

. PO43- reabsorption (PCT),

1,25 (OH)3 vitamin D production

. . Ca+ and PO43- reabsorption

Renin

(response to

JGA . blood volume)

Angiotensinogen

AT I

Angiotensin II (AT II)

Causes efferent arteriole

constriction. . GFR

. . Na+ and HCO3-

reabsorption

ACE (lung)

382

RENAL-PHYSIOLOGY (continued)

Acid-base physiology

pH PCO2 [HCO3

– ] Compensatory response

Metabolic acidosis . .  Hyperventilation

Metabolic alkalosis . . [1] Hypoventilation

Respiratory acidosis . [1] . Renal [HCO3

– ] reabsorption

Respiratory alkalosis .  . Renal [HCO3

– ] secretion

Key: [1]= primary disturbance; . . = compensatory response.

Acidosis/alkalosis

RENAL HIGH-YI E LD SYSTEMS

Henderson-Hasselbalch equation: pH = pKa + log

0.03 PCO2

[HCO3 ]

pH < 7.4

Acidosis

pH > 7.4

Alkalosis

> 40 mmHg < 40 mmHg

Respiratory

acidosis

Hypoventilation

-Acute lung disease

-Chronic lung disease

-Opioids, narcotics,

sedatives

-Weakening of

respiratory

muscles

Metabolic

acidosis with

compensation

Check anion gap

anion gap

MUD PILES:

Methanol

Uremia

Diabetic ketoacidosis

Paraldehyde

or Phenformin

Iron tablets or INH

Lactic acidosis

Ethylene glycol

Salicylates

-Hyperchloremia

Normal anion gap (8-12 mEq/L)

-Diarrhea

-Glue sniffing

-Renal tubular acidosis

PCO2 PCO2 PCO2 < 40 mmHg

Respiratory alkalosis

-Hyperventilation

-Aspirin ingestion (early)

PCO2 > 40 mmHg

Metabolic alkalosis with

compensation

-Vomiting

-Diuretic use

-Antacid use

-Hyperaldosteronism

Check arterial pH

-Airway obstruction

Anion gap = Na+ – (Cl- + HCO3

-)

383

Acid-base The following formulas give appropriate compensations for a single disorder. If the formula

compensations does not match the actual values, suspect a mixed disorder.

Metabolic acidosis Winter’s formula: PCO2 = 1.5 (HCO3

-) + 8 ± 2.

Metabolic alkalosis PCO2 . 0.7 mmHg for every . 1 mEq/L HCO3

-.

Respiratory acidosis Acute– . 1 mEq/L HCO3

– for every . 10 mmHg PCO2.

Chronic– . 3.5 mEq/L HCO3

– for every . 10 mmHg PCO2.

Respiratory alkalosis Acute– . 2 mEq/L HCO3

– for every . 10 mmHg PCO2.

Chronic– . 5 mEq/L HCO3

– for every . 10 mmHg PCO2.

Acid-base nomogram HIGH-YI E LD SYSTEMS RENAL

(Adapted, with permission, from Ganong WF. Review of Medical Physiology, 22nd ed. New York: McGraw-Hill, 2005.)

60

56

52

48

44

40

36

32

Arterial plasma [HCO3-] (mEq/L)

28

24

20

16

12

8

4

0

7.00 7.10 7.20 7.30 7.40 7.50 7.60 7.70 7.80

Arterial blood pH

100 90 80 70 60 50 40 35 30 25 20

Arterial blood [H+] (nmol/L)

120 100 90 80 70 60 50 40

20

15

10

35

30

25

Acute

respiratory

alkalosis

Acute

respiratory

acidosis

Normal

Chronic

respiratory

alkalosis PCO2

(mmHg)

Metabolic

acidosis

Chronic

respiratory

acidosis

Metabolic

alkalosis

384

RENAL-PATHOLOGY

Potter’s syndrome Bilateral renal agenesis . oligohydramnios . Babies with Potter’s can’t

limb deformities, facial deformities, pulmonary “Pee” in utero.

hypoplasia. Caused by malformation of ureteric

bud.

Horseshoe kidney Inferior poles of both kidneys fuse. As they ascend

from pelvis during fetal development, horseshoe

kidneys get trapped under inferior mesenteric artery

and remain low in the abdomen.

Casts Casts in urine: Presence of casts indicates

RBC casts–glomerular inflammation (nephritic that hematuria/pyuria is of

syndromes), ischemia, or malignant hypertension. renal origin.

WBC casts–tubulointerstitial disease, acute Bladder cancer . RBCs.

pyelonephritis, glomerular disorders. Acute cystitis . WBCs.

Granular casts–acute tubular necrosis.

Waxy casts–advanced renal disease/CRF.

Hyaline casts–nonspecific.

RENAL HIGH-YI E LD SYSTEMS

Aorta

Horseshoe

kidney

Inferior

mesenteric

artery

Red blood cell casts White blood cell casts Hyaline casts Granular casts

385

Glomerular NephrItic syndrome–hematuria, hypertension, I = inflammation.

pathology oliguria, azotemia.

1. Acute poststreptococcal glomerulonephritis– Most frequently seen in

LM: glomeruli enlarged and hypercellular, children. Peripheral and

neutrophils, “lumpy-bumpy.” EM: subepithelial periorbital edema. Resolves

humps. IF: granular pattern. spontaneously.

2. Rapidly progressive (crescentic) Rapid course to renal failure

glomerulonephritis–LM and IF: crescent- from one of many causes.

moon shape.

3. Goodpasture’s syndrome (type II Hemoptysis, hematuria.

hypersensitivity)–IF: linear pattern, anti-

GBM antibodies.

4. Membranoproliferative glomerulonephritis– Slowly progresses to renal

EM: subendothelial humps, “tram track.” failure.

5. IgA nephropathy (Berger’s disease)– Mild disease. Often

IF and EM: mesangial deposits of IgA. postinfectious.

6. Alport’s syndrome–split basement Collagen IV mutation. Nerve

membrane. deafness and ocular disorders.

NephrOtic syndrome–massive proteinuria, O = prOteinuria.

hypoalbuminemia, peripheral and periorbital edema,

hyperlipidemia.

1. Membranous glomerulonephritis–LM: A common cause of adult

diffuse capillary and basement membrane nephrotic syndrome.

thickening. IF: granular pattern. EM: “spike

and dome.”

2. Minimal change disease (lipoid nephrosis)– Most common cause of

LM: normal glomeruli. EM: foot process childhood nephrotic

effacement (see Color Image 93). syndrome. Responds

well to steroids.

3. Focal segmental glomerular sclerosis– More severe disease in HIV

LM: segmental sclerosis and hyalinosis. patients.

4. Diabetic nephropathy–LM: Kimmelstiel-

Wilson “wire loop” lesions, basement membrane

thickening (see Color Image 95).

5. SLE (5 patterns of renal involvement)–

LM: In membranous glomerulonephritis

pattern, wire-loop lesion with subendothelial

deposits.

(LM = light microscopy; EM = electron microscopy; IF = immunofluorescence)

HIGH-YI E LD SYSTEMS RENAL

386

RENAL-PATHOLOGY (continued)

Kidney stones Can lead to severe complications, such as

hydronephrosis and pyelonephritis. 4 major types:

Calcium Most common kidney stones (75-85%). Calcium Radiopaque.

oxalate (see Color Image 97), calcium phosphate,

or both. Conditions that cause hypercalcemia

(cancer, . PTH, . vitamin D, milk-alkali

syndrome) can lead to hypercalciuria and stones.

Tend to recur.

Ammonium 2nd most common kidney stone. Caused by infection Radiopaque.

magnesium with urease-positive bugs (Proteus vulgaris,

phosphate (struvite) Staphylococcus, Klebsiella). Can form staghorn

calculi that can be a nidus for UTIs.

Uric acid Strong association with hyperuricemia (e.g., gout). Radiolucent.

Often seen as a result of diseases with . cell

turnover, such as leukemia and myeloproliferative

disorders.

Cystine Most often 2° to cystinuria. Radiolucent.

Renal cell Most common renal malignancy. Most common in men ages 50-70. . incidence with

carcinoma smoking and obesity. Associated with von Hippel-Lindau and gene deletion in chromosome

3. Originates in renal tubule cells . polygonal clear cells. Manifests clinically

with hematuria, palpable mass, 2° polycythemia, flank pain, fever, and weight

loss. Invades IVC and spreads hematogenously. Associated with paraneoplastic syndromes

(ectopic EPO, ACTH, PTHrP, and prolactin) (see Color Image 98).

Wilms’ tumor Most common renal malignancy of early childhood (ages 2-4). Presents with huge,

palpable flank mass, hemihypertrophy. Deletion of tumor suppression gene WT1 on

chromosome 11. Can be part of WAGR complex: Wilms’ tumor, Aniridia,

Genitourinary malformation, and mental-motor Retardation.

Transitional Most common tumor of urinary tract system (can occur in renal calyces, renal pelvis,

cell carcinoma ureters, and bladder). Painless hematuria is suggestive of bladder cancer. Associated

with problems in your Pee SAC: Phenacetin, Smoking, Aniline dyes, and

Cyclophosphamide (see Color Image 90).

Pyelonephritis

Acute Affects cortex with relative sparing of glomeruli/vessels. White cell casts in urine are

pathognomonic (see Color Image 89A). Presents with fever, CVA tenderness.

Chronic Coarse, asymmetric corticomedullary scarring. Tubules can contain eosinophilic casts

(thyroidization of kidney) (see Color Image 89B).

Diffuse cortical Acute generalized infarction of cortices of both kidneys. Likely due to a combination of

necrosis vasospasm and DIC. Associated with obstetric catastrophes (e.g., abruptio placentae)

and septic shock.

RENAL HIGH-YI E LD SYSTEMS

387

Acute tubular Most common cause of acute renal failure. Reversible, but fatal if left untreated.

necrosis Associated with renal ischemia (e.g., shock), crush injury (myoglobulinuria), toxins.

Death most often occurs during initial oliguric phase. Recovery in 2-3 weeks.

Renal papillary Associated with:

necrosis 1. Diabetes mellitus

2. Acute pyelonephritis

3. Chronic phenacetin use

Acute renal Abrupt decline in renal function with . creatinine and . BUN over a period of several days.

failure 1. Prerenal azotemia–decreased RBF (e.g., hypotension) . . GFR. Na+/H2O

retained by kidney.

2. Intrinsic renal–generally due to acute tubular necrosis or ischemia/toxins. Patchy

necrosis leads to debris obstructing tubule and fluid backflow across necrotic tubule

. . GFR. Urine has epithelial/granular casts.

3. Postrenal–outflow obstruction (stones, BPH, neoplasia). Develops only with

bilateral obstruction.

Consequences of Failure to make urine and excrete nitrogenous 2 forms of renal failure–

renal failure wastes. acute renal failure (often due

Uremia–clinical syndrome marked by . BUN to hypoxia) and chronic

and . creatinine and associated symptoms. renal failure (e.g., due to

Consequences: hypertension and diabetes).

1. Anemia (failure of erythropoietin production)

2. Renal osteodystrophy (failure of active

vitamin D production)

3. Hyperkalemia, which can lead to cardiac

arrhythmias

4. Metabolic acidosis due to . acid secretion

and . generation of HCO3

5. Uremic encephalopathy

6. Sodium and H2O excess . CHF and

pulmonary edema

7. Chronic pyelonephritis

8. Hypertension

HIGH-YI E LD SYSTEMS RENAL

Variable Prerenal Renal Postrenal

Urine osmolality > 500 < 350 < 350

Urine Na < 10 > 20 > 40

FeNa < 1% > 2% > 4%

BUN/Cr ratio > 20 < 15 > 15

388

RENAL-PATHOLOGY (continued)

Electrolyte disturbances

Electrolyte Low serum concentration High serum concentration

Na+ Disorientation, stupor, coma Neurologic: irritability, delirium, coma

Cl- 2° to metabolic alkalosis 2° to non-anion gap acidosis

K+ U waves on ECG, flattened T waves, Peaked T waves, arrhythmias

arrhythmias, paralysis

Ca2+ Tetany, neuromuscular irritability Delirium, renal stones, abdominal pain

Mg2+ Neuromuscular irritability, arrhythmias Delirium, . DTRs, cardiopulmonary arrest

PO4

2- Low-mineral ion product causes bone loss High-mineral ion product causes metastatic

calcification, renal stones

RENAL HIGH-YI E LD SYSTEMS

389

RENAL-PHARMACOLOGY

Diuretics: site of action

HIGH-YI E LD SYSTEMS RENAL

NaCl

NaCl

Ca2+

(+PTH)

Collecting

duct

Diuretics

1. Acetazolamide

2. Osmotic agents (mannitol)

3. Loop agents (e.g., furosemide)

4. Thiazides

5. Potassium sparing

6. ADH antagonists

Proximal

convoluted

tubule

Glomerulus

Outer medulla

Cortex

Inner medulla

NaHCO3

Proximal

straight

tubule

Distal convoluted tubule

K+

H+

K+

K+

K+

H+

NaCl

(+ aldosterone)

1.

2.

2.

2.

3.

3.

4.

5.

6.

Thin

descending

limb

H2O

Loop of

Henle

Thick

ascending

limb

Collecting

tubule

H2O

(+ADH)

Na+

Ca2+

Mg2+

2Cl-

K+

Na+

2Cl-

(Adapted, with permission, from Katzung BG. Basic and Clinical Pharmacology, 7th ed. Stamford, CT: Appleton & Lange, 1997:243.)

390

RENAL-PATHOLOGY (continued)

Mannitol

Mechanism Osmotic diuretic, . tubular fluid osmolarity, producing .

urine flow.

Clinical use Shock, drug overdose, . intracranial/intraocular pressure.

Toxicity Pulmonary edema, dehydration. Contraindicated in

anuria, CHF.

Acetazolamide

Mechanism Carbonic anhydrase inhibitor. Causes self-limited

NaHCO3 diuresis and reduction in total-body

HCO3

– stores. Acts at the proximal convoluted

tubule.

Clinical use Glaucoma, urinary alkalinization, metabolic

alkalosis, altitude sickness.

Toxicity Hyperchloremic metabolic acidosis, neuropathy, ACIDazolamide causes

NH3 toxicity, sulfa allergy. ACIDosis.

Furosemide

Mechanism Sulfonamide loop diuretic. Inhibits cotransport

system (Na+, K+, 2 Cl-) of thick ascending limb

of loop of Henle. Abolishes hypertonicity of

medulla, preventing concentration of urine.

. Ca2+ excretion. Loops Lose calcium.

Clinical use Edematous states (CHF, cirrhosis, nephrotic

syndrome, pulmonary edema), hypertension,

hypercalcemia.

Toxicity Ototoxicity, Hypokalemia, Dehydration, Allergy OH DANG!

(sulfa), Nephritis (interstitial), Gout.

Ethacrynic acid

Mechanism Phenoxyacetic acid derivative (NOT a sulfonamide).

Essentially same action as furosemide.

Clinical use Diuresis in patients allergic to sulfa drugs.

Toxicity Similar to furosemide; can be used in hyperuricemia,

acute gout (never used to treat gout).

Hydrochlorothiazide

Mechanism Thiazide diuretic. Inhibits NaCl reabsorption in

early distal tubule, reducing diluting capacity of

the nephron. . Ca2+ excretion.

Clinical use Hypertension, CHF, idiopathic hypercalciuria,

nephrogenic diabetes insipidus.

Toxicity Hypokalemic metabolic alkalosis, hyponatremia, HyperGLUC.

hyperGlycemia, hyperLipidemia, hyperUricemia,

and hyperCalcemia. Sulfa allergy.

RENAL HIGH-YI E LD SYSTEMS

391

K+-sparing diuretics Spironolactone, Triamterene, Amiloride, eplereone. The K+ STAys.

Mechanism Spironolactone is a competitive aldosterone receptor

antagonist in the cortical collecting tubule.

Triamterene and amiloride act at the same part of

the tubule by blocking Na+ channels in the CCT.

Clinical use Hyperaldosteronism, K+ depletion, CHF.

Toxicity Hyperkalemia, endocrine effects (e.g., spironolactone

causes gynecomastia, antiandrogen effects).

Diuretics: electrolyte changes

Urine NaCl . (all diuretics–carbonic anhydrase inhibitors, loop diuretics, thiazides, K+-sparing

diuretics).

Urine K+ . (all except K+-sparing diuretics).

Blood pH . (acidosis)–carbonic anhydrase inhibitors, K+-sparing diuretics; . (alkalosis)–loop

diuretics, thiazides.

Urine Ca+ . loop diuretics, . thiazides.

ACE inhibitors Captopril, enalapril, lisinopril.

Mechanism Inhibit angiotensin-converting enzyme, reducing Losartan is an angiotensin II

levels of angiotensin II and preventing receptor antagonist. It is not

inactivation of bradykinin, a potent vasodilator. an ACE inhibitor and does

Renin release is . due to loss of feedback inhibition. not cause cough.

Clinical use Hypertension, CHF, diabetic renal disease.

Toxicity Cough, Angioedema, Proteinuria, Taste changes, CAPTOPRIL.

hypOtension, Pregnancy problems (fetal renal

damage), Rash, Increased renin, Lower

angiotensin II. Also hyperkalemia.

HIGH-YI E LD SYSTEMS RENAL

392 RENAL HIGH-YI E LD SYSTEMS

NOTES

High-Yield Clinical

Vignettes

Anatomy

Physiology

Pathology

Pharmacology

H I G H -Y I E L D S Y S T E M S

Reproductive

393

“Artificial insemination is when the farmer does it to the cow instead of the

bull.”

–Student essay

394

REPRODUCTIVE-HIGH-YIELD C LINICAL VIGNETTES

24-year-old male develops Metastatic spread occurs Para-aortic lymph nodes (recall

testicular cancer. by what route? descent of testes during

development).

Woman with previous cesarean What is she at . risk Placenta previa.

section has a scar in her lower for?

uterus close to the opening of

the os.

Obese woman presents with What is the diagnosis? Polycystic ovarian syndrome.

hirsutism and . levels of serum

testosterone.

Pregnant woman at 16 weeks What is the diagnosis? High hCG; hydatidiform mole.

of gestation presents with an

atypically large abdomen.

55-year-old postmenopausal What is she at . risk Endometrial carcinoma.

woman is on tamoxifen therapy. of acquiring?

REPRODUCTIVE HIGH-YI E LD SYSTEMS

395

REPRODUCTIVE-ANATOMY

Gonadal venous Left ovary/testis . left gonadal vein . left renal vein . IVC.

drainage Right ovary/testis . right gonadal vein . IVC.

Ligaments of the uterus

Suspensory ligament Contains the ovarian vessels.

of ovaries

Transverse cervical Contains the uterine vessels.

(cardinal) ligament

Round ligament Contains no important structures.

of uterus

Broad ligament Contains the round ligaments of the uterus and

ovaries and the uterine tubules and vessels.

Autonomic Erection is mediated by the Parasympathetic Point and Shoot.

innervation of the nervous system.

male sexual Emission is mediated by the Sympathetic

response nervous system.

Ejaculation is mediated by visceral and somatic

nerves.

Derivation of Acrosome is derived from the Golgi apparatus and

sperm parts flagellum (tail) from one of the centrioles. Middle

piece (neck) has Mitochondria. Sperm food supply

is fructose.

HIGH-YI E LD SYSTEMS REPRODUCTIVE

Uterine tube

Ovary

Broad

ligament

Round

ligament

of uterus

Suspensory ligament

of ovary

Posterior

surface

of uterus

Fimbria

Cardinal ligament

Acrosome

Middle

piece

Head

Tail

Neck

Nucleus

396

REPRODUCTIVE-PHYSIOLOGY

Sperm Spermatogenesis begins with spermatogonia (type A and type B). Full development takes

development 2 months. Spermatogenesis occurs in Seminiferous tubules. Type A forms both type A

and type B spermatogonia.

REPRODUCTIVE HIGH-YI E LD SYSTEMS

Secondary spermatocyte (2N)

Spermatid (N)

Spermatogonium 1° spermatocyte 2° spermatocyte Spermatid

(diploid, 2N) (diploid, 4N) (haploid, 2N) (haploid, N)

Primary spermatocyte (4N)

Junctional complex (tight junction) between

Spermatogonium Sertoli cells forms blood-testis barrier

Sertoli

cell

Basal

compartment

Adluminal

compartment

397

Male spermatogenesis

Androgens Testosterone, dihydrotestosterone (DHT), androstenedione.

Source DHT and testosterone (testis), androstenedione Potency–DHT >

(adrenal). testosterone >

androstenedione.

Targets Skin, prostate, seminal vesicles, epididymis, liver, Testosterone is converted to

muscle, brain. DHT by the enzyme 5a-

reductase, which is inhibited

by finasteride.

Function 1. Differentiation of wolffian duct system into Testosterone and

internal gonadal structures androstenedione are

2. 2° sexual characteristics and growth spurt converted to estrogen

during puberty in adipose tissue by

3. Required for normal spermatogenesis enzyme aromatase.

4. Anabolic effects– . muscle size, . RBC

production

5. . libido

HIGH-YI E LD SYSTEMS REPRODUCTIVE

Hypothalamus

GnRH

Anterior

pituitary FSH stimulates

Sertoli cells to produce:

  • ABP
  • Inhibin

Sertoli cells

Inhibin

LH stimulates

testosterone release

from Leydig cells

Testosterone

Seminiferous

tubule

Leydig

cells

Blood

vessel

PRODUCTS FUNCTIONS OF PRODUCTS

Androgen-binding Ensures that testosterone in seminiferous

protein (ABP) tubule is high

Inhibin Inhibits FSH

Testosterone Differentiates male genitalia, has

anabolic effects on protein metabolism,

maintains gametogenesis, maintains libido,

inhibits GnRH, and fuses epiphyseal plates

in bone.

FSH . Sertoli cells . Sperm production

LH . Leydig cell

398

REPRODUCTIVE-PHYSIOLOGY (continued)

Estrogen

Source Ovary (estradiol), placenta (estriol), blood Potency–estradiol > estrone

(aromatization). > estriol.

Function 1. Growth of follicle Estrogen hormone replacement

2. Endometrial proliferation, myometrial excitability therapy after menopause .

3. Development of genitalia . hot flashes and

4. Stromal development of breast . postmenopausal bone loss.

5. Female fat distribution Unopposed estrogen therapy–

6. Hepatic synthesis of transport proteins . risk of endometrial cancer;

7. Feedback inhibition of FSH use of progesterone with

8. LH surge (estrogen feedback on LH secretion estrogen . this risk.

switches to positive from negative just before

LH surge)

9. . myometrial excitability

10. . HDL, . LDL

Progesterone

Source Corpus luteum, placenta, adrenal cortex, testes. Elevation of progesterone is

Function 1. Stimulation of endometrial glandular secretions indicative of ovulation.

and spiral artery development Progesterone Prepares for

2. Maintenance of pregnancy Pregnancy.

3. . myometrial excitability

4. Production of thick cervical mucus, which

inhibits sperm entry into the uterus

5. . body temperature

6. Inhibition of gonadotropins (LH, FSH)

7. Uterine smooth muscle relaxation

REPRODUCTIVE HIGH-YI E LD SYSTEMS

Estrogen Androstenedione

Aromatase

Androstenedione Cholesterol

Desmolase

FSH

[1]

LH

[1]

Estrogen

Granulosa cell Theca cell

399

Menstrual cycle

Follicular growth is fastest

during 2nd week of

proliferative phase.

Estrogen stimulates

endometrial proliferation.

Progesterone maintains

endometrium to support

implantation.

. progesterone leads to . fertility.

Ovulation Estrogen surge day before ovulation. Mittelschmerz-blood from

Stimulates LH, inhibits FSH. ruptured follicle causes

LH surge causes ovulation (rupture of follicle). peritoneal irritation that can

. temperature (progesterone induced). mimic appendicitis.

Ferning of cervical mucosa.

Oral contraceptives prevent estrogen surge, LH

surge . ovulation does not occur.

Meiosis and 1° oocytes begin meiosis I during fetal life

ovulation and complete meiosis I just prior to ovulation.

Meiosis I is arrested in prOphase for years until

Ovulation.

Meiosis II is arrested in METaphase until An egg MET a sperm.

fertilization.

HIGH-YI E LD SYSTEMS REPRODUCTIVE

Regressing

corpus

luteum

Menstruation

Endometrium

Blood hormone levels

Ovulation

Maturing

graafian

follicle

Ovulation

Corpus

luteum

Proliferative phase Secretory phase

Progesterone

LH

Estrogen

FSH

Days

0 7 14 21 28

1° follicles

Oocyte

2° follicle

(antrum forming)

Time

Stratum

granulosum

Maturing

follicle

Antrum

Theca interna

Theca externa

Corpus

luteum

400

REPRODUCTIVE-PHYSIOLOGY (continued)

hCG

Source Syncytiotrophoblast of placenta.

Function 1. Maintains the corpus luteum for the 1st trimester by acting like LH. In the 2nd and

3rd trimester, the placenta synthesizes its own estrogen and progesterone and the

corpus luteum degenerates.

2. Used to detect pregnancy because it appears in the urine 8 days after successful

fertilization (blood and urine tests available).

3. Elevated hCG in women with hydatidiform moles or choriocarcinoma.

Menopause Cessation of estrogen production with age-linked Hormonal changes:

decline in number of ovarian follicles. Average . estrogen, .. FSH, . LH

age of onset is 51 years (earlier in smokers). (no surge), . GnRH.

Menopause causes HAVOC:

Hot flashes, Atrophy of the

Vagina, Osteoporosis,

Coronary artery disease.

REPRODUCTIVE HIGH-YI E LD SYSTEMS

401

REPRODUCTIVE-PATHOLOGY

Bicornuate uterus Results from incomplete fusion of the paramesonephric

ducts. Associated with urinary tract abnormalities

and infertility.

Congenital penile abnormalities

Hypospadias Abnormal opening of penile urethra on inferior Hypospadias is more common

(ventral) side of penis due to failure of urethral than epispadias. Fix

folds to close. hypospadias to prevent UTIs.

Epispadias Abnormal opening of penile urethra on superior Exstrophy of the bladder is

(dorsal) side of penis due to faulty positioning of associated with epispadias.

genital tubercle.

Sex chromosome disorders

Klinefelter’s syndrome Testicular atrophy, eunuchoid body shape, tall, long Common cause of

[male] (XXY), extremities, gynecomastia, female hair distribution. hypogonadism seen in

1:850 Presence of inactivated X chromosome (Barr body). infertility workup.

(see Image 107).

Turner’s syndrome Short stature, ovarian dysgenesis (streak ovary), “Hugs and kisses” (XO) from

[female] (XO), webbing of neck, coarctation of the aorta, most Tina Turner (female).

1:3000 common cause of 1° amenorrhea. No Barr body.

(see Image 108).

Double Y males Phenotypically normal, very tall, severe acne, Observed with . frequency

[male] (XYY), antisocial behavior (seen in 1-2% of XYY among inmates of

1:1000 males). penal institutions.

Pseudohermaphroditism

Disagreement between the phenotypic (external genitalia) and gonadal (testes vs.

ovaries) sex.

Female pseudo- Ovaries present, but external genitalia are virilized or ambiguous. Due to excessive

hermaphrodite and inappropriate exposure to androgenic steroids during early gestation (i.e.,

(XX) congenital adrenal hyperplasia or exogenous administration of androgens during

pregnancy).

Male pseudo- Testes present, but external genitalia are female or ambiguous. Most common form is

hermaphrodite androgen insensitivity syndrome (testicular feminization).

(XY)

True Both ovary and testicular tissue present; ambiguous genitalia. Very rare.

hermaphrodite

(46,XX or 47,XXY)

Androgen Defect in androgen receptor resulting in normal-appearing female; female external

insensitivity genitalia with rudimentary vagina; uterus and uterine tubes generally absent; develops

syndrome (46,XY) testes (often found in labia majora; surgically removed to prevent malignancy). Levels

of testosterone, estrogen, and LH are all high.

HIGH-YI E LD SYSTEMS REPRODUCTIVE

Bicornuate

uterus

Cervical

os

402

REPRODUCTIVE-PATHOLOGY (continued)

5a-reductase Unable to convert testosterone to DHT. Ambiguous genitalia until puberty, when

deficiency . testosterone causes masculinization of genitalia. Testosterone/estrogen levels

are normal; LH is normal or ..

Benign prostatic Common in men > 50 years of age. May be due to an age-related increase in estradiol with

hyperplasia possible sensitization of the prostate to the growth-promoting effects of DHT.

Characterized by a nodular enlargement of the periurethral (lateral and middle) lobes

of the prostate gland, compressing the urethra into a vertical slit. Often presents with

. frequency of urination, nocturia, difficulty starting and stopping the stream of urine,

and dysuria. May lead to distention and hypertrophy of the bladder, hydronephrosis,

and UTIs. Not considered a premalignant lesion.

Prostatic Common in men > 50 years of age. Arises most often from the posterior lobe (peripheral

adenocarcinoma zone) of the prostate gland and is most frequently diagnosed by digital rectal

examination (hard nodule) and prostate biopsy. Prostatic acid phosphatase and

prostate-specific antigen (PSA) are useful tumor markers. Osteoblastic metastases in

bone may develop in late stages, as indicated by an . in serum alkaline phosphatase

and PSA.

Hydatidiform mole A pathologic ovum (“empty egg”–ovum with no DNA) resulting in cystic swelling of

chorionic villi and proliferation of chorionic epithelium (trophoblast). Most common

precursor of choriocarcinoma. High ß-hCG. “Honeycombed uterus,” “cluster of

grapes” appearance. Genotype of a complete mole is 46,XX and is completely paternal

in origin (no maternal chromosomes); no associated fetus. PARTial mole is made up of

3 or more PARTS (triploid or tetraploid); may contain fetal PARTS (see Color Image

74).

Pregnancy-induced Preeclampsia is the triad of hypertension, proteinuria, and edema; eclampsia is the addition

hypertension of seizures to the triad. Affects 7% of pregnant women from 20 weeks’ gestation to 6

(preeclampsia- weeks postpartum. . incidence in patients with preexisting hypertension, diabetes,

eclampsia) chronic renal disease, and autoimmune disorders. Etiology involves placental ischemia.

Can be associated with HELLP syndrome (Hemolysis, Elevated LFTs, Low Platelets).

Clinical features Headache, blurred vision, abdominal pain, edema of face and extremities, altered

mentation, hyperreflexia; lab findings may include thrombocytopenia, hyperuricemia.

Treatment Delivery of fetus as soon as viable. Otherwise bed rest, salt restriction, and monitoring

and treatment of hypertension. For eclampsia, a medical emergency, IV magnesium

sulfate and diazepam.

Pregnancy 1. Abruptio placentae–premature separation of placenta. Painful uterine bleeding

complications (usually during 3rd trimester). Fetal death. May be associated with DIC. . risk with

smoking, hypertension, cocaine use.

2. Placenta accreta–defective decidual layer allows placenta to attach directly to

myometrium. Predisposed by prior C-section or inflammation. May have massive

hemorrhage after delivery.

3. Placenta previa–attachment of placenta to lower uterine segment. May occlude

cervical os. Painless bleeding in any trimester.

4. Ectopic pregnancy–most often in fallopian tubes, predisposed by salpingitis (PID).

Suspect with . hCG and sudden lower abdominal pain; confirm with ultrasound.

REPRODUCTIVE HIGH-YI E LD SYSTEMS

403

Amniotic fluid abnormalities

Polyhydramnios > 1.5-2 L of amniotic fluid; associated with esophageal/duodenal atresia, causing inability

to swallow amniotic fluid, and with anencephaly.

Oligohydramnios < 0.5 L of amniotic fluid; associated with bilateral renal agenesis or posterior urethral

valves (in males) and resultant inability to excrete urine.

Cervical pathology

Dysplasia and Disordered epithelial growth; begins at basal layer and extends outward. Classified as CIN 1,

carcinoma in situ CIN 2, or CIN 3 (carcinoma in situ), depending on extent of dysplasia. Associated with

HPV 16, 18. May progress slowly to invasive carcinoma.

Invasive carcinoma Often squamous cell carcinoma. Pap smear can catch cervical dysplasia (koilocytes) before

it progresses to invasive carcinoma. Lateral invasion can block ureters, causing renal

failure.

Uterine pathology

Endometriosis Non-neoplastic endometrial glands/stroma in abnormal locations outside the uterus.

Characterized by cyclic bleeding (menstrual type) from ectopic endometrial tissue

resulting in blood-filled “chocolate cysts.” In ovary or on peritoneum. Manifests

clinically as severe menstrual-related pain. Often results in infertility (see Color Image

77).

Adenomyosis Endometriosis within the myometrium.

Endometrial Abnormal endometrial gland proliferation usually caused by excess estrogen stimulation.

hyperplasia . risk for endometrial carcinoma. Most commonly manifests clinically as vaginal

bleeding.

Endometrial Most common gynecologic malignancy. Peak age 55-65 years old. Clinically presents with

carcinoma vaginal bleeding. Typically preceded by endometrial hyperplasia. Risk factors include

prolonged estrogen use (compare with carcinomas of cervix), obesity, diabetes, and

hypertension.

Leiomyoma Most common of all tumors in females. Often presents with multiple tumors. . incidence

in blacks. Malignant transformation is rare. Estrogen sensitive–tumor size . with

pregnancy and . with menopause. Does not progress to leiomyosarcoma (see Image

122).

Leiomyosarcoma Bulky tumor with areas of necrosis and hemorrhage, typically arising de novo (not from

leiomyoma). . incidence in blacks. Highly aggressive tumor with tendency to recur.

May protrude from cervix and bleed.

Polycystic ovarian . LH production leads to anovulation, hyperandrogenism due to deranged steroid

syndrome synthesis. Manifest clinically by amenorrhea, infertility, obesity, and hirsutism. Treat

with weight loss, OCPs, gonadotropin analogs, or surgery.

Ovarian cysts 1. Follicular cyst-distention of unruptured graafian follicle. May be associated with

hyperestrinism and endometrial hyperplasia.

2. Corpus luteum cyst–hemorrhage into persistent corpus luteum. Menstrual irregularity.

3. Theca-lutein cyst–often bilateral/multiple. Due to gonadotropin stimulation.

Associated with choriocarcinoma and moles.

4. “Chocolate cyst”–blood-containing cyst from ovarian endometriosis. Varies with

menstrual cycle.

HIGH-YI E LD SYSTEMS REPRODUCTIVE

404

REPRODUCTIVE-PATHOLOGY (continued)

Germ cell tumors

Germinomas Most common malignant germ cell tumor of the ovaries (dysgerminoma) and testes

(seminoma). Sheets of uniform cells, . hCG. Seminoma presents with painless

testicular enlargement; . risk with cryptorchidism.

Yolk sac (endodermal Aggressive malignancy in ovaries, testes, sacrococcygeal area of young children.

sinus) tumor Schiller-Duval bodies, primitive glomeruli. . AFP.

Choriocarcinoma Rare but malignant; can develop during pregnancy in mother or baby. Large,

hyperchromatic syncytiotrophoblastic cells. . hCG.

Embryonal 2nd most common testicular germ cell tumor; painful mass. Glandular with papillary

carcinoma convolutions.

Teratoma 90% of ovarian germ cell tumors. Contain cells from 3 germ layers. In females, mature

teratoma (“dermoid cyst”) is benign, while immature form is aggressively malignant. In

Men, Mature teratomas are Malignant and painful; can present with gynecomastia.

Struma ovarii–contains functional thyroid tissue (see Images 123, 124).

Ovarian non- 1. Serous cystadenoma–20% of ovarian tumors. Frequently bilateral, lined with fallopian

germ cell tumors tube-like epithelium. Benign.

2. Serous cystadenocarcinoma–50% ovarian tumors, malignant and frequently bilateral.

3. Mucinous cystadenoma–multilocular cyst lined by mucus-secreting epithelium. Benign.

4. Mucinous cystadenocarcinoma–malignant. Pseudomyxoma peritonei–intraperitoneal

accumulation of mucinous material from ovarian or appendiceal tumor.

5. Brenner tumor–benign tumor that resembles Bladder epithelium.

6. Ovarian fibroma–bundles of spindle-shaped fibroblasts. Meigs’ syndrome–triad of

ovarian fibroma, ascites, and hydrothorax.

7. Granulosa cell tumor–secretes estrogen .precocious puberty (kids). Can cause

endometrial hyperplasia or carcinoma in adults. Call-Exner bodies–small follicles filled

with eosinophilic secretions.

Testicular non-germ cell tumors

Leydig cell Benign, contains Reinke crystals; androgen producing . gynecomastia in men,

precocious puberty in boys.

Sertoli cell Benign, androblastoma from sex cord stroma.

Testicular Most common testicular cancer in older men.

lymphoma

REPRODUCTIVE HIGH-YI E LD SYSTEMS

405

Breast disease

Type Characteristics

Fibrocystic disease Presents with diffuse breast pain and multiple lesions, often bilateral. Biopsy shows

fibrocystic elements. Usually does not indicate . risk of carcinoma. Histologic types:

1. Fibrosis–hyperplasia of breast stroma.

2. Cystic–fluid filled.

3. Sclerosing–. acini and intralobular fibrosis.

4. Epithelial hyperplasia–. in number of epithelial cell layers in terminal duct

lobule. . risk of carcinoma with atypical cells. Occurs > 30 years.

Benign tumors Fibroadenoma–most common tumor < 25 years. Small, mobile, firm mass with sharp

edges. . size and tenderness with pregnancy. Not a precursor to breast cancer.

Cystosarcoma phyllodes–large, bulky mass of connective tissue and cysts. Tumor may

have “leaflike” projections.

Intraductal papilloma–tumor of lactiferous ducts; presents with nipple discharge.

Malignant tumors Common postmenopause. Arise from mammary duct epithelium or lobular glands.

(carcinoma) Overexpression of estrogen/progesterone receptors or erb-B2 (HER-2, an EGF

receptor) is common; affects therapy and prognosis.

Histologic types:

1. Ductal carcinoma in situ (DCIS)–early malignancy without basement

membrane penetration.

2. Invasive ductal, no specific type–firm, fibrous mass. Common.

3. Comedocarcinoma–ductal, with cheesy consistency due to central necrosis.

4. Inflammatory–lymphatic involvement; poor prognosis.

5. Invasive lobular–often multiple, bilateral.

6. Medullary–fleshy, cellular, lymphocytic infiltrate. Good prognosis.

7. Paget’s disease of the breast–eczematous patches on nipple. Paget cells–large

cells with clear halo; suggest underlying carcinoma. Also seen on vulva.

Risk factors Gender, age, early 1st menarche (< 12 years old), delayed 1st pregnancy (> 30

years old), late menopause (> 50 years old), family history of 1st-degree relative

with breast cancer at a young age. Risk is NOT increased by fibroadenoma or

nonhyperplastic cysts.

HIGH-YI E LD SYSTEMS REPRODUCTIVE

406

REPRODUCTIVE-PHARMACOLOGY

Antiandrogens

Finasteride A 5a-reductase inhibitor (. conversion of testosterone to dihydrotestosterone). Useful

in BPH. Also promotes hair growth–used to treat male-pattern baldness.

Flutamide A nonsteroidal competitive inhibitor of androgens at the testosterone receptor. Used in

prostate carcinoma.

Ketoconazole, Inhibit steroid synthesis; used in the treatment of polycystic ovarian syndrome to prevent

spironolactone hirsutism.

Sildenafil, vardenafil

Mechanism Inhibit cGMP phosphodiesterase, causing . cGMP, Sildenafil and vardenafil

smooth muscle relaxation in the corpus fill the penis.

cavernosum, . blood flow, and penile erection.

Clinical use Treatment of erectile dysfunction.

Toxicity Headache, flushing, dyspepsia, blue-green color vision.

Risk of life-threatening hypotension in patients

taking nitrates.

Leuprolide

Mechanism GnRH analog with agonist properties when used in When used in continuous

pulsatile fashion; antagonist properties when used fashion, it causes a transient

in continuous fashion. initial burst of LH and FSH.

Clinical use Infertility (pulsatile), prostate cancer (continuous–

use with flutamide), uterine fibroids.

Toxicity Antiandrogen, nausea, vomiting.

Clomiphene

Mechanism A partial agonist at estrogen receptors in the pituitary gland. Prevents normal feedback

inhibition and . release of LH and FSH from the pituitary, which stimulates ovulation.

Clinical use Treatment of infertility.

Toxicity Hot flashes, ovarian enlargement, multiple simultaneous pregnancies, visual disturbances.

Mifepristone (RU-486)

Mechanism Competitive inhibitor of progestins at progesterone receptors.

Clinical use Abortifacient (prevents implantation).

Toxicity Heavy bleeding, GI effects (nausea, vomiting, anorexia), abdominal pain.

Oral contraception Advantages Disadvantages

(synthetic Reliable (< 1% failure) Taken daily

progestins, . risk of endometrial and ovarian No protection against STDs

estrogen) cancer . triglycerides

. incidence of ectopic pregnancy Depression, weight gain, nausea,

. pelvic infections hypertension

Regulation of menses Hypercoagulable state

REPRODUCTIVE HIGH-YI E LD SYSTEMS

High-Yield Clinical

Vignettes

Anatomy

Physiology

Pathology

Pharmacology

H I G H -Y I E L D S Y S T E M S

Respiratory

407

“There’s so much pollution in the air now that if it weren’t for our lungs,

there’d be no place to put it all.”

–Robert Orben

“Mars is essentially in the same orbit. Somewhat the same distance from the

Sun, which is very important. We have seen pictures where there are canals, we

believe, and water. If there is water, that means there is oxygen. If there is

oxygen, that means we can breathe.”

–Former Vice President Dan Quayle

408

RESPIRATORY-HIGH-YIELD CLINICAL VIGNETTES

Patient exhibits an extended What is the disease Obstructive lung disease.

expiratory phase. process?

Tall, thin male teenager has What is the diagnosis? Spontaneous pneumothorax.

abrupt-onset dyspnea and leftsided

chest pain. There is

hyperresonant percussion on

the affected side, and breath

sounds are diminished.

Young man is concerned about Which of her proteins Dynein (Kartagener’s).

his wife’s inability to conceive is defective?

and her recurrent URIs. She

has dextrocardia.

RESPIRATORY HIGH-YI E LD SYSTEMS

409

RESPIRATORY-ANATOMY

Pneumocytes Pseudocolumnar ciliated cells extend to the Mucus secretions are swept

respiratory bronchioles; goblet cells extend only out of the lungs toward the

to the terminal bronchioles. mouth by ciliated cells.

Type I cells (97% of alveolar surfaces) line the A lecithin-to-sphingomyelin

alveoli. ratio of > 2.0 in amniotic

Type II cells (3%) secrete pulmonary surfactant fluid is indicative of fetal

(dipalmitoyl phosphatidylcholine), which . the lung maturity.

alveolar surface tension. Also serve as precursors

to type I cells and other type II cells. Type II cells

proliferate during lung damage.

Gas exchange barrier

Bronchopulmonary Each bronchopulmonary segment has a 3° Arteries run with Airways.

segments (segmental) bronchus and 2 arteries (bronchial

and pulmonary) in the center; veins and

lymphatics drain along the borders.

HIGH-YI E LD SYSTEMS RESPIRATORY

Macrophage

Alveolar

space

Capillary

lumen

Air-blood

barrier

Type I

epithelial cell

O2

CO2

Tight junction

(continuous endothelium)

Lamellar bodies

Type II

epithelial cell

Surfactant

(constitutive secretion)

410

RESPIRATORY-ANATOMY (continued)

Lung relations Right lung has 3 lobes; Left has 2 lobes and Lingula Instead of a middle lobe, the left

(homologue of right middle lobe). Right lung lung has a space occupied by

is more common site for inhaled foreign body the heart. The relation of the

owing to less acute angle of right main stem pulmonary artery to the

bronchus. bronchus at each lung hilus

is described by RALS–

Right Anterior; Left

Superior.

Oblique fissure is also found in

Opposite lung.

Horizontal fissure is Higher

than oblique fissure.

Diaphragm Structures perforating diaphragm: I 8 10 EGGs AT 12:

structures At T8: IVC. I = IVC @ 8th vertebra; EG

At T10: esophagus, vagus (2 trunks). = EsophaGus; G = vaGus @

At T12: aorta (red), thoracic duct (white), 10th vertebra; A = Aorta,

azygous vein (blue). Azygous; T = Thoracic duct

@ 12th vertebra.

Diaphragm is innervated by C3, 4, and 5 (phrenic “C3, 4, 5 keeps the diaphragm

nerve). Pain from the diaphragm can be referred alive.”

to the shoulder.

Muscles of Quiet breathing:

respiration Inspiration–diaphragm.

Expiration–passive.

Exercise:

Inspiration–external intercostals, scalene muscles, sternomastoids.

Expiration–rectus abdominis, internal and external obliques, transversus abdominis,

internal intercostals.

RESPIRATORY HIGH-YI E LD SYSTEMS

Horizontal

fissure

Trachea

Oblique

fissure

Oblique

fissure

Anterior view Posterior view

R L

bronchus

Right

bronchus

Left

L R

Sup. lobe Sup. lobe

Sup. lobe Sup. lobe

Mid. lobe

Inf.

lobe

Inf.

lobe

Inf.

Inf. lobe

lobe

4th rib

T2

Inferior view

Central tendon

Inferior vena cava (T8)

Esophagus (T10)

Aorta (T12)

Vertebrae

Rib

411

RESPIRATORY-PHYSIOLOGY

Response to high 1. Acute . in ventilation

altitude 2. Chronic . in ventilation

3. . erythropoietin ..hematocrit and hemoglobin (chronic hypoxia)

4. . 2,3-DPG (binds to hemoglobin so that hemoglobin releases more O2)

5. Cellular changes (. mitochondria)

6. . renal excretion of bicarbonate (e.g., can augment by use of acetazolamide) to

compensate for the respiratory alkalosis

7. Chronic hypoxic pulmonary vasoconstriction results in RVH

Important lung 1. Surfactant–produced by type II pneumocytes, Surfactant–dipalmitoyl

products . alveolar surface tension, . compliance phosphatidylcholine

2. Prostaglandins (lecithin) deficient in

3. Histamine neonatal RDS.

4. Angiotensin-converting enzyme (ACE)– Collapsing pressure =

angiotensin I . angiotensin II; inactivates 2 (tension)

bradykinin (ACE inhibitors . bradykinin and radius

cause cough, angioedema)

5. Kallikrein–activates bradykinin

Lung volumes 1. Residual volume (RV)–air in lung after Vital capacity is everything but

maximal expiration the residual volume.

2. Expiratory reserve volume (ERV)–air that can A capacity is a sum of = 2

still be breathed out after normal expiration volumes.

3. Tidal volume (TV)–air that moves into lung

with each quiet inspiration, typically 500 mL

4. Inspiratory reserve volume (IRV)–air in excess

of tidal volume that moves into lung on

maximum inspiration

5. Vital capacity (VC)–TV + IRV + ERV

6. Functional reserve capacity (FRC)–RV + ERV

(volume in lungs after normal expiration)

7. Inspiratory capacity (IC)–IRV + TV

8. Total lung capacity–TLC = IRV + TV + ERV + RV

HIGH-YI E LD SYSTEMS RESPIRATORY

IRV

FRC

VC

TV

ERV

RV

6.0

2.7

2.2

1.2

0

Volume

(L)

IC TLC

412

RESPIRATORY-PHYSIOLOGY (continued)

Oxygen-hemoglobin dissociation curve When curve shifts to the right,

. affinity of hemoglobin

for O2 (facilitates unloading

of O2 to tissue).

An . in all factors (except pH)

causes a shift of the curve

to the right.

A . in all factors (except pH)

causes a shift of the curve to

the left.

Right shift–CADET face right:

CO2

Acid/Altitude

DPG (2,3-DPG)

Exercise

Temperature

Pulmonary Normally a low-resistance, high-compliance system. A consequence of pulmonary

circulation PO2 and PCO2 exert opposite effects on pulmonary hypertension is cor

and systemic circulation. A . in PaO2 causes a pulmonale and subsequent

hypoxic vasoconstriction that shifts blood away from right ventricular failure

poorly ventilated regions of lung to well-ventilated (jugular venous distention,

regions of lung. edema, hepatomegaly).

1. Perfusion limited–O2 (normal health), CO2,

N2O. Gas equilibrates early along the length of

the capillary. Diffusion can be . only if blood

flow ..

2. Diffusion limited–O2 (exercise, emphysema,

fibrosis), CO. Gas does not equilibrate by the time

blood reaches the end of the capillary.

RESPIRATORY HIGH-YI E LD SYSTEMS

100

75

50

25

25 50

Cyanosis

Hb saturation (%)

PO2 (mmHg)

Hypoxemia

Normal

75 100

. O2 affinity, . P50

. metabolic needs

. Pco2, . temperature

. H+, . pH

. 2,3-DPG

Fetal Hb

. O2 affinity, . P50

. metabolic needs

. Pco2, . temperature

. H+, . pH

High altitude, . 2,3-DPG

100

75

50

25

PaO2

Normal O2

Exercise

Fibrosis

Start Length along

pulmonary capillary

End

413

Determination of physiologic dead space

VD = VT ×

(PaCO2 – PeCO2)

PaCO2

PaCO2 = arterial PCO2, PeCO2 = expired air PCO2.

V/Q mismatch Ideally, ventilation is matched to perfusion (i.e., With exercise (. cardiac

V/Q = 1) in order for adequate gas exchange. output), there is vasodilation

Lung zones: of apical capillaries,

1. Apex of the lung–V/Q = 3 (wasted ventilation) resulting in a V/Q ratio that

2. Base of the lung–V/Q = 0.6 (wasted perfusion) approaches 1.

Both ventilation and perfusion are greater at the Certain organisms that thrive in

base of the lung than at the apex of the lung. high O2 (e.g., TB) flourish in

the apex.

V/Q . 0 = airway obstruction

(shunt).

V/Q . 8 = blood flow

obstruction (physiologic dead

space).

CO2 transport Carbon dioxide is transported from tissues to the In lungs, oxygenation of

lungs in 3 forms: hemoglobin promotes

1. Bicarbonate (90%) dissociation of CO2 from

hemoglobin (Haldane effect).

In peripheral tissue, . H+

shifts curve to right,

unloading O2 (Bohr effect).

2. Bound to hemoglobin as carbaminohemoglobin (5%)

3. Dissolved CO2 (5%)

HIGH-YI E LD SYSTEMS RESPIRATORY

Zone 1

Zone 2

Zone 3

PA>Pa>Pv

Pa>PA>Pv

Pa>Pv>PA

CO2 + H2O H2CO3 H+ + HCO3-

HHb H+ + Hb-

Carbonic

anhydrase

CO2

Clfrom

peripheral tissue

(Adapted, with permission, from Ganong WF. Review of Medical Physiology, 22nd ed. New York: McGraw-Hill, 2005.)

414

RESPIRATORY-PATHOLOGY

Alveolar-arterial O2 Normal alveolar-arterial O2 difference:

difference [(A – a) DO2] < 10 mmHg.

Obstructive lung Obstruction of air flow, resulting in air trapping in the lungs. PFTs– . FEV1/FVC ratio

disease (COPD) (hallmark).

Types:

1. Chronic Bronchitis (“Blue Bloater”)–productive cough for > 3 consecutive months

in 2 or more years. Hypertrophy of mucus-secreting glands in the bronchioles

(Reid index > 50%). Leading cause is smoking. Findings: wheezing, crackles,

cyanosis.

2. Emphysema (“pink puffer”)–enlargement of air spaces and . recoil resulting

from destruction of alveolar walls. Caused by smoking (centriacinar emphysema)

and a1-antitrypsin deficiency (panacinar emphysema and liver cirrhosis) .

. elastase activity. Findings: dyspnea, . breath sounds, tachycardia, . I/E ratio.

3. Asthma–bronchial hyperresponsiveness causes reversible bronchoconstriction.

Can be triggered by viral URIs, allergens, and stress. Findings: cough, wheezing,

dyspnea, tachypnea, hypoxemia, . I/E ratio, pulsus paradoxus, Curschmann’s spirals,

smooth muscle hypertrophy, mucous plugging.

4. Bronchiectasis–chronic necrotizing infection of bronchi .dilated airways,

purulent sputum, recurrent infections, hemoptysis. Associated with bronchial

obstruction, CF, poor ciliary motility, and Kartagener’s syndrome.

Restrictive lung Restricted lung expansion causes . lung volumes (. VC and TLC). PFTs–FEV1/FVC

disease ratio > 80%.

Types:

1. Poor breathing mechanics (extrapulmonary):

a. Poor muscular effort–polio, myasthenia gravis

b. Poor structural apparatus–scoliosis, morbid obesity

2. Interstitial lung diseases (pulmonary):

a. Adult respiratory distress syndrome (ARDS)

b. Neonatal respiratory distress syndrome (hyaline membrane disease)

c. Pneumoconioses (coal miner’s silicosis, asbestosis)

d. Sarcoidosis

e. Idiopathic pulmonary fibrosis

f. Goodpasture’s syndrome

g. Wegener’s granulomatosis

h. Eosinophilic granuloma

Lung-physical findings

RESPIRATORY HIGH-YI E LD SYSTEMS

Abnormality Breath Sounds Resonance Fremitus Tracheal Deviation

Bronchial obstruction Absent/. over affected

area . . Toward side of lesion

Pleural effusion . over effusion Dullness . —

Pneumonia (lobar) May have bronchial Dullness . —

breath sounds over lesion

Pneumothorax . Hyperresonant Absent Away from side of lesion

(see Color Image 40)

415

Obstructive vs. restrictive lung disease

Note: Obstructive lung volumes > normal (. TLC, . FRC, . RV); restrictive lung volumes < normal. In both

obstructive and restrictive, FEV1 and FVC are reduced, but in obstructive, FEV1 is more dramatically reduced,

resulting in a . FEV1/FVC ratio.

Kartagener’s Immotile cilia due to a dynein arm defect. Results in male and female infertility (sperm

syndrome immotile), bronchiectasis, and recurrent sinusitis (bacteria and particles not

pushed out); associated with situs inversus.

Asbestosis Diffuse pulmonary interstitial fibrosis caused by Asbestosis and smoking greatly

inhaled asbestos fibers. . risk of pleural . risk of bronchogenic

mesothelioma and bronchogenic carcinoma. cancer (smoking not

Long latency. Ferruginous bodies in lung (asbestos additive with mesothelioma).

fibers coated with hemosiderin). Ivory-white Seen in shipbuilders and

pleural plaques (see Color Image 42). plumbers.

Neonatal Surfactant deficiency leading to . surface tension, resulting in alveolar collapse.

respiratory Surfactant is made by type II pneumocytes most abundantly after 35th week of

distress gestation. The lecithin-to-sphingomyelin ratio in the amniotic fluid, a measure of lung

syndrome maturity, is usually < 1.5 in neonatal respiratory distress syndrome.

Surfactant–dipalmitoyl phosphatidylcholine.

Treatment: maternal steroids before birth; artificial surfactant for infant.

HIGH-YI E LD SYSTEMS RESPIRATORY

0

1

2

3

4

5

6

7

8

1 2 3

Restrictive

Time (sec)

> 80%

FEV1 FVC

Normal

Lung volume (L)

Time (sec)

0

1

2

3

4

5

6

7

8

1 2 3

FEV1 FVC

FEV1

FVC

× 100 = 80%

0

1

2

3

4

5

6

7

8

1 2 3

Obstructive

Time (sec)

< 80%

FEV1 FVC

416

RESPIRATORY-PATHOLOGY (continued)

Lung cancer

Bronchogenic Tumors that arise centrally: Small Squamous center.

carcinoma 1. Squamous cell carcinoma–clear link to Lung cancer is the leading

Smoking; ectopic PTH-related peptide cause of cancer death.

production (see Color Image 36, Image 118) Presentation: cough,

2. Small cell carcinoma–clear link to Smoking; hemoptysis, bronchial

associated with ectopic hormone production obstruction, wheezing,

(ADH, ACTH); may lead to Lambert-Eaton pneumonic “coin” lesion on

syndrome (see Color Image 37) x-ray.

Tumors that arise peripherally: SPHERE of complications:

1. Adenocarcinoma (most common) Superior vena cava syndrome

2. Bronchioalveolar carcinoma (thought not to Pancoast’s tumor

be related to smoking) Horner’s syndrome

3. Large cell carcinoma–undifferentiated Endocrine (paraneoplastic)

Carcinoid tumor Can cause carcinoid syndrome (flushing, diarrhea, Recurrent laryngeal symptoms

wheezing, and salivation). (hoarseness)

Metastases Very common. Brain (epilepsy), bone (pathologic Effusions (pleural or

fracture), and liver (jaundice, hepatomegaly). pericardial)

Pancoast’s tumor Carcinoma that occurs in apex of lung and may Horner’s syndrome–ptosis,

affect cervical sympathetic plexus, causing miosis, anhidrosis.

Horner’s syndrome.

Pneumonia

Type Organism(s) Characteristics

Lobar Pneumococcus most frequently Intra-alveolar exudate .

consolidation; may involve

entire lung

Bronchopneumonia S. aureus, H. flu, Klebsiella, S. pyogenes Acute inflammatory infiltrates

from bronchioles into

adjacent alveoli; patchy

distribution involving = 1

lobes (see Image 116)

Interstitial (atypical) Viruses (RSV, adenoviruses), Mycoplasma, Diffuse patchy inflammation

pneumonia Legionella, Chlamydia localized to interstitial areas

at alveolar walls;

distribution involving = 1

lobes (see Image 119)

RESPIRATORY HIGH-YI E LD SYSTEMS

417

RESPIRATORY-PHARMACOLOGY

Arachidonic acid products

Lipoxygenase pathway yields Leukotrienes. L for Lipoxygenase and

LTB4 is a neutrophil chemotactic agent. Leukotriene.

LTC4, D4, and E4 function in bronchoconstriction,

vasoconstriction, contraction of smooth muscle,

and . vascular permeability.

PGI2 inhibits platelet aggregation and promotes Platelet-Gathering Inhibitor.

vasodilation.

H1 blockers Reversible inhibitors of H1 histamine receptors.

1st generation Diphenhydramine, dimenhydrinate, chlorpheniramine.

Clinical uses Allergy, motion sickness, sleep aid.

Toxicity Sedation, antimuscarinic, anti-a-adrenergic.

2nd generation Loratadine, fexofenadine, desloratadine.

Clinical uses Allergy.

Toxicity Far less sedating than 1st generation.

HIGH-YI E LD SYSTEMS RESPIRATORY

Phospholipase A2 Corticosteroids

Membrane lipid (e.g., phosphatidylinositol)

Zafirlukast,

Protein

synthesis

Cyclooxygenase (COX-1, COX-2)

Arachidonic acid

Lipoxygenase

NSAIDs,

Acetaminophen,

COX-2 inhibitors

Endoperoxides

(PGG, PGH)

Hydroperoxides

(HPETEs)

Montelukast

Leukotrienes

(LTB, LTC, LTD)

Prostacyclin

(PGI)

Thromboxane

(TXA)

Prostaglandins

(PGE, PGF)

Platelet aggregation

Vascular tone

Bronchial tone

Uterine tone

Uterine tone

Vascular tone

Bronchial tone

Platelet aggregation

Vascular tone

Bronchial tone

Bronchial tone

Zileuton

(Adapted, with permission, from Katzung BG, Trevor AJ. Pharmacology: Examination & Board Review, 5th ed. Stamford, CT: Appleton &

Lange, 1998:150.)

418

RESPIRATORY-PHARMACOLOGY (continued)

Asthma drugs

Nonspecific Isoproterenol–relaxes bronchial smooth muscle (ß2).

ß-agonists Adverse effect is tachycardia (ß1).

ß2 agonists Albuterol–relaxes bronchial smooth muscle (ß2).

Use during acute exacerbation.

Salmeterol–long-acting agent for prophylaxis.

Adverse effects are tremor and arrhythmia.

Methylxanthines Theophylline–likely causes bronchodilation by

inhibiting phosphodiesterase, thereby .

cAMP hydrolysis. Usage is limited because

of narrow therapeutic index (cardiotoxicity,

neurotoxicity).

Muscarinic Ipratropium–competitive block of muscarinic

antagonists receptors, preventing bronchoconstriction.

Cromolyn Prevents release of mediators from mast cells. Effective

only for the prophylaxis of asthma. Not effective

during an acute asthmatic attack. Toxicity is rare.

Corticosteroids Beclomethasone, prednisone–inhibit the synthesis

of virtually all cytokines. Inactivate NF-.B, the

transcription factor that induces the production of

TNF-a, among other inflammatory agents. 1st-line

therapy for chronic asthma.

Antileukotrienes Zileuton–A 5-lipoxygenase pathway inhibitor.

Blocks conversion of arachidonic acid to

leukotrienes.

Zafirlukast, montelukast–block leukotriene

receptors.

RESPIRATORY HIGH-YI E LD SYSTEMS

Bronchodilation

Bronchial tone

Bronchoconstriction

ACh Adenosine

cAMP

Muscarinic Theophylline

antagonists

ß-agonists

Theophylline

ATP

AMP

PDE

AC

Exposure to antigen

(dust, pollen, etc.)

Avoidance

Antigen and IgE

on mast cells

Cromolyn

Steroids

Mediators

(leukotrienes, histamine, etc.)

ß-agonist

Theophylline

Muscarinic

antagonists

Steroids

Late response:

inflammation

Early response:

bronchoconstriction

Bronchial

hyperreactivity Symptoms

Treatment strategies in asthma

(Adapted, with permission, from Katzung BG, Trevor AJ. Pharmacology: Examination & Board Review, 5th ed. Stamford,

CT: Appleton & Lange, 1998:159 and 161.)

Classic Findings

Most Common

Associations

Equation Review

H I G H -Y I E L D S Y S T E M S

Rapid Review

419

The following tables represent a collection of high-yield associations

of diseases, “buzzwords,” findings, and associated pathologies that

may be useful for quick review right before the exam.

420 RAPID REVIEW HIGH-YI E LD SYSTEMS

CLASSIC FINDINGS

Disease/Finding Association

Actinic keratosis Often precedes squamous cell carcinoma

Addison’s disease 1° adrenocortical deficiency

Albright’s syndrome Polyostotic fibrous dysplasia, precocious puberty, café-au-lait spots, short

stature, young girls

Albuminocytologic dissociation Guillain-Barré (. protein in CSF with only modest . in cell count)

Alport’s syndrome Hereditary nephritis with nerve deafness

Anti-basement membrane antibodies Goodpasture’s syndrome

Anticentromere antibodies Scleroderma (CREST)

Anti-double-stranded DNA SLE (type III hypersensitivity)

antibodies (ANA antibodies)

Anti-epithelial cell antibodies Pemphigus vulgaris

Antigliadin antibodies Celiac disease

Antihistone antibodies Drug-induced SLE

Anti-IgG antibodies Rheumatoid arthritis

Antimitochondrial antibodies 1° biliary cirrhosis

Antineutrophil antibodies Vasculitis

Antiplatelet antibodies Idiopathic thrombocytopenic purpura

Arachnodactyly Marfan’s syndrome

Argyll Robertson pupil Neurosyphilis

Arnold-Chiari malformation Cerebellar tonsillar herniation

Aschoff bodies Rheumatic fever

Atrophy of the mammillary bodies Wernicke’s encephalopathy

Auer rods Acute myelogenous leukemia (especially the promyelocytic type)

Autosplenectomy Sickle cell anemia

Babinski’s sign UMN lesion

Baker’s cyst in popliteal fossa Rheumatoid arthritis

“Bamboo spine” on x-ray Ankylosing spondylitis

Bartter’s syndrome Hyperreninemia

Basophilic stippling of RBCs Lead poisoning

Becker’s muscular dystrophy Defective dystrophin; less severe than Duchenne’s

Bell’s palsy LMN CN VII palsy

Bence Jones proteins Multiple myeloma (kappa or lambda Ig light chains in urine), Waldenström’s

macroglobulinemia (IgM)

421

HIGH-YI E LD SYSTEMS RAPID REVIEW

Berger’s disease IgA nephropathy

Bernard-Soulier disease Defect in platelet adhesion

Bilateral hilar adenopathy, uveitis Sarcoidosis

Birbeck granules on EM Histiocytosis X (eosinophilic granuloma)

Bloody tap on LP Subarachnoid hemorrhage

“Blue bloater” Chronic bronchitis

Blue-domed cysts Fibrocystic change of the breast

Blue sclera Osteogenesis imperfecta

Boot-shaped heart on x-ray Tetralogy of Fallot; RVH

Bouchard’s nodes Osteoarthritis (PIP swelling 2° to osteophytes)

Boutonnière deformity Rheumatoid arthritis

Branching rods in oral infection Actinomyces israelii

“Brown tumor” of bone Hemorrhage causes brown color of osteolytic cysts:

1. Hyperparathyroidism

2. Osteitis fibrosa cystica (von Recklinghausen’s disease)

Brushfield’s spots Down syndrome

Bruton’s disease X-linked agammaglobulinemia

Budd-Chiari syndrome Posthepatic venous thrombosis

Buerger’s disease Small/medium-artery vasculitis

Burkitt’s lymphoma 8:14 translocation; associated with EBV

Burton’s lines Lead poisoning

C-ANCA, P-ANCA Wegener’s granulomatosis, polyarteritis nodosa

Café-au-lait spots on skin Neurofibromatosis

Caisson disease Gas emboli

Calf pseudohypertrophy Duchenne’s muscular dystrophy

Call-Exner bodies Granulosa-theca cell tumor of the ovary

Cardiomegaly with apical atrophy Chagas’ disease

Cerebriform nuclei Mycosis fungoides (cutaneous T-cell lymphoma)

Chagas’ disease Trypanosome infection

Chancre 1° syphilis (not painful)

Chancroid Haemophilus ducreyi (painful)

Charcot’s triad Multiple sclerosis (nystagmus, intention tremor, scanning speech), cholangitis

(jaundice, RUQ pain, fever)

Charcot-Leyden crystals Bronchial asthma (eosinophil membranes)

Chédiak-Higashi disease Phagocyte deficiency

422 RAPID REVIEW HIGH-YI E LD SYSTEMS

CLASSIC FINDINGS (continued)

Cherry-red spot on macula Tay-Sachs, Niemann-Pick disease, central retinal artery occlusion

Cheyne-Stokes respirations Central apnea in CHF and . intracranial pressure

“Chocolate cysts” Endometriosis (frequently involves both ovaries)

Chronic atrophic gastritis Predisposition to gastric carcinoma

Chvostek’s sign Hypocalcemia (facial muscle spasm upon tapping)

Clear cell adenocarcinoma of DES exposure in utero

the vagina

Clue cells Gardnerella vaginitis

Codman’s triangle on x-ray Osteosarcoma

Cold agglutinins Mycoplasma pneumoniae, infectious mononucleosis

Cold intolerance Hypothyroidism

Condylomata lata 2° syphilis

Continuous machinery murmur Patent ductus arteriosus

Cori’s disease Debranching enzyme deficiency

Cotton-wool spots Chronic hypertension

Cough, conjunctivitis, coryza Measles

+ fever

Councilman bodies Toxic or viral hepatitis

Cowdry type A bodies Herpesvirus

Crescents in Bowman’s capsule Rapidly progressive crescentic glomerulonephritis

Crigler-Najjar syndrome Congenital unconjugated hyperbilirubinemia

Curling’s ulcer Acute gastric ulcer associated with severe burns

Currant-jelly sputum Klebsiella

Curschmann’s spirals Bronchial asthma (whorled mucous plugs)

Cushing’s ulcer Acute gastric ulcer associated with CNS injury

D-dimers DIC

Depigmentation of neurons in Parkinson’s disease (basal ganglia disorder–rigidity, resting tremor, bradykinesia)

substantia nigra

Dermatitis, dementia, diarrhea Pellagra (niacin, vitamin B3 deficiency)

Diabetes insipidus + exophthalmos + Hand-Schüller-Christian disease

lesions of skull

Dog or cat bite Pasteurella multocida

Donovan bodies Granuloma inguinale

Dressler’s syndrome Post-MI fibrinous pericarditis

423

HIGH-YI E LD SYSTEMS RAPID REVIEW

Dubin-Johnson syndrome Congenital conjugated hyperbilirubinemia (black liver)

Duchenne’s muscular dystrophy Deleted dystrophin gene (X-linked recessive)

Eburnation Osteoarthritis (polished, ivory-like appearance of bone)

Edwards’ syndrome Trisomy 18 associated with rocker-bottom feet, low-set ears, heart disease

Eisenmenger’s complex Late cyanosis shunt (uncorrected L .R shunt becomes R .L shunt)

Elastic skin Ehlers-Danlos syndrome

Erb-Duchenne palsy Superior trunk brachial plexus injury (“waiter’s tip”)

Erythema chronicum migrans Lyme disease

Fanconi’s syndrome Proximal tubular reabsorption defect

“Fat, female, forty, and fertile” Acute cholecystitis

Fatty liver Alcoholism

Ferruginous bodies Asbestosis

Gardner’s syndrome Colon polyps with osteomas and soft tissue tumors

Gaucher’s disease Glucocerebrosidase deficiency

Ghon focus 1° TB

Gilbert’s syndrome Benign congenital unconjugated hyperbilirubinemia

Glanzmann’s thrombasthenia Defect in platelet aggregation

Goodpasture’s syndrome Autoantibodies against alveolar and glomerular basement membrane proteins

Gowers’ maneuver Duchenne’s (use of patient’s arms to help legs pick self off the floor)

Guillain-Barré syndrome Idiopathic polyneuritis

“Hair-on-end” appearance on x-ray ß-thalassemia, sickle cell anemia (extramedullary hematopoiesis)

Hand-Schüller-Christian disease Chronic progressive histiocytosis

HbF Thalassemia major

HbS Sickle cell anemia

hCG elevated Choriocarcinoma, hydatidiform mole (occurs with and without embryo)

Heberden’s nodes Osteoarthritis (DIP swelling 2° to osteophytes)

Heinz bodies G6PD deficiency

Henoch-Schönlein purpura Hypersensitivity vasculitis associated with hemorrhagic urticaria and URIs

Heterophil antibodies Infectious mononucleosis (EBV)

High-output cardiac failure Wet beriberi (thiamine, vitamin B1 deficiency)

(dilated cardiomyopathy)

HLA-B27 Reiter’s syndrome, ankylosing spondylitis

HLA-DR3 or -DR4 Diabetes mellitus type 1 (caused by autoimmune destruction of ß cells)

Homer Wright rosettes Neuroblastoma

Honeycomb lung on x-ray Interstitial fibrosis

424 RAPID REVIEW HIGH-YI E LD SYSTEMS

CLASSIC FINDINGS (continued)

Horner’s syndrome Ptosis, miosis, and anhidrosis

Howell-Jolly bodies Splenectomy (or nonfunctional spleen)

Huntington’s disease Caudate degeneration (autosomal dominant)

Hyperphagia + hypersexuality + Klüver-Bucy syndrome (amygdala)

hyperorality + hyperdocility

Hyperpigmentation of skin 1° adrenal insufficiency (Addison’s disease)

Hypersegmented neutrophils Macrocytic anemia

Hypertension + hypokalemia Conn’s syndrome

Hypochromic microcytosis Iron deficiency anemia, lead poisoning

Increased a-fetoprotein in Anencephaly, spina bifida (neural tube defects)

amniotic fluid/maternal serum

Increased uric acid levels Gout, Lesch-Nyhan syndrome, myeloproliferative disorders, loop and thiazide

diuretics

Intussusception Adenovirus (causes hyperplasia of Peyer’s patches)

Janeway lesions Endocarditis

Jarisch-Herxheimer reaction Syphilis-overaggressive treatment of an asymptomatic patient that causes

symptoms due to rapid lysis

Job’s syndrome Neutrophil chemotaxis abnormality

Kaposi’s sarcoma AIDS in MSM (men who have sex with men)

Kartagener’s syndrome Dynein defect

Kayser-Fleischer rings Wilson’s disease

Keratin pearls Squamous cell carcinoma

Kimmelstiel-Wilson nodules Diabetic nephropathy

Klüver-Bucy syndrome Bilateral amygdala lesions

Koilocytes HPV

Koplik spots Measles

Krukenberg tumor Gastric adenocarcinoma with ovarian metastases

Kussmaul hyperpnea Diabetic ketoacidosis

Lens dislocation + aortic Marfan’s syndrome (fibrillin deficit)

dissection + joint hyperflexibility

Lesch-Nyhan syndrome HGPRT deficiency

Lewy bodies Parkinson’s disease

Libman-Sacks disease Endocarditis associated with SLE

Lines of Zahn Arterial thrombus

Lisch nodules Neurofibromatosis (von Recklinghausen’s disease)

425

HIGH-YI E LD SYSTEMS RAPID REVIEW

Low serum ceruloplasmin Wilson’s disease

Lucid interval Epidural hematoma

“Lumpy-bumpy” appearance of Poststreptococcal glomerulonephritis

glomeruli on immunofluorescence

Lytic bone lesions on x-ray Multiple myeloma

Mallory bodies Alcoholic liver disease

Mallory-Weiss syndrome Esophagogastric lacerations

McArdle’s disease Muscle phosphorylase deficiency

McBurney’s sign Appendicitis

MLF syndrome (INO) Multiple sclerosis

Monoclonal antibody spike Multiple myeloma (called the M protein; usually IgG or IgA), MGUS (monoclonal

gammopathy of undetermined significance), Waldenström’s (M protein = IgM)

macroglobulinemia

Myxedema Hypothyroidism

Necrotizing vasculitis (lungs) and Wegener’s and Goodpasture’s (hemoptysis and glomerular disease)

necrotizing glomerulonephritis

Needle-shaped, negatively Gout

birefringent crystals

Negri bodies Rabies

Nephritis + cataracts + hearing loss Alport’s syndrome

Neurofibrillary tangles Alzheimer’s disease

Niemann-Pick disease Sphingomyelinase deficiency

No lactation postpartum Sheehan’s syndrome (pituitary infarction)

Nutmeg liver CHF

Occupational exposure to asbestos Malignant mesothelioma

“Orphan Annie” nuclei Papillary carcinoma of the thyroid

Osler’s nodes Endocarditis

Owl’s eye CMV

Painless jaundice Pancreatic cancer (head)

Palpable purpura on legs and buttocks Henoch-Schönlein purpura

Pancoast’s tumor Bronchogenic apical tumor associated with Horner’s syndrome

Pannus Rheumatoid arthritis

Parkinson’s disease Nigrostriatal dopamine depletion

Periosteal elevation on x-ray Pyogenic osteomyelitis

Peutz-Jeghers syndrome Benign polyposis

Peyronie’s disease Penile fibrosis

426 RAPID REVIEW HIGH-YI E LD SYSTEMS

CLASSIC FINDINGS (continued)

Philadelphia chromosome (bcr-abl ) CML (may sometimes be associated with AML)

Pick bodies Pick’s disease

Pick’s disease Progressive dementia, similar to Alzheimer’s

“Pink puffer” Emphysema (centroacinar [smoking], panacinar [a1-antitrypsin

deficiency])

Plummer-Vinson syndrome Esophageal webs with iron deficiency anemia

Podagra Gout (MP joint of hallux)

Podocyte fusion Minimal change disease

Polyneuropathy, cardiac Dry beriberi (thiamine, vitamin B1 deficiency)

pathology, and edema

Polyneuropathy preceded by GI Guillain-Barré syndrome

or respiratory infection

Pompe’s disease Lysosomal glucosidase deficiency associated with cardiomegaly

Port-wine stain Hemangioma

Positive anterior “drawer sign” Anterior cruciate ligament injury

Pott’s disease Vertebral tuberculosis

Pseudopalisade tumor cell Glioblastoma multiforme

arrangement

Pseudorosettes Ewing’s sarcoma

Ptosis, miosis, anhidrosis Horner’s syndrome (Pancoast’s tumor)

Rash on palms and soles 2° syphilis, Rocky Mountain spotted fever

Raynaud’s syndrome Recurrent vasospasm in extremities

RBC casts in urine Acute glomerulonephritis

Recurrent pulmonary Pseudomonas Cystic fibrosis

and S. aureus infections

Red urine in the morning Paroxysmal nocturnal hemoglobinuria

Reed-Sternberg cells Hodgkin’s lymphoma

Reid index (increased) Chronic bronchitis

Reinke crystals Leydig cell tumor

Reiter’s syndrome Urethritis, conjunctivitis, arthritis

Renal cell carcinoma + cavernous von Hippel-Lindau disease

hemangiomas + adenomas

Renal epithelial casts in urine Acute toxic/viral nephrosis

Rhomboid crystals, positively Pseudogout

birefringent

427

HIGH-YI E LD SYSTEMS RAPID REVIEW

Rib notching Coarctation of aorta

Roth’s spots in retina Endocarditis

Rotor’s syndrome Congenital conjugated hyperbilirubinemia

Rouleaux formation (RBCs) Multiple myeloma

Russell bodies Multiple myeloma

S3 Left-to-right shunt (VSD, PDA, ASD), mitral regurgitation, LV failure (CHF)

S4 Aortic stenosis, hypertrophic subaortic stenosis

Schiller-Duval bodies Yolk sac tumor

Senile plaques Alzheimer’s disease

Sézary syndrome Cutaneous T-cell lymphoma

Sheehan’s syndrome Postpartum pituitary necrosis

Shwartzman reaction Neisseria meningitidis

Signet-ring cells Gastric carcinoma

Simian crease Down syndrome

Sipple’s syndrome MEN type IIa

Sjögren’s syndrome Dry eyes, dry mouth, arthritis

Skip lesions Crohn’s

Slapped cheeks Erythema infectiosum (fifth disease)

Smith antigen SLE

“Smudge cell” CLL

Soap bubble on x-ray Giant cell tumor of bone

Spike and dome on EM Membranous glomerulonephritis

Spitz nevus Benign juvenile melanoma

Splinter hemorrhages in fingernails Endocarditis

Starry-sky pattern Burkitt’s lymphoma

“Strawberry tongue” Scarlet fever

Streaky ovaries Turner’s syndrome

String sign on x-ray Crohn’s disease

Subepithelial humps on EM Poststreptococcal glomerulonephritis

Suboccipital lymphadenopathy Rubella

Sulfur granules Actinomyces israelii

Swollen gums, bruising, poor wound Scurvy (ascorbic acid, vitamin C deficiency)-vitamin C is necessary for

healing, anemia hydroxylation of proline and lysine in collagen synthesis

Systolic ejection murmur Aortic valve stenosis

(crescendo-decrescendo)

428 RAPID REVIEW HIGH-YI E LD SYSTEMS

CLASSIC FINDINGS (continued)

t(8;14) Burkitt’s lymphoma (c-myc activation)

t(9;22) Philadelphia chromosome, CML (bcr-abl hybrid)

t(14;18) Follicular lymphomas (bcl-2 activation)

Tabes dorsalis 3° syphilis

Tendon xanthomas (classically Familial hypercholesterolemia

Achilles)

Thumb sign on lateral x-ray Epiglottitis (Haemophilus influenzae)

Thyroidization of kidney Chronic bacterial pyelonephritis

Tophi Gout

“Tram-track” appearance on LM Membranoproliferative glomerulonephritis

Trousseau’s sign Visceral cancer, pancreatic adenocarcinoma (migratory thrombophlebitis),

hypocalcemia (carpal spasm)

Virchow’s node Left supraclavicular node enlargement from metastatic carcinoma of the

stomach

Virchow’s triad Pulmonary embolism (triad = blood stasis, endothelial damage, hypercoagulation)

von Recklinghausen’s disease Neurofibromatosis with café-au-lait spots

von Recklinghausen’s disease of bone Osteitis fibrosa cystica (“brown tumor”)

Wallenberg’s syndrome PICA thrombosis

Waterhouse-Friderichsen syndrome Adrenal hemorrhage associated with meningococcemia

Waxy casts Chronic end-stage renal disease

WBC casts in urine Acute pyelonephritis

WBCs in urine Acute cystitis

Wermer’s syndrome MEN type I

Whipple’s disease Malabsorption syndrome caused by Tropheryma whippelii

Wilson’s disease Hepatolenticular degeneration

“Wire loop” appearance on LM Lupus nephropathy

“Worst headache of my life” Berry aneurysm-associated with adult polycystic kidney disease

Xanthochromia (CSF) Subarachnoid hemorrhage

Xerostomia + arthritis + Sjögren’s syndrome

keratoconjunctivitis sicca

Zenker’s diverticulum Upper GI diverticulum

Zollinger-Ellison syndrome Gastrin-secreting tumor associated with ulcers

429

HIGH-YI E LD SYSTEMS RAPID REVIEW

Most Common …

Bacteremia/pneumonia (IVDA) S. aureus

Bacteria associated with cancer H. pylori

Bacteria found in GI tract Bacteroides (second most common is E. coli )

Brain tumor (adults) Mets > astrocytoma (including glioblastoma multiforme) > meningioma >

schwannoma

Brain tumor (kids) Medulloblastoma (cerebellum)

Brain tumor–supratentorial (kids) Craniopharyngioma

Breast cancer Infiltrating ductal carcinoma (in the United States, 1 in 9 women will develop

breast cancer)

Breast mass Fibrocystic change (in postmenopausal women, carcinoma is the most common)

Breast tumor (benign) Fibroadenoma

Bug in debilitated, hospitalized Klebsiella

pneumonia patient

Cardiac 1° tumor (adults) Myxoma (4:1 left to right atrium; “ball and valve”)

Cardiac 1° tumor (kids) Rhabdomyoma

Cardiac tumor (adults) Mets

Cardiomyopathy Dilated cardiomyopathy

Chromosomal disorder Down syndrome (associated with ALL, Alzheimer’s dementia, and endocardial

cushion defects)

Chronic arrhythmia Atrial fibrillation (associated with high risk of emboli)

Congenital cardiac anomaly VSD

Constrictive pericarditis Tuberculosis

Coronary artery involved in thrombosis LAD > RCA > LCA

Cyanosis (early; less common) Tetralogy of Fallot, transposition of great vessels, truncus arteriosus

Cyanosis (late; more common) VSD, ASD, PDA (close with indomethacin; open with misoprostol)

Demyelinating disease Multiple sclerosis

Dietary deficit Iron

Epiglottitis Haemophilus influenzae type B

Esophageal cancer Squamous cell carcinoma

Gene involved in cancer p53 tumor suppressor gene

Group affected by cystic fibrosis Caucasians (fat-soluble vitamin deficiencies, mucous plugs/lung infections)

Gynecologic malignancy Endometrial carcinoma

Heart murmur Mitral valve prolapse

MOST COMMON ASSOCIATIONS

430 RAPID REVIEW HIGH-YI E LD SYSTEMS

MOST COMMON ASSOCIATIONS (continued)

Heart valve in bacterial endocarditis Mitral

Heart valve in bacterial endocarditis Tricuspid

in IVDA

Heart valve (rheumatic fever) Mitral valve (aortic is 2nd)

Helminth infection (U.S.) Enterobius vermicularis (Ascaris lumbricoides is 2nd most common)

Hereditary bleeding disorder von Willebrand’s

Kidney stones Calcium = radiopaque (2nd most common is ammonium = radiopaque; formed by

urease-positive organisms such as Proteus vulgaris or Staphylococcus)

Liver disease Alcoholic liver disease

Location of brain tumors (adults) Supratentorial

Location of brain tumors (kids) Infratentorial

Lysosomal storage disease Gaucher’s disease

Male cancer Prostatic carcinoma

Malignancy associated with Hodgkin’s disease

noninfectious fever

Malignant skin tumor Basal cell carcinoma (rarely metastasizes)

Mets to bone Breast, lung, thyroid, testes, prostate, kidney

Mets to brain Lung, breast, skin (melanoma), kidney (renal cell carcinoma), GI

Mets to liver Colon, gastric, pancreatic, breast, and lung carcinomas

Motor neuron disease ALS

Neoplasm (kids) ALL (2nd most common is cerebellar medulloblastoma)

Nephrotic syndrome Membranous glomerulonephritis

Obstruction of male urinary tract BPH

Opportunistic infection in AIDS Pneumocystis carinii pneumonia

Organ receiving mets Adrenal glands (due to rich blood supply)

Organ sending mets Lung > breast, stomach

Ovarian tumor (benign) Serous cystadenoma

Ovarian tumor (malignant) Serous cystadenocarcinoma

Pancreatic tumor Adenocarcinoma (head of pancreas)

Patient with ALL/CLL/AML/CML ALL-child, CLL-adult > 60, AML-adult > 60, CML-adult 35-50

Patient with Hodgkin’s Young male (except nodular sclerosis type-female)

Patient with minimal change disease Young child

Patient with Reiter’s Male

Pituitary tumor Prolactinoma (2nd-somatotropic “acidophilic” adenoma)

431

HIGH-YI E LD SYSTEMS RAPID REVIEW

Preventable cancer Lung cancer

Primary bone tumor (adults) Multiple myeloma

Primary hyperparathyroidism Adenomas (followed by hyperplasia, then carcinoma)

Primary liver tumor Hepatoma

Renal tumor Renal cell carcinoma-associated with von Hippel-Lindau and acquired

polycystic kidney disease; paraneoplastic syndromes (erythropoietin, renin,

PTH, ACTH)

Secondary hyperparathyroidism Hypocalcemia of chronic renal failure

Sexually transmitted disease Chlamydia

Site of diverticula Sigmoid colon

Site of metastasis Regional lymph nodes

Site of metastasis (2nd most Liver

common)

Sites of atherosclerosis Abdominal aorta > coronary > popliteal > carotid

Skin cancer Basal cell carcinoma

Stomach cancer Adenocarcinoma

Testicular tumor Seminoma

Thyroid cancer Papillary carcinoma

Tracheoesophageal fistula Lower esophagus joins trachea/upper esophagus-blind pouch

Tumor in men Prostate carcinoma

Tumor in women Leiomyoma (estrogen dependent)

Tumor of infancy Hemangioma

Tumor of the adrenal medulla (adults) Pheochromocytoma (benign)

Tumor of the adrenal medulla (kids) Neuroblastoma (malignant)

Type of Hodgkin’s Nodular sclerosis (vs. mixed cellularity, lymphocytic predominance,

lymphocytic depletion)

Type of non-Hodgkin’s Follicular, small cleaved

Type of pituitary adenoma Prolactinoma

Vasculitis Temporal arteritis (risk of ipsilateral blindness due to thrombosis of ophthalmic

artery)

Viral encephalitis HSV

Vitamin deficiency (U.S.) Folic acid (pregnant women are at high risk; body stores only 3- to 4-month supply)

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