Pathology Flashcards
What is the most common cause of dementia in the elderly?
Alzheimer disease
Alzheimer is associated with which other genetic disease?
Down Syndrome
What are genes associated with Alzheimer’s disease?
Early onset: APP (Chr 21), presenilin-1 (Chr 14), presenilin-2 (Chr 1)
Late onset: ApoE4 (Chr 19)
PROTECTIVE: ApoE2 (Chr 19)
What are gross findings of Alzheimer’s disease?
widespread cortical atrophy
narrowing of gyri and widening of sulci
What are histological findings of Alzheimer’s disease?
Senile plaques: extracellular beta-amyloid core
Amyloid- Beta synthesized by cleaving amyloid precursor protein (APP)
Neurofibrillary tanges (intracellular, hyperphosphorylated tau protein) are associated with what disease?
Alzheimer Disease
What are clinical findings of Pick Disease?
dementia
aphasia
parkinsonian aspects
personality changes
What area of the brain is spared with Pick Disease?
parietal lobe and posterior ⅔ of superior temporal gyrus
What are gross findings of Pick disease?
Pick bodies: spherical tau protein aggregates
What are histological findings of Pick disease?
frontotemporal atrophy
What are clinical findings of Lewy body dementia?
initially dementia and visual hallucinations followed by parkinsonian features
What are histological findings of Lewy body dementia?
alpha-synuclein defect
What are clinical findings of Creutzfeldt-Jakob Disease?
rapidly progressive (wks to mos) dementia with myoclonus (“startle myoclonus”)
What are gross findings of Creutzfeldt-Jakob Disease?
spongiform cortex
What are histological findings of Creutzfeldt-Jakob Disease?
prions (PrPc –> PrPsc sheet)
Beta-pleated sheets are resistant to proteases
What are other causes of dementia?
Multi-infarct (2nd MCC of dementia in the elderly) syphilis HIV vitamins B1, B3, or B12 deficiency Wilson disease NPH
What is the pathogenesis of multiple sclerosis?
autoimmune inflammation and demyelination of CNS (brain and spinal cord)
What are clinical symptoms of a patient with multiple sclerosis?
optic neuritis (sudden loss of vision resulting in Marcus Gunn pupils) internuclear ophthalmoplegia hemiparesis hemisensory symptoms bladder/bowel incontinence
What age group does multiple sclerosis most often showing clinical symptoms?
20s and 30s
What is the Charcot classic triad of MS?
Scanning speech
Intention tremor
Nystagmus
Remember: SIN
What type of hypersensitivity is multiple sclerosis?
Type IV Hypersensitivity
What are laboratory findings of multiple sclerosis?
increased protein (IgG) in CSF
What can be seen on an MRI of a patient with multiple sclerosis?
periventricular plaques with destruction of axons.
multiple white matter lesions separated in space and time
What is the treatment for multiple sclerosis?
beta-interferon
immunosuppression
natalizumab
Symptomatic treatment for neurogenic bladder –> catheterization, muscarinic antagonists)
Symptomatic treatment for spasticity –> baclofen, GABA receptor agonist
Symptomatic treatment for pain –> opioids
What is the MC variant of Guillain-Barre Syndrome?
acute inflammatory demyelinating polyradiculopathy
What type of cells are injured in acute inflammatory demyelinating polyradiculopathy?
Schwann cells –> inflammation and demyelination of peripheral nerves and motor fibers
What are physical findings of acute inflammatory demyelinating polyradiculopathy?
symmetric ascending muscle weakness/paralysis beginning in lower extremities
facial paralysis in 50% of cases
autonomic function may be severely affected
What are laboratory findings in acute inflammatory demyelinating polyradiculopathy?
increased CSF protein with normal cell count
What pathogens are associated with acute inflammatory demyelinating polyradiculopathy?
Campylobacter jejuni and CMV
What type of support is critical in acute inflammatory demyelinating polyradiculopathy patients?
respiratory support
What are additional treatment options for patients with acute inflammatory demyelinating polyradiculopathy?
plasmapheresis
IV immune globulins
What demyelinating disease is associated with JC virus, AIDS patients, and immunocompromised transplant patients?
progressive multifocal leukoencephalopathy
What cells are destroyed in progressive multifocal leukoencephalopathy?
oligodendrocytes
Acute disseminated (post infectious) encephalomyelitis is associated with what infections?
measles or VZV
OR vaccinations (rabies, smallpox)
What is the pathogenesis of metachromic leukodystrophy?
arylsulfatase A deficiency –> buildup of sulfates –> impaired production of myelin sheath
What are physical findings of metachromic leukodystrophy?
central and peripheral demyelination with ataxia and dementia
What is the group of diseases that is related to defective production of proteins involved in the structure and function of peripheral nerves or the myelin sheath?
Charcot-Marie-Tooth Disease
What is the inheritance pattern of Charcot-Marie-Tooth Disease?
AD
What physical findings are associated with Charcot-Marie-Tooth Disease?
scoliosis and food deformities (high or flat arches)
What enzyme is deficient in Krabbe disease?
galactocerebrosidase
this deficiency then causes a buildup of galactocerebroside and psychosine –> destroys myelin sheath
What are physical findings in Krabbe disease?
peripheral neuropathy
developmental delay
optic atrophy
globoid cells
Adrenoleukodystrophy typically affects males or females?
males
What is the pathogenesis of adrenoleukodystrophy?
disrupts metabolism of very-long-chain fatty acids –> excessive buildup in nervous system, adrenal gland, and testes –> progressive disease that leads to long-term coma/death and adrenal gland crisis
What is the general definition of a seizure?
synchronized, high-frequency neuronal firing
What is the MC location for a partial (focal) seizure to originate?
medial temporal lobe
What is the difference between simple partial and complex particle seizures?
simple partial - consciousness intact
complex partial - impaired consciousness
Below are generalized seizure types. Give a brief description for each.
absence (petit mal) myloclonic tonic-clonic tonic atonic
absence (petit mal) - 3 Hz, no postictal confusion, blank stare
myloclonic - quick, repetitive jerks
tonic-clonic (grand mal) - alternating stiffening and movement
tonic - stiffening
atonic - “drop” seizures (falls to floor); commonly mistaken for fainting
What is the definition of epilepsy?
a disorder of recurrent seizures
What are the MCC of seizures by age?
Children - genetic, infection (febrile), trauma, congenital, metabolic
Adults - tumors, trauma, stroke, infection
Elderly - stroke, tumor, trauma, metabolic, infection
Unilateral pain for 15 min. - 3 hr with lacrimation and rhinorrhea is descriptive of what type of headache?
cluster headache
What is the treatment for a cluster headache?
inhaled oxygen, sumatriptan
Constant bilateral pain for > 30 min (typically 4-6 hr) with NO aura, photophobia, or phonophobia is descriptive of what type of headache?
tension headache
What is the treatment for a tension headache?
analgesics
NSAIDs
acetaminophen
amitriptyline for chronic pain
Pulsating unilateral pain with nausea, photophobia, phonophobia or “aura” for 4-72 hr is associated of what type of headache?
migraine
What is the treatment for migraine headaches?
abortive therapies (e.g. triptans, NSAIDs)
prophylactic (propranolol, topiramate, calcium channel blockers, amitriptyline)
How can you differentiate between cluster headaches and trigeminal neuralgia?
DURATION
trigeminal neuralgia produces repetitive shooting pain in the distribution of CN V and lasts (typically) for < 1 minute. The pain from cluster HAs lasts considerably longer (>15 mins)
What are causes of peripheral vertigo?
semicircular canal debris
vestibular nerve infection
Meniere disease
What will you find if you did a positional test on a patient with peripheral vertigo?
delayed horizontal nystagmus
What are causes of central vertigo?
brain stem or cerebellar lesion (e.g. stroke)
What are findings with central vertigo?
directional change of nystagmus, skew deviation, diplopia, dysmetria
What will you find if you did a positional test on a patient with central vertigo?
immediate nystagmus in any direction
What is the cause of Sturge - Weber Syndrome?
developmental anomaly of neural crest derivatives (mesoderm/ectoderm) d/t activating mutation of GNAQ gene
What are physical findings of Sturge- Weber Syndrome?
STURGE - Weber
Sporadic port - wine Stain Tram track Ca2+ Unilateral Retardation Glaucoma GNAQ gene Epilepsy
What are clinical findings of Tuberous Sclerosis?
HAMARTOMAS
Hamartomas in CNS and skin Angiofibromas Mitral regurgitation Ash- leaf spots cardiac Rhabdomyoma Tuberous sclerosis autosomal dOminant Mental retardation renal Angiomyolipoma Seizures, Shagreen patches
What are clinical findings of Neurofibromatosis Type I (von Recklinghausen disease)?
Cafe-au-lait spots Lisch nodules (pigmented iris hamartomas) neurofibromas in skin optic gliomas pheochromocytomas
What is the genetic mutation in Neurofibromatosis Type I?
mutated NF1 tumor suppressor gene (neurofibromin, a negative regulator of Ras) on chromosome 17
What are clinical findings in von Hippel-Lindau disease?
cavernous hemangiomas in skin, mucosa, organs
bilateral renal cell carcinomas
hemangioblastoma (high vascularity with hyper chromatic nuclei) in retina, brain stem, cerebellum
pheochromocytomas
What is the genetic inheritance of von Hippel-Lindau disease?
AD
What is the genetic mutation in von Hippel-Lindau disease?
mutated VHL tumor suppressor gene on chromosome 3 –> constitutive expression of HIF (transcription factor) and activation of angiogenic growth factors
What is the MC primary brain tumor in adults?
glioblastoma multiforme
What is the signature finding seen in CT with a glioblastoma multiforme?
“butterfly glioma”
What is the histological finding in gliobastoma multiforme?
“pseudopalisading” pleomorphic tumor cells
What is the 2nd MC brain tumor in adults? Is it benign or malignant?
meningioma
benign
What are gross findings of a meningioma?
often occurs in convexities of hemispheres (near surfaces of brain)
may have a dural attachment “tail”
What are histological findings in a meningioma?
whorled pattern
psammoma bodies
What is the most common cerebellar brain tumor of adults?
hemangioblastoma
What disease is associated with hemangioblastoma?
von Hippel-Lindau syndome
What brain tumor is often localized to CN VIII?
acoustic schwannoma
Bilateral acoustic schwannomas are found in what disease?
NF-2
Where do oligodendroglioma brain tumors typically localize?
frontal lobes
What are the histological findings in an oligodendroglioma?
chicken wire capillary pattern
oligodendrocytes = “fried egg” cells
What is the MC pituitary adenoma?
prolactinoma
What visual disturbances are seen with a pituitary adenoma?
bilateral hemianopia
In children, where is a pilocytic (low-grade) astrocytoma usually localized?
posterior fossa (e.g. cerebellum)
What histological findings are associated with pilocytic (low-grade) astrocytoma?
Rosenthal fibers - eosinophilic, corkscrew fibers
A highly malignant childhood brain tumor…
medulloblastoma
What is the histology of a medulloblastoma?
Homer-Wright rosettes
Solid, small blue cells
What is a complication of a medulloblastoma?
can compress 4th ventricle –> hydrocephalus
Where is the MC location of an ependymoma?
4th ventricle
What is the characteristic histology of an ependymoma?
perivascular rosettes
What is the MC supratentorial tumor of childhood?
craniopharyngioma
What are complications of a craniopharyngioma?
bitemporal hemianopia
increased intracranial pressure
endocrine dysfunction
What are complications of a cerebellar tonsillar herniation?
coma and death when these herniations compress the brain stem (and inhibit respiration)
