Pathophysiology Final Exam Vocabulary Review

Hydrocephalus

• Definition / Overview
– A neurological disorder marked by an abnormal accumulation of cerebrospinal fluid (CSF) in the ventricular system.
– Leads to ventricular dilation → raises intracranial pressure (ICP) → compresses surrounding brain tissue.
– Untreated, elevated ICP can cause ischemia, herniation, and permanent neurologic damage.

• Pathophysiology (step-wise)
– Normally, CSF is produced in the choroid plexus at ≈ 0.3\,\text{mL\,min}^{-1} (≈ 500\,\text{mL\,day}^{-1}).
– It circulates through ventricles → subarachnoid space → absorbed by arachnoid granulations into venous sinuses.
– Hydrocephalus results when:
• CSF production > absorption (over-production is rare).
• Obstruction of flow (non-communicating) e.g., aqueductal stenosis, tumors.
• Impaired absorption (communicating) e.g., post-meningitic scarring, subarachnoid hemorrhage.
– Rising ICP → reduced cerebral perfusion pressure \big(CPP = MAP - ICP\big); when CPP < 50\,\text{mmHg}, neurons become ischemic.

• Etiology / Causes
– Congenital malformations (e.g., Arnold-Chiari, Dandy-Walker).
– Infections (TORCH, meningitis).
– Intraventricular hemorrhage (common in premature neonates).
– Tumors, cysts, or traumatic obstruction.
– Post-traumatic / post-surgical scarring of arachnoid villi.

• Infant Assessment – Hallmark Findings
– Bulging anterior & posterior fontanelles.
– Rapidly increasing head circumference (crossing >2 percentile lines).
– Dilated scalp veins → “caput medusae” appearance.
– Frontal bossing; “setting-sun” eyes (downward gaze deviation).
– Irritability, high-pitched cry, poor suck/feeding, emesis.
– Seizures or developmental delay appear as disease advances.

• Diagnostics
– Head ultrasound (if fontanelle open) → ventriculomegaly.
– MRI/CT for etiology, aqueduct patency.
– ICP monitoring when symptoms ambiguous.

• Treatment
– Ventriculoperitoneal (VP) shunt: catheter + programmable valve drains CSF to peritoneum.
– Endoscopic third ventriculostomy (ETV) ± choroid plexus cauterization (ETV-CPC) in select non-communicating cases.
– Acetazolamide or furosemide (temporary CSF-production suppression).
– Serial lumbar punctures in premature IVH.

• Potential Complications of Therapy
– Shunt infection (usually skin flora; peak 1–3 mo post-implant).
– Shunt obstruction / mechanical failure → return of symptoms (emergency).
– Over-drainage → slit-ventricle syndrome, subdural hematoma.
– Abdominal complications: peritonitis, pseudocyst.
– Seizure risk persists: monitor long-term neuro-development.

• Ethical / Practical Notes
– Lifelong device dependence → requires education, rapid evaluation of headaches, vomiting, or altered LOC.
– Multi-disciplinary follow-up (neurosurgery, neurology, PT/OT).
– Discuss prognosis: cognitive outcome tied to timing & etiology of injury, not just ventricle size.

Parkinson’s Disease (PD)

• Definition / Core Concept
– Chronic, progressive neurodegenerative movement disorder.
– Caused by loss of dopaminergic neurons in the pars compacta of the substantia nigra → dopamine deficiency in the basal ganglia motor loop.

• Risk Factors
– Age >60\,\text{yrs} (strongest).
– Male sex (~1.5 : 1).
– Genetics: LRRK2, PARK1 (SNCA), PARK2 (parkin) mutations.
– Environmental: pesticide/herbicide exposure (paraquat, rotenone), rural living, well-water, manganese, repeated head trauma (boxing, sports).
– Possible protective: smoking, caffeine (epidemiologic).

• Pathologic Hallmark
– Intracytoplasmic eosinophilic inclusions = Lewy bodies composed of misfolded \alpha-synuclein + ubiquitin.
– Spread pattern follows Braak staging (olfactory bulb → dorsal motor nucleus → midbrain … cortex).

• Neurochemical Consequences
– ↓ Dopamine → disinhibition of indirect pathway & hypoactivation of direct pathway → bradykinesia/rigidity.
– Relative ↑ acetylcholine → tremor prominence.

• Cardinal Motor Signs (TRAP mnemonic)
– Tremor at rest (pill-rolling; 4–6 Hz).
– Rigidity (cog-wheel or lead-pipe).
– Akinesia / Bradykinesia (slow initiation, micrographia).
– Postural instability (late feature).
– Gait: shuffling, festination, decreased arm swing; en-bloc turning.
– Facies: masked (hypomimia), seborrheic dermatitis common.

• Non-Motor Features
– Anosmia (early), REM sleep behavior disorder, constipation.
– Depression, anxiety, executive dysfunction, dementia (PD-D).
– Autonomic: orthostatic hypotension, urinary urgency, sialorrhea.

• Management Overview
– Pharmacologic:
• Levodopa + carbidopa (first-line for symptomatic relief).
• Dopamine agonists (pramipexole, ropinirole).
• MAO-B inhibitors (selegiline, rasagiline).
• COMT inhibitors (entacapone) prolong L-dopa.
• Anticholinergics (trihexyphenidyl) for tremor dominant.
• Amantadine (NMDA blocker) for dyskinesias.
– Surgical: deep-brain stimulation (sub-thalamic nucleus or GPi) when medication refractory.
– Rehab: PT for gait, OT for ADLs, speech therapy for hypophonia.
– Nutritional: adequate protein timed apart from L-dopa doses.

• Complications
– Motor fluctuations (“wearing off”, dyskinesias) with chronic L-dopa.
– Psychosis/hallucinations (dopamine excess).
– Progressive swallowing difficulty → aspiration risk.

• Connections / Real-World Relevance
– Exposure mitigation (pesticide regulation) may lower incidence.
– Concussion prevention in sports highlights head trauma link.

Lung Cancer

• Epidemiology & Types
– Leading cause of cancer mortality worldwide.
– Non-Small Cell Lung Cancer (NSCLC) ≈ 85\% of cases:
• Adenocarcinoma (peripheral; common in non-smokers).
• Squamous cell carcinoma (central; cavitation; PTHrP hypercalcemia).
• Large-cell carcinoma (poorly differentiated).
– Small Cell Lung Cancer (SCLC) ≈ 15\%; highly aggressive, paraneoplastic (SIADH, ACTH).

• Environmental Risk Factors
– Tobacco smoking (primary) – pack-years directly correlates with risk.
– Secondhand smoke (spouse/office exposure).
– Occupational carcinogens: asbestos, arsenic, chromium, nickel, beryllium.
– Radon gas (uranium decay in homes).
– Air pollution (PM2.5 fine particulates).
– Chronic inflammatory lung disease (COPD, pulmonary fibrosis) potentiates carcinogenesis.

• Early Signs & Symptoms
– Persistent / worsening cough (>3 weeks).
– Hemoptysis (coughing blood).
– Chest pain, hoarseness (recurrent laryngeal nerve), dyspnea.
– Unexplained weight loss, anorexia, fatigue.
– Recurrent pneumonia in same lobe (obstructing lesion).
– Paraneoplastic clues: hypercalcemia (squamous), clubbing (adenocarcinoma), hyponatremia (SCLC).

• Diagnostics (brief)
– Low-dose CT screening for adults 50–80 with ≥20 pack-year history.
– CXR → CT chest → PET-CT staging.
– Histologic confirmation via bronchoscopy, CT-guided biopsy.

• Management Snapshot (NSCLC)
– Surgical resection (lobectomy) if stage I–II.
– Adjuvant / neoadjuvant chemo-radiation based on stage.
– Targeted therapy: EGFR inhibitors (osimertinib), ALK inhibitors (alectinib), PD-1 inhibitors (pembrolizumab).
– Smoking cessation improves survival, reduces second primaries.

Cerebral Palsy (CP)

• Definition / Core Idea
– Group of non-progressive motor disorders originating from injury or maldevelopment of the immature brain (prenatal to early postnatal).
– Motor impairment is permanent but clinical presentation evolves with growth.

• Pathophysiology
– Prenatal: vascular infarcts, maternal infection, hypoxic-ischemic encephalopathy, genetic anomalies.
– Perinatal: birth asphyxia, prematurity (periventricular leukomalacia), intracranial hemorrhage.
– Postnatal: meningitis, head trauma, kernicterus.
– Injury location dictates subtype (corticospinal tracts → spastic; cerebellum → ataxic; basal ganglia → dyskinetic).

• Types & Key Features
– Spastic (≈80\%): hypertonia, hyperreflexia, scissoring gait, toe-walking.
– Dyskinetic (athetoid / dystonic): involuntary writhing, fluctuating tone.
– Ataxic: coordination deficits, wide-based gait, intention tremor.
– Mixed: combo of above due to diffuse injury.

• Clinical Manifestations
– Delayed motor milestones, asymmetric hand use <18\,\text{mo} (early handedness).
– Gait specifics:
• Spastic diplegia: scissoring (hip adduction), equinus (tip-toe).
• Hemiplegia: circumduction.
• Quadriplegia: limited ambulation, wheelchair.
– Associated: intellectual disability, epilepsy, vision/hearing loss, speech delay, hip dislocation, scoliosis.

• Medications (Symptom Control)
– Oral antispasmodics / muscle relaxants:
• Baclofen (GABA-B agonist).
• Diazepam (benzodiazepine).
• Orfenadrine (Norflex) – centrally acting, suffix “-fen”.
– Local: botulinum toxin injections.
– Intrathecal baclofen pump for severe spasticity.
– Orthopedic / neurosurgical (selective dorsal rhizotomy) for contractures.

• Management Principles
– Early PT/OT, constraint-induced therapy, adaptive equipment.
– Multidisciplinary team: neurologist, orthopedist, speech therapist, social worker.
– Address comorbidities (seizures, GERD, nutrition).
– Ethical: lifelong care planning, access to inclusive education.

Multiple Sclerosis (MS)

• Definition & Key Concept
– Autoimmune, demyelinating disease of the central nervous system (CNS) characterized by disseminated inflammatory lesions separated in time and space.

• Pathophysiology
– Activated T-cells cross blood-brain barrier → target myelin basic protein.
– Demyelination → conduction block, axonal injury → irreversible disability.
– Oligodendrocyte loss; astrocytic gliosis forms scars (plaques).
– Etiologic factors: genetic (HLA-DRB1*15:01), low vitamin D, EBV infection, smoking.

• MRI Findings
– Hyperintense T2/FLAIR lesions in periventricular (“Dawson fingers”), juxtacortical, infratentorial, and spinal cord regions.
– Gadolinium enhancement = active inflammation.
– Black holes (T1 hypointense) reflect axonal loss.

• Clinical Subtypes
– CIS (Clinically Isolated Syndrome): first neuro episode.
– RRMS (Relapsing-Remitting) – most common; clear relapses with full/partial recovery.
– SPMS (Secondary Progressive) – begins as RRMS → gradual worsening.
– PPMS (Primary Progressive) – steady decline from onset; poorer prognosis.

• Early Signs & Symptoms
– Optic neuritis (painful monocular vision loss).
– Lhermitte’s sign (electric shock down spine on neck flexion).
– Paresthesias, numbness, sensory level.
– Fatigue (most common disabling symptom).
– Motor weakness, limb ataxia.
– Uhthoff’s phenomenon: symptom worsening with heat.

• Disease-Modifying Treatments (DMTs)
– Injectable interferon-β1a, β1b.
– Glatiramer acetate.
– Monoclonal antibodies (suffix “-mab”):
• Ocrelizumab (anti-CD20; only FDA-approved for PPMS).
• Natalizumab (anti-α4-integrin; risk of PML).
• Alemtuzumab, Ofatumumab.
– Oral agents: fingolimod, dimethyl fumarate, cladribine, teriflunomide.
– Acute relapse: high-dose IV methylprednisolone; plasmapheresis if steroid-refractory.

• Gender & Prevalence
– Female : male ≈ 3!:!1.
– Peak onset 20–40 yrs; more prevalent in higher latitudes (vitamin D link).

• Prognosis & Counseling
– Early initiation of DMT slows disability accrual.
– Lifestyle: stop smoking, maintain vitamin D sufficiency, exercise.
– Fertility/pregnancy: many DMTs paused; relapse rate ↓ during pregnancy, ↑ postpartum.