Pathophysiology Final Exam – Comprehensive Bullet-Point Notes

Cerebral Palsy (CP)

• Pathophysiology
• Non-progressive lesion of the developing brain ⇒ permanent motor & postural impairment.
• Injury may occur antenatally (≈ 70\%), perinatally (hypoxic-ischemic encephalopathy), or post-natally (infection, trauma).
• Defective corticospinal & extrapyramidal tracts → abnormal muscle tone, reflexes, and movement patterns.

• Major Clinical Sub-types
• Spastic (≈ 75\%) – upper-motor-neuron picture; velocity-dependent hypertonia.
• Dyskinetic (athetoid/dystonic) – basal ganglia damage; writhing or twisting.
• Ataxic – cerebellar damage; impaired balance & coordination.
• Mixed – combination of the above.

• Classic Gait Pattern (exam emphasis)
• “Scissor gait” (spastic diplegia): hip adduction, knee valgus, toe-walking, legs cross-over like scissors.

• Signs & Symptoms
• Delayed gross-motor milestones.
• Hyperreflexia, clonus, Babinski.
• Contractures, scoliosis.
• Associated: seizures, intellectual disability, strabismus, dysarthria.

• Pharmacologic Management
• Oral antispasmodics / muscle relaxants – especially agents with suffix “-fen”
• Baclofen (Lioresal®) – GABA_B agonist; ↓ reflex arc excitability; also used for low-back-pain spasms.
• Benzodiazepines (diazepam), dantrolene.
• Focal therapy: botulinum toxin type-A injections.
• Intrathecal baclofen pumps for generalized severe spasticity.

Multiple Sclerosis (MS)

• Pathophysiology
• Autoimmune demyelination of CNS white matter; oligodendrocyte loss.
• Axonal transection & gliosis → irreversible disability.

• MRI Findings
• Periventricular ovoid plaques ("Dawson fingers") on T2/FLAIR.
• Active lesions enhance with gadolinium (breakdown of BBB).
• Spinal cord lesions < 2 vertebral segments (helps distinguish from NMO).

• Clinical Phenotypes
• CIS – Clinically Isolated Syndrome (first attack).
• RRMS – Relapsing-Remitting (≈ 85\% at onset).
• SPMS – Secondary Progressive (evolves from RRMS).
• PPMS – Primary Progressive (≈ 10\%; steady decline from onset).

• Early Manifestations (first red flags)
• Optic neuritis (monocular vision loss, pain on eye movement).
• Lhermitte sign (electric shock down spine with neck flexion).
• Internuclear ophthalmoplegia (MLF lesion ⇒ adduction weakness).
• Uhthoff phenomenon (symptom worsening with heat).

• Disease-Modifying Therapies (DMTs)
• Many end with “-mab” (monoclonal antibodies):
• Ocrelizumab (CD20), Natalizumab (α4-integrin), Alemtuzumab (CD52).
• Others: Interferon-β, Glatiramer acetate, Fingolimod.

• Epidemiology
• Female:Male ≈ 3:1; peak onset 20–40 yrs; higher latitude prevalence.

Hydrocephalus

• Pathophysiology
• Imbalance between cerebrospinal fluid (CSF) production & absorption → ventricular dilation ± ↑ intracranial pressure (ICP).
• Types: obstructive (non-communicating) vs communicating vs normal-pressure.

• Etiology
• Aqueductal stenosis, intraventricular hemorrhage, meningitis, congenital malformation (Arnold–Chiari, Dandy–Walker), tumors.

• Infant Assessment Findings
• Rapid head circumference growth (> 2 percentiles).
• Bulging anterior fontanelle.
• “Sun-setting” eyes (down-gaze paresis).
• Scalp vein distension, poor feeding, irritability, high-pitched cry.

• Treatment & Complications
• Ventriculo-peritoneal (VP) shunt or endoscopic third ventriculostomy (ETV).
• Shunt malfunction → acute ICP rise (vomiting, bradycardia, ↓LOC).
• Shunt infection (often Staph epidermidis) ⇒ fever, meningismus.

Parkinson’s Disease (PD)

• Risk Factors
• Advancing age (> 60 yrs), male sex, rural living, pesticide exposure (e.g., paraquat), well-water, certain gene mutations (LRRK2, PARK7).

• Pathologic Protein
• Misfolded α-synuclein aggregates forming Lewy bodies in substantia nigra pars compacta.

• Neurochemical Basis
• Loss of dopaminergic neurons (↓ dopamine) ⇒ imbalance with acetylcholine in basal ganglia circuitry.

• Cardinal Motor Signs (TRAP)
• Tremor at rest ("pill-rolling" 4–6 Hz).
• Rigidity (lead-pipe/cog-wheel).
• Akinesia/Bradykinesia (slowness, shuffling gait, micrographia).
• Postural instability (↑ falls).

• Appearance & Gait
• Stooped posture, narrow-based shuffling, ↓ arm swing, festination, en bloc turning.
• Masked facies, seborrhea, soft monotonous speech.

Lung Cancer

• Most Common Type Overall
• Non-Small Cell Lung Cancer (NSCLC) ≈ 85\% of cases.

• Early Signs & Symptoms
• Chronic cough, hemoptysis, unexplained weight loss, chest pain, dyspnea, recurrent pneumonia.

• Causes / Environmental Risk Factors
• Smoking (∼ 85\% of cases), radon, asbestos, air pollution (PM 2.5), diesel exhaust, second-hand smoke.
• Occupational (nickel, chromium, arsenic).

• NSCLC Sub-types
• Adenocarcinoma (peripheral; most common in never-smokers).
• Squamous Cell Carcinoma (central; cavitation; paraneoplastic hypercalcemia via PTHrP).
• Large Cell Carcinoma (undifferentiated; poor prognosis).

Colon (Colorectal) Cancer

• Risk Factors
• Age > 50, familial adenomatous polyposis, Lynch syndrome, inflammatory bowel disease, high red/processed-meat diet, low fiber, obesity, smoking, alcohol.

• Precancerous Polyps
• Adenomatous polyps (tubular, villous) – dysplastic epithelium; villous > tubular risk.

• GI Bleeding Complications
• Iron-deficiency anemia (microcytic Hb < 12 g/dL), melena, hemodynamic instability.

• Bowel Elimination Symptoms (Medical Terms)
• Tenesmus (straining), hematochezia (bright-red blood per rectum), pencil-thin stools, alternating diarrhea & constipation.

• Symptoms of Metastatic Disease
• Liver mets → hepatomegaly, jaundice, elevated ALT/AST.
• Lung mets → cough, dyspnea.
• Peritoneal spread → ascites, abdominal distension.

Primary Brain Cancer

• Most Common Primary Malignancy
• Glioblastoma Multiforme (Grade IV astrocytoma).

• Clinical Presentation
• Progressive headaches (worse in morning), seizures, focal neurologic deficits (hemiparesis, aphasia), ↑ ICP signs (papilledema, vomiting).

Leukemia

• Pathophysiology
• Malignant clonal expansion of hematopoietic stem/progenitor cells in bone marrow → ↓ normal hematopoiesis.

• Blast Cell Count
• Acute leukemia diagnostic threshold: ≥ 20\% blasts in marrow/peripheral blood.
• Peripheral smear shows leukocytosis (e.g., WBC > 100\times10^9/L) with circulating myeloblasts or lymphoblasts.

• Marrow Dysfunction
• Anemia (fatigue), thrombocytopenia (bleeding), neutropenia (infections).

• Most Common Adult Type (BEST answer)
• Acute Myeloid Leukemia (AML) or, chronically, Chronic Lymphocytic Leukemia (CLL) – exam may specify.

• Splenic Complications
• Splenomegaly, hypersplenism (↑ sequestration), splenic rupture (acute abdomen).

• General Signs & Symptoms
• Fever, night sweats, weight loss ("B symptoms"), bone pain, gum hypertrophy (AML M5), petechiae.

• Bone Marrow Biopsy
• Gold standard; hypercellular marrow with blast predominance; cytogenetic studies (e.g., t(8;21), FLT3, BCR-ABL).

Lymphoma

• Hodgkin vs Non-Hodgkin (Primary Differences)
• Hodgkin: presence of Reed-Sternberg cells (CD15+, CD30+), contiguous nodal spread, bimodal age (20s & > 55).
• Non-Hodgkin: heterogeneous group; extranodal common; non-contiguous spread.

• Pathophysiology
• Malignant transformation of B (majority) or T/NK cells in lymphoid tissue.

• B-Cell Specifics & Symptoms
• B-cell NHLs (e.g., DLBCL, follicular) → painless lymphadenopathy; constitutional B symptoms.

• Risk Factors
• Immunosuppression (HIV, post-transplant), EBV, HTLV-1, H. pylori (MALT), autoimmune diseases, radiation.

• Common Lymphadenopathy Sites
• Cervical, supraclavicular, axillary, mediastinal (Hodgkin nodular sclerosis), inguinal.

General Cancer Treatments

• Targeted Therapy
• Designed for specific molecular aberrations (e.g., EGFR-TKI, BRAF inhibitors).
• Mechanism: block signaling pathways, induce apoptosis.
• ↓ off-target toxicity; resistance can develop via mutation or bypass signaling.

• Non-Target (Conventional) Therapy
• Cytotoxic chemotherapy (alkylators, antimetabolites), radiation.
• Acts on rapidly dividing cells → alopecia, mucositis, myelosuppression.