Pathology Exam Comprehensive Comparison Study Guide

NEUROLOGICAL SYSTEM

GROUP 1: Dementia and Cognitive Degeneration

Alzheimer Disease

• Core Defect: Characterized by $\beta$-amyloid plaques, tau tangles, and a decrease in acetylcholine ($\downarrow ACh$) in the nucleus basalis of Meynert.

• Cause: Mostly sporadic, with the $APOE\text{-}ε4$ allele serving as a major risk factor. Familial cases involve mutations in $APP$, $PSEN1$, and $PSEN2$.

• Key Risk Factors: Age > 65 (primary risk), presence of $APOE\text{-}ε4$, female sex, and prior head trauma.

• Presentation: Insidious onset beginning with short-term memory loss, progressing to aphasia, personality changes, and eventually global dementia.

• Distinguishing Factors: Tangles are intracellular tau; plaques are extracellular $\beta$-amyloid ($A\beta$).

• Mnemonic: 'APP + tau + ACh'.

Down Syndrome (Trisomy 21)

• Core Defect: Trisomy $21$ leads to an extra $APP$ gene on chromosome $21$, resulting in excess $A\beta$. This guarantees the development of Alzheimer pathology by age $40$.

• Cause: $95\%$ due to nondisjunction (mainly in maternal meiosis I); $4\%$ due to Robertsonian translocation ($14;21$).

• Key Risk Factors: Advanced maternal age in cases of nondisjunction. Robertsonian translocations can occur at ANY age.

• Presentation: Intellectual disability, flat facies, epicanthal folds, simian crease, hypotonia, and a protruding tongue.

• Cardiac Findings: Endocardial cushion defect (Atrioventricular [AV] canal) occurs in $40\text{--}50\%$ of cases, making it the $\#1$ structural defect.

• Cancer Risk: Significantly elevated risk for ALL (Acute Lymphoblastic Leukemia) in children and transient myeloproliferative disorder in neonates.

• GI Findings: Duodenal atresia (visible as 'double bubble' on X-ray) and Hirschsprung disease.

• Distinguishing Factors: Robertsonian translocation is not age-related; parents must be karyotyped to assess recurrence risk.

• Mnemonic: '21 = Double 1 → Duodenal atresia + ALL + Alzheimer'.

GROUP 2: Motor and Demyelinating Diseases (ALS vs. MS vs. GBS)

Amyotrophic Lateral Sclerosis (ALS)

• Location: Affects both Upper Motor Neurons (UMN) and Lower Motor Neurons (LMN). It is strictly motor-only.

• Cause: $SOD1/C9orf72$ mutations and glutamate toxicity.

• Pattern: Progressive decline without remissions.

• Key Signs: Fasciculations and atrophy (LMN signs) combined with spasticity and the Babinski sign (UMN signs). Tongue fasciculations are characteristic.

• Sensory and Reflexes: Sensory remains ALWAYS intact. Reflexes show a mix of hyperreflexia (UMN) and hyporeflexia (LMN).

• CSF and Imaging: Normal CSF. MRI is normal early on; Electromyography (EMG) shows denervation.

• Progression: Death typically occurs by respiratory failure within $3\text{--}5 years$.

• Treatment: Riluzole (a glutamate blocker).

• Mnemonic: 'Both Upper and Lower'.

Multiple Sclerosis (MS)

• Location: Central Nervous System (CNS) white matter, involving the brain and spinal cord.

• Cause: Autoimmune T-cell attack on oligodendrocytes.

• Pattern: Relapsing-remitting in $85\%$ of cases; lesions are separated in time and space.

• Key Signs: Optic neuritis (often the first symptom, presenting as painful monocular vision loss), Internuclear Ophthalmoplegia (INO/MLF), Lhermitte sign, Uhthoff phenomenon, and Charcot triad.

• CSF Findings: Presence of oligoclonal $IgG$ bands and an increased $IgG$ index.

• Imaging: Periventricular plaques, specifically 'Dawson fingers' on MRI.

• Mnemonic: 'Time AND Space'.

Guillain-Barré Syndrome (GBS)

• Location: Peripheral nerve myelin.

• Cause: Molecular mimicry following an infection, most commonly Campylobacter jejuni ($\#1$).

• Pattern: Ascending symmetric weakness that peaks and then recovers.

• Key Signs: Areflexia (occurring EARLY), ascending paralysis, and autonomic instability. Paresthesias usually precede weakness.

• CSF Findings: Albuminocytologic dissociation (elevated protein with NORMAL White Blood Cell count).

• Exam Trap: Do NOT give steroids for GBS.

• Mnemonic: 'Going Up (ascending) + CSF dissociation'.

GROUP 3: Extrapyramidal and Movement Disorders

Parkinson Disease

• Mechanism: Decrease in dopamine ($\downarrow$ dopamine) in the substantia nigra (SN) leading to a Dopamine/ACh imbalance.

• Pathology: Lewy bodies, which are aggregates of $\alpha$-synuclein, found in the substantia nigra.

• Motor Signs (TRAP): Tremor (resting, pill-rolling), Rigidity (cogwheel), Akinesia, and Postural instability.

• Non-Motor: Masked facies, micrographia, depression, and late-stage dementia.

• Mnemonic: 'TRAP'.

Huntington Disease

• Inheritance: Autosomal Dominant; $CAG$ repeat on chromosome $4$ (> 36 repeats). Shows anticipation (earlier onset in subsequent generations).

• Mechanism: Mutant huntingtin protein leads to caudate neuron death and a decrease in GABA ($\downarrow GABA$), causing chorea.

• Pathology: Caudate nucleus atrophy visible on MRI.

• Presentation: Psychiatric changes (depression, personality changes) appear FIRST, followed by choreiform movements and dementia.

• Mnemonic: 'Hunt for the CAG in the Caudate'.

Friedreich Ataxia

• Inheritance: Autosomal Recessive; $GAA$ repeat in the frataxin gene.

• Mechanism: Decreased frataxin leads to mitochondrial iron accumulation and neurodegeneration.

• Signs: Spinocerebellar, posterior column, and corticospinal degeneration. Presents with ataxic gait, dysarthria, kyphoscoliosis, and pes cavus.

• Complications: Hypertrophic cardiomyopathy is the $\#1$ cause of death, also associated with diabetes.

• Mnemonic: 'GAA → Goes Away with Ataxia'.

GROUP 4: Spine and Nerve Disorders

Disc Herniation and Nerve Root Entrapment

• L4 Root (L3–L4 disk): Sensory loss at the medial leg and foot. Quad weakness causing decreased knee extension. Loss of patellar reflex.

• L5 Root (L4–L5 disk): Sensory loss at the dorsal foot and big toe (1st web space). Motor loss results in foot drop (weak EHL and tibialis anterior). No classic reflex lost.

• S1 Root (L5–S1 disk): Sensory loss at the lateral foot and small toe. Weakness in the gastrocnemius (decreased plantar flexion). Loss of Achilles (ankle jerk) reflex. Patients cannot toe-walk.

• Mnemonic: '4 = Quad/Patella | 5 = Foot drop (big toe) | S1 = Stand on toes (Achilles)'.

Critical Spine Warnings

• Cauda Equina Syndrome: Characterized by saddle anesthesia and bowel/bladder dysfunction; this is a SURGICAL EMERGENCY.

• Trigeminal Neuralgia: Electric-shock face pain triggered by LIGHT touch. Treatment is carbamazepine. If found in a young patient, suspect MS.

GROUP 5: CNS Infections in the Immunosuppressed

PML (JC Virus)

• Cause: Reactivation of the JC polyomavirus in patients with CD4 < 200\,cells/θL.

• MRI: Multifocal white matter lesions with NO enhancement and NO mass effect.

• CSF: JC virus PCR positive.

CNS Toxoplasmosis

• Cause: Toxoplasma gondii reactivation in patients with CD4 < 100\,cells/θL.

• MRI: Ring-enhancing lesions, often multiple and located in the basal ganglia.

CNS Lymphoma

• Cause: EBV-driven B-cell lymphoma in patients with CD4 < 50\,cells/θL.

• MRI: Periventricular ring-enhancing mass (usually single).

REPRODUCTIVE SYSTEM

GROUP 6: Scrotal Swelling Comparison

Testicular Torsion

• Pain: Sudden and severe onset (within minutes).

• Examination: High-riding, horizontal testis; ABSENT cremasteric reflex (key sign); Prehn sign is NEGATIVE (no relief with elevation).

• Emergency: Surgical intervention required within $6\,hours$ to prevent infarction.

Epididymitis

• Pain: Gradual onset (hours to days).

• Mechanism: Often due to Chlamydia (< 35\,years) or E. coli (> 35\,years).

• Examination: Prehn sign is POSITIVE (relief with elevation); Cremasteric reflex is present.

Other Scrotal Findings

• Hydrocele: Transilluminates; caused by patent processus vaginalis.

• Varicocele: 'Bag of worms' appearance, usually on the left. Distinguishing Trap: A new RIGHT-sided varicocele in an older man indicates Renal Cell Carcinoma (RCC) compressing the IVC until proven otherwise.

• Spermatocele: Cyst at the head of the epididymis containing sperm; transilluminates.

GROUP 7: Orchitis, Cryptorchidism, and Hematocele

Orchitis

• Cause: Mumps (post-pubertal classic), or bacterial/autoimmune factors.

• Presentation: Swollen, tender testes with fever. Bilateral in mumps.

• Outcome: $20\text{--}30\%$ of mumps cases lead to testicular atrophy and potential infertility.

Cryptorchidism

• Mechanism: Failure of the gubernaculum; associated with prematurity or androgen deficiency.

• Presentation: Empty scrotum, inguinal mass.

• Complication: Elevated risk ($5\text{--}10\times$) of testicular cancer and infertility. Orchiopexy by $6\text{--}18\,months$ does not fully normalize cancer risk.

GROUP 8: BPH, Prostatitis, and Testicular Tumors

Benign Prostatic Hyperplasia (BPH)

• Mechanism: Transitional zone hyperplasia driven by Dihydrotestosterone (DHT).

• Presentation: Lower Urinary Tract Symptoms (LUTS) like hesitancy, nocturia, and weak stream. Smooth enlarged prostate on Digital Rectal Exam (DRE).

• Treatment: Alpha-blockers (tamsulosin) for fast relief; $5α$-reductase inhibitors (finasteride) for slow long-term treatment.

Acute Prostatitis

• Presentation: Fever, chills, dysuria; prostate is TENDER and BOGGY.

• Warning: DO NOT massage the prostate; it risks bacteremia/sepsis.

Testicular Tumors

• Who: Common in ages $15\text{--}35$; hallmark is isochromosome $i(12p)$.

• Management: NEVER perform a scrotal biopsy (risks seeding); go straight to radical inguinal orchiectomy.

• Markers: AFP elevated in yolk sac tumors; $\beta$-hCG in choriocarcinoma/dysgerminoma; LDH in seminoma.

GROUP 9: Female Endo-trio (Endometriosis vs. Adenomyosis vs. Endometritis)

Endometriosis

• Location: Endometrium OUTSIDE the uterus (ovaries, Douglas pouch).

• Sx (The 3 Ds): Dysmenorrhea, Dyspareunia, Dyschezia.

• Findings: 'Chocolate cysts' on the ovary (endometrioma).

Adenomyosis

• Location: Endometrium INSIDE the myometrium.

• Presentation: Enlarged, GLOBULAR, and BOGGY uterus with heavy menstrual bleeding (menorrhagia).

Endometritis

• Context: Infection of the endometrial lining, often postpartum.

• Presentation: Fever, purulent discharge, and tender uterus. Presence of plasma cells on biopsy confirms chronic inflammation.

GROUP 10: Vaginitis Comparison

Candidal Vaginitis

• Discharge: Thick, white 'cottage cheese'.

• pH: Normal (< 4.5).

• Microscopy: Pseudohyphae and budding yeast on KOH prep.

Bacterial Vaginosis (BV)

• Discharge: Thin, gray-white with fishy odor.

• Diagnostics: pH > 4.5, positive Whiff test (KOH), and Clue cells on wet prep.

Trichomonas

• Discharge: Frothy, yellow-green, malodorous.

• Diagnostics: pH > 4.5, motile pear-shaped flagellates. Strawberry cervix (petechiae) is a classic sign.

• Note: This is a STIs; partners must be treated.

GROUP 11: PCOS and Structural Conditions

Polycystic Ovary Syndrome (PCOS)

• Hormones: High androgens, insulin resistance, and LH:FSH > 2:1.

• Complications: Infertility, Diabetes Mellitus type $2$, and increased risk of endometrial cancer due to unopposed estrogen.

Imperforate Hymen

• Presentation: Primary amenorrhea at puberty combined with cyclic pelvic pain and a bulging bluish hymen. Leads to hematocolpos (blood in vagina).

NEOPLASIA AND SPECIAL SENSES

GROUP 12: Gynecologic Cancers

Cervical Cancer

• Driver: HPV types $16$ and $18$. HPV protein $E6$ inhibits $p53$, and protein $E7$ inhibits $Rb$.

• Presentation: Postcoital bleeding.

• Staging Trap: Hydronephrosis indicates Stage III disease (ureterovaginal obstruction).

Endometrial Cancer

• Cardinal Symptom: Postmenopausal bleeding. MUST biopsy.

• Risk Factors: Unopposed estrogen (obesity, PCOS) and Lynch syndrome.

Vulvar Carcinoma

• Presentation: Visible lesion/plaque with pruritus. Associated with lichen sclerosus in older women.

GROUP 13: Uterine Fibroids and Ovarian Tumors

Leiomyoma (Fibroid)

• Facts: Most common benign gyn tumor. Estrogen-dependent. Does NOT transform into leiomyosarcoma.

Ovarian Tumors

• Serous Epithelial: Most common; bilateral; psammoma bodies; marker is $CA\text{-}125$.

• Yolk Sac Tumor: Marker is AFP.

• Dysgerminoma: Marker is $\beta$-hCG or LDH.

• Teratoma (Dermoid): Benign; contains teeth/hair/sebum.

• Granulosa Cell Tumor: Secretes estrogen; shows Call-Exner bodies.

GROUP 14: Vertigo comparison

BPPV

• Duration: Seconds (< 1\,min).

• Trigger: Head position changes.

• Test: Dix-Hallpike POSITIVE (upbeat-torsional nystagmus).

• Treatment: Epley maneuver.

Ménière Disease

• Presentation: Triad of episodic vertigo ($20\,min \text{--} 24\,hr$), Sensorineural Hearing Loss (SNHL), and roaring tinnitus with aural fullness.

• Mechanism: Endolymphatic hydrops.

Vestibular Neuritis and Labyrinthitis

• Duration: Days to weeks (continuous).

• Distinction: Neuritis involves vertigo ONLY. Labyrinthitis involves vertigo PLUS hearing loss. Both are often post-viral.

• HINTS Exam: Central vertigo (stroke) is suggested by a NEGATIVE Head Impulse Test (HIT) plus other neuro signs.

GROUP 15: Vision Loss Patterns

• Cataract: Blurred vision with halos.

• AMD: Loss of central vision; peripheral vision PRESERVED.

• Retinal Detachment: Flashers, floaters, and a 'curtain shadow'.

• Angle-closure Glaucoma: Acute PAINFUL loss, halos, rock-hard eye; medical emergency.

• Pituitary Adenoma: Bitemporal hemianopia (cross-eyed pituitary squeeze).

• Occipital Stroke: Contralateral homonymous hemianopia with MACULAR SPARING.

• Meyer Loop (Temporal lobe): 'Pie in the sky' defect.

URINARY SYSTEM

GROUP 17: Nephritic vs. Nephrotic master comparison

Nephritic Syndrome

• Features: Mild-moderate proteinuria (< 3.5\,g/day), hematuria with Red Blood Cell (RBC) casts (pathognomonic), hypertension, and periorbital edema.

• Causes: PSGN, IgA nephropathy, Goodpasture.

Nephrotic Syndrome

• Features: Massive proteinuria (> 3.5\,g/day), hypoalbuminemia, massive pitting edema, hyperlipidemia, and lipiduria (Oval fat bodies/Maltese cross).

• Complication: High risk of thromboembolism (renal vein thrombosis) due to loss of Antithrombin III ($AT\text{-}III$).

GROUP 18: Glomerulopathies

Key Nephritic Patterns

• Post-Strep GN (PSGN): Occurs $2\text{--}3\,weeks$ after infection. IF shows granular 'lumpy-bumpy' deposits ($subepithelial humps$).

• IgA Nephropathy: Most common GN worldwide. Occurs CONCURRENTLY with URI ('synpharyngitic'). Mesangial IgA deposits.

• Goodpasture Syndrome: Hemoptysis + hematuria. LINEAR IgG along the GBM (Anti-GBM antibody against $\alpha3$ chain of type IV collagen).

Key Nephrotic Patterns

• Minimal Change Disease (MCD): Kids; steroid-responsive; foot process effacement seen only on EM.

• FSGS: Common in Black Americans; associated with $APOL1$ variants and HIV.

• Membranous Nephropathy: Spikes and domes (subepithelial granular deposits). Associated with $Anti\text{-}PLA2R$.

GROUP 19: Acute Kidney Injury (AKI)

Pre-renal AKI

• BUN:Cr Ratio: > 20 (tubules still reabsorb urea).

• FeNa: < 1\% (kidneys retaining sodium).

• Urine Osmolality: High (> 500\,mOsm).

Acute Tubular Necrosis (ATN)

• Findings: Muddy brown granular casts.

• BUN:Cr Ratio: $10\text{--}15$.

• FeNa: > 2\% (tubules are broken).

Acute Interstitial Nephritis (AIN)

• Classic Triad: Fever, Rash, and Eosinophilia (found in < 30\% of cases).

• Diagnostics: WBC casts and eosinophiluria.

GROUP 20: CKD, Alport, and RCC

Alport Syndrome

• Defect: Mutation in type IV collagen ($COL4A3/4/5$).

• Triad: Hematuria + Sensorineural hearing loss + Anterior lenticonus (eye lens defect).

Renal Cell Carcinoma (RCC)

• Cause: Often VHL mutation; hypervascular.

• Triad ($10\%$): Hematuria, flank pain, and palpable mass. Often incidentally found.

• Mets: 'Cannon-ball' lung metastases.

Cystitis

• Findings: Nitrites and leukocyte esterase positive. $E. coli$ is the $\#1$ cause ($80\text{--}85\%$).

• Distinction: Pyelonephritis includes fever and CVA tenderness.