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🧠 CNS Pathology - Systemic Pathology (Week 15)

Based on Robbins & Kumar Basic Pathology, 11th Ed.

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PART 1: KEY CONCEPTS (High-Yield for MCQs)

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1. BRAIN EDEMA, HERNIATIONS, HYDROCEPHALUS

Brain Edema

Herniation Types (HIGH YIELD!)

MCQ tip: Kernohan's notch = ipsilateral hemiparesis (paradoxical localizing sign). Duret hemorrhages = midbrain/pons midline hemorrhages from transtentorial herniation.

Hydrocephalus

• Communicating: Impaired CSF resorption (e.g., post-meningitis)
• Non-communicating (obstructive): Block within ventricular system (e.g., tumor at aqueduct of Sylvius)
• Normal pressure hydrocephalus (NPH): Triad = Wet (incontinence), Wobbly (gait), Wacky (dementia)

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2. CEREBROVASCULAR DISEASE / STROKE

Ischemic Infarct

• Most common type (80%)
• Causes: thrombosis on atherosclerosis, emboli (cardiac most common source), hypoperfusion
• Histology timeline:
  • 12-24 hrs: Red neurons (eosinophilic cell body, pyknotic nucleus)
  • 24-72 hrs: Neutrophil infiltration
  • 3-5 days: Macrophage/microglial infiltration (foam cells)
  • Weeks: Reactive gliosis, cystic cavity (liquefactive necrosis)

Intracerebral Hemorrhage

• Most common cause: Hypertension (rupture of Charcot-Bouchard microaneurysms)
• Sites: Basal ganglia (putamen most common), thalamus, pons, cerebellum

Subarachnoid Hemorrhage (SAH)

• Most common cause: Ruptured saccular (berry) aneurysm (90% in anterior circulation)
• Classic presentation: "Worst headache of my life" (thunderclap headache)
• ~25-50% die from first bleed
• Aneurysms >1 cm: ~50% bleeding risk/year
• Associated with: Autosomal dominant polycystic kidney disease (ADPKD), Ehlers-Danlos syndrome
• Complication: Vasospasm (ischemia), hydrocephalus

Epidural vs Subdural Hematoma

MCQ trap: Subdural hematoma = bridging veins, crescent-shaped; Epidural = middle meningeal artery, biconvex.

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3. MENINGITIS AND ENCEPHALITIS

Bacterial Meningitis by Age (VERY HIGH YIELD)

• CSF in bacterial meningitis: ↑ neutrophils, ↑ protein, ↓ glucose, ↑ opening pressure

Viral (Aseptic) Meningitis

• Most common cause: Enteroviruses
• CSF: ↑ lymphocytes, normal/slightly ↑ protein, normal glucose

Herpes Simplex Encephalitis (HSV-1)

• Most common sporadic fatal encephalitis
• Affects temporal lobes (hemorrhagic necrosis)
• Cowdry A inclusion bodies (intranuclear) in neurons and astrocytes
• Treat with acyclovir

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4. PRION DISEASE (Creutzfeldt-Jakob Disease)

• Caused by misfolded prion protein PrPsc
• Hallmark histology: Spongiform transformation (vacuoles in cortex/deep gray matter)
• Rapidly progressive dementia + myoclonus
• Kuru plaques: Congo red- and PAS-positive, found in cerebellum
• Variant CJD (vCJD): linked to bovine spongiform encephalopathy (BSE/mad cow); affects young adults; behavioral symptoms early; "florid plaques" in cortex

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5. NEURODEGENERATIVE DISEASES

Alzheimer Disease (AD)

• Most common cause of dementia in elderly
• Pathogenesis: Accumulation of Aβ (amyloid beta) plaques + tau neurofibrillary tangles
• APP cleavage by β-secretase + γ-secretase → pathogenic Aβ42
• Presenilin 1 & 2 mutations → familial early-onset AD
• ApoE4 allele = major risk factor for sporadic AD
• Trisomy 21 (Down syndrome) → early AD (APP gene on chr 21)
• Gross: Cortical atrophy, widened sulci, narrowed gyri (especially frontal/temporal/parietal)
• Micro: Senile (neuritic) plaques + neurofibrillary tangles + amyloid angiopathy
• Tangles correlate better with dementia severity than plaques

Parkinson Disease

• Loss of dopaminergic neurons in substantia nigra (depigmentation)
• Lewy bodies = intracytoplasmic eosinophilic inclusions (alpha-synuclein)
• Triad: Tremor (pill-rolling, resting), Rigidity (cogwheel), Bradykinesia
• • Shuffling gait, masked facies, stooped posture

Huntington Disease

• Autosomal dominant, chromosome 4, CAG repeat expansion in HTT gene
• Loss of GABAergic neurons in caudate nucleus and putamen
• Symptoms: Chorea, dementia, psychiatric disturbances
• Onset 30-50 years; anticipation (worsens in successive generations)
• Gross: Dramatic atrophy of caudate and putamen; "box-car" lateral ventricles

ALS (Amyotrophic Lateral Sclerosis)

• Loss of both upper and lower motor neurons
• UMN signs: spasticity, hyperreflexia, Babinski
• LMN signs: muscle wasting, fasciculations, weakness
• Bulbar involvement: dysarthria, dysphagia
• Cognitive function preserved (usually)
• Mutation in SOD1 gene (superoxide dismutase) in familial cases

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6. BRAIN TUMORS

MCQ tip: Brain metastases > Primary brain tumors in frequency overall. Most common primary sites that metastasize to brain: Lung (most common), Breast, Melanoma, Kidney, GI (colon) - "Lung Brings Many Bad Gifts"

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PART 2: MCQ PRACTICE (Exam-Style)

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• A) Rupture of a bridging vein
• B) Rupture of a saccular (berry) aneurysm
• C) Hypertensive Charcot-Bouchard aneurysm rupture
• D) Arteriovenous malformation

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• A) Alpha-synuclein
• B) TDP-43
• C) Tau
• D) Amyloid precursor protein

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• A) Caudate nucleus
• B) Substantia nigra
• C) Frontal cortex
• D) Hippocampus

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• A) Pilocytic astrocytoma
• B) Glioblastoma multiforme
• C) Medulloblastoma
• D) Ependymoma

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• A) Subdural hematoma
• B) Epidural hematoma
• C) Subarachnoid hemorrhage
• D) Intracerebral hemorrhage

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• A) Streptococcus pneumoniae
• B) Listeria monocytogenes
• C) Neisseria meningitidis
• D) Group B Streptococcus

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• A) Tau protein aggregates
• B) Proteinase K-resistant PrPsc
• C) Amyloid beta deposits
• D) Alpha-synuclein inclusions

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• A) Subfalcine herniation
• B) Tonsillar herniation
• C) Transtentorial (uncal) herniation
• D) Central herniation

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• A) Presenilin 1 mutation
• B) ApoE4 allele
• C) APP mutation on chromosome 21
• D) Presenilin 2 mutation

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• A) HTT gene (chr 4) - CAG repeat
• B) APP gene (chr 21)
• C) SOD1 gene
• D) MAPT gene

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QUICK-RECALL CHEAT SHEET

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• Endocrine System (Week 11-12: Thyroid, Parathyroid, Diabetes, Adrenal, MEN)
• Heart (Week 2: MI, Endocarditis, Cardiomyopathy, Valvular disease)
• Kidney (Week 5: Nephrotic/Nephritic, Glomerulonephritis, CKD)
• GI (Week 6: Barrett's, IBD, Colon Cancer, Appendicitis)

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🧠 CNS Pathology - BEGINNER FRIENDLY

"Understand it, don't memorize it"

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🔴 TOPIC 1: BRAIN EDEMA (Brain Swelling)

Why does the brain swell?

🎯 MCQ concept: Vasogenic = vessel problem. Cytotoxic = cell problem.

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🔴 TOPIC 2: BRAIN HERNIATION

3 Types You MUST Know:

• Brain pushes sideways under the falx (a sheet of dura in the middle)
• Compresses the anterior cerebral artery
• Result: Weakness in the opposite leg

• Temporal lobe gets pushed down over the tentorium
• Squeezes CN III (oculomotor nerve)
• Result: "Blown pupil" = pupil on the SAME side becomes big and doesn't react to light
• Also causes Duret hemorrhages = small bleeds in the midbrain/pons

• Cerebellum tonsils pushed into foramen magnum
• Squeezes the medulla (controls breathing and heart)
• Result: DEATH (respiratory arrest)

🎯 MCQ concept: Big pupil after head injury = CN III compressed = Uncal herniation. Same side as the brain problem.

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🔴 TOPIC 3: HYDROCEPHALUS (Too much CSF)

🎯 MCQ concept: Big ventricles on scan = hydrocephalus. In babies = big head. In adults = headache + vomiting.

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🔴 TOPIC 4: STROKE

2 Types:

• A clot blocks a blood vessel → brain gets no oxygen → brain cells die
• Most common cause of stroke overall

• A blood vessel bursts → blood damages brain
• Worse outcome than ischemic

What happens to the brain tissue after ischemia? (Timeline MCQ!)

🎯 MCQ concept: Brain does LIQUEFACTIVE necrosis (NOT coagulative like other organs). A fluid-filled cavity weeks after stroke = old infarct.

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🔴 TOPIC 5: TYPES OF BRAIN BLEEDS

SKULL
DURA MATER        ← Epidural hematoma is ABOVE dura
SUBDURAL SPACE    ← Subdural hematoma is HERE
ARACHNOID
SUBARACHNOID SPACE ← Subarachnoid hemorrhage is HERE
PIA MATER
BRAIN

A) Epidural Hematoma

• Artery bleed (middle meningeal artery)
• Cause: Temporal bone fracture (hit to the side of the head)
• Lucid interval = patient is okay → then suddenly gets worse
• CT scan: Biconvex (lens-shaped), does NOT cross suture lines

B) Subdural Hematoma

• Vein bleed (bridging veins)
• Cause: Head trauma, especially in elderly (brain shrinks with age → veins get stretched)
• CT scan: Crescent-shaped, follows the brain surface

C) Subarachnoid Hemorrhage (SAH)

• Berry aneurysm rupture (most common cause)
• Feels like: "Worst headache of my life" (thunderclap headache)
• ~25-50% die from first bleed
• Berry aneurysms are linked to kidney disease (ADPKD)

D) Intracerebral Hemorrhage

• Bleeding INTO brain tissue
• Most common cause: Hypertension
• Location: Putamen/basal ganglia (most common site)
• Mechanism: Charcot-Bouchard microaneurysms rupture

🎯 MCQ trick table:

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🔴 TOPIC 6: MENINGITIS

Which bug causes meningitis at what age? ⭐ HIGH YIELD

CSF findings in meningitis:

🎯 MCQ concept: Bacteria = neutrophils + LOW glucose. Virus = lymphocytes + NORMAL glucose.

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🔴 TOPIC 7: ENCEPHALITIS (Brain itself is infected)

Herpes Simplex Encephalitis (HSV-1) ⭐

• Most common cause of fatal viral encephalitis
• Attacks the temporal lobes (causes bizarre behavior, memory loss, seizures)
• Micro: Cowdry A inclusions (pink blobs inside cell nuclei)
• Treatment: Acyclovir (must give early!)

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🔴 TOPIC 8: PRION DISEASE (CJD)

• CJD (Creutzfeldt-Jakob Disease) = rapidly progressive dementia + jerky movements (myoclonus)
• Histology: Spongiform vacuolation = brain looks like a sponge (lots of tiny holes/vacuoles)
• This is the pathognomonic (unique) finding
• Variant CJD = linked to eating BSE-infected beef ("mad cow disease"), affects young people

🎯 MCQ concept: Spongiform changes in brain = Prion disease. No treatment. Fatal.

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🔴 TOPIC 9: NEURODEGENERATIVE DISEASES

Think of it this way: Different diseases destroy different parts of the brain

Alzheimer Disease ⭐

• Most common cause of dementia in elderly
• 2 bad proteins: Aβ plaques (outside cells) + Tau tangles (inside cells)
• ApoE4 gene = biggest risk factor for sporadic (common) type
• Down syndrome patients get Alzheimer early (their chromosome 21 has the APP gene, they have 3 copies)
• Memory loss is the first symptom

Parkinson Disease ⭐

• Lose dopamine cells in substantia nigra → brain becomes black area looks pale
• Lewy bodies = pink blob inside the neuron (made of alpha-synuclein)
• 3 main signs: Resting tremor (pill-rolling) + Rigidity + Slow movements (bradykinesia)
• Shuffling walk, mask face (no expression)

Huntington Disease ⭐

• Autosomal dominant (parent has it → 50% chance child gets it)
• CAG repeat in HTT gene on chromosome 4 (more repeats = earlier/worse disease)
• Kills neurons in caudate nucleus → lateral ventricles look like "box cars" (very dilated)
• Chorea = involuntary dance-like movements + dementia + psychiatric problems
• Onset around age 30-50

ALS (Lou Gehrig's Disease)

• Both upper motor neurons (brain/spinal cord) AND lower motor neurons die
• Patient becomes progressively paralyzed but MIND IS INTACT (can't move, can think)
• Familial cases: SOD1 gene mutation

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🔴 TOPIC 10: BRAIN TUMORS

1. Metastases are more common than primary brain tumors overall
2. In adults: malignant = Glioblastoma. In children: malignant = Medulloblastoma

The Must-Know Tumors:

• Most common malignant primary brain tumor in adults
• Pseudopalisading necrosis = tumor cells line up around dead tissue (key histology)
• Crosses corpus callosum → "butterfly glioma" on MRI
• Grade IV = worst prognosis (months to live)

• Most common benign brain tumor in adults
• Grows from arachnoid cells (meninges)
• Sits OUTSIDE the brain (extra-axial) → pushes brain but doesn't invade it
• Histology: Whorled pattern + psammoma bodies (calcified circles)
• More common in women

• Most common malignant brain tumor in children
• Located in cerebellum (posterior fossa)
• Small blue cells on microscopy
• Can spread down spine ("drop metastases")

• Most common benign brain tumor in children
• Cerebellum, Grade I
• Rosenthal fibers on histology
• Great prognosis after surgery

• Tumor of CN VIII (hearing/balance nerve) = acoustic neuroma
• Causes: hearing loss, tinnitus, balance problems
• Bilateral schwannomas = Neurofibromatosis Type 2 (NF2)

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✅ FINAL CHEAT SHEET (Stick on your wall!)

HERNIATION:
Uncal → Blown pupil (CN III) SAME side
Subfalcine → Leg weakness opposite side
Tonsillar → Death (medulla compressed)

BLEEDS:
Epidural = Artery = Lens shape = Lucid interval
Subdural = Vein = Crescent = Elderly
SAH = Berry aneurysm = Worst headache ever
ICH = Hypertension = Putamen

MENINGITIS BUGS:
Baby = E.coli / GBS
Teen = Neisseria meningitidis
Old = S.pneumoniae

CSF:
Bacteria = Neutrophils + Low glucose
Virus = Lymphocytes + Normal glucose

NEURO DEGENERATIVE:
Alzheimer = Plaques(Aβ) + Tangles(Tau) → Memory
Parkinson = Lewy bodies → Tremor
Huntington = Caudate loss, CAG repeat → Chorea
ALS = Both motor neurons → Paralysis

TUMORS:
Adult malignant = GBM (pseudopalisading necrosis)
Child malignant = Medulloblastoma (posterior fossa)
Adult benign = Meningioma (whorls + psammoma)
Child benign = Pilocytic astrocytoma (Rosenthal fibers)

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📝 QUICK MCQ DRILL (Just say A, B, C or D!)

• A) Bridging vein
• B) Middle meningeal artery
• C) Berry aneurysm
• D) Charcot-Bouchard aneurysm

• A) E. coli
• B) Listeria
• C) Neisseria meningitidis
• D) S. pneumoniae

• A) Alpha-synuclein
• B) Aβ
• C) Tau
• D) PrPsc

• A) GBM
• B) Medulloblastoma
• C) Meningioma
• D) Pilocytic astrocytoma

• A) APP on chr 21
• B) HTT on chr 4
• C) SOD1
• D) ApoE4

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🔬 ENDOCRINE PATHOLOGY - BEGINNER FRIENDLY

Weeks 11 & 12 of your syllabus

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Think of it this way: The endocrine system = glands that release hormones into blood. When those glands make too much or too little hormone, you get disease. That's basically the whole chapter!

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🟦 PART 1: THE THYROID

First - understand the basics:

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🔴 DISEASE 1: HASHIMOTO THYROIDITIS

• Most common cause of hypothyroidism in developed countries
• Autoimmune: antibodies against thyroid peroxidase (anti-TPO) and thyroglobulin
• Affects mostly middle-aged women
• Histology: lymphocytes + plasma cells + Hurthle cells (large pink cells = damaged follicular cells)
• Gross: thyroid is enlarged (goiter), pale, firm

🎯 MCQ concept: Patient with hypothyroid symptoms + enlarged thyroid + middle-aged woman = Hashimoto. Key antibody = anti-TPO.

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🔴 DISEASE 2: GRAVES DISEASE ⭐ VERY IMPORTANT

• Most common cause of hyperthyroidism
• Autoimmune: TSI (thyroid stimulating immunoglobulins) antibody binds TSH receptor → mimics TSH
• Affects mostly young women (20-40 years)

• Histology: thyroid follicles are small with scalloped edges; lots of follicular cells; lymphocyte infiltration
• Lab: ↑ T3/T4, ↓ TSH (TSH is suppressed because there's already too much hormone)

🎯 MCQ trick: Bulging eyes + hyperthyroid + young woman = Graves. Antibody = TSI (anti-TSH receptor).

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🔴 DISEASE 3: SUBACUTE (DE QUERVAIN) THYROIDITIS

• PAINFUL thyroid (this is the key difference from other thyroiditis)
• Elevated ESR (inflammation marker)
• Starts with hyperthyroid, then can go hypothyroid, then back to normal
• Self-limited (gets better on its own in 6-8 weeks)
• Histology: granulomas (giant cells eating destroyed follicles)

🎯 MCQ concept: PAINFUL goiter + hyperthyroid + elevated ESR = De Quervain (Subacute granulomatous thyroiditis).

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🔴 DISEASE 4: THYROID CANCERS

🎯 MCQ tricks:

• Psammoma bodies + empty nuclei = Papillary cancer
• Elevated calcitonin + thyroid cancer = Medullary cancer (C-cells)
• Worst prognosis thyroid cancer = Anaplastic

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🟩 PART 2: PARATHYROID GLANDS

• PTH ↑ → calcium leaves bone → enters blood → ↑ blood calcium

Hyperparathyroidism (too much PTH = too much calcium)

• Parathyroid gland problem itself (adenoma = 80% of cases)
• ↑ PTH, ↑ Calcium, ↓ Phosphate

• Body makes too much PTH as a RESPONSE to low calcium (e.g., in chronic kidney disease)
• Kidney fails → can't activate vitamin D → calcium drops → PTH goes up trying to fix it
• ↑ PTH, ↓ Calcium (that's the difference!)

🎯 MCQ tip: Primary = HIGH calcium. Secondary (CKD) = LOW/normal calcium but HIGH PTH.

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🟨 PART 3: DIABETES MELLITUS ⭐ BIGGEST TOPIC

• No insulin (Type 1)
• Insulin doesn't work (Type 2)

TYPE 1 DIABETES

• Autoimmune destruction of beta cells
• HLA-DR3 and HLA-DR4 genes (strong association)
• Anti-islet antibodies present years before symptoms
• Symptoms appear when >90% of beta cells are destroyed
• Usually young, thin patients
• Need INSULIN injections to survive

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TYPE 2 DIABETES

• NOT autoimmune
• 80-90% concordance in identical twins (strong genetics)
• Risk factors: obesity, sedentary lifestyle, age
• Usually older, overweight patients
• Amyloid deposits in islets (on histology) = islet amyloid polypeptide (IAPP)

🎯 MCQ table:

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COMPLICATIONS OF DIABETES (HIGH YIELD for MCQs)

🎯 MCQ trick: Kimmelstiel-Wilson nodules = diabetic nephropathy (nodular glomerulosclerosis). This is the PATHOGNOMONIC finding!

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🟥 PART 4: ADRENAL GLAND DISEASES

• Cortex (outside) = makes cortisol, aldosterone, sex hormones
• Medulla (inside) = makes adrenaline (epinephrine)

Remember the cortex layers with: "GFR" (like kidney filtration!)

• Glomerulosa → Aldosterone (salt)
• Fasciculata → Cortisol (sugar)
• Reticularis → Sex hormones (sex)

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🔴 CUSHING SYNDROME (Too much CORTISOL)

• Moon face (round, puffy face)
• Buffalo hump (fat deposit back of neck)
• Central obesity (fat belly, thin arms/legs)
• Purple striae (stretch marks on abdomen)
• Hypertension, hyperglycemia
• Muscle weakness, osteoporosis
• Immunosuppression (gets infections easily)

🎯 MCQ tip: Moon face + buffalo hump + purple striae = Cushing. Most common cause = exogenous steroids. Most common endogenous = pituitary adenoma (Cushing DISEASE).

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🔴 HYPERALDOSTERONISM (Too much ALDOSTERONE)

• Primary (Conn Syndrome): Adrenal adenoma makes too much aldosterone on its own
  • ↑ aldosterone, ↓ renin (adrenal is doing it on its own, so renin is suppressed)
  • ↑ Na (and BP), ↓ K (hypokalemia)
• Secondary: Kidneys are under-perfused → renin goes up → stimulates aldosterone
  • ↑ renin, ↑ aldosterone

🎯 MCQ tip: Hypertension + LOW potassium + LOW renin = Conn syndrome (primary hyperaldosteronism).

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🔴 ADRENAL INSUFFICIENCY

• Adrenal cortex itself is destroyed (most common cause: autoimmune)
• ↓ cortisol → ACTH goes HIGH (trying to stimulate) → ACTH has melanocyte-stimulating activity → HYPERPIGMENTATION of skin
• Symptoms: weakness, weight loss, hypotension, hyperpigmentation

• Pituitary makes too little ACTH → adrenal is not stimulated
• NO hyperpigmentation (ACTH is low)

🎯 MCQ tip: Dark skin (hyperpigmentation) + low BP + weakness = Addison disease (primary adrenal failure). Hyperpigmentation is the KEY distinguishing feature from secondary.

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🔴 PHEOCHROMOCYTOMA

• Sudden severe hypertension (paroxysmal - comes and goes)
• Headache, sweating, palpitations, pallor

• 10% are bilateral
• 10% are extra-adrenal (paragangliomas)
• 10% are malignant
• 10% are in children
• 10% are hereditary (associated with MEN 2, VHL, NF1)

🎯 MCQ concept: Episodic hypertension + headache + sweating = pheochromocytoma. Lab test = urine metanephrines.

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🟪 PART 5: MEN SYNDROMES (Multiple Endocrine Neoplasia)

🎯 MCQ tip:

• MEN 1 = "3 P's" (Parathyroid, Pituitary, Pancreas) = MEN1 gene
• MEN 2 = always has Medullary thyroid cancer = RET gene
• MEN 2B = MEN 2A + lip/tongue bumps (mucosal neuromas)

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✅ MCQ PRACTICE - ENDOCRINE

• A) Hashimoto thyroiditis
• B) Graves disease
• C) De Quervain thyroiditis
• D) Toxic multinodular goiter

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• A) Follicular carcinoma
• B) Medullary carcinoma
• C) Papillary carcinoma
• D) Anaplastic carcinoma

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• A) Pituitary adenoma
• B) Adrenal adenoma
• C) Exogenous steroid use
• D) Small cell lung cancer

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• A) Primary hyperparathyroidism
• B) Secondary hyperparathyroidism
• C) Hypoparathyroidism
• D) Pseudohypoparathyroidism

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• A) Essential hypertension
• B) Conn syndrome
• C) Pheochromocytoma
• D) Cushing disease

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• A) Type 2 diabetes
• B) Type 1 diabetes
• C) MODY
• D) Secondary diabetes

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• A) Secondary adrenal insufficiency
• B) Cushing syndrome
• C) Addison disease
• D) Conn syndrome

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• A) MEN 1
• B) MEN 2A
• C) MEN 2B
• D) MEN 3

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✅ ENDOCRINE CHEAT SHEET

THYROID:
Too little = Hypothyroid → Hashimoto (anti-TPO antibody)
Too much = Hyperthyroid → Graves (TSI antibody + exophthalmos)
Painful thyroid + hyperthyroid = De Quervain (viral, granulomas)

THYROID CANCER:
Papillary = Orphan Annie nuclei + psammoma = BEST prognosis
Medullary = C-cells → Calcitonin elevated = MEN 2
Anaplastic = WORST prognosis

ADRENAL:
Too much cortisol = Cushing (moon face + buffalo hump + striae)
Too much aldosterone = Conn (HTN + ↓K + ↓renin)
Too little cortisol = Addison (hyperpigmentation + low BP)
Medulla tumor = Pheochromocytoma (episodic HTN + headache + sweat)

DIABETES:
Type 1 = Autoimmune, insulitis, young, thin, HLA-DR3/DR4
Type 2 = Insulin resistance, obese, IAPP amyloid in islets
Kimmelstiel-Wilson nodules = Diabetic nephropathy

MEN SYNDROMES:
MEN 1 = 3 Ps (Parathyroid + Pituitary + Pancreas) = MEN1 gene
MEN 2A = Medullary thyroid + Pheo + Parathyroid = RET gene
MEN 2B = MEN 2A + mucosal neuromas = RET gene

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1. Thyroid - Hashimoto (hypo) vs Graves (hyper) vs De Quervain (painful) + 4 cancers
2. Parathyroid - Primary (high Ca) vs Secondary/CKD (low Ca) hyperparathyroidism
3. Diabetes - Type 1 (autoimmune, insulitis) vs Type 2 (insulin resistance, amyloid)
4. Adrenal - Cushing (cortisol), Conn (aldosterone), Addison (insufficiency + hyperpigmentation), Pheochromocytoma
5. MEN syndromes - MEN 1 (3 P's) vs MEN 2A vs MEN 2B (RET gene)

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• ❤️ Heart (MI, Endocarditis, Cardiomyopathy)
• 🫘 Kidney (Nephrotic/Nephritic, Glomerulonephritis)
• 🧫 GI Tract (Barrett's, IBD, Colon cancer)

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🔬 ENDOCRINE PATHOLOGY — FROM ZERO

Simple, concept-based, exam-ready

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🔑 THE BIG IDEA FIRST

• Gland makes TOO MUCH hormone → overactivity symptoms
• Gland makes TOO LITTLE hormone → underactivity symptoms

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🦋 PART 1 — THYROID GLAND

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🔵 DISEASE 1 — HASHIMOTO THYROIDITIS

• Most common cause of hypothyroidism in developed countries
• Who gets it? Middle-aged women (most autoimmune diseases prefer women)
• Key antibody: Anti-TPO (anti-thyroid peroxidase)
• Histology: Lots of lymphocytes + Hurthle cells (big pink follicular cells trying to compensate)
• Thyroid is enlarged (goiter) but not making enough hormone

🎯 MCQ: Hypothyroid + middle-aged woman + goiter = Hashimoto. Key = anti-TPO antibody.

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🔴 DISEASE 2 — GRAVES DISEASE ⭐ MOST IMPORTANT

• Most common cause of hyperthyroidism
• Antibody: TSI (Thyroid Stimulating Immunoglobulin) - binds TSH receptor, mimics TSH
• Who? Young women, age 20-40

1. HYPERTHYROIDISM    → weight loss, fast heart, sweating, anxiety
2. EXOPHTHALMOS       → bulging eyes (immune attack on eye muscles/fat)
3. PRETIBIAL MYXEDEMA → waxy skin thickening on the shins

• Labs: ↑ T3/T4, ↓ TSH (TSH is suppressed because thyroid is already flooded)

🎯 MCQ: Bulging eyes + hyperthyroid + young woman = Graves. Antibody = TSI (anti-TSH receptor). Remember: TSH is LOW in Graves, not HIGH.

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🟡 DISEASE 3 — DE QUERVAIN THYROIDITIS (Subacute Granulomatous)

• Key feature: PAINFUL thyroid (the only painful thyroiditis!)
• Elevated ESR (blood inflammation marker)
• Follows a URI (cold/flu)
• Self-limited: resolves in 6-8 weeks
• Histology: Granulomas with giant cells eating up destroyed follicles

🎯 MCQ: Painful thyroid + recent viral illness + hyperthyroid = De Quervain. Clue = pain + raised ESR.

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🔴 THYROID CANCERS — 4 Types

🎯 MCQ tricks:

• Empty-looking nuclei + calcified deposits in thyroid = Papillary cancer
• Elevated calcitonin + thyroid cancer = Medullary (C-cell origin)
• Worst prognosis thyroid cancer = Anaplastic

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🫘 PART 2 — PARATHYROID GLANDS

Hyperparathyroidism = Too much PTH = Too much calcium

🎯 MCQ: CKD patient + bone pain + HIGH PTH + LOW calcium = Secondary hyperparathyroidism. Primary = HIGH calcium.

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🍭 PART 3 — DIABETES MELLITUS ⭐ BIGGEST TOPIC

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TYPE 1 DIABETES

• Autoimmune (T-cell mediated destruction of beta cells)
• Strong HLA association: HLA-DR3 and HLA-DR4
• Antibodies detected years before symptoms (anti-insulin, anti-GAD)
• Symptoms appear only when >90% of beta cells are destroyed
• Typically: young, thin patient
• Needs insulin injections to survive
• Pancreas histology: "Insulitis" = lymphocytes invading the islets

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TYPE 2 DIABETES

• NOT autoimmune
• Genetics strong: 80-90% concordance in identical twins
• Risk factors: obesity, sedentary lifestyle, age, family history
• Typically: older, overweight patient
• Pancreas histology: Amyloid deposits in islets (IAPP = islet amyloid polypeptide)

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TYPE 1 vs TYPE 2 — Side by Side ⭐

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DIABETIC COMPLICATIONS ⭐

🎯 MCQ: Nodular deposits in glomeruli in a diabetic = Kimmelstiel-Wilson nodules = diabetic nephropathy.

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🟧 PART 4 — ADRENAL GLAND

• Cortex (outer) = makes cortisol, aldosterone, sex hormones
• Medulla (inner) = makes adrenaline (epinephrine/norepinephrine)

• Glomerulosa → Aldosterone (salt balance)
• Fasciculata → Cortisol (stress/sugar)
• Reticularis → Sex hormones (androgens)

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🔴 CUSHING SYNDROME — Too Much Cortisol

🌙 Moon face (round puffy face)
🐃 Buffalo hump (fat pad on back of neck)
🎀 Purple striae (stretch marks on abdomen)
🍎 Central obesity (fat belly, thin arms/legs)
💪 Muscle weakness + Osteoporosis
🔴 Hypertension + Hyperglycemia
🦠 Immunosuppressed (gets infections easily)

🎯 MCQ: Moon face + buffalo hump + purple striae = Cushing. Most common cause = exogenous steroids. Most common endogenous = pituitary adenoma (Cushing DISEASE).

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🟡 CONN SYNDROME — Too Much Aldosterone (Primary Hyperaldosteronism)

• ↑ Aldosterone, ↓ Renin (adrenal is working on its own, so the normal system is suppressed)
• Hypertension + LOW potassium (hypokalemia)
• No edema (the body "escapes" sodium retention)

🎯 MCQ: Hypertension + low potassium + LOW RENIN = Conn syndrome (primary hyperaldosteronism = adrenal adenoma).

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🔵 ADDISON DISEASE — Adrenal Insufficiency (Too Little Cortisol)

• Most common cause: Autoimmune (also TB worldwide)
• Low cortisol → pituitary releases lots of ACTH trying to fix it
• ACTH shares a precursor (POMC) with MSH → SKIN GETS DARK (hyperpigmentation)
• Symptoms: weakness, weight loss, low blood pressure, hyperpigmentation (especially skin creases, gums)

🎯 MCQ: Dark skin + low BP + weakness = Addison disease. Hyperpigmentation = PRIMARY adrenal failure (ACTH is high). NO hyperpigmentation = secondary.

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🔴 PHEOCHROMOCYTOMA — Adrenal Medulla Tumor

• Episodic (paroxysmal) severe hypertension
• Headache + Sweating + Palpitations + Pallor
• Triggered by stress, exercise, certain drugs, palpating the abdomen

• 10% bilateral
• 10% extra-adrenal (called paraganglioma)
• 10% malignant
• 10% in children
• 10% hereditary (MEN 2, VHL disease, NF1)

🎯 MCQ: Episodic hypertension + headache + sweating = pheochromocytoma. Diagnose with urine metanephrines.

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🟪 PART 5 — MEN SYNDROMES (Multiple Endocrine Neoplasia)

🎯 MCQ tips:

• MEN 1 = "3 P's" = MEN1 gene
• MEN 2A and 2B ALWAYS have medullary thyroid cancer = always check calcitonin
• RET gene mutation = MEN 2 (both A and B)
• Mucosal neuromas (bumps on lips/tongue) = MEN 2B specifically

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📝 ENDOCRINE MCQ DRILL

• A) Hashimoto B) Graves C) De Quervain D) Thyroid cancer → B Exophthalmos + hyperthyroid + young woman = Graves. TSH suppressed by excess T3/T4.

• A) Follicular B) Medullary C) Papillary D) Anaplastic → C Orphan Annie nuclei + psammoma bodies = Papillary thyroid cancer. Most common.

• A) Primary hyperparathyroidism B) Secondary hyperparathyroidism C) Hypoparathyroidism D) Conn → B CKD → can't activate Vit D → low calcium → high PTH trying to compensate = Secondary hyperparathyroidism.

• A) Adrenal adenoma B) Pituitary adenoma C) Exogenous steroids D) Lung cancer → C Cushing features = most commonly caused by prescribed steroids (iatrogenic).

• A) Secondary adrenal insufficiency B) Addison disease C) Cushing D) Conn → B Hyperpigmentation + low BP + HIGH ACTH = Addison disease (primary adrenal failure).

• A) Essential HTN B) Conn syndrome C) Pheochromocytoma D) Cushing → C Episodic crisis + elevated urine metanephrines = Pheochromocytoma.

• A) MEN 1, MEN1 gene B) MEN 2A, RET gene C) MEN 2B, RET gene D) MEN 1, RET gene → B Medullary thyroid + Pheo + Parathyroid = MEN 2A. Gene = RET.

• A) Type 2 DM B) Type 1 DM C) MODY D) Insulinoma → B Young + thin + insulitis (lymphocytes) = Type 1 DM (autoimmune). HLA-DR3/DR4.

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✅ ENDOCRINE CHEAT SHEET

THYROID:
Hypo + middle-aged woman + goiter = Hashimoto (anti-TPO)
Hyper + bulging eyes + young woman = Graves (TSI antibody)
Painful thyroid + viral illness = De Quervain (granulomas)
Orphan Annie nuclei + psammoma = Papillary cancer (best prognosis)
Elevated calcitonin = Medullary cancer (C-cells)
Worst thyroid cancer = Anaplastic

PARATHYROID:
High Ca + high PTH + adenoma = Primary hyperparathyroidism
Low Ca + high PTH + CKD = Secondary hyperparathyroidism
Bones + Stones + Groans + Psychic Moans = Hypercalcemia symptoms

DIABETES:
Type 1 = Autoimmune, insulitis, young/thin, HLA-DR3/DR4
Type 2 = Insulin resistance, obese, IAPP amyloid in islets
Kimmelstiel-Wilson nodules = Diabetic nephropathy (PATHOGNOMONIC)

ADRENAL:
Too much cortisol = Cushing (moon face + buffalo hump + purple striae)
  → Most common cause = exogenous steroids
  → Most common endogenous = pituitary adenoma (Cushing DISEASE)
Too much aldosterone = Conn (HTN + low K + LOW renin)
Too little = Addison (dark skin + low BP + HIGH ACTH)
Medulla tumor = Pheochromocytoma (episodic HTN + urine metanephrines)

MEN:
MEN 1 = 3 Ps (Parathyroid + Pituitary + Pancreas) → MEN1 gene
MEN 2A = Medullary thyroid + Pheo + Parathyroid → RET gene
MEN 2B = 2A + Mucosal neuromas → RET gene

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🔬 ENDOCRINE SYSTEM PATHOLOGY — COMPLETE BEGINNER LESSON

Based on Robbins Basic Pathology (everything from your syllabus)

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Before we start — understand ONE simple idea: Every endocrine disease = a gland makes too much or too little of its hormone. That's it. Everything else is just details of which gland, which hormone, and what goes wrong.

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🏛️ PART 1 — THE PITUITARY GLAND

• Anterior pituitary = makes 6 hormones (controls other glands)
• Posterior pituitary = stores and releases ADH + oxytocin (made in hypothalamus)

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🔴 ANTERIOR PITUITARY TUMORS (Adenomas)

🎯 MCQ tricks:

• Most common pituitary adenoma = Prolactinoma (lactotroph) → milk from breasts without pregnancy
• Child with abnormal height, big body = Somatotroph adenoma → Gigantism
• Adult with large jaw, big hands, ring no longer fits = Acromegaly

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🔵 HYPOPITUITARISM (Too little from the pituitary)

• Pituitary tumor compresses normal tissue
• Sheehan syndrome = massive bleeding after childbirth → pituitary infarct (most common cause in women of childbearing age)
• Head injury, radiation, infection

• GH first (earliest to be lost)
• Then LH/FSH (infertility, loss of libido)
• Then TSH (hypothyroid symptoms)
• Then ACTH (adrenal insufficiency symptoms)

🎯 MCQ: Woman has difficult delivery with heavy bleeding → stops producing breast milk, no periods, fatigue → Sheehan syndrome (post-partum pituitary infarction).

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🟡 POSTERIOR PITUITARY — DIABETES INSIPIDUS

• Symptoms: Extreme thirst (polydipsia) + extreme urination (polyuria)
• Urine is very dilute (like water)
• NOT the same as diabetes mellitus (no glucose involved)

🎯 MCQ: Lots of urination + very dilute urine + normal blood sugar = Diabetes Insipidus (ADH deficiency). Very different from diabetes mellitus.

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🦋 PART 2 — THYROID GLAND

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Hypothyroidism vs Hyperthyroidism — Know the symptoms

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🔴 DISEASE 1 — HASHIMOTO THYROIDITIS ⭐

• Most common cause of hypothyroidism in iodine-sufficient countries (like developed world)
• Affects middle-aged women (female:male = 10-20:1!)
• Autoimmune disease — T cells attack thyroid cells

1. Anti-TPO (anti-thyroid peroxidase) — most sensitive
2. Anti-thyroglobulin — also present

• Grossly: Enlarged, firm, pale, diffuse
• Microscopy: Lymphocytes + plasma cells + Hurthle cells (big pink follicular cells — they're damaged follicular cells with lots of mitochondria) + germinal centers

🎯 MCQ: Middle-aged woman + fatigue + cold intolerance + goiter + anti-TPO antibody = Hashimoto. Key histology = Hurthle cells + lymphocytic infiltrate.

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🔴 DISEASE 2 — GRAVES DISEASE ⭐⭐ MOST IMPORTANT

• Binds to TSH receptor → mimics TSH → constant stimulation → constant T3/T4 production
• Almost 100% of Graves patients have this antibody

1. HYPERTHYROIDISM → weight loss, fast heart, sweating, heat intolerance, anxiety
2. EXOPHTHALMOS → eyes bulge out (immune attack on retro-orbital fat and muscles)
3. PRETIBIAL MYXEDEMA → waxy, non-pitting thickening of skin on SHINS

• Grossly: Diffusely enlarged (symmetrical goiter), beefy red, vascular
• Microscopy: Follicles are small with scalloped colloid edges (colloid has bite-like indentations), lots of follicular cells, lymphocyte infiltration

🎯 MCQ traps:

• Bulging eyes + hyperthyroid = ONLY Graves (no other cause gives exophthalmos)
• TSH is LOW in Graves (confused students think it's high — it's suppressed by excess hormone)
• Pretibial myxedema in Graves is NOT due to hypothyroidism

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🟡 DISEASE 3 — SUBACUTE GRANULOMATOUS THYROIDITIS (de Quervain)

• PAINFUL thyroid — most important distinguishing feature
• Follows a viral upper respiratory infection (e.g., mumps, flu)
• Elevated ESR (erythrocyte sedimentation rate — sign of inflammation)
• Self-limiting — resolves in 6-8 weeks

🎯 MCQ: Tender/painful neck + recent viral illness + hyperthyroid + high ESR = De Quervain thyroiditis. Key = PAIN + viral prodrome + granulomas on biopsy.

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🟢 DIFFUSE AND MULTINODULAR GOITER

• Not enough iodine in diet → thyroid can't make enough hormone → TSH rises → thyroid enlarges trying to compensate
• Long standing Hashimoto
• Various stimulating factors

• Diffuse goiter = whole thyroid enlarged, uniform
• Multinodular goiter = thyroid has multiple lumps (nodules) of varying size
  • These nodules can sometimes become "toxic" (start making hormone on their own) → toxic multinodular goiter = hyperthyroidism from nodules (NOT autoimmune)

🎯 MCQ: Elderly patient from iodine-deficient area, large lumpy thyroid, no autoimmune antibodies, hyperthyroid = Toxic multinodular goiter.

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🔴 THYROID ADENOMAS

• Solitary, encapsulated nodule
• Most are non-functional (don't make hormone) — "cold nodule" on scan
• Some are "hot nodules" — make hormone → hyperthyroid
• Key distinction from follicular CARCINOMA: adenoma has intact capsule (no invasion). Carcinoma invades through the capsule.

🎯 MCQ: Single thyroid nodule + intact capsule + no capsular invasion = adenoma (benign). Capsular/vascular invasion present = carcinoma.

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🔴 THYROID CARCINOMAS — ALL 4 TYPES ⭐

1. PAPILLARY THYROID CARCINOMA (most common — 80%)

• Affects young adults and women more
• Associated with radiation exposure (e.g., Chernobyl survivors)
• Spreads via lymphatics to cervical lymph nodes (NOT via blood first)
• BRAF mutation most common genetic change

1. "Orphan Annie eye" nuclei = empty-looking, ground-glass nuclei (no nucleolus visible)
2. Psammoma bodies = concentrically calcified round structures in the tumor (looks like onion rings)
3. Nuclear pseudoinclusions and grooves

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2. FOLLICULAR THYROID CARCINOMA (15%)

• More common in areas with iodine deficiency
• Spreads via blood (hematogenous) to bone and lung (NOT lymph nodes first)
• You CANNOT distinguish adenoma from follicular carcinoma on fine needle aspiration alone — you need to see the capsular or vascular invasion on the actual resected specimen
• PAX8-PPARG fusion gene common

🎯 MCQ trick: Follicular cancer spreads to BONE via blood. Papillary cancer spreads to LYMPH NODES. Remember this difference!

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3. MEDULLARY THYROID CARCINOMA (5%)

• Associated with MEN 2A and MEN 2B (RET gene mutation)
• 25% are familial (always screen family members!)
• Produces amyloid deposits in the stroma (calcitonin deposits as amyloid)
• Lab: Elevated serum calcitonin = tumor marker

🎯 MCQ: Thyroid cancer + elevated calcitonin = Medullary thyroid carcinoma. Amyloid stroma. Associated with MEN 2. RET gene.

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4. ANAPLASTIC THYROID CARCINOMA (<5%)

• Affects elderly patients (usually 60-70s)
• Grows so fast it invades everything in the neck within weeks
• WORST prognosis of any cancer — median survival is only months
• Often arises from a pre-existing well-differentiated cancer (papillary or follicular) that de-differentiates

🎯 MCQ: Old patient + rapidly growing neck mass + fixed, hard thyroid = Anaplastic carcinoma. Worst prognosis.

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Quick Thyroid Cancer Summary Table ⭐

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🫘 PART 3 — PARATHYROID GLANDS

1. Pulling calcium OUT of bones
2. Making kidneys keep calcium (reabsorb it)
3. Activating Vitamin D → which absorbs calcium from gut

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🔴 PRIMARY HYPERPARATHYROIDISM

• Parathyroid adenoma (80-85%) — single gland tumor, most common
• Parathyroid hyperplasia (all 4 glands enlarged — seen in MEN 1)
• Parathyroid carcinoma (rare)

🎯 MCQ: High calcium + high PTH + kidney stones + bone pain = Primary hyperparathyroidism (usually parathyroid adenoma).

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🔴 SECONDARY HYPERPARATHYROIDISM

• Diseased kidneys can't activate Vitamin D
• Without Vit D → gut can't absorb calcium → calcium drops
• Low calcium → parathyroids panic → make lots of PTH

🎯 MCQ tip — THE KEY DIFFERENCE:

• Primary: HIGH calcium + high PTH
• Secondary (CKD): LOW calcium + high PTH

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🔵 HYPOPARATHYROIDISM

• Tetany = involuntary muscle spasms (carpopedal spasm — hand goes into a weird position)
• Chvostek sign = tapping the facial nerve causes facial muscle twitch
• Trousseau sign = inflating blood pressure cuff causes hand spasm
• Seizures, cardiac arrhythmias

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🍭 PART 4 — ENDOCRINE PANCREAS & DIABETES MELLITUS ⭐ BIGGEST TOPIC

• Exocrine part = makes digestive enzymes (goes into gut through a duct)
• Endocrine part = islets of Langerhans → hormones directly into blood

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DIABETES MELLITUS — DIAGNOSIS CRITERIA (know the numbers!)

• Fasting glucose ≥ 126 mg/dL
• Random glucose ≥ 200 mg/dL (with symptoms)
• 2-hour glucose on oral glucose tolerance test ≥ 200 mg/dL
• HbA1c ≥ 6.5%

🎯 MCQ: Fasting glucose 126 = diabetes. HbA1c ≥ 6.5% = diabetes. HbA1c reflects average blood glucose over the last 3 months (lifetime of a red blood cell).

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TYPE 1 DIABETES ⭐

• Autoimmune — T-cell mediated (CD8+ T cells kill beta cells)
• Gene link: HLA-DR3 and HLA-DR4 (strongest genetic risk)
• Antibodies present years before symptoms: anti-GAD (glutamic acid decarboxylase), anti-insulin
• Symptoms appear only when >90% of beta cells are destroyed
• Typically: Young, thin patients

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TYPE 2 DIABETES ⭐

1. Insulin resistance in muscle, fat, liver
2. Beta cell dysfunction — can't make enough insulin to overcome resistance

• NOT autoimmune
• Strong genetics: 80-90% concordance in identical twins
• Risk factors: Obesity, sedentary lifestyle, age, family history
• Typically: Older, overweight patient
• Develops slowly over years

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TYPE 1 vs TYPE 2 — Side by Side ⭐

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DIABETIC COMPLICATIONS ⭐⭐

• AGEs (Advanced Glycation End Products) — glucose sticks to proteins, damages vessel walls
• Sorbitol pathway — excess glucose → sorbitol builds up in cells → nerve/lens damage

Microvascular (small vessel damage):

• Most common cause of end-stage renal disease in the developed world
• Early: protein in urine (microalbuminuria)
• Histology: Kimmelstiel-Wilson nodules = round deposits in glomeruli (PATHOGNOMONIC for diabetic nephropathy)
• Also: diffuse glomerulosclerosis (more common than nodular)

• Leading cause of new blindness in working-age adults
• Non-proliferative: microaneurysms, dot hemorrhages, hard exudates
• Proliferative: new blood vessels grow (neovascularization) → VEGF driven → can bleed into vitreous

• "Glove and stocking" distribution — feet and hands go numb/tingle
• Loss of protective sensation → foot ulcers go unnoticed → infection → gangrene → amputation
• Leading cause of non-traumatic lower limb amputation

Macrovascular (large vessel damage):

• Accelerated atherosclerosis → heart attack, stroke (much higher risk than general population)
• Peripheral vascular disease → poor circulation in legs → gangrene, non-healing ulcers

🎯 MCQ: Kimmelstiel-Wilson nodules = DIABETIC NEPHROPATHY (pathognomonic). Diabetes = leading cause of end-stage renal disease + adult blindness + lower limb amputation.

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PANCREATIC NEUROENDOCRINE TUMORS (PanNETs) — Insulinoma and Gastrinoma

INSULINOMA (Beta cell tumor)

• Makes too much insulin → blood sugar drops → hypoglycemia
• Whipple's triad (classic):
  1. Symptoms of hypoglycemia (sweating, tremor, confusion)
  2. Blood glucose < 50 mg/dL during attack
  3. Symptoms relieved by giving glucose
• Most common islet cell tumor
• Usually benign (90%)
• Treatment: surgical removal

🎯 MCQ: Patient gets attacks of sweating + shakiness + confusion that go away after eating = Insulinoma. Test: prolonged fasting → hypoglycemia + high insulin levels.

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GASTRINOMA (Zollinger-Ellison Syndrome)

• Tumor makes too much gastrin → gastrin tells stomach to make too much acid → multiple, severe peptic ulcers
• Called Zollinger-Ellison Syndrome
• Ulcers in unusual locations (jejunum, multiple ulcers) — tip off that it's not ordinary peptic ulcer disease
• ~25% are associated with MEN 1
• Can be in pancreas OR duodenum

🎯 MCQ: Multiple refractory peptic ulcers + very high acid + abnormal locations = Gastrinoma (Zollinger-Ellison syndrome). Consider MEN 1 if other endocrine tumors present.

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🟧 PART 5 — ADRENAL GLANDS

CORTEX (outside) = makes steroid hormones (from cholesterol)
   ├── Zona Glomerulosa → ALDOSTERONE (salt and water balance)
   ├── Zona Fasciculata → CORTISOL (stress response, metabolism)
   └── Zona Reticularis → SEX HORMONES (androgens)

MEDULLA (inside) = chromaffin cells → CATECHOLAMINES
   └── Epinephrine + Norepinephrine (adrenaline)

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🔴 CUSHING SYNDROME — Too Much Cortisol ⭐⭐

Most common cause OVERALL = exogenous steroids (iatrogenic) Most common ENDOGENOUS cause = pituitary adenoma (Cushing Disease) — accounts for ~70% of endogenous cases

🌙 MOON FACE — fat deposits make face round and puffy
🦬 BUFFALO HUMP — fat pad on back of neck and upper back
🍎 CENTRAL OBESITY — fat belly, but thin arms and legs
🎀 PURPLE STRIAE — wide purple stretch marks on abdomen
💪 MUSCLE WEAKNESS + OSTEOPOROSIS — cortisol breaks down protein + bone
❤️ HYPERTENSION + HYPERGLYCEMIA — cortisol raises BP and blood sugar
🦠 IMMUNOSUPPRESSION — gets infections easily
😊 PSYCHIATRIC CHANGES — depression, psychosis

• Exogenous steroids → adrenal cortex becomes ATROPHIC (shut down by negative feedback)
• Endogenous (pituitary/ectopic ACTH) → adrenal cortex becomes HYPERPLASTIC (overstimulated)

🎯 MCQ: Moon face + buffalo hump + purple striae = Cushing. Exogenous steroids → ACTH LOW + adrenals atrophic. Pituitary tumor → ACTH HIGH + adrenals hyperplastic.

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🟡 CONN SYNDROME — Primary Hyperaldosteronism

• ↑ Aldosterone
• ↓ Renin (very important! Adrenal is working independently, so the normal renin pathway is suppressed)
• ↑ Sodium + blood pressure
• ↓ Potassium (hypokalemia) → muscle weakness, cramps

🎯 MCQ: Hypertension + low potassium + LOW RENIN = Conn syndrome (primary hyperaldosteronism from adrenal adenoma). Low renin is the key that tells you it's coming from the adrenal itself, not from the renin-angiotensin system.

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🔵 ADRENOGENITAL SYNDROMES — Excess Sex Hormones

• Usually a defect in 21-hydroxylase enzyme → can't make cortisol properly → ACTH goes HIGH trying to fix it → adrenal hypertrophies → makes lots of androgens as a byproduct

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🔴 ADRENAL INSUFFICIENCY — ADDISON DISEASE ⭐

• Most common cause in developed world: Autoimmune (antibodies against adrenal cells)
• Worldwide: Tuberculosis is a major cause (TB destroys adrenals)
• Low cortisol → pituitary makes lots of ACTH (trying to stimulate the dead gland)
• ACTH shares a precursor molecule (POMC) with MSH (melanocyte stimulating hormone)
• High ACTH → high MSH activity → HYPERPIGMENTATION of skin (especially in skin creases, gums, scars)

• Weakness, fatigue
• Low blood pressure (no aldosterone = no salt retention = BP drops)
• Hyperpigmentation of skin (PRIMARY only)
• Weight loss, nausea, vomiting
• Adrenal crisis = acute Addison — severe hypotension, vomiting, can die

• Adrenal is fine but not stimulated
• NO hyperpigmentation (ACTH is LOW here, so no MSH activity)

🎯 MCQ: Dark skin + low BP + weakness + high ACTH = Addison Disease (primary). Hyperpigmentation is the absolute giveaway of PRIMARY adrenal failure.

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🔴 PHEOCHROMOCYTOMA ⭐

• Paroxysmal (episodic) hypertension — BP suddenly spikes to 200+ then comes back down
• Headache + Sweating + Palpitations (heart racing) + Pallor + anxiety ("5 Ps")
• Episodes can be triggered by: stress, exercise, abdominal palpation, certain drugs, anesthesia

• 10% bilateral (both adrenals)
• 10% extra-adrenal (called paraganglioma — same tumor, different location)
• 10% malignant (hard to tell benign from malignant except by metastases)
• 10% in children
• 10% hereditary (associated with MEN 2, VHL disease, NF1)

🎯 MCQ: Episodic hypertension + headache + sweating = pheochromocytoma. Confirm with urine metanephrines. Rule of 10s!

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🔵 NEUROBLASTOMA

• Most common extracranial solid tumor in children (first 5 years of life)
• Arises in adrenal medulla or retroperitoneal sympathetic ganglia
• Makes catecholamines → urine VMA/HVA elevated (used for diagnosis)
• Different from pheochromocytoma: affects much younger children, malignant behavior
• Can metastasize widely to bone, liver, skin, lymph nodes

🎯 MCQ: Toddler/infant with abdominal mass + elevated urine VMA = Neuroblastoma (adrenal medulla). Compare: adult with episodic HTN + urine metanephrines = Pheochromocytoma.

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🟪 PART 6 — MEN SYNDROMES (Multiple Endocrine Neoplasia)

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MEN TYPE 1 — "The 3 P's" ⭐

P — PARATHYROID hyperplasia/adenoma → hypercalcemia (most common, 90%)
P — PITUITARY adenoma → prolactinoma most common
P — PANCREATIC neuroendocrine tumors → gastrinoma, insulinoma, glucagonoma

Memory trick: "MEN 1 = 3 Ps = MEN1 gene"

• Parathyroid involvement = 90% of patients (most common feature)
• Pancreatic tumors → gastrinoma causes Zollinger-Ellison syndrome here too
• Usually all 4 parathyroids are hyperplastic (vs. single adenoma in sporadic primary hyperparathyroidism)

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MEN TYPE 2A ⭐⭐

1. MEDULLARY THYROID CARCINOMA (MTC) — always present, often first tumor
2. PHEOCHROMOCYTOMA — ~50% of patients
3. PARATHYROID hyperplasia/adenoma — ~20-30%

Memory trick: "2A = Medullary + Pheo + Para"

• RET mutation → screen family members with genetic testing
• Medullary thyroid cancer can appear in childhood → prophylactic thyroidectomy recommended in gene carriers

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MEN TYPE 2B ⭐

4. MUCOSAL NEUROMAS — bumps on lips, tongue, eyelids (very distinctive)
5. MARFANOID BODY HABITUS — tall, thin, long limbs (like Marfan syndrome)

• NO parathyroid involvement (unlike 2A)
• Most aggressive of the MEN syndromes
• Medullary thyroid cancer appears earlier and more aggressively than MEN 2A

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MEN Syndromes Summary Table ⭐

🎯 MCQ tips:

• MEN 1 = 3 Ps = MEN1 gene (chromosome 11)
• MEN 2A and 2B both = RET gene + always have medullary thyroid cancer
• MEN 2B = 2A + bumps on lips/tongue (mucosal neuromas) — the picture of a patient with bumps on their lips is MEN 2B
• Key difference between 2A and 2B: Parathyroid in 2A, mucosal neuromas in 2B

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📝 FULL ENDOCRINE MCQ DRILL (14 Questions)

• A) Prolactinoma
• B) Sheehan syndrome
• C) Graves disease
• D) Hashimoto thyroiditis

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• A) Prolactin
• B) TSH
• C) ACTH
• D) Growth hormone

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• A) Graves disease
• B) De Quervain thyroiditis
• C) Hashimoto thyroiditis
• D) Toxic multinodular goiter

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• A) Hashimoto; anti-TPO
• B) Graves; TSI
• C) De Quervain; none
• D) Follicular carcinoma; none

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• A) Follicular carcinoma
• B) Medullary carcinoma
• C) Anaplastic carcinoma
• D) Papillary carcinoma

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• A) Papillary carcinoma
• B) Medullary carcinoma
• C) Follicular carcinoma
• D) Anaplastic carcinoma

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• A) Primary hyperparathyroidism
• B) Hypoparathyroidism
• C) Secondary hyperparathyroidism
• D) Addison disease

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• A) Type 2 diabetes
• B) Insulinoma
• C) Type 1 diabetes
• D) Cushing syndrome

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• A) Amyloid deposits
• B) Kimmelstiel-Wilson nodules
• C) Lewy bodies
• D) Kuru plaques

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• A) Pituitary adenoma
• B) Adrenal carcinoma
• C) Prescribed steroid medications
• D) Small cell lung cancer

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• A) Pheochromocytoma
• B) Cushing disease
• C) Conn syndrome
• D) Addison disease

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• A) Secondary adrenal insufficiency
• B) Cushing disease
• C) Addison disease
• D) Conn syndrome

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• A) Essential hypertension
• B) Pheochromocytoma
• C) Conn syndrome
• D) Cushing syndrome

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• A) MEN 1; MEN1 gene
• B) MEN 2A; RET gene
• C) MEN 2B; RET gene
• D) MEN 2A; MEN1 gene

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✅ ENDOCRINE MASTER CHEAT SHEET

PITUITARY:
Prolactinoma = milk + no periods (most common adenoma)
Somatotroph adenoma = Gigantism (child) or Acromegaly (adult)
Corticotroph adenoma = Cushing DISEASE (pituitary ACTH excess)
Sheehan syndrome = post-partum pituitary infarction (bleeding)
Diabetes Insipidus = ADH deficiency = lots of dilute urine

THYROID:
Hashimoto = hypothyroid + anti-TPO + Hurthle cells (middle-aged women)
Graves = hyperthyroid + TSI + EXOPHTHALMOS (young women) — TSH is LOW
De Quervain = PAINFUL thyroid + viral + granulomas + self-limiting
Papillary cancer (80%) = Orphan Annie nuclei + psammoma → lymph nodes → BEST prognosis
Follicular cancer (15%) = Capsular invasion → blood (bone/lung) → diagnose on resection not FNA
Medullary cancer (5%) = C-cells + calcitonin ↑ + amyloid stroma + MEN 2
Anaplastic (<5%) = elderly + fast + WORST prognosis

PARATHYROID:
Primary hyperPTH = HIGH Ca + HIGH PTH (adenoma 80%)
Secondary hyperPTH (CKD) = LOW Ca + HIGH PTH
Hypo-PTH = LOW Ca → tetany, Trousseau, Chvostek (often post-thyroid surgery)
"Bones Stones Groans Psychic Moans" = hypercalcemia symptoms

DIABETES:
Type 1 = autoimmune, insulitis, young/thin, DR3/DR4, DKA risk
Type 2 = insulin resistance, amyloid (IAPP) in islets, obese/older
Diagnose: fasting glucose ≥126 OR HbA1c ≥6.5%
Kimmelstiel-Wilson = diabetic nephropathy (PATHOGNOMONIC)
Diabetes = leading cause of: end-stage renal disease + adult blindness + lower-limb amputation
Insulinoma = hypoglycemia attacks + Whipple's triad → benign usually
Gastrinoma = multiple ulcers + high acid = Zollinger-Ellison → MEN 1 in 25%

ADRENAL:
Cortex layers (outer→inner): Glomerulosa→Aldosterone; Fasciculata→Cortisol; Reticularis→Sex hormones
"Salt, Sugar, Sex" = GFR trick

Cushing = too much cortisol
  Causes: Exogenous (most common) → ACTH low + adrenals atrophic
         Pituitary adenoma (Cushing DISEASE) → ACTH high + adrenals hyperplastic
         Ectopic ACTH (small cell lung) → ACTH very high
         Adrenal adenoma → ACTH low

Conn = aldosterone excess = HTN + low K + LOW RENIN (adrenal adenoma)

Addison = primary adrenal failure = low cortisol + HIGH ACTH + HYPERPIGMENTATION + low BP

Pheochromocytoma = adrenal medulla tumor = episodic HTN + headache + sweating
  Diagnose: urine metanephrines; Rule of 10s; hereditary: MEN 2, VHL, NF1

Neuroblastoma = CHILD + adrenal medulla + urine VMA/HVA elevated (different from pheo)

MEN SYNDROMES:
MEN 1 = 3 Ps (Parathyroid + Pituitary + Pancreas) → MEN1 gene
MEN 2A = Medullary thyroid + Pheo + Parathyroid → RET gene
MEN 2B = Medullary thyroid + Pheo + Mucosal neuromas + Marfanoid → RET gene

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🚨 3-HOUR EMERGENCY EXAM PREP

Endocrine — Visual Story Method

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🏛️ PITUITARY — Picture a CONTROL TOWER

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✈️ PROLACTINOMA

• Disease: Prolactinoma (excess prolactin)
• Gland: Anterior pituitary
• Signs: Milk from breasts (galactorrhea) + no periods (amenorrhea)
• MCQ answer: Most common pituitary adenoma

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🏀 ACROMEGALY / GIGANTISM

• Child = Gigantism (still growing → gets very tall)
• Adult = Acromegaly (bones can't grow longer, just wider → big jaw, hands, feet)
• Cause: Somatotroph adenoma → too much GH

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🩸 SHEEHAN SYNDROME

• Heavy childbirth bleeding → pituitary gets no blood → infarcts → dies
• Result: Can't make ANY pituitary hormones

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🦋 THYROID — Picture a BUTTERFLY on your neck

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🐢 HASHIMOTO = THE SLOW DESTRUCTION

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🔥 GRAVES = THE RACING ENGINE

🔥 Hyperthyroidism
👀 Exophthalmos (bulging eyes)
🦵 Pretibial myxedema (waxy shins)

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🤒 DE QUERVAIN = SICK AND SORE

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☢️ THYROID CANCERS — ONE IMAGE EACH

• Empty nuclei = "Orphan Annie eyes"
• Calcified rings = psammoma bodies
• Spreads to neck lymph nodes
• BEST prognosis (95% survive 10 years)
• Most common (80%)

• Must invade through capsule to be called cancer
• Spreads via BLOOD to bone and lung (NOT lymph nodes)
• More common where there's no iodine in the diet

• From C-cells → makes Calcitonin
• Has amyloid deposits in stroma
• Linked to MEN 2 (RET gene)
• Elevated calcitonin in blood = tumor marker

• Old patient
• Grows insanely fast, kills in months
• WORST prognosis of any cancer anywhere

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🫘 PARATHYROID — "Bones Stones Groans Moans"

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HIGH CALCIUM = HIGH PTH = HYPERPARATHYROIDISM

The ONE TABLE you need:

🎯 The only difference you need: HIGH Ca = Primary. LOW Ca = Secondary.

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LOW CALCIUM = HYPOPARATHYROIDISM

• Cause: Parathyroids accidentally removed during thyroid surgery
• Low Ca → tetany + Trousseau sign + Chvostek sign

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🍭 DIABETES — TWO STORIES

TYPE 1 — "THE ATTACK"

• Young + thin
• Autoimmune → lymphocytes in islets = "insulitis"
• No insulin → DKA (fruity breath, vomiting)
• Genes: HLA-DR3/DR4

TYPE 2 — "THE STRIKE"

• Older + obese
• Insulin resistance → pancreas overworks → eventually fails
• Amyloid deposits in islets (IAPP)
• NO autoimmune, NO HLA link

KEY DIABETIC COMPLICATIONS — REMEMBER THE 3 LEADING CAUSES:

Diabetes = #1 cause of KIDNEY FAILURE (end-stage renal disease)
Diabetes = #1 cause of ADULT BLINDNESS (retinopathy)
Diabetes = #1 cause of NON-TRAUMATIC AMPUTATION (peripheral neuropathy/vascular disease)

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INSULINOMA

• Beta cell tumor → too much insulin → hypoglycemia
• Attacks that go away after eating = insulinoma
• Whipple's triad: symptoms + low glucose + relieved by glucose

GASTRINOMA (Zollinger-Ellison)

• Tumor makes gastrin → stomach makes too much acid → ulcers everywhere
• Multiple unusual-location ulcers = think Gastrinoma
• 25% associated with MEN 1

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🟧 ADRENAL — SPLIT INTO 2 HALVES

THE CORTEX = 3 LAYERS, 3 HORMONES

Outer: Glomerulosa → ALDOSTERONE (Salt - blood pressure)
Middle: Fasciculata → CORTISOL (Sugar - stress)
Inner: Reticularis → SEX hormones (androgens)

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CUSHING = TOO MUCH CORTISOL

1. TAKING STEROID PILLS (most common overall) → ACTH goes LOW
2. PITUITARY ADENOMA making too much ACTH → ACTH HIGH → "Cushing DISEASE"
3. LUNG CANCER (small cell) making ACTH → ACTH VERY HIGH
4. ADRENAL TUMOR making cortisol itself → ACTH LOW

Moon face + Buffalo hump + Purple striae + Central obesity
+ High BP + High sugar + Muscle weakness + Easy infections

Quick ACTH rule:

• Exogenous steroids = ACTH LOW + adrenals ATROPHY
• Pituitary = ACTH HIGH + adrenals HYPERPLASIA

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CONN = TOO MUCH ALDOSTERONE

Adrenal adenoma → too much aldosterone →
→ kidneys keep Na (HIGH BP) + waste K (LOW potassium)
→ renin is SUPPRESSED (low renin = the KEY clue)

MCQ formula: HTN + Low K + LOW RENIN = CONN SYNDROME

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ADDISON = TOO LITTLE CORTISOL

Adrenal cortex DESTROYED (autoimmune) →
Low cortisol → Pituitary panics → Makes HUGE amounts of ACTH →
ACTH shares a precursor with MSH → SKIN TURNS DARK

DARK SKIN (hyperpigmentation) ← the big MCQ giveaway
Low blood pressure
Weakness + weight loss
High ACTH (primary only)

MCQ formula: Dark skin + Low BP + Weakness + High ACTH = ADDISON DISEASE

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PHEOCHROMOCYTOMA = ADRENALINE STORM

Adrenal MEDULLA tumor → bursts of adrenaline →
Sudden BP spike (220/130) + Headache + Sweating + Palpitations
Then BP comes back to normal
→ Repeat episodes

10% Bilateral
10% Extra-adrenal (paraganglioma)  
10% Malignant
10% Hereditary (MEN 2, VHL, NF1)

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🟪 MEN SYNDROMES — THE SIMPLEST WAY

MEN 1 = "3 Ps IN A TRIANGLE"

Draw a triangle with one P at each corner:
P = Parathyroid (high calcium)
P = Pituitary (prolactinoma usually)
P = Pancreas (gastrinoma/insulinoma)

GENE: MEN1

MEN 2A = "A for ADRENAL"

Medullary THYROID cancer (always)
+ Pheochromocytoma (ADRENAL = 2A clue)
+ Parathyroid

GENE: RET

MEN 2B = "B for BUMPS"

Medullary THYROID cancer (always)
+ Pheochromocytoma
+ BUMPS on lips/tongue (mucosal neuromas) ← the image is B for Bumps
+ Marfanoid body (tall and thin)
NO parathyroid

GENE: RET

Quickest MEN table ever:

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⚡ 3-HOUR PLAN RIGHT NOW

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⚡ RAPID FIRE DRILL — Answer out loud, check below

1. Young woman, bulging eyes, weight loss, fast heart → ?
2. Middle-aged woman, cold, tired, gaining weight, goiter, anti-TPO → ?
3. Painful thyroid, recent flu, high ESR → ?
4. Thyroid cancer, empty nuclei, calcified rings → ?
5. Thyroid cancer, elevated calcitonin, amyloid in stroma → ?
6. CKD patient, high PTH, LOW calcium → ?
7. High calcium, high PTH, kidney stones, bone pain → ?
8. Young thin patient, lymphocytes in islets, DKA → ?
9. Round deposits in kidney glomeruli in diabetic → ?
10. Moon face, buffalo hump, purple striae → ?
11. High BP, low K, LOW RENIN → ?
12. Dark skin, low BP, HIGH ACTH → ?
13. Episodic BP spikes, sweating, headache, urine metanephrines → ?
14. Medullary thyroid + Pheo + bumps on lips → ?

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1. Graves disease
2. Hashimoto thyroiditis
3. De Quervain thyroiditis
4. Papillary thyroid carcinoma
5. Medullary thyroid carcinoma
6. Secondary hyperparathyroidism
7. Primary hyperparathyroidism
8. Type 1 diabetes
9. Kimmelstiel-Wilson nodules (diabetic nephropathy)
10. Cushing syndrome
11. Conn syndrome (primary hyperaldosteronism)
12. Addison disease
13. Pheochromocytoma
14. MEN 2B

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🚨 GI TRACT — 25 MINUTE BLITZ

Picture a TUBE from mouth to anus. Every disease = one image.

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🔴 ESOPHAGUS

ACHALASIA — "The Locked Door"

• LES fails to RELAX → food can't enter stomach → food backs up in esophagus
• Dilated esophagus above + bird-beak narrowing on X-ray
• Cause: Loss of myenteric plexus neurons (Auerbach plexus)
• MCQ: Dysphagia to BOTH solids AND liquids from the start (vs cancer = solids first)

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ESOPHAGEAL VARICES — "The Swollen Garden Hose"

• Cause: Liver cirrhosis → portal hypertension → blood backs up into esophageal veins
• They can RUPTURE → massive life-threatening bleed
• Painless sudden vomiting of blood

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MALLORY-WEISS TEAR — "The Vomiting Rip"

• Longitudinal tear at gastroesophageal junction from forceful vomiting
• Presents: blood in vomit after repeated retching
• Associated with alcoholism

BOERHAAVE SYNDROME — "The Explosion"

• Complete perforation from extreme vomiting
• Medical emergency — air/food leaks into chest cavity
• Much worse than Mallory-Weiss

MCQ trick: Mallory-Weiss = partial tear. Boerhaave = FULL thickness rupture. Both after vomiting.

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BARRETT'S ESOPHAGUS — "Stomach Invading the Esophagus"

• Chronic acid reflux → esophagus lining transforms from squamous → intestinal columnar epithelium (goblet cells)
• This transformation = metaplasia
• Pre-malignant → can progress to adenocarcinoma
• Found in the LOWER esophagus

MCQ: Barrett's = goblet cells in esophagus = metaplasia from reflux = risk of ADENOcarcinoma (lower esophagus)

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ESOPHAGEAL CANCERS — "Location tells you the type"

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🔴 STOMACH

GASTRITIS — "Stomach Being Attacked"

• Causes: NSAIDs (aspirin), alcohol, stress (burns, trauma)
• NSAIDs block prostaglandins → lose protective mucus → acid burns stomach
• Stress ulcers: Curling ulcer (burns) + Cushing ulcer (brain injury → vagal stimulation)

MCQ: H. pylori → most common cause of chronic gastritis AND peptic ulcer disease AND MALT lymphoma AND gastric adenocarcinoma

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PEPTIC ULCER DISEASE

• Cause: H. pylori (most common) OR NSAIDs
• Duodenal ulcer = more common, associated with increased acid
• Complication: Perforation (hole through wall) → emergency surgery

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GASTRIC CANCER

• Intestinal type = glandular, associated with H. pylori, dietary factors (smoked/salted foods), intestinal metaplasia
• Diffuse type = signet ring cells (nucleus pushed to side by mucus) → linitis plastica (rigid "leather bottle" stomach)

MCQ: Signet ring cells + linitis plastica = diffuse gastric cancer. Krukenberg = ovarian met from stomach.

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🔴 SMALL INTESTINE

CELIAC DISEASE — "Wheat is the Enemy"

• Autoimmune reaction to gluten (wheat, barley, rye)
• Antibodies: Anti-tissue transglutaminase (anti-tTG), anti-endomysial
• Histology: Villous atrophy + crypt hyperplasia + intraepithelial lymphocytes
• Complication: T-cell lymphoma of small intestine (rare but serious)
• Treatment: Gluten-free diet

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CROHN'S DISEASE — "Skipping Through the Gut"

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ULCERATIVE COLITIS — "Carpet Bombing the Colon"

CROHN vs UC — THE ONE TABLE YOU NEED:

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COLORECTAL CANCER — "The Polyp Pipeline"

• Tubular adenoma → low risk
• Villous adenoma → HIGH risk of cancer (remember: "Villous = Villain")
• Tubulovillous → intermediate

• Left-sided cancer → obstruction (pencil-thin stool), rectal bleeding
• Right-sided cancer → iron deficiency anemia (bleeds slowly), large mass
• APC gene mutation → key in sporadic colon cancer
• FAP (Familial Adenomatous Polyposis) = APC mutation → 100s of polyps → inevitable cancer by age 40

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APPENDICITIS — "The Blocked Tube"

• Pain starts around navel → moves to RIGHT LOWER QUADRANT (McBurney's point)
• Fever + nausea + rebound tenderness
• Histology: neutrophils in appendix wall

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🔴 LIVER (GI Chapter includes Gallbladder/Pancreas)

GALLSTONES — "Stones in the Bag"

• Acute: RUQ pain, fever, Murphy's sign (pain on inspiration when pressing RUQ)
• Chronic: repeated attacks → thick, scarred gallbladder

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PANCREATITIS — "Fire in the Pancreas"

• Causes: Gallstones (#1) + Alcohol (#2) — "GET SMASHED" (mnemonic for all causes)
• Symptoms: Severe epigastric pain radiating to BACK, nausea
• Lab: ↑ Amylase + ↑ Lipase (lipase more specific)
• Complications: Hemorrhagic pancreatitis → Grey Turner sign (flank bruising) + Cullen sign (periumbilical bruising)
• Fat necrosis with calcium soap deposits = white chalky spots on pancreas

• Cause: Alcohol (most common in developed world)
• Fibrosis + calcifications in pancreas
• Result: Diabetes (beta cells destroyed) + Malabsorption (no digestive enzymes)

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PANCREATIC ADENOCARCINOMA — "Silent Killer"

• Most common location: HEAD of pancreas (60%)
• Symptom: Painless jaundice (bile duct blocked by tumor = no pain because it's gradual)
• Courvoisier's sign = palpable, NON-TENDER gallbladder + jaundice → think pancreatic cancer
• VERY POOR prognosis (most deadly GI cancer)
• Risk factors: Smoking, chronic pancreatitis, diabetes
• CA 19-9 = tumor marker

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⚡ GI RAPID FIRE DRILL

1. Chronic reflux → goblet cells in esophagus → risk of what cancer? → Barrett's → Adenocarcinoma
2. Vomiting hard → partial esophageal tear → ? Full thickness? → Mallory-Weiss / Boerhaave
3. Skip lesions + transmural + granulomas + fistulas → ? → Crohn's disease
4. Starts at rectum + continuous + crypt abscesses + toxic megacolon → ? → Ulcerative colitis
5. Signet ring cells + rigid stomach + ovarian mets → ? → Diffuse gastric cancer / Krukenberg
6. Celiac disease histology → ? → Villous atrophy + crypt hyperplasia
7. Most common cause of acute pancreatitis → ? → Gallstones
8. Painless jaundice + palpable GB → ? → Pancreatic head cancer (Courvoisier)
9. Fat Female Forty Fertile → ? → Cholesterol gallstones
10. Villous polyp → most likely to become → ? → Colon cancer ("Villain")

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🧠 CNS — 25 MINUTE BLITZ

Every disease = ONE PICTURE

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🏔️ HERNIATIONS — "Toothpaste being squeezed"

UNCAL (transtentorial) → CN III compressed → BLOWN PUPIL (same side)
Think: a finger poking the eye (same side as the herniation)

SUBFALCINE → compresses anterior cerebral a. → opposite LEG weak
Think: falling sideways and hurting the other leg

TONSILLAR → medulla compressed → DEATH
Think: a plug pulled from the bottom (foramen magnum)

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🩸 BRAIN BLEEDS — "Location = vessel = shape"

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⏱️ STROKE TIMELINE — "The Cleanup Crew"

Day 0-1: RED NEURONS (pink, shrunken)
Day 1-3: NEUTROPHILS (first responders)
Day 3-5: MACROPHAGES (cleanup crew, eat debris)
Weeks: CAVITY forms (brain melts = liquefactive necrosis)

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🦠 MENINGITIS — "Age = Bug"

BABY → E.coli + Group B Strep
TEEN/COLLEGE → Neisseria meningitidis
OLD → S. pneumoniae

CSF:
BACTERIAL = neutrophils + LOW glucose
VIRAL = lymphocytes + NORMAL glucose

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🧬 NEURODEGENERATION — "Each disease kills ONE specific area"

ALZHEIMER → Cortex → Aβ plaques + Tau tangles → Memory loss
Picture: An old woman forgetting, surrounded by sticky plaques

PARKINSON → Substantia nigra → Lewy bodies → Tremor at REST + Rigid
Picture: Someone with pill-rolling tremor, can't move fast

HUNTINGTON → Caudate/Putamen (striatum) → CAG repeat → CHOREA (dancing)
Picture: Someone doing an involuntary dance they can't stop. Chr 4. Autosomal dominant.

ALS → Upper + Lower motor neurons → Paralysis, MIND INTACT
Picture: Stephen Hawking — brilliant mind, can't move body

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🧠 BRAIN TUMORS — "Two ages, two main tumors"

ADULT + MALIGNANT = GBM
→ Pseudopalisading necrosis + Butterfly (crosses corpus callosum)

CHILD + MALIGNANT = Medulloblastoma
→ Posterior fossa (cerebellum) + Small blue cells + Drop mets to spine

ADULT + BENIGN = Meningioma
→ OUTSIDE brain + Whorls + Psammoma bodies + Women

CHILD + BENIGN = Pilocytic Astrocytoma
→ Cerebellum + Rosenthal fibers + Grade I (curable)

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🧩 PRION DISEASE

• SPONGIFORM vacuolation = PATHOGNOMONIC
• Rapidly progressive dementia + jerky movements (myoclonus)
• CJD. Fatal. No treatment.

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⚡ CNS RAPID FIRE

1. Blown pupil after head injury → ? → Uncal herniation (CN III)
2. Lens-shaped bleed, lucid interval → ? → Epidural (middle meningeal artery)
3. "Worst headache of my life" → ? → SAH (berry aneurysm)
4. Crescent bleed, elderly → ? → Subdural (bridging vein)
5. Teen + fever + stiff neck + rash → ? → Neisseria meningitidis
6. Bacteria CSF: cells? glucose? → ? → Neutrophils + LOW glucose
7. Cortex atrophy + plaques + tangles → ? → Alzheimer
8. Substantia nigra loss + Lewy bodies → ? → Parkinson
9. CAG repeat + chr 4 + chorea → ? → Huntington
10. Child + posterior fossa + small blue cells → ? → Medulloblastoma
11. Adult + butterfly tumor + necrosis → ? → GBM
12. Sponge-like brain + myoclonus + rapid dementia → ? → Prion disease (CJD)

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🫘 KIDNEY — 25 MINUTE BLITZ

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TWO BIG SYNDROMES FIRST — KNOW THE DIFFERENCE ⭐⭐

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NEPHROTIC DISEASES — "Protein Leakers"

MINIMAL CHANGE DISEASE

• Most common nephrotic syndrome in CHILDREN
• Normal on light microscopy (that's why it's called "minimal change")
• Electron microscopy: foot process effacement (podocytes)
• Responds beautifully to steroids

MEMBRANOUS NEPHROPATHY

• Most common nephrotic syndrome in ADULTS
• Thickened basement membrane with IgG deposits
• Can be primary or secondary (to lupus, hepatitis B, cancer)
• "Spike and dome" on electron microscopy

FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS)

• Nephrotic syndrome in adults, especially HIV, heroin use, obesity
• Focal = not all glomeruli. Segmental = not the whole glomerulus.
• Poor response to steroids, can lead to kidney failure

DIABETIC NEPHROPATHY

• Kimmelstiel-Wilson nodules = PATHOGNOMONIC
• Leading cause of end-stage renal disease

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NEPHRITIC DISEASES — "Blood in the Urine"

POST-STREPTOCOCCAL GLOMERULONEPHRITIS

• Happens 2 weeks AFTER strep throat (Group A Strep)
• Immune complexes deposit in glomeruli → inflammation
• "Lumpy bumpy" deposits on immunofluorescence
• Hematuria + RBC casts + HTN + edema
• Usually self-limiting in children — resolves on its own
• "Starry sky" or "humps" (subepithelial deposits) on electron microscopy

IgA NEPHROPATHY (BERGER'S DISEASE)

• Most common glomerulonephritis WORLDWIDE
• IgA deposits in the mesangium
• Hematuria that appears concurrent with or within days of an upper respiratory infection (NOT weeks like post-strep)
• IgA deposits on immunofluorescence

MCQ trap: Post-strep = 2 WEEKS after infection. IgA = during or 2 DAYS after infection.

GOODPASTURE DISEASE

• Autoimmune: anti-GBM antibodies (against type IV collagen in basement membrane)
• Attacks kidney glomeruli AND lung alveoli
• Symptoms: Hematuria (kidneys) + Hemoptysis (coughing blood from lungs)
• Linear immunofluorescence = pathognomonic (smooth line along basement membrane)

RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS (RPGN)

• Crescents in Bowman's space on histology = defining feature
• Rapid loss of kidney function
• Can be from Goodpasture, ANCA-associated vasculitis, post-strep

ALPORT SYNDROME

• Genetic defect in type IV collagen (same collagen as GBM)
• Defective GBM → hematuria → progressive kidney failure
• Also: sensorineural deafness + ocular abnormalities
• X-linked (boys worse)

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VASCULAR KIDNEY DISEASE

NEPHROSCLEROSIS

• Chronic HTN → arterioles thicken (hyaline arteriolosclerosis) → ischemia → kidney scars
• Kidneys become small and granular ("flea-bitten kidney" gross appearance)

MALIGNANT HYPERTENSION

• Severe acute HTN → fibrinoid necrosis of arterioles
• Onion-skin (hyperplastic arteriolosclerosis) on histology

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TUBULOINTERSTITIAL DISEASES

ACUTE TUBULAR INJURY (ATI/ATN)

• Two causes:
  1. Ischemic — shock, severe blood loss → kidney gets no blood
  2. Toxic — drugs (aminoglycosides, contrast dye), myoglobin (from crush injury)
• Muddy brown granular casts in urine (tubular cells sloughing off)
• Reversible if cause removed

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CYSTIC KIDNEY DISEASES

AUTOSOMAL DOMINANT (ADULT) PKD ⭐

• Most common hereditary kidney disease
• PKD1 gene (chromosome 16) — 85% of cases
• Bilateral huge kidneys full of cysts
• Presents in adulthood (30-50 years)
• Associated with: Berry aneurysms (SAH!), liver cysts, mitral valve prolapse
• Leads to chronic kidney failure

MCQ: ADPKD + brain aneurysm in same question = always connect them. Rupture = SAH.

AUTOSOMAL RECESSIVE (CHILDHOOD) PKD

• Presents at BIRTH or infancy
• Severe → death in infancy often
• Also affects LIVER (congenital hepatic fibrosis)

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KIDNEY TUMORS

RENAL CELL CARCINOMA (RCC)

• Most common kidney cancer in adults
• Arises from proximal tubule cells
• 3 most common types: Clear cell (most common, VHL gene) → Papillary → Chromophobe
• Associated with Von Hippel-Lindau (VHL) disease
• Paraneoplastic syndromes: can make EPO (polycythemia), PTH-rP (hypercalcemia), renin (HTN)

WILMS TUMOR (NEPHROBLASTOMA)

• Most common kidney tumor in children (age 1-5)
• WT1 gene mutation
• Large abdominal mass in a child — do NOT palpate hard (can rupture and spread cancer)

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⚡ KIDNEY RAPID FIRE

1. Child, puffy eyes, massive protein in urine, responds to steroids → ? → Minimal Change Disease
2. Adult, protein in urine, "spike and dome" on EM → ? → Membranous nephropathy
3. Dark cola urine 2 weeks after sore throat → ? → Post-streptococcal GN
4. Hematuria during/2 days after cold, IgA deposits → ? → IgA nephropathy (Berger's)
5. Hematuria + coughing blood + linear IF → ? → Goodpasture (anti-GBM)
6. Crescents in glomeruli + rapid kidney failure → ? → RPGN
7. Hereditary deafness + hematuria + collagen IV defect → ? → Alport syndrome
8. Round deposits in glomeruli in diabetic → ? → Kimmelstiel-Wilson nodules
9. ADPKD + brain aneurysm connection → ? → SAH (berry aneurysm)
10. Child + big abdominal mass + WT1 gene → ? → Wilms tumor
11. Muddy brown casts + drugs/shock → ? → Acute tubular injury

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❤️ HEART — 25 MINUTE BLITZ

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HEART FAILURE — "Left vs Right"

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ISCHEMIC HEART DISEASE — "Blocked Artery"

The 4 types:

• Stable = predictable (always on exertion)
• Unstable = unpredictable, even at rest → WARNING of impending MI

Days 3-7 = MOST DANGEROUS for complications (wall is weakest)

Day 1-2: ARRHYTHMIA (most common cause of death post-MI) — electrical system disrupted
Day 3-7: RUPTURE (free wall → hemopericardium. Septum → VSD. Papillary muscle → mitral regurg)
Weeks later: PERICARDITIS (Dressler syndrome — autoimmune, 2-8 weeks post-MI)

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CONGENITAL HEART DISEASE

Left-to-Right Shunts (L→R) — "Pink babies, lungs overloaded"

ASD = hole between atria (Atrial Septal Defect)
VSD = hole between ventricles (most common congenital defect)
PDA = ductus arteriosus doesn't close (Patent Ductus Arteriosus) → machinery murmur

Right-to-Left Shunts (R→L) — "BLUE babies (cyanotic)"

Tetralogy of Fallot = 4 defects: VSD + RVH + Overriding aorta + Pulmonary stenosis
→ Most common CYANOTIC heart disease
→ "Boot-shaped heart" on X-ray
→ Squatting relieves symptoms (increases peripheral resistance)

Transposition of Great Arteries = Aorta from RIGHT ventricle + Pulmonary from LEFT
→ Two parallel circuits instead of one → incompatible with life without mixing

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VALVULAR HEART DISEASE

RHEUMATIC FEVER / RHEUMATIC HEART DISEASE

• Strep throat (Group A Strep) → autoimmune attack on heart valves (molecular mimicry)
• Affects MITRAL VALVE most (then aortic)
• Acute: Aschoff bodies (pathognomonic granulomas in myocardium) + Anitschkow cells
• Chronic: fibrotic, thickened valve → stenosis → mitral stenosis most common result
• "Fish mouth" mitral valve on gross appearance

INFECTIVE ENDOCARDITIS

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CARDIOMYOPATHIES — "3 types of sick heart muscle"

DILATED (DCM) — "Baggy heart"
Picture: Heart balloons out like a baggy sack, too weak to pump
Cause: Alcohol (#1), viral myocarditis, genetics, Chagas disease
→ All 4 chambers dilated, systolic dysfunction

HYPERTROPHIC (HCM) — "Thick wall heart"
Picture: Heart muscle becomes massively thick (especially septum) → blocks outflow
→ Asymmetric septal hypertrophy → LVOT obstruction
→ Most common cause of SUDDEN DEATH IN YOUNG ATHLETES
→ Autosomal dominant (sarcomere protein genes, usually MYH7 or MYBPC3)

RESTRICTIVE — "Stiff heart"
Picture: Heart is stiff like a board — can't fill properly
Cause: Amyloidosis, sarcoidosis, hemochromatosis (iron)
→ Stiff walls, diastolic dysfunction

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PERICARDIAL DISEASE

PERICARDITIS

• Inflammation of pericardium
• Causes: Viral (most common), bacterial (TB), post-MI (Dressler)
• Symptom: Chest pain that IMPROVES leaning FORWARD (classic posture)
• Sound: Pericardial friction rub
• ECG: Diffuse ST elevation (saddle-shaped)

CARDIAC TAMPONADE

• Beck's triad: Low BP + Muffled heart sounds + Distended neck veins (JVD)
• Treatment: Pericardiocentesis (drain the fluid with a needle)

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⚡ HEART RAPID FIRE

1. Breathless + pulmonary edema → ? → Left heart failure
2. Ankle swelling + JVD + liver congestion → ? → Right heart failure
3. Day 4 post-MI, heart wall weakest → ? → Risk of rupture
4. Most common cause of death immediately post-MI → ? → Arrhythmia (VF)
5. Strep throat → valve damage → pathognomonic lesion → ? → Aschoff bodies (rheumatic)
6. Most common congenital heart defect → ? → VSD
7. Most common CYANOTIC congenital defect → ? → Tetralogy of Fallot
8. IV drug user + tricuspid endocarditis bug → ? → S. aureus
9. Young athlete dies suddenly + thick septum → ? → HCM
10. All 4 chambers dilated + alcohol use → ? → Dilated cardiomyopathy
11. Beck's triad (low BP + muffled sounds + JVD) → ? → Cardiac tamponade
12. Chest pain better when leaning forward → ? → Pericarditis

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🩸 HEMATOPOIETIC SYSTEM (Week 3) — 15 MINUTE BLITZ

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ANEMIAS — "Why is there not enough red blood cells?"

1. MAKING TOO LITTLE (not enough production)
2. DESTROYING TOO MUCH (hemolytic)
3. LOSING BLOOD (bleeding)

KEY ANEMIAS — ONE IMAGE EACH:

• Most common anemia worldwide
• Microcytic (small RBCs), hypochromic (pale)
• Causes: Chronic bleeding (women: periods; men: GI bleed), poor diet
• Signs: Koilonychia (spoon-shaped nails), glossitis

• Cells are BIG (megaloblastic) because can't divide properly
• B12 deficiency: from autoimmune destruction of parietal cells → no intrinsic factor → no B12 absorption = Pernicious Anemia
• Also: neurological symptoms with B12 (subacute combined degeneration of spinal cord) — NOT with folate
• Macrocytic anemia + hypersegmented neutrophils

• Mutation in HbS (valine replaces glutamic acid in beta-globin)
• Cells sickle when O2 is low → block small vessels → vaso-occlusive crises → pain
• Protective against malaria
• Complications: Splenic infarction, stroke, avascular necrosis, infections (Salmonella osteomyelitis, encapsulated bacteria)

• Defect in spectrin (RBC membrane protein) → RBCs become spheres → spleen destroys them
• Splenomegaly + hemolytic anemia + jaundice
• MCHC elevated (dense cells)

• X-linked. Stress (infection, drugs, fava beans) triggers RBC destruction
• Heinz bodies (oxidized Hb) + bite cells

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LEUKEMIAS — "Which cell is multiplying abnormally?"

ALL (Acute Lymphoblastic Leukemia) → Children (#1 leukemia in kids)
→ Lymphoblasts, TdT positive, treat and often CURE

AML (Acute Myelogenous Leukemia) → Adults
→ Myeloblasts, Auer rods (pink needle-like inclusions in blasts)

CLL (Chronic Lymphocytic Leukemia) → Elderly
→ Smudge cells on smear, indolent course

CML (Chronic Myelogenous Leukemia) → Adults
→ Philadelphia chromosome (BCR-ABL translocation t(9;22))
→ Treat with Imatinib (Gleevec)

MCQ: Auer rods = AML. Smudge cells = CLL. Philadelphia chromosome = CML. TdT positive = ALL.

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LYMPHOMAS — "Nodes vs Nodes"

• Reed-Sternberg cells = pathognomonic (owl-eye appearance — two nuclei with big nucleoli)
• B symptoms: fever + night sweats + weight loss
• Young adults + elderly (bimodal)
• Spreads CONTIGUOUSLY (node to adjacent node)
• Excellent prognosis

• No RS cells
• More common than Hodgkin
• Many subtypes — most common adult = Diffuse Large B-cell Lymphoma
• Burkitt lymphoma: t(8;14), c-MYC, starry sky pattern, associated with EBV (Africa) or HIV

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BLEEDING DISORDERS

• Trigger: Sepsis, obstetric complications, trauma
• All coagulation tests HIGH (PT, aPTT, bleeding time)
• Platelets LOW (used up)
• Fibrin degradation products (D-dimer) HIGH

• Autoantibodies destroy platelets
• LOW platelets → easy bruising, petechiae
• Normal PT/aPTT (coagulation factors fine — only platelets low)

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🫁 LUNG (Week 4) — 10 MINUTE BLITZ

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OBSTRUCTIVE LUNG DISEASES — "Can't breathe OUT"

EMPHYSEMA = alveoli DESTROYED → "air trapping"
Picture: "Pink Puffer" — thin, pursed lips breathing, barrel chest
Cause: SMOKING (centriacinar) or α1-antitrypsin deficiency (panacinar)

CHRONIC BRONCHITIS = "Blue Bloater"
Productive cough for 3+ months, 2+ consecutive years
Cause: SMOKING → Reid index increased (mucous gland hyperplasia)
Picture: Overweight, blue, coughing constantly

ASTHMA = Airway hyperreactivity
Reversible bronchoconstriction → wheezing + dyspnea
Triggers: allergens, exercise, cold air
Histology: eosinophils + Curschmann spirals + Charcot-Leyden crystals

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PNEUMONIA — "Which bug for which patient?"

Community (young healthy) → S. pneumoniae (most common)
Atypical ("walking pneumonia") → Mycoplasma pneumoniae → treats with macrolides
Hospital-acquired → S. aureus, Gram negatives
Aspiration → anaerobes (right lower lobe) → in alcoholics, unconscious patients
Immunocompromised → PCP (Pneumocystis jirovecii) → treat with TMP-SMX

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TUBERCULOSIS

• Mycobacterium tuberculosis
• Primary TB: Ghon focus (lower lobe) + Ghon complex (+ hilar node)
• Reactivation TB: UPPER lobe cavities
• Histology: Caseating granulomas (necrotic center) + Langerhans giant cells

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LUNG CANCER ⭐

MCQ: Ectopic ACTH from lung = small cell cancer. Hypercalcemia from lung = squamous cell (PTHrP). Most common lung cancer = adenocarcinoma. Smoking most associated = small cell (and squamous).

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BONES & JOINTS (Week 13) — 10 MIN

OSTEOPOROSIS vs OSTEOMALACIA vs PAGET'S

OSTEOPOROSIS = bones THIN and fragile (normal mineralization, less bone)
Cause: menopause, aging, steroids
Complication: vertebral fractures, hip fractures

OSTEOMALACIA (adults) / RICKETS (children) = soft bones (mineralization FAILS)
Cause: Vitamin D deficiency → can't mineralize osteoid
Rickets: Bowing of legs, rachitic rosary (rib beading), pigeon chest

PAGET'S DISEASE = chaotic bone remodeling (too fast → disorganized)
Enlarged skull, hearing loss, high ALP, "mosaic pattern" on histology
Risk: Osteosarcoma (rare complication)

BONE TUMORS

OSTEOSARCOMA → Most common primary bone malignancy in YOUNG (teens)
→ Distal femur/proximal tibia (around the knee)
→ "Sunburst" pattern on X-ray + Codman's triangle
→ Associated with Rb gene mutation

OSTEOCHONDROMA → Most common benign bone tumor
→ Cartilage-capped bony outgrowth

GIANT CELL TUMOR → "Soap bubble" on X-ray, epiphysis of long bone
→ Benign but locally aggressive

EWING SARCOMA → Child + diaphysis of long bone + "onion skin" on X-ray
→ t(11;22) translocation

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JOINTS — ARTHRITIS

OSTEOARTHRITIS → "Wear and tear"
→ Elderly + weight-bearing joints (knee, hip)
→ Osteophytes (bone spurs), Heberden nodes (DIP), Bouchard (PIP)
→ No inflammation markers

RHEUMATOID ARTHRITIS → Autoimmune
→ Symmetrical small joints (PIP, MCP — spares DIP)
→ RF (rheumatoid factor) positive, anti-CCP antibody
→ Pannus (inflammatory tissue destroying joint)
→ Morning stiffness improves with activity

GOUT → Uric acid crystals
→ Big toe (podagra) most common
→ NEGATIVELY birefringent, needle-shaped crystals
→ Tophi (urate deposits)
→ Trigger: alcohol, meat, diuretics

PSEUDOGOUT → Calcium pyrophosphate crystals
→ POSITIVELY birefringent, rhomboid crystals
→ Knee most common

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PERIPHERAL NERVES & MUSCLES (Week 14) — 5 MIN

MYASTHENIA GRAVIS = antibodies against ACh RECEPTORS
→ Weakness WORSE with repeated use (fatigues)
→ Ptosis (droopy eyelid) + diplopia
→ Associated with THYMOMA
→ Treat: pyridostigmine (AChE inhibitor)

LAMBERT-EATON = antibodies against VOLTAGE-GATED Ca CHANNELS
→ Weakness IMPROVES with repeated use (opposite of MG!)
→ Associated with SMALL CELL LUNG CANCER
→ MCQ trick: if paraneoplastic + weakness = Lambert-Eaton

DUCHENNE MUSCULAR DYSTROPHY
→ X-linked, boys only
→ Dystrophin gene mutation
→ Pseudohypertrophy of calves (muscle replaced by fat)
→ Gowers sign (uses hands to climb up own legs to stand)
→ Death by late teens/20s (cardiac/respiratory failure)

MYOTONIC DYSTROPHY
→ Autosomal dominant, CTG repeat
→ Can't RELAX muscles (myotonia) → grip something, can't let go

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🔑 FINAL MASTER RAPID FIRE — ALL CHAPTERS

1. Barrett's → cancer type → ?
2. Skip lesions + granulomas → ?
3. Starts at rectum + continuous → ?
4. Child + nephrotic + responds to steroids → ?
5. Adult + nephrotic + spike and dome → ?
6. Cola urine 2 weeks after strep → ?
7. Hematuria same day as cold + IgA deposits → ?
8. Hematuria + hemoptysis + linear IF → ?
9. Crescents in glomerulus → ?
10. Most common malignant heart disease in young athlete → ?
11. Reed-Sternberg cells → ?
12. Auer rods → ?
13. Philadelphia chromosome → ?
14. DIC: platelets UP or DOWN? → ?
15. Squamous cell lung cancer paraneoplastic → ?
16. Small cell lung cancer paraneoplastic → ?
17. Sunburst X-ray + teen + knee → ?
18. Negative birefringent crystals + big toe → ?
19. Weakness WORSE with use + ptosis + thymoma → ?
20. Weakness IMPROVES with use + small cell lung cancer → ?

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1. Adenocarcinoma
2. Crohn's disease
3. Ulcerative colitis
4. Minimal change disease
5. Membranous nephropathy
6. Post-streptococcal GN
7. IgA nephropathy
8. Goodpasture disease
9. RPGN
10. HCM (hypertrophic cardiomyopathy)
11. Hodgkin lymphoma
12. AML
13. CML
14. DOWN (used up)
15. Hypercalcemia (PTHrP)
16. ACTH (Cushing) or ADH (SIADH)
17. Osteosarcoma
18. Gout
19. Myasthenia gravis
20. Lambert-Eaton syndrome

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1. Right now (30 min): Read the rapid fire drills for each chapter out loud — just the questions and answers
2. Next 30 min: Close this, write on a paper the diseases and their one-line image from memory. Check what you missed.
3. Last 30 min: Rest. Drink water. You know more than you think. 💪