1List the factors that positively and negatively affect bone metabolism:*\.
Positively: BMPs, sex hormones (estrogen/testosterone), Vitamin D, and exercise.
Mechanism: Blocks osteoclasts (resorption) and boosts calcium.
Negatively: PTH, IL-1, glucocorticoids, and aging.
Mechanism: Promotes osteoclasts and lowers osteoblast (building) activity.
2What is the cause of achondroplasia?:*\ (short limbed dwarfism, most common) What are its clinical features?
Cause: Activating mutation in FGFR3.
Mechanism: Inhibits chondrocyte proliferation in growth plates.
Clinical Features:
Short stature with short proximal limbs (rhizomelia).
Bowed legs, frontal bossing, and midface hypoplasia.
3What is the cause of osteogenesis imperfecta?:*\ What are its clinical features?
Defective Type I Collagen (alpha 1 or alpha 2 mutations)
.Features: Brittle bones (fragility).Blue sclerae (translucent choroid).Hearing loss (ossicle defects).Misshapen teeth.
4What is the cause of osteopetrosis:*\? What are its clinical features?
Defective osteoclast bone resorption.
Features:
"Stonelike" bones: Dense but brittle/weak.
Cranial nerve palsies: Compressed nerves in narrowed foramina.
Recurrent infections: Reduced marrow space (anemia/leukopenia).
5What is the cause of osteoporosis? What are its clinical features? What are its histopathological findings?
Resorption > Formation (Aging or Post-menopausal ↓ Estrogen).
Clinical Features:
Asymptomatic until fracture.
Key Sites: Vertebrae (Kyphosis/height loss) and Hips.
Histopathology:
Normal quality, decreased quantity.
Thinned cortical and trabecular bone.
6What are the causes of rickets and osteomalacia? What are their clinical features? What are their histopathological findings?
Cause:
Vitamin D deficiency or abnormal metabolism.
Clinical Features:
Children (Rickets): Bowed legs, frontal bossing, rachitic rosary.
Adults (Osteomalacia): Bone pain and fracture risk.
7What is the cause of Paget’s disease of bone? What are its clinical features? What are its histopathological findings?
Cause:
Genetic (SQSTM1 mutation) + Environmental (Viral infection of osteoclasts).
Clinical Features:
Often asymptomatic.
Bone pain, deformity, and "chalk stick" fractures.
Nerve impingement (Headache/Hearing loss).
Histopathology:
Mosaic pattern: Lamellar bone with haphazard cement lines.
8List and define the types of fractures.
Simple (Closed): Skin intact.
Compound (Open): Bone pierces skin.
Comminuted: Fragmented or splintered.
Displaced: Ends are out of alignment.
Greenstick: Partial breakending (common in children).
Pathologic: Occurs in diseased bone (tumor/cyst).
9List the stages of fracture healing and the factors affecting bone healing.
Hematoma (0–1 day).
Soft Callus (0–2 weeks): Fibrocartilage.
Hard Callus (2–3 weeks+): Bony bridge.
Remodeling: Return to original shape.
10What is the cause of osteomyelitis:*\? What are its clinical features? What are its histopathological findings?
Cause:
Pyogenic bacteria (most common: S. aureus).
M. tuberculosis (Pott disease in spine).
Clinical Features:
Fever, malaise, throbbing pain, and localized edema.
Histopathology:
Sequestrum: Necrotic dead bone.
Involucrum: Surrounding shell of living reactive bone.
11What is the cause of osteoarthritis? What are its clinical features? What are its histopathological findings?
Cause: Degeneration of articular cartilage due to chondrocyte injury, aging, and repeated biomechanical stress.
Clinical Features: Pain exacerbated by use, morning stiffness, crepitus, and Heberden nodes in women.
Histopathology: Cartilage fibrillation (cracks), bone eburnation, and osteophytes
12What is the cause of rheumatoid arthritis? What are its clinical features? What are its histopathological findings?
Cause: Systemic autoimmune disease driven by CD4+ T cells and cytokines (TNF).
Clinical Features: Symmetric polyarthritis (small joints of hands/feet), swan-neckoutonnière deformities, and nontender rheumatoid nodules.
Histopathology: Chronic synovitis, synovial cell hyperplasia, and Pannus
that erodes cartilage.
13What is the cause of juvenile rheumatoid arthritis (juvenile idiopathic arthritis)? What are its clinical features? What are its histopathological findings?
Cause: Autoimmune origin (linked to HLA and PTPN22 variants) presenting before age 16.
Clinical Features: Oligoarthritis is more common than in adult RA; systemic disease is frequent; and ANA seropositivity is common while rheumatoid factor is usually absent.
Histopathology: Chronic synovitis similar to adult RA.
14What are seronegative spondyloarthropathies? List their types.
Immune-mediated disorders. HLA-B27 associated. RF negative (seronegative) affecting Sacroiliac.
Types:
Ankylosing spondylitis
IBD-associated
Psoriatic arthritis:
Reactive arthritis:
15What is the cause of gout? How many clinical presentations does it have? List them by name. What are the clinical features of gout? What are its histopathological findings?
Cause: Hyperuricemia (Urate > 6.8 mg/dL)--> crystal precipitation.
Presentations:
Asymptomatic hyperuricemia.Acute gouty arthritis.Intercritical gout (remission).Chronic tophaceous gout.
Clinical Features:
Sudden severe pain (50% in 1st MTP joint).Localized hyperemia and warmth.
Histopathology:
Needle-shaped crystals.Negatively birefringent.Tophi: Urate aggregates + giant cells.
16List the differences between gout and pseudogout.
Feature, Gout, Pseudogout
Crystal, Monosodium urate, Calcium pyrophosphate
Shape, Needle-shaped, Rhomboid-shaped
Birefringence, Negative (yellow), Positive (blue)
Joint Site, 1st MTP (Big toe), "Knees, wrists, shoulders"
17Explain group atrophy and fiber type grouping in muscle tissue.
Cause:
Repeated nerve loss (denervation) and regrowth (re-innervation).
Fiber Type Grouping:
Re-innervated fibers switch types to match the new nerve.
"Checkerboard" pattern is replaced by large clusters of the same fiber type.
Group Atrophy:
Occurs if the new "large nerve" is lost.
Leaves behind large clusters of shrunken (atrophic) fibers.
18What is the cause of Duchenne muscular dystrophy (DMD)? What are its clinical and laboratory findings? What are the histomorphological findings in tissue?
Cause:
X-linked recessive mutation; complete absence of Dystrophin.
Clinical:
Early onset (age 3–5).
Cognitive impairment.
Death in early adulthood (Respiratory/Cardiac failure).
Laboratory:
Very high CK at birth; falls as muscle mass is lost.
Histomorphology:
Segmental necrosis and regeneration.
Muscle replaced by fat and connective tissue.
19What is the cause of Becker muscular dystrophy (BMD)? What are its clinical and laboratory findings? What are the histomorphological findings in tissue?
Cause:
X-linked recessive; truncated (shortened) but partially functional Dystrophin.
Clinical:
Later onset (childhood/teens) and slower progression.
Cardiac involvement can be the primary feature.
Laboratory:
Elevated CK.
Histomorphology:
Segmental necrosis and regeneration.
20Write at least 5 microscopic features of acute neuronal injury (Red Neurons)
Cell Body: Shrinkage.
Nucleus: Pyknosis (shrunken and dark).
Nucleolus: Disappears.
Nissl Substance: Lost.
Color: Intense eosinophilia (bright red appearance).
21Write at least 4 microscopic (morphological) features of axonal injury.
Cell Body: Enlargement and rounding.
Nucleus: Peripheral displacement.
Nucleolus: Enlargement.
Cytoplasm: Central chromatolysis (Nissl substance moves to periphery).
22Explain the production, circulation, and absorption of cerebrospinal fluid (CSF).
Production:
Secreted by the choroid plexus (ventricles).
Circulation
1. Ventricles.
2. Exits via Foramina of Luschka & Magendie
3. Subarachnoid space
Absorption
Arachnoid granulations --> Venous system.
23What is hydrocephalus?
An accumulation of excessive CSF within the ventricular system, typically due to a blockage in flow or decreased absorption.
24Write the names of brain herniations, their causes, and their locations.
Subfalcine (Cingulate):
Hemisphere expansion pushes cingulate gyrus under the falx cerebri.
Transtentorial (Uncinate):
Medial temporal lobe pushed against tentorium.
Sign: "Blown pupil" (CN III palsy).
Tonsillar:
Cerebellar tonsils pushed through foramen magnum.
Life-threatening: Brainstem/medullary compression.
25Write the examination findings of brain death and vegetative state.
Brain Death:
EEG: Flat (isoelectric).
Reflexes: Absent brainstem reflexes.
Respiration: No spontaneous respiratory drive.
Vegetative State:
Cause: Survival after severe global ischemia.
Status: Profoundly impaired and non-responsive.
26Write the causes and types of intracranial hemorrhage.
Types:
Epidural: Traumatic; Arterial (Middle meningeal artery).
Subdural: Traumatic; Venous (Bridging veins).
Subarachnoid: Aneurysm rupture ("Worst headache of life").
Intraparenchymal: Hypertension or CAA (Amyloid angiopathy).
Main Causes:
Hypertension (Primary cause).
Trauma.
Vascular Malformations (AVMs).
Berry Aneurysms.
Tumors.
27Explain the terms coup injury, contrecoup injury, contusion, and concussion.
Coup: Injury at the point of impact.
Contrecoup: Injury on the side opposite the impact.
Contusion: A "bruise" caused by rapid tissue displacement, hemorrhage, and edema.
Concussion: Reversible loss of consciousness after head injury without a contusion.
28Write and explain neural tube defects.
Failure of the neural tube to close during development (folate deficiency increases risk).
Spina bifida occulta: Asymptomatic bony defect.
Myelomeningocele: CNS tissue extending through a lumbosacral vertebral defect.
Anencephaly: Absence of the brain and top of skull.
29Write the components of Arnold–Chiari malformation and Dandy–Walker syndrome.
Arnold-Chiari (Type II):
Posterior Fossa: Small.
Vermis: Extension through foramen magnum.
Associated: Hydrocephalus and lumbar myelomeningocele.
Dandy-Walker:
Posterior Fossa: Enlarged.
Vermis: Absent (agenesis).
Associated: Large midline cyst.
30What is cerebral palsy? What are the brain findings?
Definition:
Non-progressive motor deficits.
Result of prenatal or perinatal injury.
Findings:
Germinal matrix hemorrhage.
Periventricular leukomalacia: Necrosis and mineralization of white matter.
31What is meningitis? What are its clinical findings? What are the laboratory findings of bacterial, viral, and chronic meningitis?
inflammation of the protective membranes (meninges) surrounding the brain and spinal cord
Clinical Features:
Headache and Fever. Nuchal rigidity (neck stiffness). Photophobia.
Type, Cell Type, Protein, Glucose
Bacterial, Neutrophils, High, Low
Viral, Lymphocytes, Moderate, Normal
Chronic, Lymphocytes/Plasma cells, Variable, Variable
32What is prion disease? Write its types.
Definition:
Infectious misfolding of PrPsc protein.
Causes neighboring proteins to misfold (chain reaction).
Types:
Sporadic CJD: Most common.
Familial: Genetic mutation.
Iatrogenic: Medical transmission (e.g., surgery).
Variant CJD (vCJD): Linked to "mad cow" (BSE).
33What are the causes, clinical findings, laboratory findings, and histopathological findings of multiple sclerosis (MS)?
Cause: Autoimmune demyelination.
Clinical: Relapsing-remitting neurologic deficits (episodes).
Lab: CSF shows oligoclonal bands (IgG).
Histopath: Plaques of demyelinated white matter.
34What are the causes, clinical findings, laboratory findings, and histopathological findings of Alzheimer’s disease?
Cause: Accumulation of beta-amyloid and tau proteins.
Clinical: Insidious onset of dementia (progressive memory/cognitive loss).
Histopath: Aβ plaques (extracellular) and tau tangles (intracellular).
35What are the causes, clinical findings, laboratory findings, and histopathological findings of Parkinson’s disease?
Cause: Loss of dopaminergic neurons in the substantia nigra.
Clinical: Resting tremor, rigidity, bradykinesia, and postural instability.
Histopath: Lewy bodies containing alpha-synuclein.
36What are the causes and clinical findings of ALS?
Cause: Death of both upper (motor cortex) and lower (spinal cord) motor neurons.
Clinical: Muscle weakness, atrophy, and fasciculations; sensation remains normal.
37Classify brain tumors.
Primary: Gliomas (Astrocytomas, Glioblastoma), Meningiomas, Embryonal (Medulloblastoma), and Neuronal tumors.
Metastatic: The most common form (1/2 to 1/4 of all intracranial tumors).
38Which histopathological criteria are used in grading gliomas? Classify them according to grade.
Criteria: Nuclear atypia, mitoses, endothelial proliferation, and necrosis.
Grades: Grade II (Well-differentiated), Grade III (Anaplastic), and Grade IV (Glioblastoma).
39What is pilocytic astrocytoma? What are its radiological and morphological findings?
Tumor: Relatively benign (Grade I), typically in children/young adults.
Radiological: A cyst with a mural nodule.
Morphological: Presence of Rosenthal fibers (thick eosinophilic protein aggregates).
40What is the cause of Guillain-Barré syndrome (GBS)? What are its clinical and laboratory findings? What are the histomorphological findings in tissue?
Cause:
Autoimmune trigger: Post-vaccination or infection (C. jejuni, EBV, CMV, HIV).
Clinical Features:
Ascending weakness: Rapidly progressive (legs to trunk).
Risk of respiratory failure.
Lab Findings:
Combined humoral and cellular immune response.
Histology:
Mononuclear infiltrates.
Damage concentrated in nerve roots and proximal segments.
41What is the cause of Chronic inflammatory demyelinating polyneuropathy (CIDP)? What are its clinical and laboratory findings? What are the histomorphological findings in tissue?
Cause: An immune-mediated inflammatory process; often occurs with other disorders like SLE or HIV.
Clinical: Symmetrical sensorimotor polyneuropathy (weakness, numbness, pain) persisting for 2 months or more with a chronic or relapsing-remitting course.
Laboratory: Responds to plasmapheresis and immunosuppressive agents.
Histomorphology: Segments of demyelination and remyelination.
42List the types of diabetic peripheral neuropathy and explain their clinical features.
Distal symmetric sensorimotor polyneuropathy: numbness and paresthesias
Autonomic neuropathy: Changes in bowel, bladder, cardiac, or sexual function.
Lumbosacral radiculopathy: Asymmetric pain that progresses to lower extremity weakness and muscle atrophy.
43What is the cause of Myasthenia gravis? What are its clinical and laboratory findings?
Cause:
Autoantibodies block/deplete AChR (postsynaptic acetylcholine receptors).
Associated with Thymic hyperplasia (60%) or Thymoma (20%).
Clinical:
Ptosis (drooping eyelids) and Diplopia (double vision).
Weakness worsens with repetitive use.
Diagnosis:
Strength improves with cholinesterase inhibitors (e.g., Edrophonium/Tensilon test).
44Explain the differences between Lambert-Eaton myasthenic syndrome (LEMS) and Myasthenia gravis (MG).
MG is postsynaptic (AChR antibodies); LEMS is presynaptic (calcium channel antibodies).
In MG, weakness gets worse; in LEMS, strength improves as calcium builds up to release acetylcholine.
MG is linked to thymic issues; LEMS is often a paraneoplastic disorder (small cell lung carcinoma.)
Treatment: Cholinesterase inhibitors mark MG diagnosis but are not effective for LEMS.
45Explain the mechanisms of action and clinical features of toxins produced by Clostridium tetani and Clostridium botulinum.
Tetanus Toxin (C. tetani):
Mechanism: Blocks inhibitory neurons, causing increased release of acetylcholine.
Clinical: Sustained muscle contraction and spasm (tetanus).
Botulinum Toxin (C. botulinum):
Mechanism: Inhibits acetylcholine release into the synaptic cleft.
Clinical: Flaccid paralysis.
46Compare the two main types of gallstones (cholelithiasis), cholesterol and pigment stones, in terms of their formation mechanisms, macroscopic color/content, and radiological appearance.
Cholesterol Stones
Mechanism: Bile supersaturated with cholesterol.
Appearance: Pale yellow; mostly cholesterol monohydrate.
Radiology: Radiolucent (Invisible on X-ray).
Pigment Stones
Mechanism: Precipitation of bilirubin calcium salts.
Appearance: Black or Brown; contains calcium bilirubinate.
Radiology: Radiopaque (Visible - specifically Black stones).
47Compare Primary Biliary Cholangitis (PBC) and Primary Sclerosing Cholangitis (PSC) in terms of the bile duct diameters they affect, associated autoantibodies, and radiological appearances.
PBC
Ducts: Small and medium intrahepatic.
Antibody: AMA (Anti-mitochondrial).
Radiology: Usually normal.
PSC
Ducts: Large intrahepatic and extrahepatic.
Antibody: pANCA.
Radiology: "Beading" (alternating strictures and dilations).
48Write the clinical and histomorphological findings of acute and chronic cholecystitis.
Acute Cholecystitis
Clinical: Sudden RUQ pain, fever, nausea.
Pathology: Red, tense, and swollen gallbladder; neutrophil infiltration and edema.
Chronic Cholecystitis
Clinical: Recurrent colicky pain; often asymptomatic.
Pathology: Thickened gallbladder wall; extensive fibrosis and Rokitansk
Aschoff sinuses: (mucosal outpouchings).