Pathology Flashcards
OSTEOMALACIA
Softening of bone as a result of calcification failure due to vitamin D or calcium deficiency.
Can occur with renal tubular acidosis, paraneoplastic syndromes, renal failure
Chronic fatigue, bone pains and arthralgias, proximal muscle weakness, waddling gait, excessive lordosis, hypocalciuria, hypocalemia, hypophosphatemia, elevated alkaline phosphatase
Complications include nonreversible bone deformities and bone fractures
RICKETS
Defective mineralization of the osteoid matrix resulting in weakened bone
Occurs in children
Caused by deficient vitamin D and/or calcium and excess calcium loss
Often asymptomatic, bowing of long bones (genu valgum), contracted pelvic outlet, generalized tenderness, craniotabes, delay in fontanelle closure, costochondral junction thickening (Rachitic rosary), depression along the diaphragmatic insertion along the ribcage (Harrison’s groove), Pigeon breast, short stature, hypocalcemia, hypophosphatemia, elevated alkaline phosophatase,
Complications include nonreversible bone deformities and bone fractures
SCURVY
Connective tissue breakdown as a result of vitamin C deficiency
Impaired synthesis of hydroxyproline and hydroxylysine
Gum breakdown, impaired wound healing, fragile capillaries, abnormal bleeding, skin lesions, muscle, joint, and bone pain, subperiosteal hemorrhage, perifollicular petechial hemorrhages, lassitude, immunodeficiency, and death
ANKYLOSING SPONDYLITIS (AS)
Chronic autoimmune inflammation of the sacroiliac and spinal joints
90% HLA-B27+
Morning stiffness, low back and hip pain particularly at night, myalgias, anorexia, chest pain, fatigue
Complications include progressive rigidity and fixation of the lumbar spine and SI joint, iritis, aortic valve insufficiency, ascending aortitis, osteoporosis, cauda equina syndrome
FIBROMYALGIA
Non-articular rheumatic disorder with diffuse MSK pain, tender points, and non-restorative sleep
Point tenderness, aching and stiffness of the lower back, hips, trunk, and shoulders, hypermobility and joint laxity is common, myalgia, chronic fatigue, debilitating pain, insomnia due to pain, chronic illness, brain fog
Often associated with depression
GOUT
Deposition of urate crystal in tissues, particularly joints, due to high levels of uric acid in the blood.
Crystal precipitate more readily at lower temperatures
Metatarsophalangeal joint of the large toe is a common site
Acute
Precipitated by a large meal or alcohol intake
Due to IgG coating the crystals, phagocytosis by neutrophils, and the release of inflammatory mediators which cause swelling and pain.
Chronic
Long-term deposition causes the formation of nodular tophi around joints, the outer ridges of the auricle, Achilles tendon, etc.
Composed of urate crystals surrounded by fibrous connective tissue
Painful and acute inflammatory monoarthritis (commonly the big toe or knee) and gouty tophi in the chronic state.
Polymyositis
Symmetric pain and weakness of proximal limb and neck flexor muscles, distal musculature and muscles of deglutination are less commonly involved.
Symptoms develop over several weeks to months and have a waxing-waning course.
→ CD8+ cells invade muscle, >20 yoa, MC in females
Dermatomyositis
Heliotrope purple rash around eyes and extremities, periorbital swelling, Gottron’s papules or raised erythematous rash over bony prominences, V-shaped thoracic rash, cracked skin on hands, symmetrical proximal muscle weakness
Elevated serum muscle enzyme levels (CK), often +ve ANA, muscle biopsy is confirmatory
→ CD4+ cells invade muscle, as early as 5 yoa
POLYMYALGIA RHEUMATICA (PMR)
Chronic autoimmune disease in the elderly
Associated with temporal arteritis
Autoimmune synovitis present in the shoulders and hips
Proximal limb (shoulder and hip) weakness and pain, difficulty walking, morning stiffness, stiffness after inactivity, pain for > 2 months, weight loss, fever, depression, malaise, elevated ESR or CRP
Eye symptoms or headache highly suggestive of temporal arteritis
Complications include temporal arteritis which can cause blindness
REACTIVE ARTHRITIS
Autoimmune syndrome associated with HLA-B27 and systemic immune reaction to distal GI or GU infections.
Infection by Chlamydia trachnomatis, S. flexneri, Salmonella enteritidis, Shigella dysenteriae, Yersinia enterocolitica, Y. pseudotuberculosis, or Campylobacter jejuni
Triad = arthritis, urethritis, conjunctivitis/iritis/uveitis
Malaise, sacroilitis, fever, incubation period = 1-3 weeks after urethritis or diarrhea
MYASTHENIA GRAVIS
Autoimmune disorder caused by autoantibodies to acetylcholine receptors in neuromuscular junctions.
Muscle weakness which improves with rest
Women:men = 3:1
ACROMEGALY
Excessive GH secretion after the closure of the epiphyseal plates.
Usually from a somatotrophic pituitary adenoma
Enlargement of hands, feet, nose, lips, jaw, and ears, voice deeping due to vocal cord growth, weakening of the heart and kidneys, deadly
OSTEOPETROSIS
Rare genetic disorders with osteoclast dysfunction resulting in decreased bone resorption
Possibly due to carbonic anhydrase deficiency in the osteoclasts
Bone production by osteoblasts continues causing bone to become denser and more brittle.
Stunted growth, fractures, deformity, anemia, recurrent infections, hepatosplenomegaly, nerve compression resulting in blindness, deafness, and facial paralysis
Calcium and phosphate levels unaffected
Alkaline phosphatase is elevated.
CONGENITAL MYOPATHIES
Hypotonia at birth (floppy infant syndrome)
Forms
Central core disease
Loss of mitochondria and other organelles which are part of the central part of type I muscle fibers
Nemaline myopathy
Mild, non-progressive disease to severe weakness and death due to respiratory failure
Mitochondrial myopathies
Transmitted maternally as mitochondrial DNA abnormalities
MARFAN’S SYNDROME
Autosomal dominant syndrome characterized by connective tissue dysfunction
FBN1 gene encodes fibrillin-1 which is defective and results in excessive growth factor beta levels.
Long limbs and fingers, defective heart valves and aorta, dura, skeleton, lungs, hard palate, and lens of the eye (dislocation) can be affected, proximal aortic dissection
MUSCULAR DYSTROPHY
Group of genetic, progressive disorders characterized by degeneration of skeletal muscle and profound muscle wasting and weakness.
Duchenne muscular dystrophy (most common and severe)
X-linked recessive; caused by mutations in the dystrophin gene which encodes dystrophin
Initially presents in the proximal muscles of the extremities and causes compensatory hypertrophy of distal sites.
Pseudohypertophy of the calves (fat infiltrate, no contraction)
Becker’s muscular dystrophy (less severe)
X-linked recessive; caused by mutations in the dystrophin gene which encodes dystrophin
Slowly progressive muscle weakness of the legs and pelvis
OSTEOGENESIS IMPERFECTA
Autosomal dominant syndrome resulting in defective connective tissue formation
Brittle bones → fractures, scoliosis, loose joints, poor muscle tone, hearing loss risk, deformity, short stature possible
OSTEOARTHRITIS
Chronic, non-inflammatory joint disease involving the degeneration of articular cartilage and new bone (spur) formation at the margins of the joint.
Elderly women affected 10x more than men
Asymmetrical weight bearing joint and distal interphalangeal (DIP) joints
Cartilage erosion resulting in polished bone, subcondral cystic changes, osteophyte formation, and nodes (hard and painless)
Heberden’s nodes = DIP joints
Bouchard’s nodes = PIP joints
OSTEOPOROSIS
Decrease in bone mass resulting in increased fracture risk
Type I
Associated with estrogen deficiency of menopause
Common fracture locations include the wrist and spine
Type II
Associated with aging and reduced calcium absorption
Associated with hip fractures
Results from calcium deficiency, physical inactivity, hypercorticism, hyperthyroidism
OSTEITIS DEFORMANS
Bone breakdown initially followed by replacement with denser bone which leads to bone deformity
Lytic mixed with sclerotic areas
Affects the skull primarily
Can result in bowing of the femur/tibia, osteoarthritis, and fractures
AKA Paget’s disease
AVASCULAR NECROSIS
Avascular necrosis is the death of bone tissue due to a lack of blood supply.
The blood flow to a section of bone can be interrupted if the bone is fractured or the joint becomes dislocated.
Associated with long-term use of high-dose steroid medications and excessive alcohol intake.
Pain can be mild or severe and usually develops gradually.
Also called osteonecrosis
Can lead to tiny breaks in the bone and the bone’s eventual collapse.
CHONDROSARCOMA
Malignant cartilaginous tumor
Common in men between 30-60 years of age
Affects the spine, scapula, pelvis, proximal humerus, proximal or distal femur, or proximal tibia
EWING’S SARCOMA
Neoplastic, small-cell malignant tumor
Found in long bones, ribs, pelvis, scapula
Sunburst pattern seen on X-ray
Peak incidence occurs in boys under 15 years of age
Metastasizes early
OSTEOID OSTEOMA
Osteoma
benign
Sessile tumor composed of dense, well-formed bone
Insignificant unless location affects organ function
Osteoid osteoma
Small benign neoplasm
OSTEOSARCOMA
Most common primary malignant tumor of the bone
Distal femur or proximal tibia
Occurs in male aged 10-30 years of age
Destructive, mixed lytic and blastic, lifts the periosteum resulting in pain
Risk factors include bone infarcts, Paget’s disease, ionizing radiation
RHABDOMYOSARCOMA
Cancer affects skeletal muscle precursors and occurs in areas without skeletal muscle
Occurs most frequently in children
GANGRENE
Necrosis of tissues due to ischemia caused by soft tissue infection
Clostridis perfringes (wet)
Cold, painful, or numb, dry and scaly skin with poor nail and hair growth are signs of severe ischemia prior to the onset of gangrene
Ulceration occurs along with atrophy of the limb
Risk factors include trauma + infection, arterial insufficiency, atherosclerosis, diabetes, immunosuppression
Complications include sepsis, invasion to other tissues, death
NECROTIZING FASCIITIS
Causes include group A Streptococcus (group A strep), Klebsiella, Clostridium, Escherichia coli, Staphylococcus aureus, and Aeromonas hydrophila
Presentation includes skin that is red, swollen, and hot to the touch, fever, chills, nausea, vomiting, diarrhea.
The infection may spread rapidly. It quickly can become life-threatening.
Commonly referred to as “flesh-eating infection”
Causes include group A Streptococcus (group A strep), Klebsiella, Clostridium, Escherichia coli, Staphylococcus aureus, and Aeromonas hydrophila
Group A strep is considered the most common cause of necrotizing fasciitis.
OSTEOMYELITIS
Pyogenic osteomyelitis
Most commonly S. aureus
Due to sepsis in children and as a result of a compound fracture or surgery in adults
Primarily affects the distal end of femur and proximal ends of the tibia and humerus
A sleeve of new bone (involucrum) can surround the necrotic area.
Tubercular osteomyelitis
Secondary to TB infection elsewhere
Vertebrae (Pott’s disease), long bones (tibia and femur), hip, and hand and foot bones
SEPTIC ARTHRITIS
Infection of a joint with severe inflammation
Gonorrhea is the most common bacterial cause
Also caused by staph, strep, Haemophilus influenzae
Viral causes include rubella, mumps, hepatitis B, Lyme disease
Acute onset monoarticular arthritis (shoulder, wrist, knee, hip, fingers, or elbow), joint stiffness, warm tender swollen joints, leukocytosis, fever
Ehlers-Danlos syndrome
o excessive elastic tissue in skin and joint capsule
o hypermobile joints leading to severe joint degeneration
Osteogenesis imperfecta:
o defective collagen synthesis
o frequent broken bones
o blue sclera
Adult Polycystic Disease of the kidney:
o multiple cysts in both kidneys
o hypertension
o berry aneurysms
Glycogen storage disorders:
o Von Gierke-Glucose-6 Phosphatase deficiency-accumulates in the liver
o McArdle-muscle phosphorylase deficiency-accumulates in the muscle
o Pompe-maltase deficiency affects the heart pum
Lysosomal storage disorders
o Tay-Sachs-gangliosides accumulation in the brain; rapidly fatal
cherry red macula
severe mental retardation
Phenylketonuria
Amino acid disorders:
accumulation of phenylalanine due to lack of PA hydroxylase; mental
retardation
restrict dietary phenylalanine if the Guthrie test for PKA is positive