Pathoma Flashcards
What is achondroplasia and what is it caused by?
Impaired proliferation in the growth plate; common cause of dwarfism. Due to an activating mutation in the FGFR3.
Describe the extremities of a patient with achondroplasia?
They will have a normal head and chest, but shortened extremities
What is endochondral bone formation? What bones use this for growth?
Formation of a cartilage matrix which is then replaced by bone; used by long bones
What is intramembranous ossification? What bones use this for growth?
Characterized by formation of bone without a preexisting cartilage network. Flat bones develop this way (skull and ribs)
What is the reason for shortened extremities and not skull bones in patients with achondroplasia?
Long bones use endochondral ossification to develop. The mutation in FGFR3 causes impaired proliferation of cartilage leading to shortened bones.
What is osteogenesis imperfecta and what is the cause of it?
Congenital defect of bone formation resulting in structurally weak bone. Defect in type 1 collage synthesis.
What are some of the clinical features of osteogenesis imperfecta?
Multiple bone fractures - can mimic child abuse
Blue sclera - thinning of scleral collagen revealing underlying chorocoidal veins
Hearing loss - bones of the middle ear fracture easily
What is osteopetrosis and what is the cause of it?
Inherited defect of bone reabsorption resulting in abnormally thick heavy bone that fractures easily.
Due to a defect in osteoclast function. Carbonic anhydrase II deficiency also does not allow for an acidic environment.
What are the clinical features of of osteopetrosis?
Bone fractures
Anemia - due to bony replacement of the marrow
What is the treatment of osteopetrosis?
Bone marrow replacement because osteoclasts are derived from monocytes
What is Rickets/Osteomalacia and what causes it?
Defective mineralization of osteoid - osteoblasts produce osteoid which is then mineralized with calcium and phosphate.
Usually due to a deficiency of Vitamin D
How does Vitamin D act to raise serum calcium?
Intestine - increases absorption of calcium and phosphate
Kidney - increases absorption of calcium and phosphate
Bone - increases absorption of calcium and phosphate
Rickets usually presents in what age group and what are the symptoms?
Arising in children less than 1 year old
Pigeon-breast deformity
Frontal bossing (enlarged forehead) due to osteoid deposition on the skull
Rachitic rosary - due to osteoid deposition at the chostochondral junction - bone bumps on rib cage
Bowing of the legs
Osteomalacia is due to? What can it lead to?
Low vitamin D in adults - inadequate mineralization results in weak bone with an increased risk for fracture
What are the lab findings associated with osteomalacia?
Decreased serum calcium, decreased serum phosphate, increased PTH, and increased alk phos (due to osteoblasts trying to mineralize)
What is osteoporosis and what can it lead to?
This is a reduction in trabecular bone mass and can result in porous bone with an increased risk for fracture
What factors can affect peak bone mass and the rate of decline through life?
Peak bone mass is determined by - exercise, genetics, and diet
The rate can change based on diet and and exercise
What are the clinical features of osteoporosis?
Bone pain and fractures in weight-bearing areas such as vertebrae, hip and distal radius
Bone density is done using a DEXA scan
Calcium, phosphate, PTH and alk phos are all normal
What is the treatment of osteoporosis?
Diet, exercise, Vitamin D
Bisphosphonates - induce apoptosis of osteoclasts
What is Paget’s disease and what is the cause of it?
This is an imbalance between the osteoblasts and osteoclasts - leading to the osteoblast essentially going crazy
A biopsy of a person with Paget’s Disease will reveal?
Mosaic Pattern of Lamellar Bone
Cement lines
What are the clinical features of Paget Disease of the bone?
Bone pain due to microfractures
Increased hat size - skull is most often affected
Isolated elevated alk phos - mineralization of bone
What is the main complication associated with Paget Disease of the bone?
Osteosarcoma
What is osteomyelitis?
Infection of the marrow and bone
What are the most common causes of osteomyelitis?
Transient bacteremia (children) seeding the metaphysis Open-wound bacteremia (adults) seeds epiphysis
What are the most common agents for osteomyelitis?
S. aureus - most cases >90%
N gonorrhoeae - sexually active young adults
Salmonella - sickle cell disease
What are the clinical features of Osteomyelitis?
Bone pain with signs of infection
Lytic focus surrounded by sclerosis of bone on x-ray
What is Avascular Necrosis? What is the cause?
Ischemic necrosis of bone and bone marrow
Causes include trauma or fracture
What is a major risk factor of avascular necrosis?
Osteoarthritis
What is an Osteoma and where does it arise?
Benign tumor bone - most commonly on facial bones
Associated with Gardner Syndrome - FAP and Fibromatosis
What are the characteristics of an Osteoid osteoma?
Benign tumor of osteoblasts (producing osteoid) surrounded by a rim of reactive bone.
Occurs in young adults
Arises in the cortex of long bones.
What is important about the type of pain that is associated with osteoid osteoma?
Presents as bone pain that is relieved with asprin - decreased prostaglandins
How does an osteoblastoma differ from an osteoid osteoma?
Arises in the vertebrae and present as bone pain that does not respond to asprin
What is an osteochondroma?
This is a tumor of bone with an overlying cartilage cap. It arises from a lateral projection of the growth plate; bone is continuous with the marrow space
What are the characteristics of an osteosarcoma?
Malignant proliferation of osteoblasts - arises in the metaphysis of long bones usually in the distal femur or proximal tibia
Peak incidence is seen in teenagers - less common in elderly
What are the risk factors of osteosarcoma?
Familial retinoblastoma
Paget disease - osteosarcoma in elderly
radiation exposure
What is the important X-ray finding associated with Osteosarcoma?
Imaging reveals sunburst appearance and lifting of the periosteum - Codman Triangle
What is a giant cell tumor?
Tumor comprised of multinucleated giant cells and stromal cells
Arises from the epiphyseal plate - only tumor to do so
Soap Bubble appearance on X-ray
What is a Ewing Sarcoma?
Malignant proliferation of poorly-differentiated cells from neuroectoderm
Diaphysis of long bones
What is the important genetic component of Ewing Sarcoma?
11;22 translocation
What are the characteristics of a Chondroma?
Benign tumor of cartilage and usually arises from the small bones of the hand and feet
What are the characteristics of a Chondrosarcoma?
Malignant cartilage-forming tumor that arises in the medulla of the pelvis or central skeleton
What are the characteristics of metastatic tumors of the bones?
These are more common than primary bone tumors
These usually result in osteolytic lesions
Prostatic carcinoma usually produces osteoblastic lesions
What is Osteoarthritis and what is the cause?
Progressive degeneration of articular cartilage most often due to wear and tear on the bone
What are the characteristics about the types of joints that Osteoarthritis affects?
It has a limited number
Most often affects the hips, lower lumbar spine, knees, DIPs and PIPs
How will the pain present in patients with Osteoarthritis?
Joint stiffness in the morning that will worsen with activity
What are the pathologic features of Osteoarthritis?
Osteophyte formation
Disruption of the cartilage that lines the articular surface
Eburnation of subchondral bone
What are the specific nodes referred to as in osteoarthritis?
DIP - Heberden
PIP - Bouchard
What are the characteristics of Rheumatoid Arthritis?
Chronic, systemic autoimmune disease associated with HLA-DR4
It is characterized by involvement of joints - synovitis leading to a pannus (inflamed granulation tussue)
This can lead to destruction of cartilage and anklyosis
What are the clinical features of Rheumatoid Arthritis?
This presents a morning stiffness that will improve with activity. Symmetric involvement of PIP joints of the fingers.
THE DIP IS USUALLY SPARED
Rheumatoid nodules - central zone of necrosis surrounded by epitheloid histiocytes
Baker cyst - swelling of the back of the knee
What are the laboratory findings associated with RA?
IgM autoantibody against Fc portion of IgG (Rheumatoid factor)
Neutrophils and high protein in the synovial fluid
What are Seronegative Spondyloarthropathies?
Group of disorders characterized by no RF
Axial skeleton involvement
HLA-B27
This includes ankylosing spondyloarthritis, Reiter Syndrome, Psoriatic arthritis
What are the characteristics of ankylosing spondyloarthritis?
Involvement of the Sacroiliac joints of the spine
Presents with lower back pain - involvement of the vertebral bodies eventually arises leading to fusion of the vertebrae
What is Reiter Syndrome?
This is characterized by the triad of arthritis, urethritis, and conjunctivitis - weeks after an infection with Chlamydia
What are the characteristics of Psoriatic arthritis?
Patients have previous diagnosis of psoriasis
Involves the axial and peripheral joings - DIPs of the hands and feet are most common leading to sausage fingers
What are the main culprits in infectious arthritis?
N gonorrhoeae - Sexually active young adults
S aureus - older children and adults
How will infectious arthritis present?
Involve a single joint, and presents with signs of infection
Elevated white count, elevated ESR
What are the characteristics of Gout?
Deposition of monosodium urate crystals in tissues especially the joints.
Due to hyperuricemia - due to overproduction or decreased excretion of uric acid - product of purine metabolism
How does acute gout present?
Exquisitely painful arthritis of the big toe
MSU crystals deposit in the joint triggering an acute inflammatory reaction
Alcohol may contribute to this
What can chronic gout lead to?
Tophi - white chalky aggregates of uric acid crystals with fibrosis and giant cell reaction in soft tissue and joints
What will the lab findings be associated with gout?
Hyperuricemia
Synovial fluid has needle-shaped crystals with negative birefringence under polarized light
What is pseudogout?
Resembles gout clinically but is due to deposition of calcium pyrophosphate dihydrate (CPPD) synovial fluid will show rhomboid-shaped crystals with weakly positive birefringence
What are the characteristics of Dermatomyositis?
Inflammatory disorder of the skin and skeletal muscle Some cases are associated with caricinoma PERIMYSIAL INFLAMMATION (CD4)
What are the clinical features of Dermatomyositis?
Bilateral proximal muscle weakness; possible distal involvement late in the disease
Rash on upperlids and malar rash
Red papules
What are the laboratory findings of Dermatomyositis?
Increased CK
Positive ANA
Positive Anti-Jo-1 antibody
What is polymyositis?
Inflammatory disorder of skeletal muscle
Resembles dermatomyositis but without skin involvement
Endomysial inflammation (CD8)
What is X-linked muscular dystrophy?
Degenerative disorder characterized by muscle wasting and replacement of skeletal muscle with adipose
Due to defects in the dystrophin gene
What is the dystrophin gene?
It is important for anchoring muscles cytoskeleten to the extracellular matrix
Mutations can be spontaneous - large gene
What is Duchenne MD and how will it present?
It is a deletion of the dystrophin gene - presenting as proximal weakness at the age of 1 and progresses to involve the distal muscles
These patients will have Calf pseudohypertrophy and elevated creatine kinase
What is Becker’s muscular dystrophy?
Mutated dystrophin gene - much milder
What is Myasthenia Gravis?
Autoantibodies against the postsynaptic acetylcholine receptor at the NM junction
What are the clinical features of Myasthenia Gravis?
Muscle weakness that worsens with use and improves with rest - usually leading to ptosis
Improvement with acetylcholinesterase agents
What is a lipoma?
Benign tumor of adipose - most common
What is a liposarcoma?
Malignant tumor of adipose tissue
LIPOBLAST
What is a Rhabdomyoma?
Benign tumor of skeletal muscle
What is a Rhabdomyosarcoma?
Malignant tumor of skeletal muscle
Most common malignant tumor in children
RHABDOMYOBLAST - Desmin positive
Vagina is classic site in younger girls
What are the characteristics of Atopic Dermatitis?
Pruritic, erythematous, oozing rash. Usually involves face and flexor surfaces. Type I hypersensitivity reaction - associated with asthma and allergic rhinitis
What are the characteristics of Contact Dermatitis?
Pruritic, erythematous oozing rash with vesicles and edema
Arises upon exposure to allergens such as poison ivy and nickle
What are the characteristics of Acne Vulgaris?
Comedones and pustules
Due to chronic inflammation of hair follicles and associated sebaceous gland
What causes the comedones and pimples in acne vulgaris?
Hormone-associated increase in sebum production and excess keratin production blocks follicles forming comedones
P. acnes infection produces lipases that break down sebum leading to proinflammatory FAs that result in inflammation
What is Psoriasis and what causes it?
Well-circumscribed, salmon-colored plaques with silvery scale usually on extensor surfaces and the scalp. This is due to excessive keratinocyte proliferation
What are the histological findings associated with psoriasis?
Acanthosis - epidermal hyperplasia
Parakeratosis - hyperkaratosis with retention of keratinocyte
Thinning of the epidermin above elongated dermal papillae
What is Lichen Planus?
Pruritic, planar, polygonal, purple papules
Wrists, elbows and oral mucosa
STRONG ASSOCIATION WITH HEP C VIRUS
What is the histological finding associated with Lichen Planus?
Inflammation at the dermal-epidermal junction leading to saw tooth appearance
What is Pemphigus vulgaris?
Autoimmune destruction of desmosomes between keratinocytes
Due to IgG antibody against desmoglein
What are the findings associated with Pemphigus Vulgaris?
Acantholysis of stratum spinosum resulting in suprabasal blisters.
Basal layer remains attached to the basement membrane due to hemidesmosomes in the BM
Thin walled blisters that rupture easily
How will IF appear in pemphigus vulgaris?
IgG surrounding keratinocytes in a fish net appearance
What is bullous pemphigoid?
Auto-immune destruction of the hemidesmosomes between basal cells and the underlying basement membrane.
Due to IgG antibody against hemidesmosome of basement membrane.
How will Bullous pemphigoid present?
Basal layer will be detached from the BM. Tense bullae that do not rupture easily
IF along basement membrane
What are the characteristics of Dermatitis Herpetiformis?
Autoimmune deposition of IgA at the tips of the dermal papillae
Presents with pruritic vesicles and bullae that are grouped
Strong association with celiac disease
What are the characteristics of Erythema Multiforme?
Hypersensitivity reaction characterized by targetoid rash and bullae
Appearance due to central epidermal necrosis surrounded by erythema
Most commonly associated with HSV infection
What are the characteristics of Seborrheic Keratosis?
Benign squamous proliferation of the elderly
Coin-like waxy appearance.
Characterized by keratin pseudocyst
What are the characteristics of Basal Cell carcinoma?
Malignant proliferation of the basal cells in the epidermis
Presents as an elevated nodule with central ulcerated crater surrounded by dilated vessels
Classically on the upper lip
What are the risk factors of Basal cell carcinoma?
UVB-DNA damage prolonged exposure to sunlight
What are the characteristics of squamous cell carcinoma?
Malignant proliferation of squamous cell characterized by keratin pearls.
Ulcerated mass on the lower lip
Melanocytes use what enzyme to synthesize melanin?
They use tyrosinase which takes tyrosine and converts it to melanin
What is Vitiligo?
Localized loss of skin pigmentation due to autoimmune destruction of melanocytes
What is albinism?
Congential lack of pigmentation due to a defect in tyrosinase - impairing melanin production
Can involve the eyes and skin
What are freckles?
Small tan macules that are due to increase number of melanosomes
What is a Nevus (mole)?
Benign proliferation of melanocytes
Acquire begins as nests of melanocytes at the dermal-epidermal junction
Grows by extension into the dermis - compound nevus
Junctional component is eventually lost resulting in intradermal nevus
What are the characteristics of a melanoma?
Malignant neoplasm of melanocytes most common death from skin cancer
Risk factors are based on UVB-induced DNA damage
What are the ABCD’s of a melanoma?
Asymmetry
Borders are irregular
Color is not uniform
Diameter is greater than 6mm
What are the two growth phases of a melanoma?
Radial growth horizontally along the epidermis and superficial dermis
Vertical growth deep into the dermis - determines the prognosis
What is impetigo?
Superficial bacterial skin infection most often due to S aureus.
Most commonly affects children
Presents as erythematous macules that are on the face
Rupture of pustules results in erosions of dry, crusted honey colored serum.
What are the characteristics of cellulitis?
Deeper, dermal infection, due to S aureus
Red, tender swollen rash
Can progress to necrotizing fasciitis
What is a Verruca?
Flesh-colored papule with rough surface
Due to HPV infection
Found on hands and feet
What are the characteristics of Molluscum Contagiosum?
Firm, pink umbilicated papules due to poxvirus. Affected keratinocytes show cytoplasmic inclusions - molluscum bodies
What is Leser-Trelat sign?
Sudden onset of multiple seborrheic keratoses and suggests underlying carcinoma of the GI tract
