Clinical Correlates

Question 1

Chondroma vs Chondrosarcoma

Answer 1

Benign and malignant tumors in cartilage respectively

Do not metastasis often due to avascular it’s of cartilage, must get into perichondrium to have a chance of metastasis

Question 2

Calcification of cartilage

Answer 2

Occurs via deposition of CaPO4 crystals in the ECM during aging and repairing

• most common in hyaline cartilage repairs especially in costal cartilages

Question 3

Osteosarcoma

Answer 3

Cancer from osteoprogenitor cells.

Very rare

Question 4

Metastatic bone tumors

Answer 4

Skeleton is very common site of metastasis since small blood and lymphatic vessels from the entire body move through bones.

Question 5

Osteopetrosis

Answer 5

Dense heavy bones caused by osteoclast deficiencies in ruffled borders

• dont possess ruffled borders and cannot resorb bone well at all.
• thickening of bones causes obliteration of marrow cavity, ultimately causing depressed blood cell formation and overall anemia
• most patients that experience osteopetrosis have mutations in cell proton-ATPase pumps and/or chloride channels.

Question 6

Osteoporosis

Answer 6

Excessive bone formation causes calcium loss in bones and overall reduced density.

• not caused by calcium deficiencies but excess osteoclast activity.

DEXA scans are used to screen for osteoporosis.

Question 7

Osteomalacia

Answer 7

Mineralization of ECM is impaired causing increased spongy bone and decreased compact bone. Soft bones develops and causes easy breaking.

• use of tetracycline as a fluorescent label can be used to screen for this.

Question 8

Osteitis fibrosis cystica

Answer 8

Increased osteoclast activity removes bone matrix and replaces it with fibroids tissue

• caused by hyperparathroidism increasing activity of osteoclasts.
• appear moth eaten bones in xrays

Question 9

Osteogenesis imperfecta

Answer 9

Osteoblasts produce deficient type 1 collagen due to mutations

• usually mutation is replacement of “Gly” amino acid with another amino acid.
• marked by significant fragility of bones. “Brittle bone disease”
• four specific types of osteogenesis imperfecta

Question 10

Bone fracture repair

Answer 10

Damaged blood vessels from bone fractures create a hematoma.

Clotted blood, tissue debris and cell-free bone are moved by macrophages and osteoclasts

Periosteum and endosteum form a soft callus of fibrocartilage tissue around the fracture site.

Callus is gradually replaced by woven bone

Woven bone is eventually resorted and replaced with lamellar bone.

Question 11

Pituitary dwarfism vs gigantism

Answer 11

Lack of growth hormone and IGF-1 causes little growth of epiphyseal cartilage

Excess of growth hormone or IGF-1 causes excessive epiphyseal cartilage growth.

Question 12

Acromegaly

Answer 12

Similar to gigantism and crawfish in that excess GH and IGF-1 are present.

However this is in adults, where epiphyseal plates dont exist. Instead bones become THICKER rather than longer.

Question 13

Rheumatoid arthritis

Answer 13

Autoimmune disorder that causes Chronic inflammation of synovial membrane causes thickening of CT and stimulates releases of collagenases and hydrolysis enzymes from macrophages

• causes destruction of articular cartilage and direct contact of bone into the joint.

Question 14

Rickets

Answer 14

Osteomalacia in children essentially

Bone matrix does not calcify normally along the primary ossification enter (sometimes distorts the epiphyseal plate).

Causes bones to grow more slowly and often become deformed.

• deficiency is caused usually by insufficient calcium in diet or insufficient steroid pro hormone Vitamin D

Question 15

Osteoarthritis

Answer 15

Gradual loss of articular cartilage due to physical or pathological damage or old age.

Question 16

Scurvy

Answer 16

Vitamin C (ascorbate) deficiency

• greatly decreases tension strength of collagen fibers due to lack of intrachain H-bond formation between collagen.
• causes easy bruising, loose teeth and poor gums
• poor wound healing and bone development

Question 17

Menkes syndrome

Answer 17

mutations in ATP7A (a cu2+ transporter) causes lack of intraceuular Cu2+.

Causes improper cross-linking of collagen.

• most notable characteristics are weak muscle tone, sagging facial features and “kinky hair” disease (brittle hair).

X-linked recessive disease (70%)
De-novo (30%)

Question 18

Wilson’s disease

Answer 18

Caused by copper toxicity.

Question 19

Type 1 osteogenesis imperfecta

Answer 19

mild bone fragility, hearing loss and blue sclera in eyes

• MOST COMMON w/ BEST PROGNOSIS*
• usually survive and is an autosomal dominant inheritance

Question 20

Type 2 osteogenesis imperfecta

Answer 20

Almost always lethal in perinatal period

• almost always lethal and is usually inherited in autosomal recessive pattern
• can be a de novo mutation
• MOST SEVERE*

Question 21

Type 3 osteogenesis imperfecta

Answer 21

Multiple fractures at birth, short stature, and increased spinal curvatures.

severe but not as bad as type 2

Question 22

Ehlers-Danlos syndrome (EDS)

Answer 22

Defective collagens of processing enzymes.

Two forms

• classic form = collagen 5 defect
• vascular form = collagen 3 defect

Clinical symptoms = hyperextensible skin, hypermobile joints and increased fragility of skin tissue. (Also may have blue sclara in eyes)

can be severe since arteries become defective

Question 23

Marfan syndrome

Answer 23

Mutations in fibrilin-1 group

Autosomal dominant, pleiotropic disorder.

Clinical signs =
-arachnodactyly (unusually long spidery fingers and tall overall)

• ectopic lens (lens dislocation) and abnormally weak arteries
• weak arteries can cause sudden death in midlife due to rupture of aorta
• ALWAYS positive sign = thumb and little finger overlap the wrist and can touch each other

Question 24

Williams-Beuren syndrome

Answer 24

Chromosomal deletion of #7, which encodes for elastin

Affects multiple genes

Occurs due to random events and is unlikely to be inherited

Clinical signs:

• developmental disorders
• distinctive “long” facial features and cardiovascular problems

Question 25

LAMA2-related muscular dystrophy

Answer 25

Mutations in LAMA2 gene (specifically (a)-2 subunit in lamina 2 and 4 groups)

Autosomal recessive disorder

Clinical signs:

• general muscle weakness and atrophy
• can be severe early onset or mild late onset

Question 26

Hypertrophy vs hyperplasia

Answer 26

Increased muscle mass typically occurs due to sustained increase load.

Individual size of myofibers or the number of myofibers can increase

Question 27

Atrophy and hypotrophy

Answer 27

Decrease muscle mass typically due to decrease load on muscles, loss of Innervation or pathological reasons

Question 28

Leiomyomas

Answer 28

Benign tumors in smooth muscle myofibers

Typically dont cause problems

In uterine = fibroids

Question 29

Cardiac ischemia

Answer 29

Loss of oxygenated blood to cardiac cells leads to myocardial infarction.

Question 30

Duchenne muscular dystrophy

Answer 30

Mutation of dystrophin gene leads to defective dystrophin linkage between cytoskeleton and ECM

Presents 3-5 years old

Causes muscle wasting and muscle cell damage. Muscle biopsy is required to confirm presence

X-linked recessive disorder.

Question 31

Becker muscular dystrophy

Answer 31

Mutation in dystrophin gene similar to duchenne except with a later presentation in life

Presents 17-20 years old.

Question 32

Myasthenia gravid

Answer 32

Autoimmune disorder where antibodies target acetylcholine receptors

Question 33

Spinal muscular atrophy

Answer 33

Gene mutation that encodes for survival motor neuron (SMN) protein required for survival of somatic spinal motor neurons

Question 34

Wernicke-Korsakoff Syndrome

Answer 34

Thiamine deficiency causes decreased thiamine pyrophosphate coenzyme

Disrupts proper use of ATP in all systems, especially in central nervous system

Question 35

Leigh syndrome

Answer 35

Caused by mutation to the PDH complex or ATP-synthase

Rare progressive neurodegenerative disorder

Question 36

Chronic lactic acidosis

Answer 36

Deficiency in the activity of the (a)-subunit of the PDH complex

• is an X-linked dominant disorder

Question 37

Arsenic Poisoning

Answer 37

Arsenide forms thiolase bonds with lipoid acid making it unavailable.

Causes neurological disturbances and death

Question 38

CPT-2 deficiencies

Answer 38

Caused by 70 different mutations

Affects cardiac and skeletal muscle specifically and disables fatty acid oxidation

-autosomal recessive and usually is fatal.