Pathology - S2B3 - Bone - Bone 1

Front 1

List & describe the major components of Bone

Back 1

1. Epiphysis = end of long bone that is originally separated from the main bone by a layer of cartilage but later becomes united to the main bone through ossification

2. Metaphysis = zone of growth between Epiphysis & Diaphysis during development of a bone

3. Diaphysis = shaft of the long bone
-rigid outer shell of compact bone (Cortex) surrounding central Medullary area filled with thin bone trabeculae & hematopoietic marrow

Front 2

List & describe the major components of Bone

Back 2

1. Epiphysis = end of long bone that is originally separated from the main bone by a layer of cartilage but later becomes united to the main bone through ossification

2. Metaphysis = zone of growth between Epiphysis & Diaphysis during development of a bone

3. Diaphysis = shaft of the long bone
-rigid outer shell of compact bone (Cortex) surrounding central Medullary area filled with thin bone trabeculae & hematopoietic marrow

Front 3

Describe the Zones in the Epiphyseal Plate

Back 3

1. Resting Zone = not much goes on but Chondrocytes are alive
2. Proliferating Zone = where all the cell division occurs in the Growth Plate
3. Hypertrophic Zone = chondrocytes enlarge & secrete EC matrix
-Longitudinal & Transverse Septa
-Longitudinal Septa projects down into the Metaphysis

Front 4

Cartilage Matrix
-Fibrils = Collage type II
-Proteoglycan granules = black dots b/w the fibrils
-Water

Back 4

What is seen here?

Front 5

Mineralization occuring almost exclusively in the Longitudinal Septa = deposition of Calcium Hydroxyapatite

Back 5

What is this picture showing?

Front 6

Describe the process of Mineralization

Back 6

In Proliferative Zone there are Matrix Vesicles on the lateral edges of Chondrocytes
-Matrix Vesicles bud off and are distributed into the newly forming matrix; become entrapped between collagen fibrils
-deposition of Calcium Hydroxyapatite

Front 7

Describe Matrix Vesicles

Back 7

-On the membrane are lipids & proteins that are Ca+ binding
-once the vesicle gets close to the mineralization front, there is increase in Alkaline Phosphatase = hydrolyzed Phosphate + Ca accumulate in the center of the vesicle -> precipitation of Hydroxyapatite
-Hydroxyapatite Crystals break through the outer membrane of Vesicles & extend into EC space
-exposed crystal grows

Front 8

What is seen here?

Back 8

Longitudinal Septum under EM

Front 9

Edge of Trabeculum of Bone & Marrow (lining it are Osteoblasts
-Green = Calcium
-Red = Osteoid = Type I Collagen -> becomes mineralized by deposition of Calcium Hydroxyapatite

Back 9

What is this picture showing?

Front 10

Bone Matrix that has been decalcified -> Collagen I Fibers

Back 10

What is seen here?

Front 11

What is the cause of Scurvy?

Back 11

deficiency of Ascorbic Acid (Vitamin C)

Front 12

What is the pathogenesis of Vitamin C deficiency?

Back 12

Vitamin C is necessary for the Hydroxylation of Proline & Lysine in Collagen synthesis
-Hydroxylations sites are anchors for cross-linking of alpha-chains
-deficiency leads to Collagen with reduced tensile strength

Front 13

What are the clinical manifestations of Scurvy?

Back 13

1. Swollen gums
2. Subperiosteal hemorrhage
3. bleeding into joint spaces
4. Purpura & petechiae
5. impaired wound healing

Front 14

Vitamin C deficiency = Scurvy
-weak blood vessels due to Collagen defect
-hemorrhage under the periosteum of the calverium

Back 14

What would cause this?

Front 15

Scurvy
-Growth Plate with disordered cellular array = chondrocytes are very close to eachother b/c of deficiency of synthesis & secretion of Collagen Type II
-accumulation of blood vessels underneath the Growth Plate

Back 15

What is the cause of this?

Front 16

What is the cause of Rickets & Osteomalacia?

Back 16

Vitamin D deficiency

Front 17

What is the pathophysiology of Vitamin D deficiency?

Back 17

Vitamin D deficiency -> decreased Ca++ absorption in gut -> decreased Calcification of Osteoid matrix

Front 18

What are the clinical manifestations of Rickets?

Back 18

Skeletal deformities = due to disruption of mineralization at Epiphyseal plates
-Craniotabes = soft skull bones
-Rachitic Rosary = overgrowth of costochondral joint
-Pigeon breast = outward protrusion of sternum
-Lumbar lordosis = spinal curvature
-Bowing of the legs

Front 19

List the 3 ways of pathogenesis of Rickets

Back 19

1. Dietary deficiency of Vitamin D3
2. impaired absorption of Ca+ & PO4
3. impaired tubular reabsorption of PO4

**growing bones can't get enough Ca++ or PO4 to support mineralization -> bones become soft & flexible

Front 20

Top = Pigeon Breast = Pectus Carinatum
Bottom = Rachitic Rosary = Costochondral thickening due to enlargement of the Growth Plate

Vitamin D deficiency = Rickets

Back 20

What are the names of these abnormalities & what is the cause?

Front 21

Section through a Ricketic rib
-Cartilaginous & bony part of the Costochondral junction
-tremendous thickening of the Growth Plate & primarily the Hypertrophic Zone

Back 21

What is seen here? What is the cause?

Front 22

Rickets growth plate
-only see the Hypertrophic Zone throughout the entire length of the Growth Plate

Back 22

Left is normal, what is the right?

Front 23

List 5 possible causes of Osteomalacia

Back 23

1. impaired absorption of Vitamin D due to Sprue, persistent mild diarrhea, or inadequate intake
2. dietary deficiency of Ca++ or PO4
3. Hyperphosphaturia in Vitamin D resistant rickets
4. Aluminum toxicity
5. Malignant tumors = Oncogenic Osteomalacia

Front 24

Diseases characterized by DECREASED MINERALIZATION OF NEWLY FORMED BONE, usually caused by deficiency or abnormal metabolism of Vitamin D

Back 24

Rickets = in children

Osteomalacia = in adults

Front 25

Osteomalacia
-hypomineralization of bones = Osteopenia
-INCREASED ALKALINE PHOSPHATASE

Back 25

Diagnosis?

Front 26

What are the typical lab findings in Osteomalacia?

Back 26

1. normal to low Ca++ & Phosphorus

2. Increased ALK PHOS

Front 27

Osteomalacia
-trabeculae have core of calcified bone, but are surrounded by coat of unmineralized osteoid
-Osteoblasts are lining the bone surfaces
-Alkaline Phosphatase is coming from Osteoblasts

Back 27

What is the picture on the Right showing?

Front 28

Pseudofractures in Osteomalacia
-not fractures but are translucent, poorly calcified linear zones
-PAINFUL

Tx = Vitamin D + Calcium

Back 28

What is seen here? What is the treatment?

Front 29

What are the clinical manifestations of Osteomalacia?

Back 29

1. Bone pain

2. fractures of veterbrae, hips, wrist

Front 30

Decreased bone mass, resulting in thin, fragile bones that are susceptible to fracture

Back 30

Osteoporosis

Front 31

What are the clinical features of Osteoporosis?

Back 31

1. Compression fractures of Vertebral bodies = shortened stature & kyphosis
2. Bone Pain & fractures
3. Back pain

Front 32

List the risk factors for developing Osteoporosis

Back 32

1. Hereditary = defective Vitamin D receptor gene
2. Loss of ovarian endocrine function = Estrogen deficiency
3. Diet deficient in Calcium, Vitamin D
4. Smoking
5. prolonged Steroid therapy
6. inactivity or weightlessness (astronauts)

Front 33

Why does Estrogen deficiency predispose to Osteoporosis?

Back 33

Estrogen inhibits production of Osteoclasts; enhances Osteoblasts

Front 34

Right = Osteoporotic Vertebral body -> leads to compression fracture

Back 34

What is this picture showing?

Front 35

What are the lab findings associated with Osteoporosis?

Back 35

Normal Calcium, Phosphorus, & Alkaline Phosphatase

**compared to Osteomalacia, which has elevated Alk Phos

Front 36

Osteoporosis

Back 36

Dx?

Front 37

Osteoporosis = bone trabeculum is thin

Back 37

What is seen here?

Front 38

What are treatments for Osteoporosis?

Back 38

1. Estrogen replacement (still be evaluated)

2. Bisphosphonates = anti-osteoclast agents to inhibit bone resorption

3. Ca & Vitamin D

Front 39

Localized disorder of bone remodeling, resulting in excessive bone resorption followed by disorganized bone replacement, producing thickened but weak bone that is susceptible to deformity & fracture

Back 39

Paget's disease

Front 40

What are the clinical manifestations of Paget's disease?

Back 40

1. Bone pain

2. Bone growth = increase in hat size

Front 41

Abnormal bone architecture caused by increase in both Osteoblastic & Osteoclastic activity

Back 41

Paget's Disease

Front 42

Paget's disease = Hyperostosis Frontalis Interna

Back 42

This is the Calverium. What is the disease?

Front 43

Paget's disease
-increased Alk Phos
-normal Calcium & Phosphorus

Back 43

Diagnosis?

Front 44

Paget's disease
-Osteoclasts are resorbing
-Osteoblasts are putting more Osteoid (red) back in = reason for increased Alk Phos

Back 44

What is this picture showing?

Front 45

Paramyxovirus, measles, or RSV infection = Paget's Disease
-Osteoclast is seen that is enlarged with more nuclei than normal

Back 45

What is the proposed etiology of this disease?

Front 46

Paget's disease
-tremendous overgrowth of bone with more Osteoid (red) due to Osteoblastic activity
-thickening of bone Trabeculae with reduction in marrow space

Back 46

What bone condition is seen here?

Front 47

Mosaic Cement lines = Paget's disease
-mixed osteoblastic & osteoclastic activity leads to new bone formation

Back 47

What is the name for this? What is the disease?

Front 48

What are the complications of Paget's Disease?

Back 48

1. High-output Cardiac Failure = due to increased bone vascularity resulting from numberous AV shunts within the marrow

2. Fractures = although bone is thick, it lacks strength

3. Hearing loss = due to narrowing of the auditory foramen

4. Osteogenic Sarcoma in older age

Front 49

A 6-year-old girl is brought in complaining of joint pain. Further inspection reveals a thin, malnourished girl with hemarthrosis, multiple purpura, & ginvival swelling & bleeding. Her mother tells you that she has not been eating a well-balanced diet due to financial situations. Dx?

Back 49

Scurvy = Vitamin C deficiency

results in inability to Hydroxylate Lysine & Proline resides on Collagen (are used for Cross-linking to make fibrils)

Front 50

A 5-year-old boy is brought in concerned of Skeletal abnormalities: protrusion of the sternum, thinning of the occipital & parietal bones resulting in a squared appearance of the head, & rachitic rosary. Dx?

Back 50

Rickets = Vitamin D deficiency = decreased Ca+ absorption = decreased calcification of the Osteoid Matrix

Front 51

A 74-year-old man presents with the following:
-bone pain in left thigh
-bilateral hearing loss
-increase in hat size
-Lab: increased ALP

Dx?
What 2 things may this put him at risk for?

Back 51

Paget's disease

Osteosarcoma
High-output cardiac failure