L84- PTH and Non-Neoplastic Bone

Question 1

What does the normal histology of PArathyroid look like? What kinds of cells?

What’s a good sign of an abnormal gland in adults?

Answer 1

CHIEF CELLS = contain granules of PTH and bluish/clear color

Oxyphil cells = pink, granular and contain mitochondria

Fat cells (less in kids)

if you lose fat cells - ABNORMAL!

Question 2

What are the features (gross, micro, clinical) of a Parathyroid Adenoma?

Answer 2

solitary, monoclonal

Gross: Large, circumscirbed, tan to red-brown

Micro: more cells, less fat

Mostly Chief Cells!!!

Clinical: Primary HyperPTH

see pic

Question 3

What happens in Parathyroid Hyperplasia? Gross? Micro? Clinical? CAuses?

Answer 3

Hyperplasia all 4 glands but sometimes not

Gross - similar to adenoma

Micro- more cells, less fat, more blue

can cause primary or secondary Hyper PTH

Causes often MEN!!!!!

Question 4

What are clinical clues for PArathyroid Carcinoma?

Answer 4

High Serum CA or PTH

Palpable mass

Vocal cord paralysis

Densely adhered to surrounding tissue at surgery

Question 5

What are some pathological clues for parathyroid carcinoma?

Answer 5

Fibrous Bands

Mitotic activity

Vascular invasion

See pic

Question 6

What are causes of primary and secondary/tertiary hyperparathyroidism?

Answer 6

Primary - 85% adenoma, 10% hyperplasia, 5% ectopic, 1% carcinoma

Secondary - Hyperplasia

Tertiary - start w/ secondary and exogenous drive for more PTH causes adenoma in background of hyperplasia

Question 7

Pathological results of Hyperparathyroidism in other organs?

Answer 7

Metastatic Calcification - deposition of calciium in other tissues arund the body (Nephrocalcinosis ex)

Urinary Stones

Bone

Question 8

What are the normal elements of bone that are cellular and non-cellular?

Answer 8

Non-Cellular

• Organic Matrix - Type 1 Collagen for structure and Ca-Hydroxyapatite for hardness

Cellular:

OB - produce and lay down bone then get absorbed into matrix and turn into Ostoecytes

OC - resorb bone - multinucleated

Osteocytes - mechanotransduction - feels where stresses are and send OB there

Question 9

What does Woven vs Lamellar bone mean?

Answer 9

Woven Bone: quick and dirty, pathologic in adults, bone remodeling quickly (after a break for example) and blasts come in and lay bone down later

vs

Lamellar Bone: Stronger bone built more slowly by remodeling woven bone

seen in normal adult bone

LOOK FOR PARALLEL LINES

see pic

Question 10

Describe Cortex/Cortical bone vs Medullar/Trabecular bone?

Each made of what? Adds what characteristic to bone?

Answer 10

Cortex - Cortical bone = outer rim, made almost entirely of bone matrix, strength

Medullar/Trabecular Bone = center of bones, made of thin, interconnecting bony trabeculae and in between is fat/hematopoeitc precursors (marrow)

gives lightness to bone

Question 11

There are 2 Pathways for Bone Formation. Describe the Intramembranous Ossifcation PAthway and where is an example of this happening?

Answer 11

Bones of the Skulll

Stromal Mesenchyme makes bones and direct deposition by OB w/ o cartilage

also seen in subperiosteal bone

Question 12

Describe the process of Endochondral Ossification of bone.

Answer 12

START w/ CARTILAGE!!!!

Have various zones

Reserve zone = cartilage

Zone of Proliferation of Chondrocytes that form nests/lines

Zone of Hypertrophy = cells getting bigger

Zone of mineralization =Ca laid down in cartilagenous matrix

Primary Trabeculae = ossified cartilagenous matrix replaced by lamellar or woven bone

SEE PIC

Question 13

Name some of the Developmental Disorders of bone that we will discuss….get your mind warm!

Answer 13

Skeletal Dysplasia

Achrondroplastic

Thanatophoric

OI

Osteopetrosis

Paget’s

Question 14

What is the most common growth plate disorder? Causes? Genes? Presentation?

Answer 14

Achondroplastic Dysplasia!

Autosomal Dominant FGFR3 Mutation - inhibits cartilage formation and can’t lay down proper framework for growth

Presentation: shortening of extremitiies, normal trunk length, enlarged head

Question 15

What is Thanatophoric Skeletal dysplasia?

Answer 15

Different mutatiuon of FGFR3 that is FATAL at or near birth due to hypoplastic chest and respiratory insufficiency :(

Question 16

What is the Most common inherited CT disorder? What causes it? Features?

Answer 16

Osteogenesis Imperfecta aka Brittle Bone disease

Cause: Abnormalities of Type 1 Collagen leads to bone weakness

There arre 4 different types

Clinical Features:

Fractures

BLUE SCLERA (transluscent bc so thin)

Hearing impairment (bad ossicles)

Dentinogenesis Imperfecta

Question 17

There are 4 types of OI. Which are mild vs severe? AR vs AD? Features of all?

Answer 17

Type 1 = AD and mildest - normal stature, Increased fractrures, sclera, hearing, teeth

Type 2 = AR and most severe- fractures and DEATH IN UTERO

Type 3 = AD/AR (75% and 25% respectively)

• growth retardation, Kyphoscoliosis, fractures, hearing etc

Type 4 = AD

• short stature, moderate fragiliy, normal all else

Question 18

What is “Marble Bone Disease”? What causes it? Signs/Symptoms?

Treatment?

Answer 18

Osteopetrosis = genetic defect in Osteoclastic resorption process

[dont resorb bone properly and get solid chuck of bone w/ no trabeculae in medullary cavity - no remodeling and remain in Woven Bone State]

Range from mild to severe and AD or AR

CURED BY BM TRANSPLANT - osteoclasts from monocyte precursors

Question 19

What do you see on radiology and pathology for Osteopetrosis?

Answer 19

Radiology - solid bones w/ no medullary cavity

“Erhlenmyer Flask Deformity” - thickening at one end and narrow at another

Pathologic - medullary cavity filled w/ unresorbed primary spongiosa

Bone only woven not lamellar

Question 20

Osteitis Deformans = PAget Disease

What is it? What are the 3 phases and what do you see histologically?

Answer 20

LESIONS!!! INCREASED RISK OF FRACTURE

1) Lytic Phase - OC activity w/ large nucleo and lots of them
2) Mixed Phase - OC continue and OB lay down new bone; Fibrovascular tissue in marrow space
3) Osteosclerotic Phase - lamellar bone w/ mosaic pattern - almost accelular - thickened bone w/ remodeling at angles

Question 21

What happens to adults/kids’ bone in Vitamin D deficiency?

Answer 21

Osteomalacia - adults

• increased osteoid and lots of Collagenous matrix that gets thicker but no calcification - see bone loss eventually

see picture

Ricket’s - Children

• widened, abnormal growth plate, enlarged zone of proliferation, no zone of mineralization, disorganized primary spongiosa

Question 22

What are the 3 types of bone lesions seen in Hyperparathyroidism?

Answer 22

Generalized bone resorption

Brown Tumors

Osteitis Fibrosa Cystica = combo

Question 23

What does Generalized bone resorption look like? pathology? Radiology? What bone most affected?

Answer 23

Increased OC and OB activity

Bones are bigger but weaker

Sub-Cortical Bone most affected - RAdioluscent on XR under cortex

See Dissecting Osteitis - Railroad tracts as OC tunnels into bone

Question 24

What happens in Brown Tumor of bone? what do you see?

Answer 24

Aggregates of OC and REactive Fibrovascular tissue secondary to Microfractures, hemorrhage, and spindle cell formation

Hemosiderin Macrophages

Form mass lesion that can be mistaken for neoplasms

Histo similar to Giant Cell tumor but here is Giant Cell Reparative Granuloma

Question 25

What do you see in Osteitis Cystica Fibrosa?

Answer 25

Severe manifestation of hyperPTH rarely seen in US but get

• combo brown tumors and generalized bone resorption

Severe subcortical bone loss

Cyst formation - burnt out brown tymors = MOTH EATEN!!!!

Question 26

What are the causes of renal osteodystrophy?

Answer 26

Elevated PTH

Elevated Phosphate

Decreased Vitamin D

Bone changes associated w/ Chronic renal failure

Question 27

What are the features of Renal Osteodystrophy?

Answer 27

Osteoporosius

Osteitis Cystica Fibrosa - brown tumors and genrealized resorption

Osteomalacia - failure of mineralization

Osteosclerosis

Growth retardation