L84- PTH and Non-Neoplastic Bone Flashcards
What does the normal histology of PArathyroid look like? What kinds of cells?
What’s a good sign of an abnormal gland in adults?
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!
What are the features (gross, micro, clinical) of a Parathyroid Adenoma?
solitary, monoclonal
Gross: Large, circumscirbed, tan to red-brown
Micro: more cells, less fat
Mostly Chief Cells!!!
Clinical: Primary HyperPTH
see pic
What happens in Parathyroid Hyperplasia? Gross? Micro? Clinical? CAuses?
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!!!!!
What are clinical clues for PArathyroid Carcinoma?
High Serum CA or PTH
Palpable mass
Vocal cord paralysis
Densely adhered to surrounding tissue at surgery
What are some pathological clues for parathyroid carcinoma?
Fibrous Bands
Mitotic activity
Vascular invasion
See pic
What are causes of primary and secondary/tertiary hyperparathyroidism?
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
Pathological results of Hyperparathyroidism in other organs?
Metastatic Calcification - deposition of calciium in other tissues arund the body (Nephrocalcinosis ex)
Urinary Stones
Bone
What are the normal elements of bone that are cellular and non-cellular?
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
What does Woven vs Lamellar bone mean?
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
Describe Cortex/Cortical bone vs Medullar/Trabecular bone?
Each made of what? Adds what characteristic to bone?
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
There are 2 Pathways for Bone Formation. Describe the Intramembranous Ossifcation PAthway and where is an example of this happening?
Bones of the Skulll
Stromal Mesenchyme makes bones and direct deposition by OB w/ o cartilage
also seen in subperiosteal bone
Describe the process of Endochondral Ossification of bone.
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
Name some of the Developmental Disorders of bone that we will discuss….get your mind warm!
Skeletal Dysplasia
Achrondroplastic
Thanatophoric
OI
Osteopetrosis
Paget’s
What is the most common growth plate disorder? Causes? Genes? Presentation?
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
What is Thanatophoric Skeletal dysplasia?
Different mutatiuon of FGFR3 that is FATAL at or near birth due to hypoplastic chest and respiratory insufficiency :(
What is the Most common inherited CT disorder? What causes it? Features?
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
There are 4 types of OI. Which are mild vs severe? AR vs AD? Features of all?
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
What is “Marble Bone Disease”? What causes it? Signs/Symptoms?
Treatment?
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
What do you see on radiology and pathology for Osteopetrosis?
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
Osteitis Deformans = PAget Disease
What is it? What are the 3 phases and what do you see histologically?
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
What happens to adults/kids’ bone in Vitamin D deficiency?
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
What are the 3 types of bone lesions seen in Hyperparathyroidism?
Generalized bone resorption
Brown Tumors
Osteitis Fibrosa Cystica = combo
What does Generalized bone resorption look like? pathology? Radiology? What bone most affected?
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
What happens in Brown Tumor of bone? what do you see?
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
What do you see in Osteitis Cystica Fibrosa?
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!!!!
What are the causes of renal osteodystrophy?
Elevated PTH
Elevated Phosphate
Decreased Vitamin D
Bone changes associated w/ Chronic renal failure
What are the features of Renal Osteodystrophy?
Osteoporosius
Osteitis Cystica Fibrosa - brown tumors and genrealized resorption
Osteomalacia - failure of mineralization
Osteosclerosis
Growth retardation
