Glaucoma

1. .
WOLLEGA UNIVERSITY
INSTITUETE OF HEALTH SCIENCE,
SCHOOL OF NURSING AND MIDWIFERY
DEPARTMENT OF NURSING
INDIVIDUAL ASSIGNMENT : ADVANCED PATHOPHYSIOLOGY
TITLE: PATHOLOGY OF MUSCULOSKELETAL SYSTEMS
BY: REBIRA WORKINEH
FEBRUARY, 2023
NEKEMTE, ETHIOPIA

2. PATHOLOGY OF MUSCULOSKELETAL SYSTEMS
STUDENT NAME ID NO
REBIRA WORKINEH 1500418
SUBMITTED TO: DR. JEBESSA GEMECHU (MD, ASSISTANT PROFESSOR
OF PATHOLOGY)
SUBMISSION DATE: FEBRUARY, 2023
NEKEMTE, ETHIOPIA

3. OUTLINES
Introduction
Congenital disorders of bone & cartilage
Metabolic bone diseases
Osteonecrosis
Tumors of adipose tissue

5. Introduction…
Function
Forms the body
framework
Enables the body to
move
Protection of viscera
Transmission of forces generated
by muscles
Basic Functions
of Bone
Mineral homeostasis
Production of blood cells

6. Congenital Disorders of Bone & Cartilage
Osteogenesis Imperfecta ( Brittle bone disease)
 Is a rare congenital bone disease ,1-5/100,000-150,000 childbirths
 It has four types, focused on type one and type two.
Type I
 Is an autosomal dominant
 Is compatible with life
they usually live
Type II
 Is an autosomal recessive
 Is more severe, most die in the uterus before birth
 Die from multiple fracture before birth or during
delivery

7. …
 In these types there is an abnormality in two genes: COLIA1 & COLIA2
 These two genes are mutated in this case
 Mutation of these genes causes abnormality in the structure of type 1 collagen
 Amino acids chains alpha 1 and alpha 2 form collagen 1 defected
Collagen 1
 Provide structures for skin,
Joints, Teeth, Eyes, Cartilage
(ear), Ligaments & Bones
Collagen 2
 Found in elastic cartilage to provide joint support
 Has anti-inflammatory property to reduce pain and
inflammation

8. Symptoms of Osteogenesis Imperfecta (OI)

9. Embryo with osteogenesis imperfecta
type II
Baby with osteogenesis imperfecta
type I

10. Achondroplasia
 Is the most common skeletal dysplasia and a major cause of dwarfism.
 Is an autosomal dominant disorder resulting in retarded cartilage growth.
 Patients with achondroplasia usually have normal brain capabilities and
mental status, they are not retarded.
 Their trunk is of normal size, the problems are in the upper and lower limbs
which are shorter than usual.
 There is no sexual preference (it can affect both genders). 1:15000
live births

11. Pathogenesis
 An epiphyseal line of growth plate is found in children.
 This area controls the growth of bone.
 It closes down when the growth is complete.
 When (FGFR3) is mutated, there is a gain of function mutation of this gene, which
acts on the growth plate (the epiphyseal line) → inhibits chondrocyte proliferation
→ making the epiphyseal line of growth plate close prematurely.
 As a result, the bone stops growing and the patient suffers from dwarfism
 Affects all bones that develop by endochondral ossification

13. Thanatophoric Dysplasia
 Is the most common lethal form of dwarfism, affecting about 1 /20,000 live births
 The same as achondroplasia, but more severe and causes respiratory failure & death
Features
o Thanatophoric means death-loving
o Lethal
o Extreme shortening of the limbs
o Extreme frontal bossing of the skull
o Extreme small thorax, which will be the cause of fatal respiratory failure

14. Short arms and extra folds of skin
Thanatophoric dwarf, often lethal

15. Osteopetrosis ( Marble bone disease)
 Is rare hereditary bone disease
 Failure of the osteoclastic activities, thus no remodeling of the bone
 Obliteration of the marrow cavities
 Development of secondary anemia
 The bone has poor mechanical properties, thus fractures very easily
 Delayed eruption of teeth and osteomyelitis are quite common

16. …
Has two types
Malignant or infantile type
 Severe bone fragility resulting in multiple fracture
 Autosomal recessive infantile is severe/lethal phenotype
 Death usually occurs before puberty
Benign type
 Bone changes are less severe and are diagnosed late in life
 An autosomal dominant adult forms with mild clinical manifestations

17. Metabolic Bone Diseases
 Many nutritional, endocrine, and other disorders affect the development of the
skeletal system.
 Nutritional deficiencies causing bone disease include
o Deficiencies of vitamin C (Scurvy)
o Deficiencies of vitamin D (Rickets and Osteomalacia)
 These disorders are characterized by inadequate osteoid, also called osteopenia
 The most important clinically significant osteopenia is osteoporosis

18. Osteoporosis
 Is a health condition that weakens bones, making them fragile and more likely
to break
 Develops slowly over several years and is often only diagnosed when a fall or
sudden impact causes a break ( fracture)
 Hence, has been called “silent disease” because bone mass is lost over many
years with no sings or symptoms
 Is characterized by reduced bone mass, increase in erosion , making bone
vulnerable to fracture.

19. …
 The rate of bone resorption is greater than the rate of bone formation,
resulting in a reduced total bone mass
 The bones become progressively porous, brittle, and fragile, they
fracture easily under stress that would not break normal bone.
 Frequently results in compression fractures in the thoracic, lumbar spine,
neck of femur, and the wrist.
 Occur in both genders ,but F > M and white people > black people
 After the age 50, osteoporosis can affect all people equally

20. …
 The bone is composed of a connective tissue called osteoid (a collagen).
 Osteoid is formed by osteoblasts and resorbed by osteoclast.
 Osteoid needs to be mineralized by the deposition of calcium phosphate on it.
 The deposition of calcium phosphate ossifies the osteoid.
 Note: Osteoid is the bone with the organic material only (collagen I).
 After mineralization (addition of inorganic materials) it is called bone.

21. …
 The ossification is normal but there is a general reduction in bone mass &
volume.
 With osteoporosis, there will be an increase in calcium, phosphorus and
alkaline phosphatase levels in serum
 There is the decrease in the thickness of the trabecula and cortical bone
 i.e. bone mass is decreased without disruption of architecture.

22. …
 Osteoporosis can affect any bone but mainly the long bones and the vertebral
column.
 Trabecular bone is affected before cortical bone.
 It’s found in greater amount in vertebral bodies and pelvis.
 Cortical bone is found in the greatest amount in the long bones.

25. Type of Osteoporosis
Primary osteoporosis
 Refers to senile & postmenopausal osteoporosis
 Women are at increased risk of osteoporosis after menopause
o There is a relationship between estrogen and osteoporosis.
o The drop of oestrogen will induce osteoporosis.
o The drop in estrogen will stimulate some inflammatory cells

26. …
This will increase the secretion of certain cytokines
oTumor necrosis factor (TNF)- OPG-Osteoprotegerin
oInterleukin 1
oInterleukin 6 &
oInterleukin 8 ( sometimes)
Cytokines stimulates certain receptors on the surface of osteoclast
oRANK &
oRANKL
When stimulated, the osteoclast will become more mature, active &
Cause more absorption than usual and the end result will be osteoporosis.

27. Dx and Rx of Osteoporosis
 It is difficult to diagnose.
Plain X-ray
 Can detect it only when 30% - 40% of bone mass is already lost.
DXA scan
 Use densitometry to see if the bone mass is decreased by a known reference rate.
 Bone loss rarely exceeds 1% per year
 May be treated with
o Hormone replacement therapy
o Oral bisphosphonates &
o Vitamin D

28. Paget’s Disease
 Also known as dystrophic bone disease or Osteitis Deformans
 Are due to fault in the metabolism and turnover (normal bone is replaced by ill-
formed bones), is unknown cause
 Clinically:
o Age- After 40 years
o Sex- More in males
 Site- Most commonly affects the skull, femur, tibia, pelvic bones, & vertebrae

29. Stages
 Initial Resorptive phase – In this phase there is sudden resorption of the bone
 Vascular phase - There is haphazard osteoblast activity and the symptoms are more
pronounced
 Final or Sclerotic phase - Mineralization of the previously deposited matrix with
diminished cellularity and vascularity of the lesion.

30. Pathophysiology
Initially, there is osteoclastic bone resorption
↓
In the 2nd phase, there is both osteolysis and osteogenesis
↓
As bone turnover continues, a classic mosaic (disorganized) pattern of bone develops
↓
In the final phase ↓ed osteoclasts and ↑ed osteoblasts
↓
Paget's disease

31. …

32. Diagnosis ,Treatment & Complication
Radiography
 Haphazard arrangement of the newly formed bone providing patchy radiopaque
pattern termed as cotton wool appearance
 There may be hypercementosis of the tooth roots
Serum
 There is an increase in the alkaline phosphatase.
Rx: Symptomatic by analgesics
 Left sided heart failure leading to death
 Sarcomatous transformation in 2% of cases
Complications

33. Cotton wool appearance Hypercementosis

34. Rickets
 Osteomalacia affecting children where the skeleton is not fully developed
(osteofied).
 It is caused by “Vitamin D” metabolism abnormalities which leads to inadequate
mineralization of the epiphyseal cartilage & the osteoid.
 Characterized by:
o Gap in skull
o Large head
o Bowing head
o Pseudo-fracture

36. The 10 Important Clinical Features in Rickets

37. Osteomalacia
 Is a metabolic bone disease that occurs in adults
 Normal collagen production but inadequate mineralization
 Results in accumulation of un-mineralized matrix (increased osteoid)
 Thus, trabeculae of the bone is soft and weak
 Characterized by:
o Distortion in the skull bone, gaps in the skull.
o Abnormality in the rib cage known as pigeon chest
o No bowing of legs

38. Pigeon breast: Is a deformity of the chest characterized by a protrusion of
the sternum and ribs.

39. Causes
 Caused by lack of vitamin D & abnormal calcification of the bone
 Renal failure
 Hyperparathyroidism
 There is no reduction in the volume but a reduction in the calcified bone (the
amount of calcium)
 Vitamin D is activated by the kidney after absorption

40. …
 Renal failure will impair the activation of vitamin D causing osteomalacia
 This is called renal osteodystrophy
 Osteomalacia is called renal osteodystrophy when secondary to renal disease

41. Pathophysiology
Decreased renal activation of vitamin D
↓
Hypocalcemia
↓
Hyperparathyroidism
↓
Osteoclastic activation
↓
Bone resorption

42. Diagnosis & Management
Diagnosis
 x-ray
 Laboratory studies
 Urine excretion of calcium and creatinine is low
Management
 Dietary
 Sunlight
 Surgery

43. Osteonecrosis
 Also called avascular necrosis, Aseptic necrosis, Ischemic necrosis
 Bones are made up of living cells that need a blood supply to stay healthy.
 In osteonecrosis, blood flow to part of a bone is disrupted.
 This results in death of bone tissue, and the bone can eventually break down and
the joint will collapse.
 Most commonly occurs in hip, other common sites: shoulder, knees & ankles
 People of any age can get osteonecrosis, but typically 30s - 40s.

44. …
Risk factors
 Injury
 Medications
 Excessive alcohol and tobacco use
 Medical conditions
 Medical interventions
Clinical Findings
 Initial may be asymptomatic
 Tenderness around affected joint
 Restricted & painful active & passive
movements
 Neurologic deficit
 Joint deformity and swelling

45. Diagnosis of Osteonecrosis
X-ray
 Can’t detect early signs of osteonecrosis
MRI
 Detect early signs of osteonecrosis
(CT) Scan
 Creates a clear image

46. Treatment of Osteonecrosis
 Treatment depends on: age, the stage of the disease, type of bone affected and the
amount of damage
Nonsurgical Approaches
Surgery
 Core decompression surgery
 Osteotomy
 Bone graft
 Total joint replacement

47. Tumors of adipose tissue
 Adipose tumors are mesenchymal neoplasms that form the largest group of
human tumors.
 Include benign tumors such as the very common lipomas and rare
malignant tumors with various degrees of clinical aggressiveness.
o Lipoma
o Liposarcoma

48. Lipoma
 Is a benign soft tissue tumor composed of adipose tissue enclosed in a
capsule of connective tissue.
 Is the most common benign form & non-cancerous growth of soft tissue.
Site
 Occurs in the upper half of the body, particularly the trunk and neck
 But they can develop in any other site, including hands and feet
 Exception: Tip of nose, cartilaginous part of ear, shaft of penis and eyelid

49. Clinical Features of Lipoma
Lipomas are generally,
o Soft to the touch
o Movable
o Localized
o Lobular, fluctuant, skin free
o Non tender and painless
o They usually occur just under the skin, but
occasionally may be deeper
o Most are less than 5 cm in size.
.

50. Diagnosis of Lipoma
o Is usually done clinically: Hx & P/E.
o Ultrasound and MRI to differentiate lipomas & liposarcomas
o CT scan are occasionally required.
o Alternatively, fine-needle aspiration (FNAC) may be used to evaluate
suspicious lesions.
o X-ray of regional area

51. Liposarcoma
 This malignancy is rare , but is found in a lesion with the clinical appearance of a lipoma.
 Is the 2nd most common form of soft tissue sarcoma in adults- 20%
 Grossly, well circumscribed but not encapsulated
Type: well- differentiated, myxoid, round cell, pleomorphic & differentiated
 Occurs in older individuals typically in 50-80 years of age, but more males > females
Pathology
 The lipoblast is a hallmark of liposarcoma

52. Dx. & Rx. of Liposarcoma
Diagnosis
 Plain radiographs
 MRI
 CT scan
Treatment
Operative
Marginal resection without radiotherapy
 Well-differentiated liposarcoma
Wide surgical resection with adjuvant
radiotherapy
 Intermediate and high grade liposarcomas

53. References
 Pathology and Genetics of Tumors of Soft Tissue and Bone. [4]
 Diagnostic Pathology: Soft Tissue Tumors E-Book. Elsevier
Health Sciences. p. 44. ISBN 978-0-323-40041-1. [5]
 Robbins and Cotran Pathologic Basis of Disease 9th Edition

54. THANKS