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Sandra phase 1 > MSK physiology > Flashcards

MSK physiology Flashcards

1
Q

Where does endochondral ossification take place?

A

All bones below the skull except for the clavicle

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2
Q

When does endochondral ossification start

A

2 months in utero

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3
Q

What does endochondral ossification use as a blueprint

A

Hyaline cartilage for ossification

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4
Q

1st stage of endochondral ossification

A

Perichondrium becomes vascularised:

Blood vessels supply new nutrients to mesenchymal cells, causing differentiation

Newly formed osteoblasts gather at the diaphysis wall to form a bone collar.

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5
Q

The starting point for ossification

A

Primary ossification centre

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6
Q

2nd phase of endochondral ossification

A

Chondrocytes within a central cavity enlarge causing the matrix to calcify

Calcified matrix impermeable to nutrients, causing cell death

Central clearing forms where cells have died (supported by the bone collar)

Healthy chondrocytes elsewhere cause elongation

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7
Q

3rd phase of endochondral ossification

A

Periosteal bud invades cavity-causing formation of spongy bone

Bud consists of artery, vein, lymphatics and nerves. It also delivers osteogenic cells.

Osteoclasts degrade cartilage matrix while osteoblasts deposit new spongy bone

Bone continues to elongate elsewhere

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8
Q

4th phase of endochondral ossification

A

The primary ossification centre continues to enlarge

Osteoclasts break down the newly formed spongy bone

The medullary cavity begins to form

Cartilaginous growth now only with epiphysis

The bony epiphyseal surface begins to form

A secondary ossification centre may appear at one or both epiphysis

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9
Q

5th phase of endochondral ossification

A

Epiphyses ossify

Secondary ossification centres usually only appear after birth

Longer bones more likely to have two secondary centres

Short bones have only one centre irregular bones may have several

Cartilage now remains on bone surfaces and at epiphyseal plates

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10
Q

When does intramembranous ossification occur

A

In utero before week 8

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11
Q

From what does intramembranous ossification occur

A

All bone formed from hyaline cartilage and fibrous membrane

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12
Q

What bones are formed from intramembranous ossification

A

Cranial bones and clavicles formed this way mostly flat bones

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13
Q

First stages of intramembranous ossification

A

Early in development, you have mesenchymal stem cells that aggregate to form osteoblast by differentiate

Form an ossification centre

Osteoblasts begin to secrete osteoid (unmineralised bone)

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14
Q

2nd stages of intramembranous ossification

A

Peripheral mesenchymal cells continue to differentiate.

Osteoblasts secrete osteoid inward towards the ossification centre.

Osteoblasts become trapped in osteoid, causing differentiation into osteocytes.

Osteoid calcified and hardened after several days

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15
Q

3rd stages of intramembranous ossification

A

Osteoid continues to be deposited and assembles in a random manner around the embryonic blood vessels

Finely woven trabeculae formed

Mesenchyme begins to differentiate into periosteum

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16
Q

4th stages of intramembranous ossification

A

Lamellar (compact) bone replaces woven bone at the outer edge

Layered

Internal spongy bone remains

Vascular tissue within trabecular spaces forms red marrow

Osteoblasts remain on bone surfaces to remodel when needed

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17
Q

Summary of intramembranous ossification

A

Bone forms from membrane or cartilage

Mostly flat bones

Mesenchymal cells differentiate

Osteoblasts direct growth

Woven bone forms

Lamellar bone and outer periosteum forms

Surface osteoblasts remodel as reacquired (stress)

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18
Q

What is cartilage

A

Type of connective tissue

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19
Q

Function of bones

A

Storage of minerals (eg. calcium hydroxyapatite)

Transmission of body weight

Protection of vital organs and structures

Anchorage - lever system for movement

Determination of body shape

Raises body from the ground against gravity

Houses bone marrow to facilitate haematopoiesis

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20
Q

Types of bones

A

Long bones
Short bones
Flat bones
Sesamoid bones
Irregular bones
Pneumatic bones

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21
Q

Bone Development classification

A

Bones are classified into three groups according to their method of development (ossification)

3 groups include:

  1. membranous bones
  2. cartilaginous bones
  3. Membrocartilaginous bones
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22
Q

Membranous bones

A

Also called dermal bone

These bones have an Intramembranous method of ossification

Membranous sheets formed by condensation of mesenchyme

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23
Q

Example of membranous bones

A

Flat bones of the skull
Bones of face
Maxilla
Zygomatic

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24
Q

Cartilaginous bones + example

A

Have Intracartilaginous method of ossification

Example:
Ribs
Vertebrae
Bones of limb

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25
Q

Membrocartlagenous bones

A

Have both types of ossification

Intramembranous
Intracartilgenous

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26
Q

Example of membrocartilagenous bone

A

Occipital
Temporal
Sphenoid bone
Mandible & Clavicle

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27
Q

Regional classification of bones

A

Axial Skeleton
Appendicular skeleton

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28
Q

Axial skeleton

A

Bones of head and trunk
Consists of 80 bones

E.g skull bone
Rib cage
Vertebral column
Ossicles of middle ear

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29
Q

Appendicular skeleton: what does it include + examples

A

Includes: Pectoral girdle
Upper extremity
Pelvic girdle
Lower extremity

E.g: Tibia
Fibula
Ulna
Radius

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30
Q

Long bones

A

Have more length than width

Contain a tubular shaft called the diaphysis

The ends of the long bone are called epiphysis

Contains red marrow in the cavities of spongy bone (red blood cell production)

Epiphyseal line

2 types:

  • Typical long bone
  • The miniature long bone
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31
Q

Typical long bones

A

Have considerable length

e.g humerus, Radius, ulna, femur, tibia, fibula

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32
Q

Miniature long bone

A

Have short length

E.g

  • Metacarpals & phalanges of the hand
  • Metatarsals & phalanges of foot
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33
Q

Short bones

A

Have almost the same length width and thickness

Irregularly shaped
Have limited movement
Spongy bones with an outer covering of the compact bone

E.g bone of wrist & ankle

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34
Q

Flat bone

A

Thin and curved plates
Have a broad surface for muscle attachment

e.g sternum & ribs

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35
Q

Irregular bones

A

Have irregular shape with several processes

Eg hip bone + bones of the face

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36
Q

Sesamoid bones

A

Bony nodules embedded in tendon or muscle

The number is not fixed

Acts as a pulley and protects the tendon from a trauma

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37
Q

Sesamoid example

A

The knee cap (patella), embedded in tendon of quadriceps femoris muscle

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38
Q

Accessory bones

A

Not always present in the body

Further divided into 3 groups:
Supernumerary bones
Wormian bones
Hetrotropic bones

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39
Q

Supernumery bone

A

Bones are the extra centre of ossification which doesn’t fuse with the main bone

E.g
OS Vesalianum, adjacent to tuberosity of 5th metatarsal bone

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40
Q

Wormian bone

A

Extra bones in skull structure

E.g lambdoid bone

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41
Q

Heterotropic bone

A

Form in muscles of other soft tissue

E.g Riders bone

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42
Q

Characteristics of skeletal cartilage

A

Contains lots of water which helps resist tension and compression

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43
Q

Characteristics of short, irregular and flat bones

A

Thin plates of spongy bone covered by compact bone

No well-defined cavity for the bone marrow to sit-in

Hyaline cartilage covers surfaces involved with joints

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44
Q

What is diaphysis made up of?

A

The compact bone surrounding the medullary cavity

In adults, it contains yellow bone marrow which is high in fat

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45
Q

What do epiphyses contain

A

Spongy bone within compact bone and cartilage on the joint surface

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46
Q

What is the epiphyseal line a remnant of?

A

Epiphyseal plate

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47
Q

What is the periosteum

A
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48
Q

What does endosteum do

A

Covers the internal spongy bone layer as well as canals pass-through.

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49
Q

Where can you find red marrow

A

Cavities of spongy bone

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50
Q

Microscopic anatomy of the bone

A

Osteogenic cell
Lacuna
Osteocyte
Osteoblast
Osteoclast
Canaliculi
Lamellae

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51
Q

What are osteogenic cells

A

Stem cells that differentiate are found in the periosteum and endosteum

If the bone is growing these flattened or squamous cells can differentiate into other types at certain times

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52
Q

What do osteoblasts do?

A

Build bone

Scerete bone matrix that consists of collagen and other proteins and therefore causes bone growth

They are actively mitotic and cube-shaped while active

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53
Q

What happens when osteoblasts are surrounded by bone matrix

A

Differentiate to become osteocytes

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54
Q

Osteocytes function

A

Mature cells that monitor and maintain the bone matrix communicating information to other cells

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55
Q

Bone lining cells

A

Flat cells found on the surface of the bone
Help maintain the matrix

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56
Q

Bone classification on a microscopic level

A

Primary (Woven): Rough Plan *
Made quickly
Disorganised
No clear structure

Secondary (Lamellar): Final Piece * Made slower
Organised
Clearly structured

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57
Q

Osteoclast

A

Large cells with multiple nuclei use enzymes to break down bone. This is a normal process called resorbtion that releases minerals to be transferred into the blood

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58
Q

What is an osteon

A

Series of lamellae which are hollow tubes arranged like the rings of a tree trunk.

Within each lamella are collagen fibres running in a specific direction with crystals of bone salts in between

As we proceed inward the next lamellae will have its fibres running in another direction all the way to the centre

It’s the alternating pattern that gives compact bone its ability to withstand torsion

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59
Q

Central canal

A

The open region at the centre containing blood vessels and nerve fibres that serve the cells in that osteon

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60
Q

Perforating canal

A

The shorter canal that perpendicularly allows for connections to run all the way from the periosteum to the central canal of the medullary cavity

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61
Q

What are lacuna filled with

A

Osteocytes
Connected by cannaliculi

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62
Q

What is interstital lamallae

A

Fill in gaps between osteons

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63
Q

Circumferential lamellae

A

makeup circumference of diaphysis surrounding all the osteons

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64
Q

Chemical composition of bone

A

Organic components
Cell (osteoblasts, osteocytes)
Osteoid (organic part of bone matrix) - made up of ground substance + collagen fibres which are secreted by osteoblasts

Inorganic components
Hydroxyapatites (crystals of calcium phosphate) - account for hardness of bone

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65
Q

3 Important hormones involved in calcium and phosphate regulation

A

Vitamin D
Parathyroid hormone
Calcitonin

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66
Q

Where is 99% of calcium stored

A

in bone

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67
Q

Why do we need to regulate calcium and phosphate levels

A

Calcium is important for muscle contraction, nerve conduction

Phosphate is important for biochemical processes and energy

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68
Q

When does parathyroid hormone secrete calcium (stimulated)

A

When there is a decrease in plasma Ca2+

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69
Q

What does parathyroid hormone target

A

Bone

Kidney

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70
Q

What effect does parathyroid hormone have on the bone (summary)

A

to break down minerals so calcium and phosphate can enter plasma. This increases calcium and phosphate levels in plasma

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71
Q

What effect does parathyroid hormone have on the kidneys

A

Targets enzymes 1 alpha hydroxylase. This converts 25 OH cholecalciferol to 1,25 DiOH cholecalciferol (calcitriol)

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72
Q

What is the name of the active form of vitamin D ?

A

calcitriol

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73
Q

Calcitriol function

A

Calcitriol stimulates bone to break down minerals into calcium and phosphate.

Calcitriol has a negative feedback on the parathyroid gland

Calcitriol also stimulates the GIT to increase calcium and phosphate absorption

Calcitriol targets the nephrons
PCT: Stimulates the reabsorption of calcium increasing plasma calcium levels
DCT: Stimulates reabsorption of calcium as well increasing plasma calcium levels

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74
Q

Vitamin D synthesis + activation

A

U.V reacts with 7 Dehydrocholesterol and converts it to cholecalciferol (Vitamin D3) -this takes place in the skin

In liver vitamin D3 (cholecalciferol) gets converted to 25 OH cholecalciferol (calcidiol)

In kidney 25Oh cholecalciferol gets converted via enzyme in the kidneys (1 alpha hydroxylase) into 1,25 diOH cholecalciferol

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75
Q

Inactive form of vitamin D

A

25 OH cholecalciferol

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76
Q

Vitamin D and parathyroid hormone

A

Increase calcium plasma levels

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77
Q

Role of calcitonin

A

Decrease in calcium plasma levels

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78
Q

What stimulates the secretion of calcitonin

A

Increase in calcium plasma levels stimulates the thyroid gland to secrete calcitonin

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79
Q

What does calcitonin have the opposite effect as

A

Parathyroid hormone

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80
Q

Osteoblast vs osteoclast

A

Osteoblast: build bone
Osteoclast: break down bone

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81
Q

Process of the breakdown of minerals in the bone due to PTH

A

Osteoblast has a PTH receptor when PTH binds it does three things:

  • Osteoblast proliferation
  • Stimulate the expression of RANK ligand on the osteoblast
  • stop osteoblast from making osteoprotegerin (OPG)

Preosteoclast expresses a receptor called the RANK receptor.

The rank ligand expressed on the osteoblast will bind to the RANK receptor of the osteoclast, as it is no longer inhibited by OPG

This causes the osteoclast to proliferate and differentiate. The proliferation + differentiation of osteoclast is further stimulated by macrophage colony-stimulating factor(MCSF) binding to the C-FMS receptor of osteoclast.

(Pre)osteoclast → Active osteoclast and will become multinucleated

Active osteoclast will secrete HCl eating away at the bone causing bone resorption and allowing minerals (Calcium + phosphate) to leave

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82
Q

What does Osteoprotegerin do?

A

Inhibits the activity of RANK ligand binding onto another receptor for example the RANK receptor of the (pre) osteoclast

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83
Q

Causes of bone fracture

A

Trauma

Vitamin A deficiency

Low bone density

Age

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84
Q

What do fractures lead to?

A

Tears and destroys blood vessels which carry nutrients to the bone

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85
Q

How is a fracture classified?

A
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86
Q

The first stage of fracture healing

A

Hematoma formation

Blood accumulates forming the hematoma this causes the death of some cells and swelling and pain associated with the area.

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87
Q

2nd stage of fracture healing

A

Fibrocartilaginous callus formation (soft callus). This occurs a few days after hematoma formation

Blood vessels are regrowing

Type of meshwork from granulated tissue forms the callus

Outside the fracture where the periosteal is, the external callus is formed.

Granulation tissue fills in the gap where the fracture is and rejoins the fractured bones together

Essentially what the soft callus does

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88
Q

What is the third stage of fracture repair

A

REPAIR: Bony callus formation

The soft callus previously formed will become a bony callus with the help of other tissue

New blood vessels are formed

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89
Q

Final stage of fracture healing

A

REMODEL: Bone remodelling stage

The bony callus will remodel to become fine bone therefore healing occurs

Compact bone is laid down and osteoblastic activity is also increased

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90
Q

Osteomyelitis

A

When a bacteria (staphylococcus) van infects a bone during a fracture or through the bloodstream

Once infected the person starts feeling severe pain and swelling of the bone injured site

The bacteria usually affects the ends of long bone

The bacteria causes necrosis of the cells so the bone cells begin to die, pus formation and previously strong bones will become weak

If left untreated osteomyelitis becomes chronic and a lot of bone cells can begin to die

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91
Q

What is spongy bone

A

Trabecular bone makes up the inner bone

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92
Q

Compact bone

A

Dense bone made up of osteons

Forms outer bone

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93
Q

Ends of long bone

A

Epiphyses the ends of the long bone are separated by metaphysis to the centre of the bone

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94
Q

The Centre of the bone (shaft) called

A

Diaphysis

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95
Q

The hollow centre of the bone is called and what does it contain

A

Medulla which can contain bone marrow

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96
Q

What are osteoblasts responsible for

A

Building bone

Have a single nucleus and sits on the bone surface

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97
Q

What are osteoclasts responsible for?

A

Breaks down bone, and multinucleated

resorbing cells. They contain large amounts of lysosomes.

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98
Q

What are osteocytes and can you differentiate them from other bone cells

A

mature bones cells from trapped osteoblasts

Cytoplasmic projections, single nucleus

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99
Q

Osteoprogenitor cells

A

Progenitor cells that become osteoblasts

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100
Q

Cells of the bone

A

Osteocytes

Osteoblasts

Osteoclasts

Osteoprogenitor

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101
Q

What makes up the periosteum

A

Surrounds compact bone, also contain pain fibres

outer fibrous layer: protects bones and provides attachment for tendons and ligaments

inner cellular layer: contains osteoprogenitor cells differentiate into osteoblasts (secretes bone matrix) and chondroblasts (produce cartilage)

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102
Q

What surrounds the periosteum

A

Blood vessels which penetrate bone through canals allowing to supply inside of bone

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103
Q

What is the functional unit of compact bone

A

Osteon

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104
Q

What is a ligament

A

Binding one bone to another bone

Made up of fibrous connective tissue

Ligaments aids mechanical joint stability and guide joint motion. Ligaments also prevent excessive motion.

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105
Q

Hierarchy of ligament structure

A
106
Q

Tendon vs Ligament

A
107
Q

joint classification by degree of movement

A

Synarthroses

Immobile

Mostly fibrous

Eg. Between skull sutures, manubriosternal joint

Amphiarthroses

Slightly Mobile

Mostly cartilaginous

Eg. Intervertebral discs, pubic symphysis

Diarthroses

Freely mobile

Mostly synovial

Eg. Hip,shoulder joint, elbow joint

108
Q

Joint classification by structure

A

Fibrous

  • Held together by fibrous tissue

Cartilaginous

  • Held together by cartilage

Synovial

  • Held together by a synovial fluid-filled capsule
  • All have articulations of cartilage, a joint capsule, a joint cavity, synovial fluid, and reinforcing ligaments
  • In some joints bursa (eg. in the hip) or menisci (eg. In the knee) are present
109
Q

Types of synovial joints

A

Hinge joint

Pivot joint

Ellipsoid/ Condyloid joint

Gliding/Plane joint

Ball and socket joint

Saddle joint

BSHPEP

110
Q

Ball and Socket joint

A

Ball & Socket

  • A ball within a socket (pretty much as the name suggests)
  • Wide range of movement in all planes
  • Shoulder and hip joint
111
Q

Condyloid joint/Ellipsoid joint

A

Condyloid

  • Oval sitting within the oval cavity
  • Movement in two planes
  • Metacarpophalangeal
112
Q

Hinge joint

A

Hinge Joint

  • Elongated oval in a curved socket
  • Large range of movement in a single plane
  • Elbow
113
Q

Pivot joint

A

Pivot

  • Bone pivots around an axis
  • Allows a large amount of rotation
  • C1/C2
114
Q

Saddle joint

A

Saddle

  • Two saddle-shaped surfaces articulating
  • Movement in two planes
  • Thumb
115
Q

Gliding Joint

A

Gliding

  • Two flat surfaces articulating
  • Limited movement in 2 planes
  • Carpal joints
116
Q

What is cartilage + characteristics?

A

Avascular, flexible tissue

It contains:

cartilage cells (chondrocytes)

Proteoglycans

Glycosaminoglycans

Collagen fibres

Elastic fibres

117
Q

Function of chondrocytes

A

Cartilage cells that secrete extracellular matrix

118
Q

Types of cartilage

A

Hyaline cartilage

Elastic cartilage

Fibrocartilage

119
Q

Components of hyaline cartilage

A
120
Q

The appearance of hyaline cartilage

A

Smooth or glassy appearence

121
Q

Where can you find hyaline cartilage

A

Nose

Trachea

Larger bronchi

Cartilages of the larynx

Articular surfaces of movable joint

Epiphyseal plates of long bone

Costal cartilage

122
Q

Perichondrium what is it?

A

Dense connective tissue covers the surface of hyaline cartilage except for on the surface of movable joints

Contains vascular supply to cartilage

Two layers: outer fibrous

inner chondrogenic

Contains: Type 1 collagen fibres + fibroblast

123
Q

Where are chondroblasts found

A

inner layer of perichondrium

124
Q

Chondroblasts differentiate to become

A

Chondrocytes

125
Q

Types of collagen

A

Type I

Type II

Type III

Type IV

126
Q

Type I collagen

A

Strongest and most abundant form

Found in tissues where increased tensile strength is required:

Bone

Tendon

Cornea

Skin

127
Q

Type II collagen

A

Spongy type that absorbs shock from compressive forces

Found in tissues where compressive forces occur

Cartilage

Vitreous Body

Nucleus Pulposus

128
Q

Type III collagen

A

Webby type that assists with pulling forces

Found in tissues where pulling force occurs

Blood vessels

Uterine Tissues

Fetal Tissues

Granulation Tissues

129
Q

Type IV collagen

A

Located in basement membrane to provide stabilisation of the cell

Kidney

Ear

Eye

Skin

130
Q

Collagen synthesis

A
  1. Guests: glycine (the most abundant amino acid in collagen). There is only a single collagen chain known as preprocollagen
  2. Water + Lemon: hydroxylation + Vitamin C (in order for hydroxylation to occur you need vitamin C)
  3. Sweets: Glycosylation (formation of hydrogen&disulfide bond). The bonds result in a triple helix (procollagen)

The first three steps occur in R.E.R → Golgi Body → leave the cell

  1. Guests Leave Home: Procollagen leaves cells via exocytosis
  2. Procollagen → Tropocollagen undergoes proteolytic cleavage. Tropocollagen is insoluble in water
  3. Covalent bonds between 3 tropocollagen (enzyme lysyl oxidase. copper is also required) → collagen
131
Q

Osteogenesis imperfecta

A

If there is a problem in glycosylation in collagen synthesis then there will be a defect in forming a proper triple helix

132
Q

Vitamin C deficiency

A

Scurvy

133
Q

Maturation of bone cell

A

Mesenchymal stem cell/osteoprogenitor → Osteoblast → osteocyte → Osteoclast

134
Q

What do osteoblasts secrete

A

osteoid

135
Q

What does osteocyte regulate?

A

Existing bone

136
Q

How are osteocytes formed?

A

When osteoid is mineralised with crystals of hydroxyapatite, the osteoblasts are trapped within the bone and become less synthetically active osteocytes. differentiate and form osteocytes. Supplies nutrition to bone

137
Q

What type of cell is an osteoclast

A

Phagocytic cells

Erode and recycle bone matrix

Work with osteoblasts to maintain calcium homeostasis. It also responds to mechanical stress

138
Q

What is bone remodelling?

A

Old, brittle bone tissue is removed or resorbed and replaced by new tissue

Continuous process

Bones are resorbed by osteoclasts and remade by osteoblasts

139
Q

When does bone remodelling occur

A

Reshaping bones after a fracture

Repairing micro-cracks - form when bones are under stress

140
Q

Composition of lamellae

A

Organic part → collagen

Inorganic part (hydroxyapatite) → calcium phosphate

141
Q

What is in the centre of each osteon

A

Haversian canal

Blood supply and innervation

142
Q

What is the medullary canal lined by

A

spongy/cancellous bone

143
Q

What is the epiphysis made up of

A

spongy bone mostly

Spongy bone is made up of crosslinking roads called trabeculae- add resistance to mechanical stress

144
Q

Bone Formation

A
  1. Osteoblasts sense microcracks at their location e.g bones are bearing too much weight
  2. Osteoblasts secrete Rank L(receptor activator of nuclear factor Kappabeta ligand)
  3. Rank L binds to RANK receptors on the surface of nearby monocytes
  4. Monocytes fuse together to form a multinucleated osteoclast cell (RANK L also helps the osteoclast to mature and activate in order to start resorbtion bones)
  5. Osteoclast secretes lysosomal enzymes (collagenase mostly) and digests collagen in the organic matrix

Secretes HCl which dissolves hydroxyapatite into calcium and phosphate ions

  1. This drill pits on the bone surface known as Howship’s Lacunae
  2. Ions enter Bloodstream
  3. There is a scattering of osteocytes in the bony matrix and when they get freed up by the dissolving bone they get phagocytosed by osteoclasts
  4. Osteoblasts also secrete osteoprotegerin. Binds to RANKL. This slows down the activation of osteoclasts
  5. Once osteoclasts have completed their job undergoes apoptosis
  6. Following bone resorbtion osteoid seam is secreted (a substance to fill in lacunae created by osteoclasts)
  7. Calcium and phosphate deposit on the seam forming hydroxyapatite
  8. As osteoblasts keep producing new bony material, many get trapped within tiny lacunae and become osteocytes
145
Q

What is Wolff’s Law

A

Bones that bear a lot of weight remodel at a high rate

146
Q

What is RANK L responsible for in bone remodelling

A

Initiate remodelling

147
Q

What is osteoprotegerin responsible for in bone remodelling

A

Turn off remodelling

148
Q

How do osteoclast and osteoblast communicate and signalling

A

Communicate via cytokines, OPG and RANK signalling

Cytokines are:

REDUNDANT: Diff types can perform one job

PLEIOTROPIC: can initiate effect on many diff tissues

149
Q

What is RANKL

A

Receptor activator of nuclear factor kappa-B ligand

Expressed by osteoblasts

Plays an important osteoclast formation, function and survival

150
Q

What is RANK

A

Receptor activator of nuclear factor kappa-B

Located on osteoclast precursors and mature osteoclasts

151
Q

What is OPG

A

Osteoprotegerin

Binds to and inhibits RANKL

Expressed by osteoblasts and other tissues including spleen, bone marrow, heart, liver and kidneys

Protective against bone loss

152
Q

Give an example of a long bone.

A

Humerus.

153
Q

Give an example of a flat bone.

A

The skull.

154
Q

Give an example of an irregular bone.

A

Vertebrae.

155
Q

What is the axial skeleton?

A

The part of the skeleton consists of the head and trunk.

156
Q

What are osteoblasts derived from?

A

Mesenchymal stem cells.

157
Q

What is the function of osteoblasts?

A

They synthesise a type 1 collagen-rich matrix, osteoid. (They contain large amounts of RNA for this function).

158
Q

What are osteoclasts derived from?

A

Hematopoietic stem cells.

159
Q

Give 5 reasons for bone remodelling?

A
  1. Replace woven bone for lamellar.
  2. Response to exercise.
  3. Repair damage.
  4. Obtain calcium.
  5. Form bone shape.
160
Q

What type of bone does endochondral ossification produce?

A
161
Q

What type of bone formation uses a cartilaginous pro-former?

A

Endochondral ossification.

162
Q

Describe primary bone.

A

Newly formed, poorly organised. Calcium is in an amorphous form. This bone is heavy and weak.

163
Q

Describe secondary bone.

A

Organised collagen. Calcium is in a crystalline form (hydroxyapatite). This bone is lighter and stronger and replaces primary bone.

164
Q

In the blood approximately how much calcium is bound to plasma proteins?

A

About 50% is bound to plasma proteins, notably albumin.

165
Q

In the blood approximately how much calcium is ionised?

A

Just less than half.

166
Q

In the blood approximately how much calcium is complexed?

A

A very small amount is complexed, bound to citrate/phosphate etc.

167
Q

What are the 3 ways in which the calcium in the blood is distributed?

A
  1. Ionised - metabolically active and is the most important for cellular function.
  2. Bound to plasma proteins - non metabolically active.
  3. Complexed e.g. citrate, phosphate.
168
Q

What is the affect of alkalosis on ionised calcium?

A

Alkalosis increases the pH, this increases the negative charge on albumin and so affects ionisation as more calcium binds to albumin and less is ionised.

169
Q

Give 4 sources of calcium.

A
  1. Dairy products.
  2. Oily fish.
  3. Cereal.
  4. Broccoli.
170
Q

Where in the intestine is calcium actively absorbed?

A

Duodenum and jejunum.

171
Q

Where in the intestine is calcium passively absorbed?

A

Ileum and colon.

172
Q

Where does the majority of Ca2+ reabsorption happen in the kidney?

A

At the PCT.

173
Q

Where does active Ca2+ reabsorption happen in the kidney?

A

DCT - this is where PTH will act.

174
Q

Where in the body can Calcium come from to enter the blood?

A
  1. Absorbed from the intestine.
  2. Resorbed from bone.
  3. Reabsorbed at the kidney.
175
Q

What do C-cells release?

A

Calcitonin.

176
Q

What is the effect of low phosphate levels in the body?

A

Poor mineralisation of bone can result in rickets, osteomalacia, pain and fractures etc.

177
Q

Give 3 dietary sources of phosphate.

A
  1. Protein.
  2. Dairy.
  3. Seeds and nuts.
178
Q

Give 3 regulators of phosphate.

A
  1. PTH.
  2. 1,25-(OH)2-vitD.
  3. FGF-23 = major regulator!
179
Q

What is the action of PTH with regards to phosphate homeostasis?

A

It increases phosphate absorption at the intestine and decreases phosphate reabsorption at the kidney.

180
Q

What triggers the release of FGF-23?

A
  1. High phosphate levels.
  2. PTH.
  3. 1,25-(OH)2-vitD.
181
Q

What is the action of FGF-23?

A

It acts to decrease phosphate levels!
1. It increases phosphate excretion at the kidneys.

  1. It decreases 1-hydroxylase meaning less 1,25-(OH)2-vitD is produced and so less phosphate will be absorbed from the intestine.
182
Q

What is the function of PHEX?

A

It breaks down FGF-23 when phosphate levels have decreased.

183
Q

What could happen if there was a dysfunction of PHEX?

A

FGF-23 wouldn’t be broken down and so serum phosphate would be very low and urinary phosphate would be high. You would be unable to mineralise bone - osteomalacia.

184
Q

What is klotho and what is its function?

A

Klotho is a transmembrane protein that modifies FGF receptors making them specific for FGF-23.

185
Q

What would be the affect on FGF-23 if you were vitamin D deficient?

A

You would have low phosphate levels as less will be absorbed from the intestine and so FGF-23 would be low as its trigger is high phosphate levels.

186
Q

Define coupling.

A

Bone formation occurs at sites of previous resorption.

187
Q

Define balance in osteoblast/osteoclast communication.

A

The amount of bone removed by osteoclasts should be replaced by osteoblastic activity.

188
Q

What would be the affect on bone if you had unopposed RANK ligands?

A

There would be increased bone loss as more osteoclasts would be stimulated due to the lack of OPG.

189
Q

What is the affect of increased activity on bone?

A

Increased activity means there are higher than customary strains on the bone and so you get bone formation.

190
Q

What is the affect of decreased activity on bone?

A

Decreased activity means there are lower than customary strains on the bone and so you get bone loss.

191
Q

What is osteomalacia?

A

An inability to mineralise bone.

192
Q

What is the usual cause of osteomalacia?

A

Vitamin D deficiency.

193
Q

What is the DEXA T score range for osteopenia?

A

-1.5 -> -2.5.

194
Q

What is the DEXA T score range for osteoporosis?

A

-2.5 or lower.

195
Q

Name 4 risk factors FRAX uses in determining the 10-year probability of osteoporotic fracture.

A
  1. Family history of parental hip fracture.
  2. Smoking status.
  3. Use of glucocorticosteroids.
  4. Diagnosis of rheumatoid arthritis.
196
Q

In osteoporosis what would the blood tests of bone profile look like?

A

Everything would be normal! Normal calcium, phosphate, PTH, alkaline phosphate etc. Osteoporosis is a problem with bone density, not mineralisation.

197
Q

What compound is a marker of increased bone turnover?

A

Alkaline phosphatase.

198
Q

What type of muscle fibres are slow-twitch?

A

Type 1.

199
Q

By what process do type 1 muscle fibres get energy?

A

Oxidative processes and so have lots of mitochondria.

200
Q

What type of muscle fibres are very sensitive to fatigue?

A

Type 2b.

201
Q

What type of muscle fibres would be found in postural muscles?

A

Type 1.

202
Q

By what process do type 2a muscle fibres get energy?

A

Oxidative and glycolytic energy processes.

203
Q

By what process do type 2b muscle fibres get energy?

A

Glycolytic processes.

204
Q

What type of muscle fibres are fast twitches?

A

Type 2a and 2b.

205
Q

Define fracture.

A

A breach in the continuity of bone.

206
Q

When muscle fibres are stained to demonstrate the presence of fibrillar ATPase, which muscle fibres appear darker stained?

A

Type 1 muscle fibres, they have lots of fibrillar ATPase for oxidative energy processes and lots of mitochondria.

207
Q

What 5 things need to be considered in describing a fracture?

A
  1. Site - which bone? Proximal/distal?
  2. Pattern - oblique, transverse, spiral etc.
  3. Displacement - % displaced, angulation.
  4. Joint involvement (intra-articular).
  5. Skin involvement - breach in skin is an orthopaedic emergency.
208
Q

What are the 3 principles of fracture management?

A
  1. Reduce the fracture, and alignment.
  2. Immobilize the fracture - stability!
  3. Rehabilitate the patient.
209
Q

What contains more type 1 collagen, ligament or tendon?

A

Tendon.

210
Q

Briefly describe the composition of ligaments and tendons?

A

Dense connective tissue consisting of parallel fibres. There are fibroblasts that synthesise and remodel the ECM. The tissue is sparsely vascularised.

211
Q

What percentage of ligaments and tendons is the extracellular matrix (ECM)?

A

80%.

212
Q

What is the name of the connective tissue that surrounds the fascicles of a tendon?

A

Endotenon.

213
Q

What is the name of the connective tissue that surrounds tendons?

A

Epitenon.

214
Q

What are the entheses?

A

Where a tendon or ligament inserts into the bone.

215
Q

What are the two types of insertion into entheses?

A
  1. Fibrous.
  2. Fibrocartilage.
216
Q

How is a fibrous insertion formed?

A

Through intramembranous ossification.

217
Q

How is a fibrocartilage insertion formed?

A

Through endochondral ossification. There is a gradual change: ligament -> fibrocartilage -> mineralised cartilage -> bone.

218
Q

Name 3 things that can decrease the tensile strength of tendons.

A
  1. Ageing.
  2. Pregnancy and postpartum.
  3. Immobilisation.
219
Q

What can increase tendon and ligament tensile strength?

A

Physical training.

220
Q

Give 3 functions of joints.

A
  1. Allows movement in 3 dimensions.
  2. Bears weight.
  3. Transfers load evenly onto the musculoskeletal system.
221
Q

Give an example of a fibrous joint.

A

Teeth, sutures in the skull etc.

222
Q

Give an example of a cartilaginous joint.

A

Intervertebral discs, costal cartilages etc.

223
Q

How are joints classified functionally?

A

Functional classification focuses on the amount of movement at a joint.

224
Q

Give an example of a synarthroses joint.

A

Sutures in the skull, teeth etc.

225
Q

Give an example of an amphiarthroses joint.

A

Costal cartilages, intervertebral discs etc.

226
Q

Give an example of a diarthrosis joint.

A

Hip joint.

227
Q

What are bursae?

A

Fluid filled sacs lined by synovial membrane.

228
Q

What are menisci?

A

Discs of fibrocartilage.

229
Q

What is the function of hyaline cartilage in a synovial joint.

A

It provides a frictionless surface and acts to resist compressive loads.

230
Q

Describe hyaline cartilage.

A

High water content, low cell content and no blood supply.

231
Q

What is the function of synovial fluid?

A

It lubricates the joint by covering the articulating surfaces. It acts to reduce friction.

232
Q

What are the clinical consequences of high uric acid?

A

Hyperuricemia can lead to the formation of uric acid crystals. These crystals are deposited in the joints and can cause inflammation, pain, swelling and redness. Hyperuricemia

233
Q

What clinical condition can be caused by hyperuricemia?

A

Gout.

234
Q

What is the end product of purine metabolism?

A

Uric acid.

235
Q

What is the effect on the solubility of uric acid if the pH decreases?

A

It becomes less soluble.

236
Q

Give 2 examples of purines.

A
  1. Guanine.
  2. Adenine.
237
Q

What is the function of purines?

A

They are important building blocks of DNA and RNA.

238
Q

Name 5 dietary sources of purines.

A
  1. Meat.
  2. Offal; liver, heart, kidney.
  3. Seafood.
  4. Soya, yeast extracts.
  5. Fructose.
239
Q

Why are men more commonly affected by gout than women?

A

Oestrogen promotes uric acid excretion.

240
Q

Give 5 risk factors of gout.

A
  1. CHD.
  2. Diabetes.
  3. Obesity.
  4. High blood pressure.
  5. Excessive alcohol consumption.
241
Q

What does a bone profile blood test look at?

A
  1. Minerals.
  2. Proteins.
  3. Enzymes.
242
Q

What would the bone profile for osteomalacia look like?

A
  1. Low serum calcium.
  2. Low serum phosphate.
  3. High parathyroid hormone (release is triggered by low Ca2+).
243
Q

What is the function of T-tubules?

A

Conduct stimulatory impulses.

244
Q

What connective tissue binds fasciculi to form muscles?

A

Epimysium.

245
Q

What connective tissue binds muscle fibres to form fasciculi?

A

Perimysium.

246
Q

What connective tissue is found in between each muscle fibre?

A

Endomysium.

247
Q

A patient has low calcium but normal phosphate. What two hormones are responsible?

A

PTH and calcitonin.

248
Q

Give 3 places where osteoporotic fractures are common.

A
  1. Hip.
  2. Wrist.
  3. Vertebral column.
249
Q

What enzyme, expressed in osteoclasts, resorbs bone?

A

Cathepsin K.

250
Q

What is the average recommended daily intake of calcium?

A

700mg.

251
Q

What has been injured in the knee that results in hyperextension?

A

Posterior cruciate ligament.

252
Q

How would you describe a fracture with more than 2 bone fragments?

A

Comminuted.

253
Q

Which component of bone confers the mechanical property of stiffness?

A

Mineral

254
Q

Which of these are dietary sources of phosphate?

A

Chicken

255
Q

Which of these factors is the main regulator of serum calcium concentration?

A

Parathyroid hormone

256
Q

Which is true of both tendons and ligaments?

A

Can sustain high tensile strength

257
Q

Which is a physiological function of synovial fluid?

A

Reduce friction with joint movement

258
Q

Which is true of the anterior cruciate ligament?

It is much less commonly injured than the posterior cruciate ligament

It is much less commonly injured than the posterior cruciate ligament

It is often injured in twisting injuries

It resists posterior translation of the tibia

It resists valgus force on the knee

A

It is often injured in twisting injuries

259
Q

Which bone cells sense strain in the skeleton?

A

Osteocytes

Osteocytes are osteoblasts which become embedded in the bone matrix. They sense mechanical strain and send signals to osteoblasts to increase bone formation when strain is high, and decrease formation when strain is low. Therefore high strain activity leads to bone formation and immobility leads to bone loss. Osteoclasts resorb bone and osteoblasts form bone.

260
Q

Which of these is the third stage of fracture healing?

A

Repair

261
Q

Which is true of skeletal muscle?

Fast-twitch fibres have mainly aerobic metabolism

Contraction is generated by attachment and detachment of myosin heads on actin filaments

Fast-twitch fibres have mainly aerobic metabolism

It has an inherent rhythm

Skeletal myocytes are mononucleated

A

Contraction is generated by attachment and detachment of myosin heads on actin filaments

Sandra phase 1 (16 decks)

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