1
Q
Characteristics of Four Basic Types of Tissue
A
1) Nervous-
- Cells-intertwining elongated processes
- ECM-none
- Main functions- transmission of nervous impulses
2) Epithelial-
- Cells-aggregated polyhedral cells
- ECM- very small amount
- Main f(x)n- lining of surface or body cavities, glandular secretion
3) Muscle-
- Elongated contractile cells
- ECM- moderate amount
- Main f(x)n- movement
4) Connective
- cells- several types of fixed and wandering cells
- ECM- abundant amount
- Main f(x)n- support and protection
2
Q
The Preparation of Tissue for Light Microscopy
A
1) Fixation
- to preserve tissue morphology and molecular composition (12 h)
2) Dehydration in graded concentrated ethyl alcohol (70% up to 100%)
- to replace tissue water with organic solvents (6-24h)
3) Clearing in benzene, xylene or toluene
- to impregnate the tissues with a paraffin or a plastic resin solvent (1-6h)
4) Embedding in melted paraffin at 60 degrees C or plastic resin at room temperature
- paraffin or resin penetrates all intercellular spaces and even into the cells, making the tissues more resistant to sectioning (1-3h)
1) Fixation
2) Sectioning
3) Staining
3
Q
Staining tissues
A
- used to localize and distinguish cell and tissue components
- Acidic stains (eosin) bind basic structures and components *cytoplasmic proteins
- Basic stains (hematoxylin) bind acidic tissue components (nucleic acids, RNA)
- the stain mixture of hematoxylin and eosin (H and E) is commonly used to distinguish the nucleus from the cytoplasm
4
Q
Epithelium
A
- meaning upon nipple
- has closely coherent cells that form cellular sheets that cover and line the many surfaces and lumens of the body
- one can distinguish between covering epithelia and glandular epithelia
5
Q
Functions of the Epithelium
A
- cover surfaces
- provide protection
- secrete and adsorb various substances
- transport particles
Thin, simple- transport
Thick stratifed-protection
6
Q
Simple squamous
A
- lining of vessels (endothelium); serous lining of cavities; pericardium; pleura; peritoneum (mesothelium)
- fascilates the movement of the viscera (mesothelium), active transport by pinocytosis (mesothelium and endothelium), secretion of biologically active molecules (mesothelium)
7
Q
Simple cuboidal
A
- covering the ovary, thyroid
- covering and secretion
8
Q
Simple columnar
A
- lining of intestine, gallbladder
- protection, lubrication, absorption, secretion
9
Q
Pseudostatified
A
- lining of trachea, bronchi, nasal cavitiy
- protection, secretion; cilia-mediated transport of particles trapped in mucus
10
Q
Transitional: domelike to flattened,depending on the functional state of the organ (type of pseudostratified)
A
- bladders, ureters, renal calyces
- protection, distensibility
11
Q
Stratified Squamous Keratinized
A
- epidermis
- protection; prevents water loss
12
Q
Stratified Squamous (non-keratinized)
A
- mouth, esophagus, larynx, vagina, anal canal
- protection, secretion; prevents water loss
13
Q
Statified Cubodial
A
- sweat glands, developing ovarian follicles
- protection, secretion
14
Q
Stratified Columnar
A
- conjunctiva
- protection
15
Q
General Features of Epithelial Cell Morphology
A
-polyhedral due to packing- columnar, cuboidal, squamous
- shape of nucleus corresponds to the shape of the cell
- most epithelial cells rest on CT
- digestive, respiratory, urinary system this underlying layer is called lamina propria
- irregularities in the contact area provide more area of contact
- small evaginations of the lamina propia are called papillae
16
Q
Basal Lamina and Basement Membrane
A
- separates epithelial cells and CT
- composed of type IV collagen, laminin, entactin, and proteoglcans
- anchoring fibrils of type IV collagen attach the basal laminae to CT
- only visible with electron microscope, dense 20-100 nm of fine fibrils called lamina dense
- in some tissues, reticular fibers (type III collagen) are associated with the basal lamina forming a reticular lamina
- this thick layer of basal lamina and reticular lamina- basement membrane
17
Q
Intercellular Adhesion and Intercellular Junctions
A
- the cohesion of epithelial cells is important for their function
- cadherins and interdigitations of lateral membrane contribute to this cohesion
- some epithelial (like in intestine) a junctional complex of zonula occludens (tight junction) and zonula adherens as well as desmosomes and gap junctions are found on the lateral surfaces
- zonulae occuludens play an important role in permeability
- hemidesmosomes help bind some epithelial cells to the basal lamina
18
Q
Cell Specialization
A
- apical surface of many epithelial cells is modified to increase surface area or move particles
- microvilli are fingerlike extensions
- the microvilli and glycocalyx of small intestine are the striated border
- a slightly larger complex of microvilli of cells is on the proximal renal tubule and called the brush border
- sterocilia- long, nonmotile, extensions of apical surface in epidymis and ductus deferens
- cilia in respiratory system
- 9+2 arrangement of microtubules and are covered by cell membrane (5-10 microns long and 0.2 microns in diameter) and has basal body below plasma membrane
19
Q
Rules for classifying epithelia
A
- all have two, some have three
- first: number of layers (simple, stratified, pseudostratifeid)
- second: shape of cells at most superficial layer (squamous, cubodial or columnar)
- third: if free surface of cell has cilia or kerain
20
Q
Myoepithelial cells
A
-branched contractile cells found in secretory units of mammary, sweat and salivary glands
21
Q
Endothelium
A
-simple squamous epithelium lining blood and lymphatic vessels
22
Q
Mesothelium
A
-simple squamous epithelium lining body cavities such as the peritoneum
23
Q
Epithelioid cells
A
-some tissues contain cells that are closely associated so that they resemble an epithelium
24
Q
Epithelial Cell Renewal
A
- intestinal epithelial are renewed 4-6 days by mitotic activity of stem cells located in the lower portion of the intestinal glands (crypts of Lieberkuhn)
- skin cells are replaced in most sites 28 days and arise from stem cells in the basal layer of the epidermis
- in more complex glands can have longer lifespans
25
Responses to Stress
- epithelial cells can respond to stress by atrophy (death),
- hypertrophy (increase in size)
- hyperplasia (increase in number)
- dysplasia (change in organization)
- metaplasia (transformation to another cell type)
Ex) Metaplasia in respiratory epithelium of a smoker into stratified squamous epithelium
26
Skin overview
- heaviest organ (16% TBW)
- mechanical and permeability barrier
- sensory and immunologic input
- regulator of homeostatsis
- endocrine and exocrine functions
- useful site for drug delivery in lipid- soluble substances that can be absorbed through the skin
- 1/3 of tumors in adults
27
Skin layers
- epidermis- epidermal pegs or ridges downwards
- dermis- layer of CT that includes dermal papillae
- hypodermis- not part of skin but binds skin to underlying tissue
28
Thick and Thin Skin
- distinguished by thickness of the epidermal layer
| - thick is found on palms and soles and lacks epidermal appendages such as hair follicles and sebaceous glands
29
Layers of Epidermis
1) Stratum basale- a single cell layer of stem cells
2) Statum spinosum- mitotically active prickle cell layer
3) Stratum granulosum- non-proliferating cells with stained granules
4) Stratum lucidum- clear layer seen only in thick
5) Stratum corneum- keratinized cell "ghosts"
30
Keratinocytes
- keratinizing epidermal cells that are predominant cell type
- keratin assembled into filaments in the stratum basale and stratum spinosum
- Keratohyaline granules are synthesized in the upper portion of the spinous layer
- they are dense, non-membrane bound masses pf filaggrin and other proteins associated with keratin
- these same cells are also producing lamellar bodies that contain a lipid mixture that is discharged to form the epidermal water barrier
31
Melanocytes
- NCC derived
- located in stratum basale
- numerous processes that extend between keratinocytes to which their melanin granules are transferred
- melanin is synthesized in melandocyle and packaged in melanosomes
- the melanin granules are phagocytozed by keratinoxytes as they bud off of the tips of melanocyte
- the number is same in all races
- differences in the number and distribution of melanin granules in keratinocytes
- tanning darkens preexisting melanin and accelerates new melanin synthesis
32
Langerhans Cells
- antigen-presenting cell derived from bone marrow (2-8 % of epidermal cells)
- can be stained with gold chloride
- have racket shaped organelle called a Birbeck Granule
- one component of SALT (skin associated lymphoid tissue) play a role in delayed-type hypersensitivity reactions
33
Merkel Cells or epithelial tactile cells
- found in stratum basale
- more numerous in thick skin
- TEMs show small neurosecretory granules
- associated with an expanded terminal bulb of an afferent nerve fiber
- the Merkel cell and neurite complex functions as a sensitive mechanoreceptor in areas like finger tips
- Merkel cell carcinomas- rare, difficult to treat, 2x mortality
34
Connective Tissue
Def- the tissue that forms a continuum with the other 3 major tissues to maintain a functionally integrated body
Functions- primarily structural. Characterized on the basis of its extracellular matrix
Examples- Organ capsules, tendons and ligaments, areolar tissue filling spaces, fat, cartilage and bone
35
Development of CT
- develops from embryonic mesenchyme
- mesenchyme forms from embryonic mesoderm or neural crest
- these mesenchymal cells have an oval nucleus with prominent nucleoli and a small amount of cytoplasm
- they can also function as stem cells in adult tissue
36
Components of CT
```
Extracellular Matrix
-ground substance
-protein fibers
-tissue fluid
Connective Tissue Cells
-Resident CT cells
-Immigrant CT cells
```
37
Resident Connective Tissue Cells
- cells in CT that are derived locally and present in relatively constant numbers
- includes- Mesenchymal cells, fibroblasts, fibrocytes, reticular cells, and adipocysts.
38
Mesenchymal Cells
- precursors of CT cells
- some remain undifferentiated in adult CT and serve as stem cells for new fibroblast, smooth muscle or endothelial cell differentiation
- called pericytes or adventitial cells when found near blood vessels
- have large nucleus with prominent nucleoli and less cytoplasm than fibroblasts
39
Fibroblasts
- more numerous and ubiquitous
- they synthesize and secrete the ECM including CT fibers
- they are synthetically and mitotically active, where when resting they are a fibrocyte (shorter, more heterochromatin, acidophilic cytoplasm)
- oval, euchromatic nucleus with several prominent nucleoli and basophilic cytoplasm because lots of RER
40
Reticular Cells
- fibroblast-like cells that produce reticular fibers in hematopoietic, lymphoid and adipose tissue
- stellate-shaped cells with an oval euchromatic nucleus ( like an Idaho potato) with a prominent nucleolus
41
Adipocytes
- specialized for lipid storage
- called signet ring cells because they have a single droplet of lipid that displaces the nucleus and the cytoplasm to the edge of the cell
- lipid can be preserved via osmium tetroxide fixation
42
Immigrant CT Cells
- migrate in from the blood or bone marrow
- include macrophases, mast cells, plasma cells, other blood derived cells (lymphocytes, monocytes, neutrophils, eosinophils, and basophils)
43
Macrophages
- monocytes travel in the blood and migrate into CT to form macrophages
- fixed macrophage- histiocyte
- smaller than fibroblasts with heterochromatic, kidney,shaped nucleus and cytoplasm filled with vacuoles and granules
- seen by injecting live animals with trypan blue (colloidal dye)
44
Mononuclear Phagocyte System
Cell type; Location; Main Function
- Monocyte; Blood; Precursor
- Macrophage; CT, lymph, lungs; Immunological
- Kupffer Cell; Liver; Immuno
- Microglia; CNS; Immuno
- Langerhands Cell; Skin; Antigen presentation
- Osteoclast; Bone; Digest bone
- Multinuclear giant cell; CT (fusion of several mp); digests foreign bodies
45
Mast Cells
- largest of CT cells (20-30 microns in diameter)
- cytoplasm filled with membrane bounded basophilic granules containing heparin, histamine, chrondrotin sulfate, and ECF-A
- involved in allergic reactions
- found around blood vessels
46
Plasma Cells
- differentiate from antigen stimulated B cells
- primary producers of immunoglubulins
- large ovoid cells
- eccentric nucleus, abundant RER, "clock face" nucleus, clear zone near nucleus with Golgi and centriole, basophilic
- lamina propria of gut
47
Functions of CT cells
Cell Type; Main Product; Main Function
- Fibroblast; Fibers and Ground Substance; Structural
- Plasma Cell; Antibodies; Immunologic
- Lymphocyte; Immune cells; Immunologic
- Eosinophil; Phagocytosis; Immunologic
- Macrophage; Phagocytosis; Defense
- Mast cell; Histamine, hep.; Defense
- Adipocyte; fat, heat; storage, heat
48
Ground Substance
- the viscous mixture that binds cells to CT fibers
- consists of glycosaminoglycans (GAGs), proteoglycans, and multiadhesive glycoproteins (e.g. laminin and fibronectin)
- functions are both structural and physiological. Hormones and growth factors have reservoirs in the ground substance
49
CT Fibers
-long slender protein polymers that make up different types of connective tissue. The predominant fiber type gives specific properties to the tissue
50
Collagen Fibers
- greater than 50 nm fibrils make 1-20 micron diameter fibers (biggest)
- dense regular tissue such as tendon the fibers are arranged in parallel and appear white in fresh tissue and stain an homogenous pink color with eosin
51
Collagen Types and Functions
Fibril Forming:
Type I- most widespread, resists tension
II- cartilage, resists pressue
III-reticular fibers, flexible meshwork
Fibril associated:
Type XII- binds type II
Form network:
Type IV- BM meshwork
Anchoring
VII- anchors BM to collagen fibers
52
Basement mebrane
Basal lamina plus lamina reticularis equals basement membrane
53
Collagen Diseases
Osteogenensis imperfect- single nucleotide change in type I gene produces aortic rupture, fractures
- Scurvy (Vit C deficiency)- impaired wound healing
- Ehlers-Danlos Type IV- Type II collagen faulty; aortic and intestinal ruptures
54
Reticular Fibers
- composed of fibrils less than 50 nm in diameter and make 0.5 to 2 micron diameter fibers
- composed mainly of collagen type III
- flexible network in organs such as lymph nodes, liver, red bone marrow, and spleen
- synthesized by fibroblasts, reticular cells, Schwann cells, and smooth muscle cells
55
Elastic Fibers
- composed mainly of protein elastin
- fibers range in diameter from 0.1 to 10 microns
- a lot of crosslinking of elastin- rubber band properties
- have no axial periodicity and are abundant in elastic ligaments and arteries
- different fibers
- Oxytalan which contaion fibrillin
- elaunin fibers as well
- theres is an elastin core surrounded by microfibrils
Oxytalan fibers resist pulling so there can be different stretchiness
Marfan's Syndrome- mutations in fibrillin gene; aortic rupture and hypermobile joints
56
CT fiber staining
- Collagen- pink in H and E stain
- Reticular- Pink in H and E section, but not distinguishable from collagen fibers without silver stain
- Elastic: Pink in H and E but not distinguishable from collagen fibers without Picro-Orcein stain
57
Connective Tissue Classification
Connective Tissue Proper
- Loose (areolar)
- Dense
- Regular
- Irregular
Connective tissue with special properties
- Adipose tissue
- Elastic tissue
- Reticular CT
- Mucous tissue
Supporting Connective Tissue
- Cartilage
- Bone
58
Loose (areolar) CT
- intervening spaces
- more cellular than dense CT
- lots of resident cells
- found in lamina propria, mesentery, and papillary layer of the dermis
- positioned between tissues and allows movement
59
Dense irregular CT
- more fibers than cells
- fibers are interwoven
- found in organ capsules, reticular layer of the dermis and periosteum
60
Dense Regular CT
- more fibers than cells
- fibers arranged in parallel bundles or sheets
- found in tendons, ligaments, and cornea
61
Reticular CT
- previously called hemopoietic tissue of the subgroup CT with special properties is made of reticular cells and reticular fivers
- creates specialized microenvironments for cells in bone marrow, lymph nodes and the spleen
62
Adipose Tissue
- Ct with special properties
| - Unilocular (common, yellow) or Brown
63
Unilocular fat
- cells with a single droplet of fat
- more abundant
- occurs beneath skin as well as in and around more organs
- store fatty acids in triglycerides and function as the largest repository of energy in the body
- thermal insulator
- fills spaces helping to position some organs
- develops from undifferentiated mesenchymal cells via lipoblasts
64
Multilocular fat
- occurs in the human fetus
- transform chemical energy into heat
- large number of capillaries and the numerous mitochondria containing colored cytochromes
- develops from undifferentiated mesenchymal cells via lipoblasts before birth and appears to be important in the first months of postnatal life in producing heat to protect the newborn from cold
65
Supporting CT
- cartilage
| - bones
66
Cartilage
- modified CT that provides support
- consists chiefly of extracellular tissue
- cells (chondrocytes) are located in lacunae
67
Locations of cartilage
- nose
- articular cartilage
- costal cartilage
- intervertebral discs
- pubic symphysis
- external ear
- epiglottis
68
Functions of Cartilage
- support of soft tissues
- forms articular surfaces of long bones
- growth in length of long bones
69
Composition of ECM
- composed of proteoglycans aggregates (aggrecans) and type II collagen
- the composition of the ECM permits cartilage to bear mechanical stress without permanent distortion
-begin with core proteins and add GAGS (glycosaminoglycans)- linear polymers of repeating disaccharide units
- the type II collagen determines the tissue shape and produces tensile strength
- the proteoglycan aggregates give resilence to tissue and allow it resist deformation
- ECM also contains noncollagenous proteins
- the GAGs in cartilage are mainly
a) chondroitin sulfate 4
b) chondroitin sulfate 6
c) keratan sulfate
-these proteoglycans then bind to a core of hyaluronic acid with link proteins
70
Morphology of Chondrocytes
- round diffuse nucleus
- prominent nucleolus
- cytoplasm contins lots of RER
- well-developed Golgi
- mitochondria
-it is a typical protein secreting cell
71
Perichondrium
- formed from mesenchyme surrounding center of chondrification
- composed of two layers
1) Outer fibrous layer
- type I collagen and fibroblasts
2) Inner (chondrogenic layer)
- more cellular in composition
- chondroblasts (can divide through fetal life)
72
Appositional growth
a) mitosis of chondroblasts
b) differentiation of one daughter cell in chondrocyte
1) chondrocytes produce and secrete ECM
2) chondrocytes end up in lacunae
c) adds new cells and ECM to surface
d) persists but remains latent in the adult
73
Interstital growth
a) growth from within
b) condrocytes are capable of mitosis for a while
c) daughter cells produce ECM
d) produces clusters of cells called isogenous groups (cell nests)
e) diminishes with age
74
Consequences of Cartilage being avascular
- contains no capillaries to nourish its cells
- receives nutrition from blood vessels of perichondrium
- consequences:
1) size limitation
2) low metabolic rate
3) poor repair potential of tissue
4) systemic drug treatment is difficult
75
Types of cartilage
1) hyaline
2) elastic
3) fibocartilage
76
Hyaline cartilage distribution
- articular surfaces
- costal cartilages
- nose
- larynx
- trachea
- bronchi
- epiphyseal plate
77
ECM of hyaline cartilage
- proteoglycan aggregates and type II collagen
- tends to be basophilic
- capsular matrix
- immediately surrounding each lacuna
- more basophilic
- richer in sulfated glycosaminoglycans
- interterritiorial matrix- less basopilic)
- type II collagen
- 10-20 nm diameter fibrils
- lack 64 nm peroidicity
- both components of matrix are produced by chondrocytes
- responsible for nutrition of chondrocytes
- chondrocytes fill lacunae in living cartilage
- subjected to degenerative processes like calcification of the matrix
78
Elastic cartilage
Location:
- external ear
- epiglottis
- eustachian tube
- larynx
ECM:
- more flexible than hyaline
- less homogenous in appearance than hyaline
- contains numerous elastic fibers (stain with orcein dyes)
Chondrocytes:
Identical to those in hyaline
-less susceptible to degenerative or age related changes than hyaline
79
Fibrocartilage
Location:
- intervertebral discs- the annulus fibrosus
- pubic symphasis
- menisci
- some tendons
Chondrocytes: same
ECM:
- reduced amount of ground substance
- increased amount of collagen
- causes matrix to be eosinophilic, much of collagen may be type I
- transition between hyaline cartilage and dense regular CT
- no perichondrium associated
80
Intervertebral disk
- hyaline cartilage- cartilage end plates
- dense regular CT-intervertebral ligaments
- fibrocartilage- annulus fibrosus
81
Functions of Bone
- supports fleshy structures
- protects vital organs
- harbors bone marrow
- reservoir of calcium
- involved in body movement
82
Similarities between Cartilage and Bone
- bone is also a supporting CT
- bone consists mostly of ECM
- osteocytes reside within lacunae
- bone is surrounded by specialized CT (periosteum)
- however also has endosteum (specialized CT with osteogenic potential and lines the inner surface of the bone)
- bone can grow by means of appositional growth
83
Differences between Bone and Cartilage
- interstitial growth does not occur in bone
- more regular arrangement of cells and fibers in bone
- bone is vascularized and has nerves
- calcification of the ECM is a normal process in bone
84
Types of bone
1) Compact bone- cortical bone
| 2) Spongy bone- cancellous, trabecular
85
General structure of a long bone
diaphysis: cylindrical part, thick outer layer of compact bone with thin marrow cavity containing spongy bone
epiphysis: bulbous ends, spongy bone covered by thin layer of compact bone
86
Microscopic anatomy of compact bone
Composed mostly of ECM
-ECM is laid down in lamellae (collagen fibers within each lamella are oriented in parallel, collagen fibers of one lamella are perpendricular to those of adjacent lamellae)
- lacunae are small cavities that are uniformly spaced throughout the ecm
- an osteocyte exists within each of the lacunae
- canaliculi are small channels that radiate in all directions through the ecm from each lacuna, they connect with canaliculi of adjacent lacunae
- processes of adjacent osteocytes are in contact with one another by gap junctions (can exhange ions and small molecules- chain of about 10 cells)
87
Types of lamellar organization
1) Haversian systems (osteons)
Haversian canals- run parallel to long axiss of the bone and contain small blood vessels, loose CT, and nerves
Volkmann canals- run at oblique angles to long axis of the bone. They connect Haversian canals to each other and to the free surface
2) Inner circumferential- lamellae (just beneath the endosteum)
3) Outer circumferential- lamellae (just beneath the periosteum)
4) Intersitial lamellae (wedge shaped regions between osteons)
88
ECM of Bone
1) Organic matrix (osteoid)- tends to be eosinophilic
type I collagen
non-collagenous proteins
ground substance
-glycosaminoglycans (less sulfated than cartilage)
-proteoglycans (no aggregrates)
responsible for toughness and resilience
2) Inorganic matrix
calcium phosphate )hydroxyapatite
thin plates or crystals
associated with collagen fibers
responsible for hardness
89
Periosteum
Outer fibrous layer
1) Consists of dense irregular CT
2) has few fibroblasts
3) blood vessels which enter Volkman's canal
4) some of its collagen fibers anchor periosteum to bone (Sharpey's fibers)
Deeper (cellular layer)
1) has osteogenic potential
2) appearance depends on functional state
3) osteoblasts present during embryonic and postnatal growth
4) osteoprogenitor cells present in adults
a) not actively making bone
b) low profile
c) compact chromatin
d) less basophilic cytoplasm than osteoblast
e) can be reactivated
90
endosteum
1) more delicate single layered structure
2) lines surfaces of vascular channels
3) covers the trabeculae of spongy bone
91
Spongy bone
a) consists of 3D lattice of branching bony trabeculae
b) forms interconnecting spaces- lined by endosteum, filled with bone marrow
c) intercellular substance is lamellar- not concentrically arranged around a canal, not penetrated by blood vessels, no Haversian canals, nourished from surface via canaliculi
d) osteocytes are identical to those of compact bone
1) only nuclei are visible in H and E sections
2) processes extend into canaliculi
92
Remodeling of bone (functional adaptation)
- begins almost immediately (in both bone types)
- involves the relative activity of osteoblasts and osteoclasts
- provides maximal strength with minimum bone mass and removes microdamage
- osteocytes may function as the mechanotransducers of local strain in bone
- spongy bone is more responsive to changes to load than compact bone
- in compact bone, Haversian systems are formed, resorbed and replaced throughout life
- intersitital lamellae in compact bone are persisting fragments of previous Haversian sysyems
- osteoclasts
93
Osteoclasts
Location: small pits on surface of bone (Howship's lacunae or resorption bays
Morphology:
1) large cells
2) multinucleated
3) eosinophilic cytoplasm
4) ruffled border
5) rich in mitrochondria and lysosomes
6) attached to bone by podosomes which form a tight seal
Origin: Fusion of monocytes
94
Osteoclast Function
1) break down of organic matrix by means of lysosomal hydrolytic enzymes (cathepsins)
2) dissolution of bone mineral by creating an acid environment (sealing zone)- proton pump in membrane of ruffled border
3) fate of degraded bone proteins and inorganic matrix components
a) taken up by osteoclasts by means of endocytosis
b) transcytosed in vesicles through cytoplasm
c) released through free surface of osteoclast
95
Osteoporosis
1) bone resorption exceeds bone formation when estrogen levels fall
2) enhanced osteoclastic activity
3) skeletal fragility and increased susceptibility to fractures
a) vertebral fractures are most common
b) hip fractures are most debilitating
4) treated with bisphosphonates (alendronate)
a) stable analogs of pyrophosphate
b) reduce osteoclast formation, function and survival
c) prolonged treatment may lead to osteonecrosis (especially of jaw bones)
5) also common in men over 50
96
Fiber
1) A very elongated cell (muscle cell)
2) Components of the extracellular matrix
3) Processes of neurons (axons)
97
General characteristics of smooth muscle
- not striated
- innervated by autonomic nervous system (involuntary)
- slow contracting
- found in the walls of hollow viscera and blood vessels (regulates lumen size)
- capable of regeneration after injury)
98
Appearance of smooth muscle cells
Fibers (cells):
a) elongated and taped
b) average length about 200 um
c) average diameter about 5 um
d) Single, spindle-shaped euchromatic nucleus located in middle of the cell
e) Cytoplasm (sarcoplasm) is homogeneous and eosinophilic
f) arranged in bundles or sheets, held together by CT, staggered arragement of fibers, overlapping cells, difficult to observe with light microscope
99
General characteristics of skeletal muscle
1) innervated by cerebrospinal nerves (voluntary)
2) rapidly contracting
3) cross striated
4) makes up the somatic musculature
5) capable of regeneration after injury
100
Epimysium
- surrounds the entire muscle
| - dense irregular CT
101
Perimysium
- binds muscle cells into fascicles (bundles)
| - loose CT
102
Endomysium
- surrounds individual muscle fibers
| - reticular fibers
103
CT in skeletal muscle
- epimysium, perimysium, endomysium
- integrates action of contractile units
- supports blood vessels and nerves
104
Skeletal muscle fibers
- long cylindrical cells that lie close together in bundles
- each cell is enclosed by a sarcolemmma
- each cell is mulinucleated, that are elongated and peripheral and have diffuse chromatin
- cells are cross striated due to the presence of myofibrils
- average length about 20 mm
- average thickness about 50 um
105
Sarcomere banding pattern
- A band- dark
- I band- light
- Z line/disk- cross linking of thin myofilaments, transmission of force, signal transduction, interface between contractile apparatus and cytoskeleton
- H band- less dense region in middle of the A band (lacks thin filaments)
- M line- thin dense line in the middle of the H band (lateral connections between adjacent thick filaments
106
Sarcomere
- portion of a myofibril between 2 adjacent Z lines
| - unit of contraction
107
Titin
- a giant muscle protein
- extends from M line to Z lines
- maintains the organization of the myofilaments in the sarcomere
- acts as a passive elastic element in the I band
- attaches thick filaments to Z disk
108
Satellite cells in skeletal muscles
- mononucleated
- lie between basal lamina and sarcolemma
- spindle shaped
- inconspicuous nucleoli
- scanty cytoplasm containing few organelles
- have no myofilaments
- responsible for skeletal muscle regeneration
109
Time frame of skeletal muscle regeneration
- satellite cells are activated within 2 hours of injury
- they begin to proliferate within 2-3 days
- cellular architecture is restored in about 2 weeks
110
Cells involved in skeletal muscle regeneration
- muscle dervied stem cells
- bone marrow stem cells with myogenic potential
- blood vessel associated progenitors- mesangioblasts (vessel associated stem cells) and pericytes
- however satellite cells are the major players in skeletal muscle regeneration. They are of clinical importance to muscular dystrophies and sports injuries. They increase in number upon injury and after exercise, and they decrease with age
111
Skeletal muscle fiber types
Red fiber
white fiber
intermediate fiber
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Red Muscle fibers
Type I
- small diameter
- numerous mitochondria
- high myoglobin content
- derive energy from oxidative phosphylation
- fatigue resistant
- adapted for slow contractions over a prolonged period of time
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White Muscle fibers
Type IIB
- larger diameter
- fewer mitochondria
- low myoglobin content
- readily fatigued
- derive energy from anaerobic glycoysis
- adapted for rapid contraction
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Intermediate Fibers
Type IIA
- intermediate size, myoglobin content and number of mitochondria
- fatigue resistant
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General characteristics of Cardiac muscle
- has cross striations
- innervated by autonomic nervous system (involuntary)
- rapidly contacting
- makes up walls of the heart
- capable of regeneration???
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Differences between cardiac and skeletal muscle
- branching morphology
- single nucleus per fiber
- centrally placed nucleus
- intermediate in size (between skeletal and smooth)
- less distinct cross striations
- presence of intercalated discs
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Intercalated discs
- interface between adjacent cardiomyocytes
- occur at the level of Z lines
- presence of gap junctions and adhering junctions (desmosomes and intermediate junctions)
- functions:
a) mechanical attachment between cells
b) transmission of electrical and chemical stimuli
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Cardiac muscles and granules
- presence of secretory granules
- can be observed in atrial musculature
- plays a role in regulation of cardivascular homeostasis by controlling water and electrolyte balance and blood pressure
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Regenerative capacity of cardiac muscle
1) cardiac muscle stem cells
2) bone marrow stem cells
3) umbilical cord, embryonic, and induced pluripotential stem cells (IPSC)
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Conducting system of the heart
SA node -> AV node -> AV bundle -> branches -> Purkinje fibers
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Similarities between Cardiac and Purkinje muscle fibers
- centrally place nuclei
- branching and anastomosing fibers
- presence of cross striations
- just deep to endocardium
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Differences between cardiac and purkinje muscle fibers
- modifications for conduction
- Purkinje fibers are larger
- Myofibrils are displaced toward periphery of Purkinje fibers
- Purkinje fibers are richer in glycogen
- intercalated discs are seldom observed in Purkinje fibers
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Muscular dystrophies
1) characterized by progressive muscular weakness and wasting
2) believed to be due to an intrinsic defect in the muscle itself
3) Duchenne type
a) inherited as a sex-linked recessive
b) almost exclusively found in males
c) begins at the age of 5
d) patient often dies in adolescence
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Polymyositis
- acute progressive disease that usually begins in adult life
- early signs include muscular weakness and tenderness
- may be rapidly fatal
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Neurogenic atrophy
- secondary to a neurological problem
- most common cause is motor neuron disease
a) anterior poliomyelitis
b) amyotropic lateral sclerosis (ALS)
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Differential diagnosis of generalized muscle disease
1) size and shape of muscle fibers
2) distribution of fiber abnormalities
3) presence of inflammation
4) qualitative and quantitative changes in CT
5) fiber degeneration or regeneration
6) special architectural features
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Smooth muscle disease
Atherosclerosis
a) disease of large and medium sized arteries
b) often causes serious clinical consequences
c) focal thickening of inner portion of arterial wall
1) from of the ECM components of lesions
2) accumulate intercellular lipid
3) probably promote deposition of lipid in ECM
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Cardiac muscle disease
1) ischemic heart disease
a) myocardial infarction
2) inflammatory lesions of the heart
a) rheumatic fever
3) valvular lesions
a) bacterial endocarditis
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Disorders of the conducting system
a) most vulnerable part of the system is the AV bundle and its right and left branches
b) injury may result from
1) myocarditis
2) chronic myocardial ischemia
3) myocardial infarction
4) trauma during cardiac surgery
5) invasion by metastatic tumors
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What is the most common heart arrhythmia
A. fib
- cardiomyocytes in the LA start to send signals
- ventricles start not to squeeze properly
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Motor Neuron
- cell body = perikaryon
- chromatophilic substarnace (RER and free polyribosomes) = Nissel bodies
- dendrites
- oligodendrocyte (CNS)
- Schwann cell (PNS - neurolemmocyte
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Nerve fibers
- in a peripheral nervous system consist of axons enveloped by a sheath cell called a Schwann cell (neurolemmocyte)
- small axons are usually unmyelinated and thicker axons are myelinated
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Types of Neurons
- Bipolar- in the retina, olefactory epithelium
- Multipolar- muscle cells
- Pseudounipolar- sensory
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Unmyelinated fibers
- most small unmyelinated axons are enclosed in a simple fold of a Schwann cell
- some very thin axons may share a fold
- a single Schwann cell can cover many small axons
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Myelinated fibers
- thicker axons are myelinated in the PNS by a Schwann cell wrapping around the axon multiple times (forming the mesaxon)
- the wrapping squeezes out the Schwann cell's cytoplasm
- the remaining cytoplasm leaves a chevron shaped irregularity called a Schmidt Lanterman cleft
- the lipid component of myelin is not preserved by formalin fixation and standard histological preparation
- the place where one Schwann cell is adjacent to another Schwann cell is called a node of Ranvier and the node is covered by interdigitating cytoplasmic processes
- during the wrapping the process of the cytoplasm is extruded from between the two apposing plasma membrane of the Schwanna cell, which then fuse, inner leaflet to inner leaflet, to form the major dense line in the myelin
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Nerves
- bundles of nerve fibers that may contain both myelinated and unmyelinated axons and both motor and sensory fibers
- the CT surrounding the nerve fibers provides organization to the nerve
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Epineurium
-the outer coat of dense irregular to loose connective tissue
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Perineurium
- the most prominent and visible coat
- forms a longitudinal bundle (fasicles) of axons
- made of several layers of specialied fibroblastic cells (epitheloid myofibroblasts) that form tight junctions with one another
- this arrangement provides a barrier to the passage of most macromolecules that protects nerve fibers and helps maintain the internal microenvironment
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Endoneurium
-the Schwann cell-ensheathed axons are surrounded by a delicate layer of reticular fibers
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Ganglia
- perpheral clusters of cell bodies of neurons that are surrounded by satellite cells
- sensory and autonomic ganglion can be easily distinguished at the level of the light microscope by certain morphological features
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Sensory ganglia
- contain cell bodies of pseudounipolar neurons
- no synapses within ganglion
- numerous myelinated fibers
- neurons have a central nucleus and a regular ring of satellite cells
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Autonomic ganglia
- contain cell bodies of multipolar neurons
- synapses in ganglion
- numerous unmyelinated fibers
- neurons have an acentric nucleus and smaller cell bodies
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Specialized termini
- motor end plate
- free endings
- Meissner's corpuscles
- Pacinian corpuscles
- muscle spindles
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Termination of motor axons
- motor neurons project axons from the spinal cord that branch out at the skeletal muscle and terminate at the motor end plate. Numerous synaptic vesicles can be found in the exapanded axonal terminus
- the postsynaptic membrane of the skeletal muscle contains junctional folds and acetylcholine receptors
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Receptors of Peripheral afferent fibers
- initiate a nerve impulse in response to a stimulus
- can be classified as exteroreceptors, enteroreceptors, and proprioreceptors
- based on the associated CT one can distinguish simple nonencapsulated (free Endings) from encapsulated endings
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Meissner's corpuscles
- encapsulated endings found in dermal papillae of hairless skin
- they are touch receptors responsive to low frequency stimuli
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Free nerve endings
-bare axons are important for the sensations from the skin of hot and cold itching touch and pain
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Pacinian corpuscles
- hypodermis and deeper dermis of skin
- 1 mm or larger
- mechanoreceptors that respond to pressure and vibration
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Muscle spindles
- encapsulated receptors in skeletal muscle that are important proprioreceptors
- contain specialized muscle fibers called intrafusal fibers in a fluid filled space
- sensory serve fibers exiting the capsule send signals about the extrafusal muscle fiber length and relay this information to the spinal cord where it plays a role in reflexes involved maintaining posture and coordinating walking
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Myelin fixative
-Osmuim fixed and stained with Toluidine blue
