Basic Tissues Final Flash Deck 1

Front 1

LIGHT MICROSCOPE or bright field microscope

Back 1

Resolution: minimum distance between 2 closely positioned objects
where 2 objects detected as separate entities (quality of the glass prisms will
impact resolution) – the ability to distinguish two distinct objects as two distinct objects.
a. Wavelength of illuminating source
b. Numerical aperture (NA)
2. Pathway of Light
a. ROYGBIV

Front 2

What's the path of a Light Microscope

Back 2

Light source is the illuminator --> condenser (focuses)  sample (stage is where the specimen is located) --> passes through/absorbed --> objective lens (magnify 4x-100x) --> ocular lens --> retina

Front 3

What microscope is good for living cells and tissues?

Back 3

Phase contrast microscope

Front 4

Differential Interference Contrast Microscope

Back 4

similar to phase contrast, but uses additional prisms and polarizers to generate contrast in fixed or living specimens; 3D image

Front 5

What's a good microscope for studying proteins?

Back 5

Fluorescent Microscope

Front 6

Birefringence

Back 6

refractive index dependent on the polarization/direction of light

Front 7

What microscope is good for oriented molecules such as collagen and HAP?

Back 7

Polarization Microscope

Front 8

Fluorochromes

Back 8

labeling fluorescing compounds – usually a tagged antibody is used for this.

Front 9

1. Fixation

Back 9

a. Preservation of structure
b. Cross link macromolecules together --> freeze tissue in near native configuration
c. Formalin (37% formaldehyde): cross-linking of amino acids without precipitation
d. Artifacts: shrinkage

Front 10

Describe.
2. Decalicification
3. Dehydration
4. Clearing

Back 10

2. Decalcification: removal of calcium
3. Dehydration: removal of water by alcohols more and more % alcohol up to 100%
4. Clearing: replacement of alcohols with xylene (more complex organic solvents), etc. tissue becomes transparent in xylene

Front 11

5. Embedding

Back 11

paraffin wax block with tissue inside, plastic resins

Front 12

6. Sectioning

Back 12

using a machine called a microtome, or cryostat (freezing microtome) – tissue is slowly moved further out and get sliced and put onto a slide.

Front 13

Rehydration

Back 13

(reverse the process and decrease percent alcohol step by step to prep for staining)

Front 14

Basophilia Stain

Back 14

Hematoxylin stain negatively charged things like DNA and RNA - bluish tint known as basophilic.

Front 15

Acidophilia

Back 15

1. Tissue stains more readily with acid dyes like eosin Binds to positive charged items (E): cytoplasm
2. Acid dye carries (-) charge which binds to (+) charged molecules

Front 16

Metachromasia

Back 16

change of dye color when reacting with tissue components – components that stain purple with toluidine blue are known as Metachromatic.

Front 17

Sudan black

Back 17

for lipids

Front 18

PAS

Back 18

glycoproteins and other carbohydrate-rich molecules forms a magenta precipitate.

Front 19

Direct Method
Indirect Method (uses a fluorescent antibody)

Back 19

Direct and indirect methods of immunocytochemistry. Left, An antibody against the antigen was labeled with a fluorescent dye and viewed with a fluorescent microscope. The fluorescence occurs only over the location of the antibody. Right, Fluorescent-labeled antibodies are prepared against an antibody that reacts with a particular antigen. When viewed with fluorescent microscopy, the region of fluorescence represents the location of the antibody.

Front 20

IMMUNOFLUORESCENT MICROSCOPY

Back 20

1. Fluorescent molecules attached to antibodies
2. Excitation and emission of light waves

Front 21

What Microscope:

1. Light source: electrons from heated tungsten filament
2. Electromagnetic coils: lenses
3. Sample Preparation: limited ability of electrons to penetrate biological molecules
a. Fixation
1) Glutaraldehyde: cross links proteins
2) Osmium tetroxide: stabilizes lipids and proteins
b. Use of uranium and lead (stains): increase contrast
 
This is coupled to a computer

Back 21

Transmission Electron Microscope (TEM)

Front 22

SCANNING ELECTRON MICROSCOPE (SEM)

Back 22

Fixed sample coated with thin film of heavy metal atoms (like uranium and lead to stain the tissue to withstand the electron beam.)
Electrons pass over surface
3. Good to study Cell surface features of bone, enamel, dentin: cell surface plus metal

Front 23

FREEZE FRACTURE (CRYOFRACTURE) EM

Back 23

1. Rapid freezing – liquid Nitrogen and fracture the surface
2. Fracturing tissue
3. Coating fractured tissue with platinum
4. Study of metal replica – good for studying membrane type structures

Front 24

AUTORADIOGRAPHY - PULSE CHASE STUDIES

Back 24

1. Use of radioisotopes
2. Trace chemical pathways in cells: good for studying metabolism of proteins, carbohydrates, lipids, nucleic acids. Measure the amount of radioactivity.

Front 25

TISSUE CULTURE

Back 25

1. Organ and cell culture
2. Use of microelectrodes: ion concentrations, injections of antibodies and fluorescent dyes
3. Cell differentiation

Front 26

RECOMBINANT DNA TECHNOLOGY

Back 26

1. Manipulation of proteins, DNA, etc.
2. Replacement of damaged genes

Front 27

What is the embryonic origin of epithelium?

Back 27

Mainly from Ectoderm and Endoderm, but also Mesoderm

Ectoderm– Skin and its appendages (hair and sweat glands), mammary glands
Endoderm–Liver, pancreases, GI and respiratory tracts
Mesoderm–Reproductive system, Blood vessels and body cavities

Front 28

Epithelium comes As a sheet of closely apposed cells, separating a space (lumen) from underlying tissue.
but also as __________ of invaginated epithelium cells

Back 28

gland

Front 29

What are the basic functions of epithelium?

Back 29

Protection (Skin)
Absorption and Transcellular transport (intestinal epithelium)
Secretory (glandular epithelium)
Sensation (olfactory neuroepithelium)
Contractibility (myoepithelial cells)

Front 30

What tissue is found here:

pulmonary alveoli
blood and lymph vessels
pleural
peritoneal cavities

Back 30

simple squamous

Front 31

What tissue is found here:

ducts of many glands
Ovary
Some kidney tubules

Back 31

simple cuboidal

Front 32

What tissue is found here:

digestive tract
Gallbladder
large ducts of glands

Back 32

simple columnar

Front 33

esophagus

Back 33

stratified squamous non keratinized

Front 34

ducts of the sweat glands

Back 34

stratified cuboidal

Front 35

Goblet cells (mucus-secreting cells) are commonly found in? columnar and pseudostratified epithelium

Back 35

columnar and pseudostratified epitheliu

Front 36

Stratified transitional epithelium

Back 36

Ureters, Bladder,
Proximal urethra-organs

Front 37

Collectively, microvilli borders: brush-like or striated by light microscopy.

Increase intervillar spaces and facilitate?

Back 37

absorption/secretion

Front 38

Cilia have 9 microtubule doublets + 2 central microtubule “spokes” that make up what is known as?

Back 38

Ciliary Axonemes and Cilia is found in the lungs, oviduct, and vestibular apparatus and are hair-like Propelling substances over the surface of the epithelium via rapid rhythmic oscillations Or sensention

Front 39

Stereocilium

Back 39

Found in the epididymus. Increase surface area and facilitating the movement of molecules

Front 40

Keratinization

Back 40

Protection from Abrasion or Desiccation waterproof ie. palm of hand

Front 41

What are some functions of intercellular Junctions?

Back 41

Seals (occluding junctions - zonula occludens) claudins - Seals to prevent the flow of materials between the cells

Adhesion (adhesive or anchoring junctions)

Communication (gap junctions)

Front 42

What adheres epithelial cells to Basal Lamina?

Back 42

hemidesmosome

desmisomes have intermediate filaments

Front 43

What comprises a junctional complex?

Back 43

A junctional complex:

a zonula occludens,

a zonula adherens and

a desmosome.

Front 44

A gap junction has connexons and what are they comprised of?

Back 44

6-connexins

Front 45

Basal Lamina

Back 45

Extracellular material between the epithelial basal surface and underlying connective tissue

Also found between adjacent epithelial cells

Front 46

Reticular fibers secreted by connective tissue cells (reticular lamina) may be closely associated with the?

Back 46

basal lamina.

Front 47

What are the components that make the basal lamina?

Back 47

Composed mainly of type IV
collagen, laminin and
heparin sulfate (a proteoglycan

Note. BL are only visible by electron microscopy

Front 48

What is the function of Basal Lamina?

Back 48

Barrier: Filtration –Kidney

Cell-to-cell interactions:
Attachment to connective tissue
Receptors (Integrins) attach to BL components

Compartmentalization or separation

Polarity

Tissue scaffolding: development and regeneration

Front 49

The basement membrane is a thicker structure visible by light microscopy which is composed of either:
two fused basal laminae ( or a?

Back 49

basal lamina and a reticular lamina

Front 50

In the Kidney:
BM of several tubules and of the structures within single glomerulus Function to?

Back 50

Support and filter

Front 51

Focal basal cell layer disruptions occur in?

Back 51

cancers/ carcinomas

Front 52

Metaplasia

Back 52

is the reversible replacement of one differentiated cell type with another mature differentiated cell type. The change from one type of cell to another may generally be a part of normal maturation process or caused by some sort of abnormal stimulus. In simplistic terms, it is as if the original cells are not robust enough to withstand the new environment, and so they change into another type more suited to the new environment.

Front 53

Glands

Back 53

Formed by epithelial cells that secrete a fluid of different composition than blood or intercellular fluid.

Secreted substances can be ions, secretory polypeptides or proteins, lipids or glycoproteins.

Front 54

Secretory Granules

Back 54

secreted are generally stored in the glandular epithelia
in small membrane-bound vesicles
Ex. Parotid salivary gland

Front 55

cytokines

Back 55

cell to cell communication

Distance between secretion and target:


Autocrine: target self
Paracrine: target cell in vicinity
Endocrine: far, blood/lymph

Front 56

Autocrine

Back 56

target self

Front 57

Paracrine

Back 57

target cell in vicinity

Front 58

Endocrine

Back 58

Far, blood/lymph

Front 59

What are the two glandular secretion pathways?

Back 59

Constitutive: make and release no signaling molecules
Regulated: concentrate and store signaling for releasing (Neural/endocrine)

Front 60

Exocrine glands

Back 60

have ducts

Front 61

What are the two structural types of multicellular exocrine glands?

Back 61

Simple glands: one unbranched duct. : Secretory portion may be tubular, coiled tubular, branched tubular, or acinar (Flask-shaped).

2. Compound glands: more than one duct that branches repeatably. Secretory portion may be tubular, acinar or tubuloacinar.

Front 62

Merocrine

Back 62

Exocrine gland that functions via exocytosis w/o loss of cytoplasm. It's the most common form of secretion.

Front 63

what regulates exocytosis in salivary acinar cells?

Back 63

cAMP and Ca

Front 64

Holocrine exocrine gland functions by?

Back 64

the whole cell is a discharge

Front 65

Sebaceous gland

Back 65

Sebaceous gland
simple, branched, acinar glands
holocrine mode of secretion

Front 66

Apocrine

Back 66

Apocrine: secretory product and a portion of the cytoplasm
Ex. mammary glands and specialized sweat glands

Front 67

Serous producing cells

Back 67

Serous producing cells- watery secretions; usually intensely stained with eosin; nuclei usually rounded or oval.

Glycoproteins:
N-linked to the β-amide of asparagine .

Front 68

Mucous producing cells

Back 68

Mucous producing cells- viscous, slimy secretions; appear empty by routine H/E; nuclei often flattened against base of cell

Glycoproteins: :
O-linked to the hydroxyl groups of serine or threonine

Front 69

What cell surounds the acini?

Back 69

Myoepithelial cells

Front 70

Anesthetic Diffusion

Back 70

Absorbed by non-neuronal tissue
Diluted by interstitial fluid
Removed by capillaries and lymphatics
Hydrolyzed-inactivated

Front 71

Teeth is embedded in alveolar bone a type of?

Back 71

CT and by PDL another CT

Front 72

What are the functions of CT?

Back 72

Connects, Cushions, Supports, Fills space
Protects
bone protects underlying organs
mast cells-inflammation
plasma cells- antibodies
phagocytes- engulf foreign substances
Barrier under epithelium – protects from the outside world. Anus/esophagus epithelium
Contains nerves- sensation
Contains blood vessels, lymphatics
nutrient, waste, gas exchange

Front 73

CT comprises?

Back 73

Cells
Fixed and wandering
Fibers
collagen, elastic
Ground substance
GAGs, proteoglycans, adhesive proteins
Tissue fluid
Biological Considerations

Front 74

Mesenchyme

Back 74

Mesenchyme cells --> these give rise to the fiberblasts which are the work horse and they produce and gives rise to adipocytes, etc.

Front 75

Fibroblast

Back 75

Synthesize extracellular matrices such as:
Fibers
Collagen
Elastin
They synthesize the Ground substance such as:
Glycosaminoglycans
Proteoglycan
Synthesize growth factors
influence growth and differentiation
Lots of interactions between CT and epithelium

Front 76

What are the differences between a fibroblast and a fibrocyte?

Back 76

Fibroblast- active
abundant, irregularly branched cytoplasm
ovoid, large pale staining nucleus
well developed RER, golgi – because these are making proteins that they are going to secrete
Fibrocyte- inactive (quiescent)
it becomes spindle shaped, few cell processes
it becomes smaller, darker, elongated nucleus
only a small amount of RER

Front 77

Fibroblasts make?

Back 77

collagen fibers

Front 78

What is the major cell type in CT?

Back 78

fibroblast - thin elongated cell - spindle shaped

Front 79

Adipocyte

Back 79

It Stores lipids
Energy supply
Offers Padding, protection, shock absorber
Insulation
Generation of heat (brown fat)
Visceral fat has a Endocrine function – have to do a lot with inflammation

Front 80

Adipocytes develop from?

Back 80

Mesenchyme --> lipoblast -->
multilocular/unilocular adipocyte

Front 81

Unilocular is a?

Back 81

white fat cell
One lipid droplet (white-yellow, carotenoids)
polyhedral shaped (50-150 um) Large
signet ring cell- lipids dissolved in routine histology cell with vacuole and eccentric flattened nucleus

More overweight someone is the larger the adipose cells become

Front 82

Multilocular is?

Back 82

a brown fat cell


many lipid droplets and mitochondria
color due to blood vessels and mitochondria with cytochromes
polygonal, smaller than unilocular
heat producing
newborn
adults


Newborns don’t have a lot of protection so they need a way to survive and the brown fat is heat producing to keep themselves warm

Recently brown fat found in Adults, which set up a race with pharmacompanies to figure it out and what they could do with it.

PET scan inject radioactive compound … analog of glucose. Taken up by actively metabolizing cells. PET machine can then detect this activity

Front 83

Fat as an Endocrine organ.

Back 83

Macrophages surrounded by fat cells are secreting a number of biologically active materials/fa
Endocrine function of fat changes with an increase in obesity. The cells give off a different cascade of molecules. Leptin is up. The fat cells produce a great number of bioactive material Ex. Leptin

TNF alpha lowers adiponectin??

Endothelial cells let more macrophages in

Front 84

Q: T/F In the model Model linking periodontitis and obesity with inflammatory related chronic diseases, if a patients RER/Golgi had a mutation that impaired secretion of newly synthesized proteins, this would not effect periodontitis.

Back 84

FALSE

Front 85

Q: Your patient is borderline obese and has high levels of obesity related inlfammaotory cytokines. You recommend intense periodontal therapy. Based on our proposed model of obesity and periodontal disease, this recommendation does what?

Back 85

aims to lower biologies that relate both obesity and periodontal disease.

Front 86

Macrophage

Back 86

Phagocytic
antigen presenting
long living
fixed in the tissues and wandering/can wander and travel in the blood stream
Mononuclear Phagocyte System – very important in the normal signaling of adipose tissue

Front 87

What is the precursor to the macrophage?

Back 87

monocyte - will move from the blood stream to the tissue and will differentiate into a macrophage

Front 88

Kupffer cell

Back 88

liver

Front 89

microglia

Back 89

nervous tissue

Front 90

Langerhans cells

Back 90

Skin - Antigen presentation

Front 91

Phagocytosis

Back 91

Lysosome will fusen with a phagosome and the lysosomal enzymes will kill the microbes

Front 92

Opsinization

Back 92

Phagocytosis increased when the foreign material/microorganism is covered by antibodies or its antigens bind complement.

This enhances the ability of it to be phagocytized.

Front 93

Q You have decided to be an academic dentist who will study the link between obesity and periodontal disease. You receive a link from Life Line Cell Tech that they are selling pre-adipocytes. In the lab, if they are differentiated into adipocytes and in the presence of oral bact. Secrete obesity related inflammatory cytokines, will they be a good model for you to use?

Back 93

Yes

Front 94

Giant cell

Back 94

A giant cell is a mass formed by the union of several distinct cells (usually macrophages). It can arise in response to an infection, such as from tuberculosis, herpes, or HIV, or foreign body.

Front 95

Name a cell that is metachromatic.

Back 95

Mast cell

Front 96

Mast Cell

Back 96

oval to round
IgE on surface
filled with metachromatic secretory granules that are filled with:
histamine
heparin
neutral proteases
ECF-A (eosinophil chemotactic factor of anaphylaxis)
NCF (neutrophil chemotactic factor)
leukotrienes
prostaglandins
cytokines

Front 97

How do the secretions of granules in Mast cells work?

Back 97

Antigen binds to IgE receptor
a Calcium event occurs and there is a fusion of these granules and a release

ECF for eosinophils
NCF for neutrophils, drawing neutrophils to the area

Other pathway converts Arachidonic acid and secretes Leukotrines and Thromboxanes and Prostaglandyns

Front 98

What happens during anaphylactic shock?

Back 98

all of the bodies in mast cells degranulate and you have a real life and death situation

Front 99

Plasma Cells arise from?

Back 99

arise from B-lymphocytes
ovoid, basophilic
well developed rer
juxtanuclear golgi secretes antibodies

Front 100

Leukocytes - white blood cells

Back 100

migrate from blood
increase in inflammation
Neutrophil – kill bacteria by phago
Eosinophil – kill parasitic infection
Basophil – analogous to mast cells
lymphocyte
monocyte – precursor to macrophage

Front 101

Eosinophil

Back 101

WBC that helps with parasitic bacteria

Front 102

Pericyte

Back 102

surface of capillaries and veinules
rounded cell that wraps around
contractile- involved in blood flow control
very important in wound healing- gives rise to connective tissue and blood vessels (i.e undifferentiated stem cell-like)

Front 103

Various Stem Cells

Back 103

MSCs- multipotent mesenchymal stem cells
bone marrow, adipose tissue, umbilical cord blood
Give rise to different cell lineages
Regenerative medicine, therapy
Dental MSCs

Front 104

Name the following multi potent stem cells:

DPSCs
SHED
PDLSCs
SCAP
DFPCs

Back 104

DPSCs- post natal dental pulp stem cells
SHED- stem cells from exfoliated deciduous teeth
PDLSCs- periodontal ligament stem cells
SCAP- stem cells from apical papilla
DFPCs- dental follicle precursor cells

Rootword for formation potential: Osteogenic, dentinogenic, cementogenic, adipogenic, chondrogenic, myogenic, neurogenic

Front 105

What are the cells found in Areolar CT 1?

Back 105

Fibroblasts, Mesenchyme, Adipocyte

Front 106

What are the cells found in Areolar CT 2?

Back 106

Mast cells, Macrophage, lymphocyte, Plasma cell

Front 107

Name the 3 CT fibers.

Back 107

Collagen, Reticular, Elastic

Front 108

Name Collagen that forms long fibrils.

Back 108

Types 1,2,3,5, and 11

Front 109

Fibril associated collagens do what?

Back 109

bind collagen fibers together.

Types 9, 12, 14

Front 110

Network forming collagens

Back 110

forms basal lamina
type 4, 8, and 10

Front 111

Type 7 collagen forms what?

Back 111

anchoring fibrils. binding collagen fibers to basal lamina

Front 112

Structure of a collagen fibril.

Back 112

overlapping array

Front 113

Osteogenesis Imperfecta

Back 113

Change in one nucleotide gene for Type 1. spontaneous fractures

Front 114

Scurvy

Back 114

lack of Vit C --> ulceration of gums, hemorrhages

Front 115

Reticular fibers are what type of collagen.

Back 115

Type III


thinner and more carbohydrate than type I fiber
stains black with silver stain
produced by reticular cell
they produce a scaffolding network

Front 116

Elastic Fibers

Back 116

Can stretch 150% of length
Fiber composed of
Outer sheath- microfibrils of fibrillin (glycoprotein)
Surrounds Inner core- amorphous core of elastin

Elastic fibers are required in areas that need to expand and contract Ex. Blood vessels

Front 117

Marfan Syndrome

Back 117

mutation in fibrillin, defects in a protein

Front 118

ECM interactions regulating TGF beta

Back 118

TGF beta gets up regulated. – disregulation of growth factor – gets embedded in the CT can become a sink or a source for growth factors.

They put mutation into the mouse they were able to treat the mouse with pharmaceuticals, they were able to reverse the pathology of Maphan Syndrome, which led to the next phase: clinical trials.

Thrombospondin

Front 119

Ground Substance

Back 119

are complex of macromolecules
they fill the space between fibers and cells
organizes tissue topography, supports cell migration, orients cells, induces cell behavior
Can bind growth factors, cytokines-reservoir
3 classes of compounds
Glycosaminoglycans
Proteoglycans
Multiadhesive glycoproteins.

Fibronectin is a G.S. protein

Front 120

GAGs

Back 120

repeating dissacharide of uronic acid and sugar
hydrophilic polyanions (can bind cations such as sodium)
part of Proteoglycan
very important in regulating osmotic pressure leads to increased water content- firmness, flexibility

Front 121

Proteoglycans

Back 121

Protein core + GAGs (coming off of them can attract water)

GAG molecules are found within CT Ex. Hyaluronic acid

Front 122

What is the major protein of basement membranes?

Back 122

Type IV Collagen

Front 123

Mulitadhesive glycoproteins

Back 123

is a globular protein with carbohydrate
Very functional in cell-cell and cell-substrate interactions

Front 124

What are the Two major multi adhesive glycoproteins?

Back 124

Fibronectin – can bind cells, collagens, and GAGs
laminin - can also bind cells, collagens, and GAGs, basement membrane

Front 125

Fibronectin - Laminin

Back 125

binding domains
cells
collagens
GAGs

Front 126

Tissue Fluid

Back 126

similar to blood plasma in ions
similar to blood plasma in diffusable substances
contains low molecular weight plasma proteins
circulation to feed cells and remove waste

Front 127

Arterial side, when the hydrostatic pressure is greater than the Osmotic pressure, water then goes where?

Back 127

leaves the venules to the arterial side. It works both ways and goes back and forth

Front 128

Tissue Fluid Movement

Back 128

hydrostatic pressure from blood
water leaves capillary

colloid osmotic pressure- plasma proteins
water enters capillary

Front 129

Edema

Back 129

increase in tissue fluid, i.e. swelling

Front 130

Areolar CT

Back 130

Fills space between muscle, supports epithelial tissue, sheaths lymphatics and blood vessels
fibroblasts and macrophages most numerous- contains numerous other all cell types
flexible, well vascularized- loose consistency

Front 131

Name the two types of Dense CT.

Back 131

Irregular collagen fiber bundles- no orientation
3-d network- resists stress all directions

Regular collagen fiber bundles - in a pattern
collagen fibers aligned linearly with fibroblasts

Front 132

Dense CT

Back 132

less flexible & more resistant than loose
offers resistance and protection
fewer cell types
mostly collagen

Front 133

What CT might you find in tendon?

Back 133

Dense regular CT

Front 134

Elastic CT

Back 134

bundles of parallel elastic fibers
between is thin collagen fibers, fibroblasts
yellowish color
occurs infrequently
found in some ligaments
vertebral column, penis

Front 135

Reticular CT

Back 135

loose CT of reticular fibers and specialized fibroblasts (reticular cells)
forms a 3-d network to support cells
reticular cells cover fibers and ground substance producing sponge-like structure
produces microenvironment for hematopoietic and lymphoid organs (found in bone marrow, lymph nodes, spleen)

**Stains silver - lymphoid tissue, spleen

Front 136

Mucous CT

Back 136

in umbilical cord; pulp of young teeth
abundance of ground substance
primarily hyaluronic acid
Wharton‘s jelly (umbilical cord)
cells- mainly fibroblasts

Front 137

Adipose Tissue

Back 137

White (unilocular) and brown (multilocular)
cells are packed and subdivided into lobules with loose CT sheaths
make lipoprotein lipase- transported to luminal surface of endothelial cells to hydrolyze chylomicrons
endocrine organ

Front 138

Lipid Transport

Back 138

Adipocyte <----> Capillary

Front 139

Can epithelium be influenced by underlying CT?

Back 139

Yes it can.

Heterotransplants of epithelium/CT- normal
tongue ep/buccal CT- tongue-like differentiation
Heterotransplants of epithelium/CT- altered
palate ep/buccal CT produces buccal-like keratinization (differentiation)***
changed, it didn’t stay palate went to buccal
palatal or buccal ep/tongue CT produces tongue-like epithelium

Front 140

Wound Healing Surgical Incision

Back 140

Incisional space fills clotted blood, fibrin, blood cells; dehydration forms scab
<24 hrs- neutrophils appear (kill bacteria)
by 72 hrs- macrophages replace neutrophils
injest proteolytic debris
provide growth factors to stimulate fibroblast growth, collagen secretion, neovascularization

Front 141

When do the neutrophils show up in wound healing?

Back 141

The 1st 24 hours to kill bacteria.

by 72 hrs- macrophages replace neutrophils
injest proteolytic debris

Front 142

Inflammation

Back 142

Complex reaction to injuries
fluid and leukocyte leakage; systemic responses
Leads to repair
Protects
When inflammation goes wrong --> Basis of many chronic diseases
rheumatoid arthritis; hypersensitivity

Blood vessels get leaky during inflammatory response. Increase in blood flow. Neutrophils get drawn in in case of bacterial infections. The body is set to draw in the types of cells it needs in order to repair itself.

Front 143

When inflammation goes wrong it is the Basis of many chronic diseases. Name one.

Back 143

rheumatoid arthritis; hypersensitivity

Front 144

What's the difference between acute and chronic inflammation?

Back 144

Acute- short duration; leakage, extravazation

Chronic- longer duration; cell based; neovascularization, fibrosis, necrosis

Front 145

What is the differentiating pathway of an Osteoprogenitor?

Back 145

O.P. --> Preosteoblast --> Osteoblast --> Ostocyte

Front 146

Osteoprogenitors

Back 146

OSTEOPROGENITORS
1. Extensive proliferation: growth, repair, re-organization
2. Near free bone surfaces, few cell layers from active osteoblasts
3. Alkaline phosphatase negative

Front 147

Pre-osteoblasts

Back 147

PRE-OSTEOBLASTS
1. Limited proliferation (some mitotic ability) and this leads to a more differentiated cell
2. Alkaline phosphatase positive

Front 148

In an Osteoclast the ruffled border represents what?

Back 148

where the acids and enzymes are released.

Front 149

Intramembranous Bone Formation

Back 149

1. Mesenchyme -->lead to osteoblasts
2. Woven bone - is primary spongiosa – weak bone
3. Mature spongy bone - secondary spongiosa --> part of this then becomes --> CB
4. Compact bone

Front 150

What process will get rid of
the hyaline cartilage and woven
bone to make way for the newly
synthesized spongy bone?

Back 150

Absorption process

Front 151

OSTEOBLASTS (mature cell) – do not undergo mitosis at all.

Back 151

1. Synthesize bone (collagen type I & non collagenous proteins)
2. Strongly positive for alkaline phosphatase (bone formation index)
3. Functions
a. Secretion --> bone matrix (osteoid) as well as beginning of osteoid degradation
b. Osteoid (uncalcified bone matrix) resorption
c. Osteoclast stimulating factor(s)

Front 152

Bone lining cells are?

Back 152

“resting” osteoblasts – resting cell. – more elongated flattened cells lying on the outside of trabelcula.

Front 153

Osteocytes

Back 153

1. Osteoblasts that become trapped in their own matrix
2. Important mechanosensory (mechanotransduction) role, maintain bone matrix
3. Form a syncytium through gap junctions between their processes: called connexins

Front 154

Osteoclasts

Back 154

1. Bone resorption by osteoclast tightly coupled with bone formation by osteoblast
Large and multinucleated (4-20 nuclei)
3. Bone marrow-derived (monocyte-macrophage lineage / CFU-GM)
5. Numerous large lysosomes, abundant mitochondria, well developed Golgi, some RER

Front 155

What cell type is found in Howship's Lacuna?

Back 155

Osteoclasts.


7. Sealing/adhesion /circumferential zone: attachment to mineralized bone matrix
8. Ruffled border: cell membrane thrown into many folds representing site of active resorption
9. Receptors for calcitonin, but not for PTH, Vitamin D3, or cytokines

Front 156

What is the osteoclasts mechanism?

Back 156

Osteoclast mechanism: GMP/CFU-GM  MCS-F binds to receptor on macrophage --> osteoclast precursor  induction of RANK on precursor -->RANK interacts with RANKL produced by stroma cells --> RANKL binds to RANK receptor on osteoclast precursor -->fully activated osteoclast --> bone resorption

Front 157

OPG (Osteoptrotogera) prevents what?

Back 157

Osteoclast formation

Front 158

RANK receptor + RANK =

Back 158

Osteoclast formation

Front 159

RANK + OPG =

Back 159

prevents osteoclast formation

Front 160

Osteocytes

Back 160

"professional" mechanosensory cells

Front 161

Osteoclasts

Back 161

have calcitonin receptors

Front 162

What is:

Large, multinucleated
Monocyte precursor
Howship’s lacunae
Ruffled border
Sealing zone
Calcitonin receptors
Bone resorption

Back 162

Osteoclast

Front 163

Zone of rest or reserve

Back 163

chondorcytes random

Front 164

Zone of proliferation

Back 164

mitosis, isogenous groups, beginning of matrix synthesis

Front 165

Zone of maturation

Back 165

completion of matrix synthesis, partial glycoprotein breakdown

Front 166

Zone of hypertrophy

Back 166

– enlargement of lacunae

Front 167

Zone of provisional calcification

Back 167

matrix mineralization
Calcium brought into hyaline cartilage matrix through periosteal buds --> calcifies --> limited diffusion of nutrients --> apoptosis (death) of hypertrophic chondrocytes
b. Vertical septae fully calcified, whereas, transverse septae do not calcify

Front 168

Zone of degeneration

Back 168

cartilage resorption

Front 169

Zone of Bone Formation

Back 169

periosteal buds bring in mesenchymal cells --> osteoblasts --> form bone on cartilage remnants: primary spongiosa (woven bone) --> resorption and disappearance --> secondary (lamellar) spongiosa

Front 170

Secondary Ossification center

Back 170

Epiphyseal plate

Front 171

What ends secondary growth?

Back 171

When the epiphyseal plate disappears

Front 172

Cartilage is elongated as a result of?

Back 172

Mitotic activity

Front 173

How does the osteoid layer become ossified?

Back 173

Ca with osteoblasts so that gets calcified first.

Front 174

Bone remodeling of Spongy and Compact with Rubin's Path ARF (ARRFR)

Back 174

1. Process by which bone grows and is turned over
2. No net gain or loss in bone mass
3. ARF Sequence Phases (ARRFR)
a. Activation (1 week)
b. Resorption (2 weeks) - osteoclasts go to work
c. Reversal (1.5 weeks) – osteoclasts go away and then the osteoblasts come in.
d. Formation (13.5 weeks)

Front 175

Monocytes in BVs give rise to?

Back 175

osteoclasts

Front 176

Modeling is

Back 176

net gain in bone

Front 177

What are the bone remodeling regulation players?

Back 177

Calcium and phosphate
PTH – stimulates osteoclasts to resorb bone – acts on the kidney tubules to increase absorption.
Vitamin D – calcium shortage in children - rickets
Calcitonin – stimulates bone formation
Growth and thyroid hormones – they affect all growth processes in the body.
Bone morphogenic proteins

Front 178

Cytokines

Back 178

Cell-cell communication
b. Interleukins (IL-1, IL-6): osteoclast recruitmen

Front 179

FGF

Back 179

FGF: neurovascularization and wound healing, stimulation of osteoblast precursor cells
d. PDGF: wound repair stimulates bone resorption and osetoblast precursors
e. IGFI and IGFII: ↑ bone collagen matrix and ↓ collagenase levels

Front 180

BMPs

Back 180

are osteoinductive

Front 181

TGFS

Back 181

stimulates precursor cells of osteoblast lineage and on bone collagen formation

Front 182

Insulin has a direct effect on what bone cell?

Back 182

Osteoblast

Front 183

Glucocorticoids have what effect on bone?

Back 183

inhibition of bone resorption and collagen degradation

Front 184

coupling

Back 184

– formation with resorption ie osteoblast/osteoclast

Front 185

Long bone is completely made by

Back 185

hyaline cartilage which is later replaced by bone

Front 186

nucleus pulposis

Back 186

is the intervertebral disc of a spinal cord

Front 187

What are the functions of bone?

Back 187

Functions: skeletal support, skeletal muscle attachment, protective (skull around brain), metabolic, hematopoietic organ, dynamic material

Front 188

When one part of the mandible is shorter than the other.

Device is screwed into the bone and it is fractured and the screws adjust to pull the bone apart to allow for more and more growth to occur...this is known as?

Back 188

Distraction Osteogeneis

Front 189

Long bone: epiphysis

Back 189

wider spherical ends

Front 190

Long bone: diaphysis

Back 190

shaft

Front 191

Long bone: metaphysis

Back 191

cone shaped transitional region

Front 192

Epiphyseal plate

Back 192

responsible for growth of long bone

Front 193

What are the classifications of bones?

Back 193

BONE CLASSIFICATION
1. Long bones
2. Short bones
3. Flat bones
4. Irregular bones – sphenoid, ethmoid
5. Sesamoid bones – associated with tendons and ligaments giving additional strength. Patella

Front 194

5. Haversian/Compact/Dense/Cortical bone:

Back 194

external part of bone

Front 195

6. Spongy/Cancellous/Trabecular bone:

Back 195

lattice of branching bony spicules or trabeculae

Front 196

7. Articular hyaline cartilage:

Back 196

ends of long bones

Front 197

9. Periosteum (covers outer surface) and Endosteum: lines?

Back 197

inner surface: soft CT

Front 198

10. Skull:

Back 198

compact bone-inner and outer plates/tables; spongy bone between: diploe

Front 199

8. Periosteal (external surface) and Endosteal?

Back 199

(internal surface)

Front 200

By volume____________ bone here is predominant
By weight ______________ bone is predominant

Back 200

Spongy; compact

Front 201

What are the two bone types in long bone?

Back 201

spongy and compact

Front 202

Periosteum has what two layers?

Back 202

a. Outer layer: fibroblastic
b. Inner layer: osteogenic

Also contains Sharpey's fibers

Front 203

Endosteum

Back 203

thin single layer of flat squamous-like cells lining the walls of all cavities in the bone

Front 204

4. Periosteal and Endosteal Circumferential Lamella:

Back 204

lamellae around the outer and inner circumference of the shaft

Front 205

5. Osteons/Haversian Systems:
What parts make up a system?

Back 205

basic structural unit of compact bone
a. Central/Haversian Canal: diameter: 22-110 :m
b. Surrounded by Haversian Lamellae
c. Lacunae: contain osteocytes, filled with extracellular fluid (ECF)
d. Canaliculi: thin channels containing osteocyte cytoplasmic processes

Front 206

6. Volkmann’s Canals:

Back 206

transverse/oblique channels without lamellae --> Haversian canals

Front 207

7. Interstitial Lamellae:

Back 207

angular fragments of previous concentric and circumferential lamellae

Front 208

8. Cement lines
a. Arrest lines -

Back 208

bone formation resumes after an interruption

Front 209

Cement Lines: b. Reversal lines -

Back 209

bone formation follows bone resorption.

Front 210

9. Spongy/Cancellous/Trabeculae bone:

Back 210

not penetrated by blood vessels: NO osteons

Front 211

Osteoprogenitor cell -

Back 211

A mesenchymal cell that differentiates into an osteoblast. Also called preosteoblast.

Front 212

What is found inside a bone lacuna?

Back 212

Osteocyte

Front 213

TYPES OF BONE
1. Primary/Immature/Woven Bone:

Back 213

very cellular, no organization of collagen, less ground substance and mineral
2. Secondary/Mature/Lamellae/Trabeculae Bone: less cells, highly organized collagen arrangement, more ground substance and mineral

Front 214

Types of BONE
2. Secondary/Mature/Lamellae/Trabeculae Bone:

Back 214

less cells, highly organized collagen arrangement, more ground substance and mineral

Front 215

Interdental septum contains what kind of bone?

Back 215

spongy bone

Front 216

Synarthrotic joints - limited or no movement. Please name the various types.

Back 216

a. Synostosis - bony tissue sutures
b. Synchondrosis - hyaline cartilage
c. Syndesmosis - pubic symphysis
d. Gomphosis – PDL – more of a shock absorber

Front 217

Diarthrosis joint is freely movable, what layers does it have?

Back 217

a. Fibrous layer
b. Synovial layer - synoviocytes

Front 218

What comprises Bone Matrix?

Back 218

1. Inorganic matrix
a. Hydroxyapatite crystals
b. Hydration shell
c. Mineralization process – nucleation cores
d. Measurement of calcification
1 Osteomalacia
2 Osteitis fibrosa cystica
2. Organic matrix
a. Type I and Type V collagen
b. NCPs

Front 219

What is the mineral portion of the bone matrix?

Back 219

1. 65% of dry weight
a. Slender rod-like hydroxyapatite [Ca10 (PO4)6 (OH)2]
b. HAP responsible for hardness and resistance
c. Hydration shell
2. Mineralization Process
3. Measurement of Calcification: fluorescent antibiotic tetracycline
a. Osteomalacia – occurs in Ricketts
b. Osteitis fibrosa cystica -
4. Certain soft tissue susceptible to calcification: ectopic

Front 220

What is the organic portion of the bone matrix?

Back 220

ORGANIC MATRIX: 35% of matrix
1. Collagen
a. Type I collagen: 85 to 90% of bone total proteins
b. Bone Type I collagen: triple helical, super coiled, typical 67 nm cross banding
c. Type I collagen in bone greater number of cross-links than in soft tissue
2. Noncollagenous Proteins (NCPs)
a. 10 -15% of total bone protein
b. Bone cells synthesize and secrete as many molecules of NCP as it does collagen

Front 221

What are the bone attachment molecules?

Back 221

1 Fibronectin (FN): mediates cell attachment and bone cell spreading; produced by osteoblast
2. Thrombospondin (TSP): mediates adhesion, not spread; binds calcium
3. Osteopontin (OP): role in osteoclast attachment via integrin receptor; binds calcium; produced by osteoblasts and osteoclasts
4. Bone sialoprotein (BSP)
a. In osteoblasts, osteocytes and recently in osteoclasts
b. Bone sialoprotein: role in osteoclast attachment? Role in binding calcium

Front 222

1 Fibronectin (FN):

Back 222

mediates cell attachment and bone cell spreading; produced by osteoblast

Front 223

2. Thrombospondin (TSP): mediates?

Back 223

adhesion, not spread; binds calcium

Front 224

3. Osteopontin (OP): role in?

Back 224

osteoclast attachment via integrin receptor; binds calcium; produced by osteoblasts and osteoclasts

Front 225

4. Bone sialoprotein (BSP)

Back 225

a. In osteoblasts, osteocytes and recently in osteoclasts
b. Bone sialoprotein: role in osteoclast attachment? Role in binding calcium

Front 226

PROTEOGLYCANS

Back 226

1. Macromolecules that contain GAG side chains attached to a central core protein
2. Chondroitin sulfate: attached to 3 separate core proteins - Versican - Decorin - Biglycan
3. Heparin sulfate: facilitates interaction of osteoblast with extra-cellular macromolecules

Front 227

2. Chondroitin sulfate:

Back 227

attached to 3 separate core proteins - Versican - Decorin - Biglycan

Front 228

3. Heparin sulfate:

Back 228

facilitates interaction of osteoblast with extra-cellular macromolecules

Front 229

OSTEOCALCIN [3 (-CARBOXY GLUTAMIC ACID (GLA) CONTAINING PROTEINS)

Back 229

1. Produced by osteoblasts
2. Regulated by 1,25 dihydroxy vitamin D3
3. Gla confers Ca2+ binding properties
4. Important signal in bone turnover and may act as a chemo-attractant to osteoclast precursors

Front 230

GROWTH FACTORS

Back 230

1. Factors synthesized by cells of the osteoblast lineage: fibroblast growth factors (FGFs), insulin-like growth factors (IGFs), and transforming growth factor-ß molecules (TGF-ßs), bone morphogenetic proteins (BMPs), possibly platelet derived growth factor (PDGF)
2. Also synthesized by cells intimately associated with bone, such as chondrocytic cells, endothelial cells, and fibroblasts: PDGF, FGFs, IGFs
3. Predominant growth factors in bone: IGF-II, TGF-$, IGF-I

Front 231

1. Alkaline phosphatase

Back 231

a. Used as an index of bone formation in serum
b. May also function in mineralization

Front 232

2. Osteonectin:

Back 232

phosphorylated glycoprotein
a. High affinity for binding ionic calcium and hydroxyapatite and collagen
b. May play a role as modulator of mineralization and function in tissue remodeling/bone remodeling

Front 233

Only cell inside bone is?

Back 233

an osteocyte

Front 234

Steps to fracture repair.

Back 234

1. A fracture hematoma forms
2. A fibrocartilaginous (soft) callous forms
3. A hard bony callous forms
4. The bone is remodeled

Front 235

What are the 3 types of cartilage?

Back 235

Hyaline, Elastic, and Fibro

Front 236

Cartilage

Back 236

INTRODUCTION
1. Special form of C.T.
2. Semirigid supporting tissue
3. Avascular and aneuralar
4. Types: hyaline, elastic, fibro

Low oxygen type of tissue. Diffusion transfers the nutrients through the gel-like framework.

Front 237

Where are chondrocytes embedded?

Back 237

in lacuna

Front 238

Hyaline and Elastic is what type of collagen?

Back 238

Type II

Front 239

Fibro is what type of collagen?

Back 239

Type I

Front 240

Hyaline Cartilage

Back 240

articulating cartilage. Long bone ends (articulating cartilage), Trachea, ribs/costal cartilages, Primary Bronchi and secondary bronchi. Supporting type of tissue as you exhale and inhale.

Front 241

Elastic Cartilage is found where?

Back 241

the ear, and epiglottis – it bends

Front 242

Remnant of the notochord forms the Nucleus pulposis – forms the soft-gelatinous central part of the intervertebral disc. Anulus fibrosis surrounds it and it is?

Back 242

a fibrocartilage.

Front 243

Fibrocartilage is located?

Back 243

between the vertebrae, helps to make up the intervertebral disks. Pubic Symphysis held together by fibrocartilage.

Front 244

Perichondrium

Back 244

mitotic layer: outer fibrous and inner chondrogenic layer – surrounds the tissue and acts as a capsule.

Front 245

chondroblast.

Back 245

It traps itself in a lacuna, then changes its name to Chondrocyte. Similar to Osteoblast --> Osteocyte

Chondroblasts (chondrogenic cell/chondrocyte)
a. Precursor to and smaller than chondrocyte
b. Well developed organelles
c. Basophilic cells
5. Chondrocytes in lacunae
a. Large cell, well developed organelles
b. Isogenous groups: progeny of one cell
c. Synthesis and maintenance of tissue

Front 246

Hyaline Cartilage

Back 246

1. PAS+ and metachromatic with Toluidine Blue
2. Considerable amount of collagen: Types II (dominant), IX, X, XI
GAGs – proteoglycans – aggrecan – chondronectin – the ones with the Sulfur
Gives off the metachromatic properties
4. Water (60-80% wet weight) → for resilience cushioning – in synovial fluid

Front 247

Is Hyaline Cartilage metachromatic?

Back 247

Hyaline cartilage is metachromatic, but it can also be stained with PAS because they are high in carbohydrates. Hyaline has tightly and loosely bound water, which is needed for movement areas and it is released into synovial cavity. Because of the sulfur in the cartilage, it doesn’t stain blue it stains reddish.

Mast cells are also metachromatic and will stain blue.

Front 248

What type is the strongest cartilage?

Back 248

Type I

Hyaline is Type II, but can resist a intermittant pressure a certain kind of pressure

Front 249

Besides Type II collagen, what other types are found in Hyaline?

Back 249

Type IX helps stabilize the cartilage matrix.

Type X as well in bone formation. Major type is Type II though

Front 250

Pericellular capsule

Back 250

surrounds the cell, surrounds every lacunae

Front 251

Difference between Inter-territorial and Territorial matrix.

Back 251

Inter-territorial matrix is found between the isogenous groups and territorial matrix is within the isogenous groups.

Front 252

Chondronectin is a?

Back 252

typical glycoprotein that attaches the chondorcyte to a collagen fibril. They hold things together.

Front 253

Chondorgenic cells give rise to?

Back 253

chondroblasts --> matrix is laid down, cell becomes trapped and then you have a chondrocyte.

Front 254

Elastic cartilage

Back 254

1. Withstand repeated bending
2. Similar to hyaline cartilage except presence of elastic fibers
3. External ear, external auditory meatus, eustachian tube

Elastic fibers have a different refractive index than the rest of the tissue

Front 255

Fibrocartilage

Back 255

FIBROCARTILAGE
1. Poorly defined limits
2. Transition tissue
3. Chondrocytes arranged in rows
4. No perichondrium
5. Good tensile strength
6. Intervertebral disc: nucleus pulposus + annulus fibrosis; pubic symphysis; tendon-bone attachments

Front 256

What are the Two types of growth of Cartilage?

Back 256

appositional growth and Interstitial growth

Interstitial growth: expansion from within – we have chondrocytes in the pc of cartilage in side increases the internal dimension. This does not happen in bone except for hyaline cartilage in epiphyseal plate ex. Long bones.

Appositional growth: increase in width of bone, perichondrium required – adding on cartilage from the outside

Front 257

How is cartilage formed?

Back 257

1. Mesenchyme --> chondroblasts --> chondrocytes

Front 258

Interstitial growth:

Back 258

expansion from within – we have chondrocytes in the pc of cartilage in side increases the internal dimension. This does not happen in bone except for hyaline cartilage in epiphyseal plate ex. Long bones.

Front 259

Appositional growth:

Back 259

increase in width of bone, perichondrium required – adding on cartilage from the outside

Front 260

DEFICIENCIES in the following cause:

1. Vitamin A
2. Vitamin C
3. Vitamin D

Back 260

1. Protein/Vitamin A --> reduction in epiphyseal plate thickness
2. Vitamin C: scurvy --> epiphyseal plate distortion
3. Vitamin D: rickets --> absence/poor calcification

Front 261

Skeletal muscle

Back 261

strong quick discontinuous, voluntary contraction

Front 262

Cardiac muscle

Back 262

strong, quick, continuous involuntary contraction

Front 263

Smooth muscle

Back 263

Weak, slow, involuntary contraction

Front 264

What are the 3 types of skeletal muscle fibers?

Back 264

Red Fibers – Slow Oxidative
White Fibers – Fast Glycolytic
Intermediate – Fast Oxidative/Glycolytic

Front 265

Sarcosomes

Back 265

- mitochondria

Front 266

Myofibrils

Back 266

– contractile elements

Front 267

Define the following skeletal CT coverings:

1. Epimysium
2. Perimysium
3. Endomysium

Back 267

Connective Tissue Coverings:
Epimysium – dense CT around muscle
Perimysium – dense CT around fascicle
Endomysium – delicate CT around fiber

Front 268

Development of Skeletal Muscle

Back 268

from Myoblasts
Satellite Cells- source of stem cells in adult muscle that can repair damage

Front 269

Hypertrophy

Back 269

increase in cell size

Front 270

Following damage the myofiber, what happens?

Back 270

satellite cells are activated to enter the cell cycle and proliferate allowing for expansion of the myogenic cell population (B),
These activated satellite cells are characterized by high expression of MRFsMyoD and Myf5.
The proliferative phase is followed by Myoblast terminal differentiation and characterized by the upregulation of the MRF’sMyogenin and Mrf4 (C)
new myofiber formation (upon innervation) (D)

Front 271

Sarcomeres

Back 271

repeating contractile units

Front 272

A Band

Back 272

– anisotropic, dark band, composed of thick filaments, myosin

Front 273

I Band

Back 273

-- isotropic, light band, thin filaments, actin

Front 274

Z Line

Back 274

-- in the center of the I-band, sarcomere is from Z-line to Z-line

Front 275

H Zone

Back 275

– in the center of the A-band

Front 276

M Line

Back 276

-- in the center of the H Zone

Front 277

F Actin

Back 277

– filaments of actin embedded in the Z-line

Front 278

Tropomyosin

Back 278

– filamentous protein that fills the groove in F-actin and binds Troponin.

Front 279

What are the 3 types of Troponin

Back 279

Troponin
TnT—Troponin subunit that binds tropomyosin
TnC– Troponin subunit that binds calcium
TnI—Troponin subunit that inhibits actin-myosin interaction

Front 280

α-Actinin

Back 280

—Actin linking protein located at the Z-line,

Front 281

Desmin

Back 281

– Intermediate filament located in muscle

Front 282

Titin

Back 282

is the largest known molecule and functions as a molecular spring and is responsible for passive elasticity in SK muscle. It connects the Z-line to M-line

Front 283

Nebulin binds to

Back 283

actin and is thought to set the length of the thin filament

Front 284

Sarcoplasmic Reticulum

Back 284

—special SER in muscle. Sequesters and releases calcium

Front 285

What are the components of the SR?

Back 285

Components
Terminal Cisternae – I band, calciquestrin
Tubular Channels – A band
H Sacs – H zone
T-tubules—penetrations of the cell membrane deep into the muscle cell cytoplasm.

Front 286

Terminal Cisternae

Back 286

– I band, calciquestrin

Front 287

Tubular Channels

Back 287

– A band

Front 288

H Sacs

Back 288

– H zone

Front 289

T-tubules

Back 289

—penetrations of the cell membrane deep into the muscle cell cytoplasm.

Front 290

Contraction of Skeletal Muscle

Back 290

Contraction
Sliding Filament Mechanism
Motor End Plate
Acetylcholine Receptors – sarcolemma

Front 291

Role of collagen in Cardiac muscle

Back 291

collagen I and III that attach to the cardia muscle cells and keep them registered.

Front 292

Intercalated Disc

Back 292

At sarcomere ends, connect myocytes

There’s a vertical and horizontal component. It connects one cell to the other cell via a fascia adherens. It replaces the Z-line, which is also made of actin. Then it goes through the gap junctions and goes through another z-line.

Principle intermediate filament for muscle is desmin

Front 293

The principle intermediate filament for muscle is?

Back 293

desmin

Front 294

Perkinji cells.

Back 294

are 5 – 6 times bigger than a cardiac muscle cells.
close to endocardium, specialized cardiac muscle cells

Front 295

Cardiac Muscle

Back 295

– Muscle cells
Cytoplasm– Full of organelles, myofibrils
Striations – not as distinct as in skeletal muscle
Nuclei – centrally located
Myofibrils- not as uniformly distributed as skeletal
Mitochondria– abundant and interspersed in cytoplasm
Branching and Anastomosing of Fibers
Sarcoplasmic Reticulum – less defined than in skeletal muscle

Front 296

Myoendocrine

Back 296

Cardiodilatins (CDD) or atrial natriuretic polypetides – vasodilation

Front 297

Location of Smooth Muscle

Back 297

Location – tubular organs
Form – Spindle shaped with centrally located nucleus
Similar cells-- myoepithelial cells, pericytes, myofibroblasts.
Light Microscopic Structure
Elongated
Nonstriated
Overlapping

Front 298

Smooth Muscle Filaments

Back 298

Thin Filaments – 30-80 Å, composed of actin
Dark Patches – cytoplasmic dense bodies
subplasmalemma dense plaques
Anchoring Filaments – 100 Å, desmin IF,
links together bodies and plaques
Thick Filaments – 120-160 Å, composed of myosin
Sliding Filament Mechanism – calmodulin dependent

Front 299

Smooth Muscle contraction

Back 299

1. SM contraction is the result of Actin-Myosin interactions that result in sliding filaments. However, the stimulus for SM contraction can be:

2. Neural, Stretch, Gap Junction electrical, or Humoral .

3. SM in different locations are stimulated by different mechanisms.

Front 300

Smooth Muscle-like cells

Back 300

Myoepithelial cells- have the properties of epithelial cells, but they are also contractile. Located in sweat, mammary and salivary glands

Myofibroblasts- have the properties of fibroblasts, but they are also contractile. Important in wound healing and scar contraction.

Front 301

Myoepithelial cells

Back 301

- have the properties of epithelial cells, but they are also contractile. Located in sweat, mammary and salivary glands

Myofibroblasts- have the properties of fibroblasts, but they are also contractile. Important in wound healing and scar contraction.

Front 302

Myofibroblasts

Back 302

- have the properties of fibroblasts, but they are also contractile. Important in wound healing and scar contraction.

Front 303

Smooth Muscle and Disease

Back 303

Asthma- SM in Bronchi contracts and limit aid flow.
Atherosclerosis- SM proliferation contribute to lumen narrowing

Myofibroblasts –Fibrotic diseases like cirrhosis or lung responses to smoking
Myoepithelial cells- Lactation failure due to lack of response to oxytocin.

Front 304

Asthma

Back 304

Asthma- SM in Bronchi contracts and limit aid flow.
Atherosclerosis- SM proliferation contribute to lumen narrowing

Front 305

What are the general properties of the collagen gene family?

Back 305

Most abundant connective tissue protein in vertebrates (ca. 25% by weight – mostly Type I)
Confers the property of tensile strength
Primary determinant of tissue form
Serves as a scaffold for cell attachment and mineralization

Front 306

The collagens comprise a family of?

Back 306

28 extracellular matrix proteins.
Each is a product of a unique genetic loci
Therefore, a substantial portion of the human genome is devoted to the collagen gene family

Front 307

Common features of collagen.

Back 307

1. All of them are made up of Oligomers of 3 polypeptide chains (α-chains)

2. They Contain regions (domains) of triple helix

3. 1º amino acid sequence of the triple helical domain is repeating 3 amino acids [gly-X-Y]n
X=proline usually, Y usually hydroxyproline

4. Unusual post-translational modifications of hydroxyproline and hydroxylysine (also present in elastin, acetylcholinesterase, osteocalcin (bone protein), and complement component C1q)

Front 308

What are the Fibril forming collagens?

Back 308

e.g. types I-III, V and XI

Front 309

What are the Network forming collagens that form mesh-like arrays?

Back 309

e.g. collagen types IV, VI, VII, VIII and X

Front 310

What are the Fibril associated collagens with interrupted triple helices (FACIT)?

Back 310

e.g. collagen types IX, XII, XIV and XVI (“chimeric” proteins)

Front 311

What are the Transmembrane collagens that link cells with ECM?

Back 311

collagen types XIII, XVII (aka BPAG2)

Front 312

Type II collagen has how many alpha chains?

Back 312

only 1. Hyaline cartilage – all 3 alpha come off the same chain

Front 313

Type IV collagen

Back 313

has 5 alpha chains and is the major collagen of most basement membranes

Front 314

Type VII collagen

Back 314

has 1 alpha chain and is the anchoring fibril of the basement membrane

Front 315

Type XII collagen

Back 315

has 1 alpha chain. Tendons, ligaments, muscle insertions in association with collagen type I. Non-collagenous domains contain fibronectin and von Willibrand clotting factor-like domains.

Front 316

What is the structure of collagen?

Back 316

Made up of 3 alpha chains – need glycine and every 1st position, which allows each alpha chain to form a tight right handed alpha helix. Helps with tensile strength.
Because glycine is at every 3rd position, the R groups are outward projecting, which protects the peptide bond.

Front 317

The X in the triple helix type I collagen domain is usually?

Back 317

proline

Front 318

The Y in the triple helix type I collagen domain is usually?

Back 318

Hydroxyproline

Front 319

What do tight turns of the Type I collagen helix do?

Back 319

force the functional groups of the amino acids in X and Y positions to radiate from the peptide bond back bone of the α chains, hence collagen is resistant to most proteases (steric hinderance).

Front 320

That is the precursor to collagen

Back 320

procollagen


The cell secretes propeptidases that cleaves off the propeptides of the procollagen and then they self assemble into a collagen fibrils.

Front 321

Type I collagen C and N telopeptides

Back 321

C- and N-telopeptides: Short sections at the carboxy and amino termini of the type I collagen protein that do not assemble into the collagen triple helix

During degradation of the type I collagen protein both C- and N-telopeptides are locally released. Levels can be measured in urine, serum or gingival crevicular fluid as a measure of collagen degradation

Front 322

How is the collagen molecule stable?

Back 322

1. Repeated glycines allow the formation of a tight α-helix and maximal intra chain hydrogen bonding

2. Proline, an imido acid, limits rotation around the peptide bond

3. Hydroxy-proline and lysine allow intrachain hydrogen bonding

4. Inter-molecule covalent bonds between derivatives of lysine and hydroxylysine formed extra-cellularly

Front 323

Why do collagen fibrils have a banded appearance?

Back 323

1/4 staggered arrays

The ¼ region fits a crysallite of hydroxyappitite just perfectly inside the space, giving significance in regards to mineralization

Front 324

During Collagen biosynthesis, where do the post translational modifications take place?

Back 324

Occurs in the cisternae of the ER or the leaflets of the golgi

Front 325

Why do we need a procollagen form?

Back 325

C and N propeptides prevent intracellular fibril formation

Front 326

C propeptides, register the three α chains within the cisternae of the ER, allowing formation of?

Back 326

the triple helix in a C→N direction

Front 327

What are some post translational modifications that occur with collagen?

Back 327

Disulfide bond formation
Hydroxylation of proline and lysine by prolylhydroxylase. Under-hydroxylation results in scurvy
Glycosylation of hydroxylysine
Extra-cellular processing of C and N propeptides (Ehlers-Danlos syndrome)
Covalent crosslinks between derivatives of lysine and hydroxylysine (Lathynism)

Front 328

Prolyl hydroxylase in the cisternae of the ER requires ascorbate (vitamin C), Fe++, O2 and α-ketoglutarate for activity. The enzyme can only act on nascent procollagen α-chains prior to formation of the triple helix. Under hydroxylation of newly synthesized collagen results in?

Back 328

scurvy

Front 329

The inability to synthesize ascorbate (vitamin C) is due to a mutation in?

Back 329

gulonolactone oxidase gene

Front 330

Lysyl oxidase, which is involved in the biosynthesis of collagen is present in the cisternae of the ER and requires Cu++ as a cofactor. Failure to extract copper from the diet results in?

Back 330

Menke’s disease.

Front 331

Lysyl oxidase, which is involved in the biosynthesis of collagen, can be inhibited by β-amino proprionitrile (found in sweat peas) resulting in?

Back 331

lathyrism.

Front 332

Aldehyde derivatives of lysine are essential to the formation of?

Back 332

extracelluar collagen cross links.

Front 333

Procollagen α1(I) gene is divided into approximately 50 exons, most exons are 54 bp in length and the remaining are a multiples of?

Back 333

9 bp

Front 334

What are the cues for exon/intron genome organization?

Back 334

1. FACIT collagen domains containing non-collagenous sequences have been “spliced in” from other genes such as fibronectin and von Willibrand’s clotting factor in the case of type XII collagen.

2. Chromosome location. The genes for α chains for heterotrimeric collagens (e.g. types I, V, IX) are always found on separate chromosomes.

3. Nucleic acid sequence. Each exon begins with the triplet codon for glycine and ends with the codon for a “Y” amino acid.

Front 335

For collagen, the smallest number of [gly-X-Y]n that can form a thermodynamically stable triple helix at 37°C is?

Back 335

54 bp long. (6 triplets X 3 nucleotides/codon X 3 codons = 54 nucleotides)

Front 336

Most abundant ECM protein is?

Back 336

collagen. Collagens impart tensile strength
Other desirable physical properties:
Tissue pliancy
Volume for tissue growth and cell migration
Linkage of ECM proteins into a unified matrix
Cell matrix interactions
Others

Front 337

Guanidine is used in protein extraction and collagen extraction, what agent is guanidine?

Back 337

a chaotropic agent. It induces chaos…

Front 338

Non Collagen Protein: Elastin

Back 338

1. Ultrastructure
Amorphous component
Microfibrillar component

2. Properties
Rubber-like, high molecular weight protein
Insoluble in most solvents

3. Composition
33% glycine, 10-13% proline or hydroxyproline, 40 hydrophobic amino acids (very few hydrophobic amino acids in collagen)
Contains desmosine, a post translational derivative of lysine

Front 339

We Can isolate precursor of elastin by?

Back 339

growing animals in a copper deficient diet and extract a 72 kDa protein without crosslinks (= tropoelastin)

Front 340

More recently the elastin gene has been sequenced
What Two domains have been described?

Back 340

Small domains with lysine-derived crosslinkages (desmosine)
Large domains enriched in hydrophobic amino acids

Front 341

Why is elastin an elastic molecule?

Back 341

With long sequences of hydrophobic amino acids and inside the body they are trying to make their surface area as close as possible. When pulling them outward and letting go they’ll recoil because of the aqueous environment. That is why it is an elastic molecule.

We also have a mean high blood pressure that is relatively high and this correlates with the number hydrophobic amino acids in elastin

Front 342

Fibronectin

Back 342

1. Abundant serum and ECM protein

2. Functions: decorates collagen, fibrin and other ECM molecules during development and wound healing

3. Facilitates cell migration both in wound healing and development (eg neural crest cell migration)

Front 343

Cell migration is facilitated for cells that express cell adhesion molecules (eg some classes of integrins) that specifically bind the RGD sequence repeats of fibronectin.

RGD is comprised of what AA's?

Back 343

arginine, glycine, aspartic acid

Front 344

Collagen is turned over pretty quickly. Is the half-life of collagen the same in all tissues?

Back 344

No

Skin: 50.4 days
Palate 21.4 days
***Periodontal Ligament 8.0 days***
Ginviva 11.4 days

Front 345

Periodontal ligament is richly supplied with vasculature implying what?

Back 345

a high metabolic rate

Front 346

Fibrillar collagens are highly resistant to most?

Back 346

proteases

Front 347

Bacterial collagenases (e.g. P. gingivalis collagenase) cleave fibrillar collagens at each?

Back 347

glycine residue (done to invade tissue)

Front 348

During degradation, Vertebrate collagenases bind to the?

Back 348

“hinge region” of type I collagen and make a single cut in each α-chain generating 2 fragments ¼ and ¾ the length of intact type I collagen (ends start to fray and denature become gelatin)

Other proteases then complete the degradation of the partially denatured collagen molecule

Front 349

The hinge region is between what two AAs?

Back 349

leucine and glycine

Front 350

Periodontal ligament fibroblasts both synthesize and degrade?

Back 350

collagen fibrils

Front 351

Vertebrate collagenases are members of what family?

Back 351

Matrix Metalloproteinase family.
More than 23 MMPs characterized in the human
Most share a homologous 27 kD active site (don’t need to know the size)

Front 352

MMPs require what at their active site in order for proteolysis to occur?

Back 352

Require divalent Zn++ as a co-factor at the active site for proteolysis to occur. ***NEED TO KNOW.

Also Require Zn++ and Ca++ for enzyme conformational stability

Front 353

MMPs, Most are synthesized as proenzymes
and are Are inhibited by?

Back 353

TIMPS - Tissue Inhibitors Metalloproteinases (in the ECM) or systemically by serum α2-macroglobin

Can be divided by substrate specificity into: collagenases, gelatinases, stromelysins and matrilysins

Front 354

MMP 1 and 8

Back 354

Collagenases

1 - CT
8 - Inflammatory cells

Front 355

MMP 14

Back 355

A membrane type MMP - PMN

Front 356

Most MMPs are synthesized as a proenzyme, locally activated by proteinases such as?

Back 356

plasmin or trypsin

Front 357

local proteinases are activated by other proteinases, such as?

Back 357

plasminogen activator, released in sites of inflammation and wound healing
MMP expression can be up-regulated by increased transcription, eg. pro-inflammatory cytokines (TNF-α, IL-1, IL-6) increase especially MMP-8
MMPs are inhibited locally by issue inhibitors of metaloproteinases (TIMPs 1-4) and systemically by α2-macroglobin

Front 358

MMP expression can be up-regulated by?

Back 358

increased transcription, eg. pro-inflammatory cytokines (TNF-α, IL-1, IL-6) increase especially MMP-8

Front 359

MMPs are inhibited locally by?

Back 359

issue inhibitors of metaloproteinases (TIMPs 1-4) and systemically by α2-macroglobin

Front 360

MMP1 has a higher affinity for Zinc than?

Back 360

MMP8. Tetracycline will bind to the active site of all MMPs, but at low dose can bind to MMP8 and inhibit it.

Periostat (doxacycline) is a low dose form of a derivative of tetracylcine – pill form

Front 361

Thin actin and thick myosin filaments overlap w/ each other in a hexagonal array in cross section.
What is their ratio?

Back 361

????

Front 362

How is contractile force generated?

Back 362

- myosin backbone swings its cross-bridge arms + globular heads out to bind to the thin actin filament - the arm bends, pulls actin towards center, Z-lines move closer, sarcomeres shorten, fiber shortens
this is happening in opposite directions on both ends of the myosin rod. grab, pull, release... grab again, pull, release... grab again... like climbing a rope remember that there are 6 actin thin filaments surrounding every 1 myosin thick filament

Front 363

Where does the ATP energy come from to create contractile force?

Back 363

- Myosin heads have a high affinity for ATP in the resting state - Myosin heads have ATP-ase enzymes in them

Front 364

1. myosin head + ATP (resting state), what happens next?

Back 364

2. myosin head + ATP grabs on to actin --> forms a cross-bridge of actin + myosin + ATP
3. ATP hydrolysis --> actin + myosin + ADP --> allows the myosin arm to bend and pull the actin filament
4. ADP released --> actin + myosin “Rigor Complex”
5. but ATP is also needed to break the cross-bridge b/t actin and myosin to relax the muscle

Front 365

6. if no ATP is available --> actin-myosin cross-bridge is

Back 365

locked --> rigor mortis

Front 366

• Tropomyosin =

Back 366

blocks the actin active site where myosin would bind for contraction.

Unblocked = contractile state
Blocked = relaxed state

Front 367

Troponins. There are 3.

Back 367

- M = binds to Tropomyosin
- I = intermediate linked
- C = binds Ca++

Front 368

During contraction = Ca++ binds to?

Back 368

Troponin --> Troponin conformation change --> Tropomyosin unblock --> cross-bridge formed

Front 369

During relaxation = there is no Ca++ bound to?

Back 369

Troponin --> Tropomyosin blocks actin’s binding site

Front 370

What regulates Ca++ in the cytoplasm?

Back 370

at rest [Ca++] = 10-7 M
activated [Ca++] = 10-5 M
equilibrium constant = 2 x 10-6 M meaning that 50% of Ca++ binded + 50% not binded

Front 371

Contraction occurs during what Ca concentration?

Back 371

- contract = if [Ca++] is higher than 2 x 10-6 M --> Ca++ will bind to Troponin-C --> Tropomyosin unblocked

Front 372

Relaxation occurs during what Ca concentration?

Back 372

- relaxed = if [Ca++] is lower than 2 x 10-6 M --> Ca++ will not bind to Troponin-C --> Tropomyosin blocks

Front 373

no significant amt of Ca++ comes into the cytoplasm from the extracellular fluid b/c?

Back 373

there are too many myofibrils blocking

Front 374

Sarcoplasmic Reticulum

Back 374

Sarcoplasmic Reticulum
- stores Ca++ (bound to Calciquestrin)
- has ligand-gated calcium channels that bind to Ca++ from T-tubule system for initiation of contraction
- Ca++/ATP-ase pump = cytoplasmic Ca++

Front 375

T-tubule

Back 375

T-tubule system
- different from the SR system
- continuous w/ the extracellular fluid
- weaves in bt myofibrils (straws)
- closely approaches the terminal cisternae of the SR, but never connects / make contact with it

Front 376

What is the signal that triggers cytoplasmic Ca++ influx?

Back 376

1. depolarization of the sarcolemma (there are very few voltage-gated Ca++ channels here)
2. action potential transfer to the T-tubule system
3. T-tubule membrane opens up its voltage-gated Ca++ channels
4. allows Ca++ into the narrow space b/t T-tubule and SR
5. Ca++ binds to receptors in the SR
6. Ca++ channels in the SR open and release Ca++ into cytoplasm --> 100x increase in [Ca++]

Front 377

When Ca binds to Troponin C, what happens next?

Back 377

7. Ca++ binds to Troponin-C due to equilibrium constant > 2x10-6 M

8. Tropomyosin moves out of the way to unblock the Actin binding site (relaxed state)

9. Myosin heads + ATP form a cross-bridge w/ Actin

10. ATP hydrolysis allows the Myosin arms to bend and pull the Actin filaments --> contraction

11. ATP is needed to break the Myosin-Actin cross-bridge --> relaxation

12. SR Ca++/ATP-pase pump removes Ca++ from the cytoplasm back into the SR --> relaxation

Front 378

What is the Series Elastic Component of muscle for locomotion?

Back 378

muscle --> tendon (the series elastic component) --> bone

1. Actin-Myosin System generates the tension force
2. Tendons demonstrate elastic elongation that is proportional to the force imposed on it by muscle

• As long as the Actin-Myosin System is producing tension, tendons will continue to stretch and exert progressively increasing force on the bone until it becomes enough to actually move the bone

Front 379

TWITCH =

Back 379

the actual tension force produced by a muscle in response to one action potential.

how much tension force is produced depends on how many Myosin-Actin cross-bridges are formed

reduced tension force results from either stretching or contracting too much... beyond maximum stretch yields no overlap of thick and thin filaments anymore beyond maximum contraction = thin actin filaments from opp. Z-Lines overlap

Because of this, thin filaments are no longer at an optimum distance from thick filaments for good overlap and formation of cross-bridge

Front 380

TETANUS =

Back 380

the constant full expression of tension produced by the Actin-Myosin System that is only possible when the rate of action potentials is above the “critical frequency”

Side comments...
- this is not associated to the disease Tetanus
- under normal conditions, your body cannot produce a tetanus state
- in both cases, rate of action potentials is below the critical frequency
- tetanus state is not physiologically possible & can only be artificially generated - producing a tetanus state is the only accurate way to measure muscle potential

Front 381

Active Tension + Passive Tension =

Back 381

total tension (tetanus)

Front 382

Skeletal muscle cells

Back 382

- large size = surface area... requires lots of SR for Ca++ storage in prep for contraction (Calciquestrin)
- contraction depends on SR Ca++ --> into cytoplasm to initiate pre-contractile events
(if the skeletal muscle depended on Ca++ coming from ECM (like in nerve transmission),
it would be impossible for the Ca++ to diffuse through all the stacked layers of muscle fibers)

Front 383

Smooth Muscle cells

Back 383

- small size = increased surface area... does not depend as much on SR for Ca++ storage (Calmodulin)

- contraction depends on ECM Ca++ --> into the cytoplasm to initiate pre-contractile events (like in nerve) • does not have a Parallel Elastic Component that skeletal muscle has

Front 384

Cardiac Muscle Cells

Back 384

- intermediate in size, surface area, complexity, uses both sarcolemma + SR for cytoplasmic Ca++ influx

- muscle fibers are connected to e/o by Gap Jxns (connexons) --> forms a network / “Syncitium”

- action potentials involve a large amount of voltage-gated Ca++ ion channels voltage-gated Na+ ion channels open = influx of Na+ --> fast depolarization
voltage-gated Ca++ ion channels open = influx of Ca++

Front 385

Blood

Back 385

Properties:
bright to dark red color
viscous
slightly alkaline (pH = 7.4)
Accounts for approx. 7% of the total body weight
Average total blood volume = 5 L / 5.5 kg
70 ml per Kg body weight

Front 386

Clot =

Back 386

Formed elements + serum

Front 387

serum

Back 387

plasma without the clotting factors

Front 388

Name some anti-coagulants

Back 388

heparin, EDTA, citrate

Front 389

Blood in a centrifuge will have what three layers?

Back 389

Bottom – red cells
Upper – plasma
Middle – buffy coat: white cells and platelets

Front 390

Plasma

Back 390

Fluid component of blood comprising about 55% of total blood volume
Pale yellow aqueous (90%) solution of
proteins (7-8%)
electrolytes and ions (0.9-1%)
organic molecules (1-2%)

Front 391

Plasma Proteins

Back 391

1. Albumin - most abundant and maintains colloid pressure.
2. Globulins. Gama = antibodies secreted by plasma cells. Alpha and Beta are non-imune globulins
3. Fibrinogen = blood clot

Front 392

Other plasma components

Back 392

Electrolytes: Na+, Ca2+, K+, Mg2+, Fe2+, Cl-, HCO3-, PO43-, SO42-
Regulate osmotic balance and maintain pH
Imbalance of electrolytes – serious medical condition
Nutrients: amino acids, glucose, lipids
Building blocks of macromolecules and production of energy
Enzymes: alkaline phosphatase (ALP), creatinine kinase (CK), aspartate transaminase (AST), lactate dehydrogenase (LDH)
Hormones
Blood gases: O2, CO2, N2
Waste products: urea, uric acid, creatinine, ammonium salts
transported to kidneys for removal from the body

Front 393

Erythrocytes

Back 393

Most numerous (5 x 1012 / L of blood)
Red color because of hemoglobin
Survival in circulation: 120 days
Transport O2 from lungs to tissues
and CO2 away from tissues

Front 394

Platelets or Thrombocytes

Back 394

Second most numerous cell type in blood (250 x 109 / L of blood)
Produced by fragmentation of cytoplasm of megakaryocytes (large multinucleate cells) in bone marrow
Survival in circulation: 10-12 days
Role in hemostasis

Front 395

Leukocytes (5 x 10^9 /L of blood)

Back 395

1. Neutrophils - Bacteria
2. Eosinophils - Parasites
3. Basophils - Anaphylactic and inflammatory

Front 396

Monocytes

Back 396

mature into macrophages and produce cytokines for inflammatory response.

Front 397

Lymphocytes 33% of WBCs

Back 397

T-Lymphocytes - cell mediated
B-Lymphocytes - humoral immunity

Front 398

Order of most to least WBCs

Back 398

Neutrophils, Lymphocytes, Eosinophils, and Basophils

Front 399

CBC

Back 399

Complete Blood Count

Front 400

Hematocrit

Back 400

packed cell volume (PCV) - %
amount of space (volume) RBCs take up in blood

Front 401

mean corpuscular (cell) volume (MCV) – fL (10-15)

Back 401

average volume of RBCs
measure of RBC size
(Hct / RBC #) x 10

Front 402

mean corpuscular (cell) hemoglobin (MCH) – pg

Back 402

average weight of Hb in an RBC
measure of RBC weight
(Hb / RBC #) x 10

Front 403

mean corpuscular (cell) hemoglobin concentration (MCHC) – g / dL

Back 403

average concentration (relative to cell size) of Hb in an RBC
measure of how many RBCs in a certain amount of fluid
(Hb / Hct) x 10

Front 404

red cell distribution width (RDW) - %

Back 404

measure of size variation of RBCs

Front 405

Mean Platelet Volume (MPV) – fL

Back 405

measure of the average amount (volume) of platelets

Front 406

What are the 3 Romanowsky's Blood Stains?

Back 406

Wright’s stain – simpler method
Giemsa stain – more complex stain; for delicate staining characteristics and detection of blood parasites
May-Grünwald stain – good for routine work

Front 407

Wright’s stain

Back 407

– simpler method

Front 408

Giemsa stain

Back 408

– more complex stain; for delicate staining characteristics and detection of blood parasites

Front 409

May-Grünwald stain

Back 409

– good for routine work

Front 410

RBC

Back 410

no DNA/nucleus 120 days in the circulation
1 circ cycle 20 sec.

Front 411

Reticulcytes

Back 411

immature RBCs and still has rRNA - no nucleus

Front 412

high reticulocyte is found in?

Back 412

Anemia


*bleeding and premature destruction of RBCs

Front 413

Low reticulocyte count causes

Back 413

vitamin / mineral deficiency
BM malignancy
radiation (chemotherapy)
chronic infection
drugs

Front 414

Hb

Back 414

RBCs packed with hemoglobin = O2-carrying protein
hemoglobin = large protein composed of 4 amino acid chains each bound to an iron-containing heme group
the heme group consists of an iron (Fe) ion, which is the site of O2 binding
Hb also carries CO2 that binds to N-terminal groups of the globin chains

8 globin genes

Front 415

Where is heme synthesized?

Back 415

in mitochondria and cytoplasm of immature RBCs

Front 416

Normal Hb: globin chains a, b, g, and d (z and e 3 -10 wks gestation)

Back 416

Adult : Hb A - HbA1: a2b2 (97%); HbA2: a2d2 (2-3%); HbF (1%)
Fetus: Hb F - a2g2
oxyhemoglobin: Hb carrying O2
carbaminohemoglobin: Hb carrying CO2

Front 417

Abnormal Hb:
carboxyhemoglobin:
methemoglobin:

Back 417

Abnormal Hb:
carboxyhemoglobin: binds to CO instead of O2
methemoglobin: Fe2+ to Fe3+; cannot bind O2

Front 418

Increased RBC # is called?

Back 418

erythrocytosis or polycythemia

Front 419

A decreased RBC # is called?

Back 419

decreased number: anemia, erythropenia (erythrocytopenia)

Front 420

anisocytosis

Back 420

same or variable RBCs

Front 421

RBC sizes and colors

Back 421

normal – normocytic
small – microcytic
large: macrocytic/megalocytic

color – blood smear; [Hb]
normal – normochromic;
pale – hypochromic
darker: hyperchromic

Front 422

poikilocytosis

Back 422

shape; normal biconcave vs. different and oddly shaped cells

Front 423

Blood smear distribution:
rouleaux
Red cell agglutination

Back 423

distribution in the blood smear

rouleaux – like stack of coins; due to increase in high MW plasma proteins

red cell agglutination – due to antibody on surface of RBCs

Front 424

Red cell inclusions

Back 424

Pappenheimer bodies – small basophilic inclusions in cell periphery

basophilic stippling - small basophilic inclusions throughout cell

Howell-Jolly bodies – large round densely stained inclusions on edge of cell; nuclear remnant

Front 425

Polycythemia

Back 425

Characterized by increased Hct

Front 426

Polycythemia Rubra Vera PV

Back 426

chronic myeloproliferative disease
due to increased red cell proliferation in bone marrow (BM)
rare; most prevalent in Ashkenazi Jews

Front 427

Acute blood loss in Anemia is caused by?

Back 427

trauma
surgery
symptoms and signs related to hypovolemia (decreased blood volume); hypotension, palpitations, tachycardia, fainting, shock

Front 428

Chronic Blood loss in Anemia

Back 428

gastrointestinal bleeding due to
ulcers
gastritis
cancer
hemorrhoids
non-steroidal anti-inflammatory drugs (e.g. aspirin, ibuprofen)
heavy menstrual bleeding
childbirth
symptoms: fatigue, pallor, dyspnea, (shortness of breath), dizziness

Front 429

Iron Deficiency anemia

Back 429

Insufficient iron stores due to
poor diet
poor iron absorption / utilization
body iron stores are depleted by prolonged bleeding
Common in menstruating and pregnant women
CBC: low reticulocytes, MCV, MCH, ferritin (iron-storing protein

Front 430

Sideroblastic Anemia

Back 430

abnormal incorporation of iron into the heme group of Hb
toxic accumulation of iron in mitochondria = ringed sideroblasts
classified as:
hereditary – enzyme deficiency (genetic); deficiency of enzyme involved in heme synthesis
secondary - drug-induced or alcohol-induced, lead poisoning; inhibition of enzymes involved in heme synthesis
idiopathic – cause not known; primarily in elderly

Front 431

Anemia of Chronic Disease

Back 431

CBC:
low or normal MCV
normal to decreased serum iron levels
normal to increased serum ferritin
blood smear: marked rouleaux formation due to increased plasma protein concentration

Front 432

Alpha Thalassemia is caused by what deletion?

Back 432

1, 2, 3, or 4 a globin genes

Front 433

Beta Thalassemia is caused by?

Back 433

caused by mutations in the b globin gene cluster

Front 434

B-Thalassemia is also known as?

Back 434

Cooley's Anemia

most severe form; both b-globin genes are defective
reduced or absent Hb A1; increased Hb A2 and Hb F (up to 98%)
Lab findings:
CBC: low Hb, Hct, MCV

Front 435

Beta Thalassemia minor

Back 435

mildest form; one b-globin genes is defective
moderately reduced Hb A1; increased Hb A2 (4-8%) and Hb F (2-5%)
Lab findings:
CBC: normal Hb, low MCV, high RBCs (distinct from iron deficiency)

Front 436

alpha Thalassemia

Back 436

deficient or no synthesis of a-globin chains
severity of disease depends on number of a-globin chains deleted

Front 437

If 1 alpha-globin chain is deleted what A-Thalassemia do you have?

Back 437

"silent" carrier

asymptomatic; only identified by pedigree and DNA analyses

Front 438

If 2 alpha-globin chain is deleted what A-Thalassemia do you have?

Back 438

A-thalassemia trait

a-thalassemia trait: mild hypochromic microcytosis

Front 439

If 3 alpha-globin chain is deleted what A-Thalassemia do you have?

Back 439

hemoglobin H disease


Hemoglobin H disease: production of Hb H (b4)
moderately severe microcytic anemia (due to reduced Hb synthesis and hemolysis); hepatosplenomegaly

Front 440

If 4 alpha-globin chain is deleted what A-Thalassemia do you have?

Back 440

hemoglobin Barts hydrops fetalis


most severe form of a-thalassemia;
complete absence of a-globin chains; hemoglobin Barts (g4)
incompatible with life - stillbirth by 3rd trimester or shortly after delivery
Hydrops fetalis: fluid buildup in multiple organs, cardiac failure, massive hepatosplenomegaly
Toxemia in mother carrying fetus with Barts hydrops fetalis

Front 441

Hydrops fetalis

Back 441

fluid buildup in multiple organs, cardiac failure, massive hepatosplenomegaly
Toxemia in mother carrying fetus with Barts hydrops fetalis

Front 442

Macrocytic Anemias

Back 442

elevated MCV
impaired DNA synthesis but normal RNA synthesis
usually due to B12 and folic acid deficiency
other causes
gastrointestinal disorder or surgery
chemotherapy
chronic alcoholism
hypothyroidism
liver disease (hepatitis)
splenectomy
common; commonest in elderly

Front 443

Macrocytic anemias – B12 deficiency

Back 443

Causes:
inadequate dietary intake (in vegans)
intestinal malabsorption due to lack of intrinsic factor (gastrectomy, pernicious anemia)
increased requirements during pregnancy
Years to develop deficiency because of sufficient body stores

Front 444

Macrocytic Anemias - Folic Acid deficiency

Back 444

Causes:
Poor diet (no fresh fruits/vegetables) or overcooked food
intestinal malabsorption due to alcoholism, gastrectomy, Crohn’s disease
increased requirements during pregnancy
certain drugs (anticonvulsive) impair intestinal folic acid absorption
deficiency develops fast; body stores only for 3 months
Lab findings, Signs & Symptoms: same as in B12 deficiency
Treatment: Folic acid supplement

Front 445

Hemolytic disorders

Back 445

reduction in RBC lifespan and compensatory increase in rate of erythropoiesis
Causes: incompatible blood transfusion, cancer, drugs, etc.

Front 446

intravascular or extravascular hemolysis:

Back 446

extravascular: most common form of hemolytic anemia
premature destruction of RBCs by macrophages in spleen, liver, BM
intravascular: abnormal breakdown of RBCs within blood vessels

Front 447

Hemolytic Disorder Pathophysiology

Anemia – frequently absent because of increased erythropoiesis
jaundice – increased RBC breakdown products; increased bilirubin
cholelithiasis – gall stones; due to increased bilirubin
splenomegaly

Back 447

hemoglobinuria – passing of Hb in urine
hemoglobinemia – too much Hb exceeds binding capacity of haptoglobin and cannot get cleared from body
growth retardation and delayed puberty
hypertrophic skeletal changes – due to BM expansion

Front 448

G6PD deficiency

Back 448

Glucose-6-phosphate dehydrogenase - red cell enzyme
Role: protects red cell proteins from endogenous or exogenous oxidant stress
Mechanism: converts glucose to ribose-5-phosphate - NADPH production
NADPH prevents building up of free radicals within cells
G6PD deficiency – hereditary enzyme deficiency; malaria immunity
increased susceptibility of RBCs to oxidant stress - hemolysis
most common enzyme deficiency
X-linked recessive disorder affecting more males than females

CBC: low RBC count and Hb, high reticulocyte count

Front 449

In G6PD what are the triggers of hemolysis?

Back 449

ingestion of drugs (antimalarial, aspirin) - induce oxidant stress on RBCs
ingestion of fava beans – divicine
viral infections: lung infection, hepatitis - activated neutrophils
Reason: production and release of free radicals

Front 450

Sickle Cell Disease

Back 450

Genetic disorder - change in hemoglobin structure due to mutation in the Hb gene
Normal Hb: Hb A; substitution of glutamic acid by valine – Hb S

Result: distortion of RBC shape from biconcave to half-moon (sickle) shape - Sickle cell disease

Carriers are resistant to malaria

low MCV, Hb; high WBC, neutrophils, lymphocytes, platelets, reticulocytes; Hb S

Front 451

Diapedesis:

Back 451

migration of WBCs through vessel walls to tissues

Front 452

What are the granulocyte WBCs?

Back 452

Neutrophils – normal value : 2000-7500/ml; 60-70% WBCs
Eosinophils - normal value : < 450 / ml; <4% of WBCs
Basophils - normal value : < 200 / ml; <1% of WBCs

Front 453

What are the Agranulocyte WBCs?

Back 453

Lymphocytes – normal value : 1000-4000/ml; 20-35% WBCs
Monocytes – normal value : < 900 / ml; 5% of WBCs
Both granulocytes and agranulocytes possess lysosomes

Front 454

Neutrophils

Back 454

Function: defense against acute bacterial and fungal infection
Move to site of infection by chemotaxis
Engulf invading microbes – phagocytosis
Kill by releasing toxic substances stored in their granules

Front 455

Neutrophils have what 3 types of granules?

Back 455

Azurophilic (primary) – lysosomes; largest and fewest; bactericidal
Specific (secondary); smallest and most numerous; bactericidal
Tertiary – facilitate diapedesis

Front 456

Hypersegmented neutrophils:

Back 456

6 or more lobes; Vitamin B12 or folic acid deficiency; interferes with DNA synthesis

Front 457

Hyposegmented neutrophils:

Back 457

defect in chromatin synthesis e.g. Pelger-Huet anomaly; myelodysplasia

Front 458

Eosinophils

Back 458

produced in BM; 4-5 hours in bloodstream
bilobed nucleus; pale blue cytoplasm with large orange-red granules
Specific granules – contain proteins with cytotoxic effect, neutralization of histamine
Azurophilic granules – lysosomes: enzymes destroy parasites


respond to chemotactic stimuli, phagosytose and kill
Function: defense against parasitic infestation, dampen allergic reaction

Front 459

Basophils

Back 459

lobed S-shape nucleus with large purple-staining cytoplasmic granules
Specific granules – histamine, slow-reacting substance-A (SRS-A); vasodilation
Azurophilic granules – lysosomes

Front 460

Basophil function

Back 460

Function: initiators of inflammatory processes, involved in anaphylactic, hypersensitivity, and inflammatory reactions
antigen triggers release of IgE
IgE binds to basophil surface receptors
cell degranulates and releases inflammatory mediators (histamine) to surrounding tissues

Front 461

There are 3 types of lymphocytes based on what?

Back 461

3 types depending on
size
amount of cytoplasm
presence or absence of cytoplasmic granules
Small - most numerous, dense homogeneous nucleus; N/C >90%
Medium - less dense, somewhat heterogeneous nucleus; N/C 80%
Large - (granular or agranular) lymphocytes; N/C 40-60%

Front 462

What are the 3 types of Lymphocytes?

Back 462

T cells – differentiate in thymus; (75-80%); cell-mediated immunity
B cells - differentiate in BM; (15%); plasma cells; humoral immunity
Natural killer cells (NK) - programmed to kill foreign, virally altered cells, some types of tumor cells; (5-10%); cell-mediated immunity
larger than B and T cells
contain large cytoplasmic granules – large granular leukocytes

Front 463

Monocytes

Back 463

in blood stream for a short time, then migrate to tissues where they mature into actively phagocytic macrophages
Function: body’s defense against bacterial and fungal infections; also ingest and break down dead and dying body cells
during inflammation
monocyte leaves blood vessels at site of inflammation,
transforms into a tissue macrophage, and
phagocytoses bacteria, other cells and tissue debris

Front 464

What is the most common type of Leukopenia?

Back 464

Neutropenia -Susceptibility to bacterial & fungal infections – reduced phagocytosis

Front 465

Neutrophila

Back 465

Causes:
Acute infections (bacteria, viruses, parasites, fungi)
noninfectious: inflammatory conditions (rheumatic fever, gout)
metabolic conditions (ketoacidosis, uremia)
cancer, MI, burns, drugs (steroids), stress / strenuous exercise

Front 466

Leukocytosis - Monocytosis

Back 466

Causes:
inflammatory disorders (granulomatous disease)
infections (TB, syphilis)
autoimmune disorders (lupus, rheumatoid arthritis)
connective tissue disorders (ulcerative colitis, collagen vascular disease)
cancer (leukemia, Hodgkin’s Disease)

Front 467

Infectious Mononucleosis

Back 467

cause of lymphocytosis
also known as “mono”, “glandular fever” or “the kissing disease”
spread primarily by saliva; sneezing and coughing
virus-induced – Epstein-Barr virus (EBV); type of herpes virus
EBV infects epithelial cells and B cells
95% of population exposed to EBV by 40 – most no symptoms
virus lingers in inactive form in WBCs until gets reactivated - IM

**Atypical Lymphocytes

Front 468

Leukemias

Back 468

malignant disorders of blood characterized by uncontrolled proliferation of hematopoietic cells

Front 469

Acute Leukemia

Back 469

Acute: uncontrolled proliferation of immature blood cells – blasts
rapid, usually fatal, survival less than 6 months
impaired BM function

Front 470

Chronic Leukemia

Back 470

Chronic: uncontrolled proliferation of well-differentiated mature blood cells
long-term disease, often long survival
incidental findings during routine exam

Front 471

Acute Lymphocytic/Lymphoblastic Leukemia (ALL)

Back 471

Proliferating cell – primitive lymphoid cell
Most common leukemia in children <15 years (60-70%)
Principal cause of cancer deaths in children; peak incidence age 4
Treatable and potentially curable – half the children (age 2-10) are cured
Poor prognosis for adults
Classified according to lymphocytes and state of maturation
Early B cell
Pre-B cell
Mature B cell
Early T cell
Mature T cell

Front 472

Acute Myeloid / Myelogenous Leukemia (AML)

Back 472

Proliferating cell – primitive myeloid cell
Occurs at all ages, from neonatal to adult
incidence increases with age; most common acute leukemia in adults
20% of acute leukemia in children
In blood smear cytoplasm contains inclusions, Auer rods, diagnostic

****Auer Rods****

Front 473

Chronic Lymphocytic Leukemia (CLL)

Back 473

proliferating cells – mature but incompetent lymphocytes, don’t make antibodies in response to antigens; 95% B lymphocytes
accounts for 2/3 of chronic leukemias ; most common over 60 yrs
male : female ratio 2:1
early stages asymptomatic; later s fatigue, weight loss, lymphadenopathy, hepatosplenomegaly
Lab findings:
CBC: leukocytosis 5-10x higher WBC count, low Hb and platelets

Front 474

Chronic myeloid / myelogenous Leukemia (CML)

Back 474

results in myeloid marrow hyperplasia
accounts for 1/3 of chronic leukemias ; young adults (10-20 yrs) and middle age (50-60 yrs)
due to Philadelphia chromosome mutation; translocation between chromosome 9 and 22

Front 475

Chronic myeloid / myelogenous Leukemia (CML)

Back 475

chronic: 3-5 yrs; asymptomatic
acute: 2-4 months; increased blasts (>30%) in blood and BM
No response to treatment – blast crisis
fever, weakness, fatigue, anorexia, weight loss, splenomegaly, anemia, infection

Front 476

Lymphomas

Back 476

Solid tumors that arise in lymphoid tissue but then spread to other solid tissues, blood and BM
3rd most common malignancy in children
2 types:
Hodgkin’s Lymphoma / Disease:
Non-Hodgkin’s Lymphoma:

Front 477

Hodgkin's Lymphoma

Back 477

2 types: classic and nodular
95% have classic form
presence of rare malignant Hodgkin’s Reed-Sternberg cells
Unknown cause; genetic and environmental e.g. EBV

Front 478

Non Hodgkin's Lymphoma

Back 478

associated with chronic inflammatory diseases e.g. rheumatoid arthritis
often develops after organ transplantation in immunosuppressed patients
Causes: unknown
Genetic – chromosomal translocations
Viral - HIV, EBV
90% of NHL B-cell lymphomas; 10% T-cell lymphomas

Front 479

Bence-Jones Proteins that are excreted in urine are diagnostic for?

Back 479

Multiple Myeloma

plasma cells produce abnormal proteins (e.g. Bence-Jones). plasma cells accumulate in bone marrow – pressure on walls – bone pain, fractures

Front 480

Platelets

Back 480

Also known as thrombocytes – thrombos (Greek) = clot
Smallest blood cell (2-4mm diameter) - 200,000 – 400,000/mL
life span: 10-12 days
derived from cytoplasm fragmentation of megakaryocytes (giant multinucleated cells) residing in BM
promote blood clotting and help repair gaps in the walls of blood vessels, preventing blood loss

Front 481

What has the following characteristics:
small, disk-shaped, non-nucleated cell fragment
peripheral light blue-stained transparent zone, the hyalomere, and central darker zone with purple granules, the granulomere

Back 481

Platelets

Front 482

Hyalomere

Back 482

Microtubules – allow platelets to maintain their discoid shape
Actin / myosin – contraction – platelet movement & aggregation
Surface-opening system – take up and release molecules
Dense-tubular system – calcium storage, prevent platelet stickiness

Front 483

Granulomere

Back 483

Mitochondria
Glycogen deposits
Enzymes – catabolize glycogen, consume O2, and generate ATP
Granules – 3 types: a, d, l

Front 484

This granule deals with vessel repair, blood coagulation, and platelet aggregation.

Back 484

A-granules

Front 485

This granule contains Ca, ADP, ATP, histamine, serotonin
and facilitates platelet adhesion and vasoconstriction.

Back 485

Delta granules

Front 486

This granule contains lysosomal enzymes
and clot resorption

Back 486

gamma granules (lysosomes)

Front 487

Heomstasis

Back 487

clotting mechanism of blood; Sequence of events leading to cessation of bleeding by formation of a stable plug (clot)

Front 488

What are the stages of hemostasis?

Back 488

Vascular wall injury and exposure of sub-endothelial collagen
Vasoconstriction
Formation of platelet plug
Coagulation cascade
Formation of fibrin clot (plug)
Healing and fibrinolysis

Front 489

What are the platelet functions

Back 489

Adhesion to the injured surface
Shape change
Release of granule contents
Aggregation

Front 490

What is the mechanism of Hemostasis? Part I

Back 490

1. blood vessel wall injured, collagen fibers exposed at damaged site
2. release of endothelin (vasoconstrictor) and von Willebrand factor (vWF) which binds exposed collagen fibers
3. Platelets adhere to exposed collagen by binding to vWF and they get activated (platelet activation)
Platelet shape transformation
Platelet degranulation
Platelet aggregation
- Primary hemostatic plug (loose)

Front 491

Mechanism of Hemostasis Part II

Back 491

4. conversion of fibrinogen to fibrin
Platelet cross-linking by fibrin
Secondary hemostatic plug (solid)
Blood coagulation

5. Clot shrinks
Clot Retraction

6. Clot dissolves after fibrin degradation by proteolytic enzyme plasmin
Clot Removal - Fibrinolysis
Vessel wall repaired

Front 492

Intrinsic Clotting Pathway

Back 492

1. Begins with activation of F XII by
surface contact
2. F XII interacts with F XI
3. F XI activates F IX → (F IXa)
- calcium required
4. F IXa forms complex with F VIII
5. F VIII converts F X → F Xa
Calcium and phospholipid required

Front 493

Extrinsic Clotting Pathway

Back 493

Predominant pathway
1. Depends on release of tissue factor (TF) - thromboplastin (F III)
2. TF released from endothelial cells at damaged site
3. TF binds F VII
- calcium required
4. F VIII converts F X → F Xa

Front 494

What is the Common Clotting Pathway?

Back 494

1. Activation of F X → F Xa
2. F Xa in presence of calcium, phospholipid and F V converts
prothrombin (F II) → thrombin (F IIa)
3. Thrombin converts
fibrinogen (soluble) → fibrin (insoluble)
(Fibrinogen – F I)
4. Fibrin polymerizes to a gel
5. Thrombin converts F XIII → F XIIIa
6. F XIIIa cross-links fibrin
- solid clot

Front 495

Main Steps to Hemostasis**** KNOW THESE

Back 495

1. Activation of F X → F Xa
2. F Xa in presence of calcium, phospholipid and F V converts
prothrombin → thrombin
3. Thrombin converts
fibrinogen (soluble) → fibrin (insoluble)
4. Fibrin polymerizes to a gel
5. Thrombin converts F XIII → F XIIIa
6. F XIIIa cross-links fibrin
- solid clot

Front 496

Prothrombin time and Thrombin time

Back 496

Prothrombin time (PT) – time sample takes to clot; normal 10-14 sec


thrombin time (TT) - normal 9-13 sec
ability to form clot from fibrinogen in presence of thrombin

Front 497

Thrombocytosis (reactive)

Back 497

Increased platelet count - >500,000 / mL
Causes:
genetic (JAK2 mutation)
infection / inflammation
iron deficiency
malignancy / chemotherapy reaction
splenectomy

Front 498

Essential Thrombocythemia (primary)

Back 498

Malignant disorder – increased platelet count >1,000,000 / mL
Rare in children and young adults; diagnosis at 60 yrs
Causes: as in thrombocytosis
Lab findings:
Blood smear: platelet clumps, variation in size, shape, granulation

Front 499

Thrombus

Back 499

Thrombus: clot that develops and persists in an unbroken blood vessel
May block circulation, leading to tissue death
Blockage of coronary artery – Myocardial Infarction

Front 500

Embolus:

Back 500

a thrombus that becomes dislodged or fragmented freely circulating in the blood stream; thromboembolism

Front 501

Disseminated Intravascular Coagulation (DIC)

Back 501

triggered by potent stimuli that activate both F XII and tissue factor
form ation of microthrombi and emboli throughout the microvasculature
Thrombosis and hemorrhage
consumption of coagulation factors and platelets, generation of FDPs that have antihemostatic effects

Front 502

Hemophilia

Back 502

sex-linked recessive inherited genetic disorder
caused by deficiency or defect in a clotting factor
severe bleeding even after mild injuries e.g. skin cut, and may bleed to death after more severe injuries
spontaneous hemorrhages in body cavities, e.g. major joints, intracranial, urinary tract

Front 503

Hemophilia A defect?

Back 503

defect in factor VIII

only males are affected by hemophilia A (transmitted from their mothers)
females have one defective X chromosome
females develop hemophilia only when they have the abnormal gene in both X chromosomes - rare

Front 504

Hemophilia B defect?

Back 504

Hemophilia B - defect in factor IX (Christmas Factor)

Front 505

von Willebrand’s disease (vWD)

Back 505

defects in concentration, structure, or function of vWF
defective platelet plug formation
autosomal dominant trait with varying penetrance
most common blood clotting disorder – 1:8,000-10,000 persons
females and males are equally affected in a heterozygous state
Signs & Symptoms:
easy bruising
prolonged bleeding after surgery or dental procedure
epistaxis (nose bleed)
mucosal bleeding, soft tissue hemorrhage

Front 506

Thrombocytopenia

Back 506

Platelet count < 100,000 / ml; very serious when < 50,000 / ml
Bleeding from small vessels, skin, GI tract
Purpura and petechiae – purple spots and patches on skin
autoimmune disease: antibodies are formed to one's own platelets and destroy the platelets
Caused by
Decreased platelet production
Increased platelet destruction

Front 507

Idiopathic Thrombocytopenic Purpura (ITP)

Back 507

caused by accelerated antibody-mediated platelet consumption
platelets are destroyed in spleen by macrophages
acute and self-limiting (2 to 6 weeks) in children
cause of death: Intracerebral hemorrhage
secondary to another disorder e.g. SLE, HIV

Front 508

Ontogeny of Hematopoiesis

Back 508

2 – 10 weeks gestation: yolk sac
2 weeks post-conception: “blood islands”; erythroid precursors
6 weeks gestation: granulocytes and megakaryocytes
7+ weeks gestation: lymphocytes in lymph sacs

Front 509

CFU-GEM give rise to?

Back 509

myeloid cells (granulocytes, erythrocytes, monocytes, megakaryocytes (platelets)) - myelopoiesis

Front 510

CFU-L give rise?

Back 510

to lymphoid cells (B, T, NK cells) – lymphopoiesis

Front 511

CSFs

Back 511

Growth factors or colony-stimulating factors (CSFs) affect blood cell proliferation and differentiation
stimulate proliferation of immature (progenitor and precursor) cells
support the differentiation of maturing cells
enhance the functions of mature cells
CSFs also stimulate cell division and differentiation of progenitor cells of the granulocytic and monocytic series

Front 512

Growth Factors: Proliferation of stem cells

Back 512

Stem Cell Factor (SCF)
Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF)
IL-3 and IL-7

Front 513

Epo:

Back 513

kidney-secreted hormone produced in response to hypoxia
stimulates production of globin, the protein component of Hb

Front 514

What are the stages in Red Blood Cell formation?

Back 514

1. Proerythroblast
2. Basophillic erythroblast
3. Polychromatic erythroblast
4. Orthochromatic erythroblast (not capable of Mitosis)
5. Reticulocytes (not capable of Mitosis)

Front 515

Granulopoiesis

Back 515

CFU-GM →neutrophils
CFU-Eo →eosinophils
CFU-Ba → basophils

Front 516

Neutrophilic Metamyelocyte and Stab/Band Cell

Back 516

have no cell division

Front 517

Megakaryoblast → Megakaryocyte under hormonal stimulation by?

Back 517

thrombopoietin