Histology Exam 1 Flashcards
(181 cards)
1
Q
How is a slide made.
A
Fixation - preserves cells in tissue and prevents degradation
Embedding - tissue blocked in molton paraffin or other medium
Cutting - usually on a microtome
Staining - to color cells
-Hematoxylin: basic dye that stains many negative compounds
-Eosin: acidic dye that stains net cationic compounds, like amino group of protein backbone
Veiwing- on a microscope
2
Q
4 Types of Tissues
A
Epithelial Tissue- covers, lines, glands
Connective Tissue - packing, supportm transport, storage
Muscle Tissue - contraction, movement
Neural Tissue - signaling, coordination
-They are defined by morphology and function
3
Q
Epithelial Tissue
A
Functions:
-physical protection, control permiability/absorption/transportation, produce specialized secretions, receptor for cell-to-cell signaling
Characteristics:
-Polarity- Apical surface and the basolateral surface
-avascular and highly regenerative
4
Q
Classification of Epithelia tissue
A
First Name: Simple - one layer, Stratified - more than one layer
Second Name: based on the shape of the top layer of cells - cells closest to the exterior or the lumen
Squamous, Cuboidal, Columnar
Additional Categories: Transitional, Pseudostratified, Cilia, Sterocilia, Microvilli
5
Q
Simple Squamous Epithelium
A
Funtions: Absorption and diffusion- lungs and undothelium, Filtration- endothelium and portions of renal tubules, Lubrication - serosae, mesothelia, endothelia, inner cornea of eye
6
Q
Mesothelium
A
lines body cavity
7
Q
Endothelium
A
lines heart and blood vessels
8
Q
Simple Cuboidal Epithelium
A
single layer of cube like cells with large spherical central nuclei
Functions: Limited protection, Secretion, Absorption
Found in the glands and ducts and portions of the renal tubules
9
Q
Simple Columnar Epithelium
A
single layer of tall cells with oval nuclei toward the basal surface, may have microvilli cilia and goblet cells
Straited Border - intestine
Brush Border - renal
Functions: Protection, Secretion and Absorption
Found in the lining of much of digestive track, gallbladder, renal collecting ducts
10
Q
Pseudostratified Columnar Epithlium
A
looks very similar to simple solumnar, nuclei give more of a stratified appearance
Function: Protection, Secretion
Found in lining of nasal cavity, respirator tract, portions of male reproductive tract
11
Q
Stratified Squamous Epithelium
A
Composed of several layers of cells, top layer is flat and bottom laters are any shape
May or may nor have keratin, “Moist” areas have no keratin, “Dry” areas have keratin
Functions: Protection of underlying areas subjected to abrasion, pathogens and chemical attack
Found in surface of skin, lining of throat, first 2/3 of esophagus, rectumnn, anus and vagina
12
Q
Transitional Epithelium (Urothelium)
A
several cell layers, basal cells are cuboidal
can distinguish b/w stratified cuboidal b/w apical cells are dome shaped when not stretched, flat when stretched and only found in the urinary system
Function: Allows for expansion and recoil after stretching
13
Q
Stratified Cuboidal Epithelium
A
typically two layers of cells thick, RARE
Functions: secretion
Found in some sweat and mammary glands
14
Q
Stratified Columnar Epithelium
A
limited distribution in the body
to distinguish look at the nuclei, basal cells look more cuboidal, can have goblet cells
Function: Protection
Found in pharynx, epiglottis, male urethra, lining of some glandular ducts (salivary), mammary glands and anus
15
Q
Types of Glands
A
Endocrine glands- release hormones into the intestinal fluid and they have no ducts
Exocrine glands - produces secretions onto epithelial surfaces through ducts, use merorcrine apocrine and halocrine secretion
Paracrine glands - single cells in some epithelia release factors that influence cells beside them
16
Q
Merocrine Secretion
A
-is produced in the golgi apparatus
-is released vesicles (exocytosis)
example is sweat glands or salivary glands
17
Q
Apocrine Secretion
A
-is produced in the golgi apparatus
-is released by shedding cytoplasm
example is mammary gland, ciliary gland or ceruminous glands
18
Q
Holocrine Secretion
A
-is released by cells bursting, killing gland cells (apoptosis)
-gland cells replaced by stem cells
example is sebaceous gland
19
Q
Glandular Epithelia
A
is a form of a paracrine secretion -goblet or mucous cells -unicellular exocrine glands -scattered among epithelia example is intestinal lining
20
Q
Types of Secretion by glandular epithelia
A
- several cell-specific compounds
- exported out of glandular cells into ducts or blood vessels
1. Serous glands - watery secretions that stain darker on a film
2. Mucous glands - secrete mucins, slimy, many glycosylated proteins, stains wash out b/c compounds are water soluble, nuclues pushes towards basal layer
3. Mixed exocrine glands - both serous and mucous
21
Q
Multicellular Glands
A
Classification includes the structure of the duct where it can be simple, having no divisions, or compound, divided.
The shape of the secretory portion of the gland can be tubular or alveolar/acinar
There can also be a relationship b/w ducts and glandular areas, branched
22
Q
Mucus Membrane / Mucosa
A
- surface epithelium with or without glands
- has lamina propria as a supporting CT layer
- sometimes it is a smooth muscle layer called the musclaris mucosa
23
Q
Serous Membranes / Serosa
A
- lines body cavities (plura, aracardium, perotineum)
- lining epithelium
- basement membrane
- medothelium is the supporting CT layer
- DO NOT contain glands, but have watery surface secretions
24
Q
The Basement Membrane
A
-a specialized structure sandwiched between an epithelial cell layer and underlying CT stroma, ahrd to see with stains but can be viewed in EM
Basal Lamina
-Lamina Lucida, a space b/w the lamina densa and epithelial cells containing fibronectin CAMs and laminin receptors
-Lamina Densa, a discrrete layer of electron-dense matrix material that is used for cell attachment
Reticular Lamina - reticular fiber layer, part of CT and not Epithelia
25
Connective Tissue
-used for packing, storage, support and transport
-characterized by extracellular matrix, a mix of macromolecules that support and surround cells
-extracellular fibers: collagen, elastic, reticular
-cells often secrete the ECM and are scattered within
Types: Connective Tissue Proper, Bone, Blood, Hematopoetic Tissue, Cartilage, Adipose Tissue, Lymphatic Tissue
26
Ground Substance
intestinal fluid, cell adhesion proteins and proteoglycans
- a clear substance with high viscosity and water content
-can see with some frozen methods and PAS stain, cannot see with H&E
The Ground Substance is made of Proteoglycan, Glycoproteins and Glycosaminoglycans
27
The Extracellular Matrix
Functions:
- Provides mechanical and structural support
- Biomechanical barrier
- Regulation of metabolism of tissue
- Coordinates cell migration and movement
- Provides information to cells about their environment
28
Collagen Fibers
a family of fibrous proteins that form trimers
-extremely tough, not branched, high tensile strength
Type 1, 2, and 3
29
Type 1 Collagen
very abundant in skin and bone
- provide resistance to force and stretch
- white in fresh tissue
- usually pink and wavy in H and E sections
- distinctive banding pattern in EM
30
Type 2 collagen
found in cartilage
- provides resistance to intermittant pressure
- cartilage, notocord, intervertebral discs
31
Type 3 collagen
Reticular fibers are a delicate network of this type
- does not bundle, has thin branches
- surround small blood vessels and support soft tissue organs
- initial stages of wound healing
- support stroma in hemtopoetic and lymphatic tissues
32
Elastic Fibers
fibers are thinner than collagen, branched, tissues can occur as fibers or large sheets as in lamellae.
1. Elastin (core) - a rubber-like protein that allow the connective tissue to snap back to its original shape after it is stretched
high level of Gly- hydrophobic, randomly coils
2. Fibrillin (microfibrils) - organizes the elastin into fibers
absence of this leads to Marfan's Syndrome which is what Abe Lincoln had!
33
Proteoglycans
big proteins, lots of little sugar groups attached
| -core protein with one of many GAG chains
34
Glyocaminoglycans
long sugar chain with disaccharide branches
| -highly polar, so attract water
35
Glycoproteins
- proteins that have ogliosaccharide side chains attached
| - important for cell adhesion
36
Hyaluronic Acid (Hyaluronan)
- A GAG that is really LONG
- can displace a large volume of water
- is not modified because it is made outside the cell on its surface
- does not contain sulfate nor form a proteoglycan
- BUT proteoglycans can bind to it to form proteoglycan aggregates, these aggregates have high turgor pressure and add extra cushion to tissues like cartilage
- has important job in fixing cells and other molecules in the matrix, anchoring complexes attach to it when they are repairing cells.
37
Cells of Connective Tissue Proper
Resident Cells- stay in the tissue
| Transient Cells- wander in, out and through tissues
38
Resident Cells
Fibroblasts/fibrocytes/myofibroblasts - secrete the matrix and maintain it
Macrophage - scavenger cells that engulf pathogens or damaged cells
Adipcytes - fat cells
Mesenchymal Cells - stem cells
Mast cells - stimulate local inflammation, contain histimine and herapin
39
Transient Cells
Monocytes (macrophages)
Lymphocytes/Plasma Cells - WBCs, adaptive immunity
Granulocytes - neutrophils, eosinphils, basophils
40
Fibroblasts
- major cell type of general CT
- makes colalgen, elastic and reticular fibers
- studies suggest can make all the ECM components
- near collagen fibers
- usually nuclues only visible and is long and cigar shaped
41
Fibrocytes
an inactive fibroblast that is thought to be a fibroblast precursor for functions like wound healing
42
Myofibroblasts
- a CT cell that is part fibroblast, part muscle cell
- associated with smooth muscle actin
- looks like a fibroblast but can contract
- not smooth muscle b/c it is not surrounded by an external lamina and can work alone or in a group
43
White Blood Cells
Monocytes/Macrophages
Lymphocytes/Plasma Cells
Granulocytes
Mast Cells
44
Monocytes/Macrophages
big classical WBC that eats stuff
dark, kidney shaped nucleus
open clear cytoplasm
monocyte is precursor that looks similar
45
Lymphocytes/Plasma Cells
involved in adaptive immunity
dark, round nuclei
often no signs of cytoplasm
46
Granulocytes
WBCs that can be present depending on pathology
have dark multi-lobed nuclei
can tell apart from staining of their cytoplasm
47
Mast Cells
involved in inflammation and immunity
big cells with many large cytoplasmic granules
differentiate in CT
48
General Connective Tissue Types
```
Loose Irregular
Reticular
Dense Regular
Dense Irregular
Elastic
```
49
Loose Irregular (Areolar) CT
Functions: wraps and cushions organs, holds and convey interstital fluid
Locations: under epithelial tissues, packages organs, surround capillaries
Matrix: gel like with all 3 finer types-low collagen
Cells: fibroblasts, WBCs
-generally less cells more fibers
50
Reticular CT
Function: network of reticular fibbers that supports functional cells
Locations: lymph nodes, bone marrow, spleen, liver
Matrix: loose ground substance (stroma)
Cells: functional cells for specific tissue (parenchyma)
51
Dense Regular CT
Functions: withstands great tensile stress pulling in one direction
Locations: tendons, ligaments, aponeurosis, deep fascia
Matrix: mostly collagen fibbers- very organized
Cells: primarily fibroblasts, few and scattered
52
Dense Irregular CT
Functions: withstands tension exerted in many directions, provides structural strength, prevents over expansion
Locations: dermis of skin, submucosa of digestive tract, fibrous capsules of organ and joints
Matrix: Irregularly packed collagen fibbers (looks like building insulation)
Cells: few cells, most are fibroblasts, some WBCs
53
Elastic CT
-dense regular CT is dominated by elastic fibbers
-need specialized stains for elastic fibbers
Functions: stabilizes positions of vertebrae (ligamentum flavum and ligamentum nuchae) and penis, cushions and permits expansion and contraction of organs
Locations: b/w vertebrae, ligaments supporting penis transitional epithelia, blood vessels walls
54
Adipose Tissue
type of Loose CT populated by fat cells - adipocytes
Function: storage of triglycerides, insulation, metabolism
Types: Unilocular (white fat), Multilocular (brown fat)
55
Unilocular Adipose tissue
white fat, is the most common
Functions: stores fat, absorbs shock, slows heat loss (insulation - endocrine function
Locations: greater momentum, mesentery, behind the eyes, around organs, sub dermal, etc.
Matrix: reticular fibers containing high blood supply and nerves
Cells: Adipocytes
-big cytoplasm with washed out area that is the lipid droplet
-nuclei are flattened against side
56
Weight Regulation
-paths from the brain (hypothalamus/anterior pituitary) to gut to adipose tissue
-controls fat mobilization and deposition
Short term (daily metabolism and appetite): Ghrelin (GI tract) and Peptide YY (PPY- also in GI tact)
Long term: Leptin (Adipose tissue), Insulin (Pancreas)
57
Leptin (the Ob gene)
- prevents obesity
- adding more gene for leptin back to these knockouts caused them to loose 30% of their body weight in two weeks
- obese humans show high serum levels of leptin-meaning they are resistant to leptin biochemically
- people who have lost weight and anorexics show low levels of leptin
58
Insulin
- major pancreatic hormone
- regulates blood glucose levels by causing uptake of glucose into cells
- enhances fat storage-conversion glucose into triglycerides in the adipocyte
- inhibits fat breakdown-inhibits action of hormone-sensative lipase
- lack of insulin causes all aspects of fat breakdown and use for providing energy to be greatly enhanced
59
Multilocular Adipose Tissue
brown fat, less common in humans, infants have a higher %
Function: metabolism-when stimulated by nervous system, fat breakdown is unregulated, releasing energy
absorbs energy from surrounding tissue
Matrix: reticular fibers, has higher blood supply than white
Cells: multilocular adipocytes with many mitochondria (cytochrome oxidase)
60
Thermogenin (Uncoupling protein)
-protein in mitochondrial membrane
-uncouples fatty acid oxidation pathway from respiration
protons travel back into the inter membrane space without passing through ATP synthase
energy that should have been made into ATP is released as extra heat - thermogenesis
61
Making of Adipocytes
Mesenchymal stem cells - form fibroblasts, adipocytes, muscle or bone
PPARy/RXR differentiate into unilocular adipocytes
PRDM16/PGC-1 differentiate into multilocular adipocytes
-adipocytes generate during childhood
-lipid storage changes
62
Muscle TIssue
Function: contraction
Appearance:
looks like meat
might have banding or not
nuclei are usually pushed to side or central
usually staines more darkly than CT, usually much more regular than CT
63
Nervous Tissue
Function: signalling, control
Appearance:
Looks frothy like sea foam
might have visible fibbers or fibbers in cross section
nuclei are usually very small if at all visible
usually stains more lightly than CT, usually more regular than CT
64
The integument
```
is the largest system of the body
-15-20% of total body mass, 1-5mm thick
Made up of two partL
Cutaneous membrane (skin)
Epidermal derivatives - hair follicles and hair, sweat glands, sebbacous glands, nails, mammary glands
```
65
Functions of the skin
Protection - underlying tissues and organs
Excretion - salts, water, and organic wastes
Thermoregulation - insulation and cooling
Endocrine functions - secretes hormones, cytokines, and growth factors; makes vitamin D3
Storage - lipis
Sensation - detects touch, pressure, pain, and temperature
66
The Layer Cake
Epidermis: superficial layer
-orthokeratinized stratified squamous epithelium
-no nerves or vessels, 4-5 layers
Dermis: underlying layer connective tissue layer
-2 layers, holds blood supply and nerves to feed epidermis
Hypodermis (subcutaneous layer, superficial fascia): mot part of the skin, it is deep to the dermis
-primarily adipose tissue
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Keratinocytes
- major cell type of epidermis
- movement and differentiation creates cell layers
- made to separate the organism from its external environment
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Kertins
- cytokeratins - major family of structural proteins of the epidermis
- found in hair, nails, horns, and baleen
- form intermediate filaments by cross linking b/w polymers
- 85% of a fully differentiated keratinocyte
- no kertin = no water barrier
69
Vitamin D3
Cholecalciferol (vitamin D3)
-made by keratinocytes, in the presence of UV radiation
Calcitriol
-D3 is converted in liver and kidneys, aids in absorption of calcium and phosphorus
-insufficient vitamin D3 can cause rickets in children and will cause osteomalica in adults - condition with weak bones and muscle pain
70
Stratum Basale
Stratum germinativium, basal layer
- single row of cells, cuboidal to low columnar
- closely spaced nuclei
- adjacent to dermis
- contains stem cells
- constanly dividing and pushing up layers and growing sideways to replace basal wounds
- cell to cell is desmosomes
- cell to basal layer is the hemidesmosomes
- melanin first deposits here by melanocytes
71
Stratum Spinosum
the spiny layer
-8-10 layers of dividing cells
-cytoplasmic processes, bundles of intermediate keratin filaments, attached at desmosomes
NODE OF BIZZOZERO
-cells shrink until cytockeletons stick out
-layers towards surface assume squamous shape
72
Stratum Granulosum
the granule layer
- 2-3 layers thick
- contains the keratohyaline granules - combine with the intermediate filaments to form keratin fibrils, are basophilic
- begin to die by apoptosis
- become lammelated - excrete a waterproofing glycolipid as they become cornfield
- above this layer is a water barrier
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Stratum Lucidum
the clear layer
- thin translucent layer of dead keratinocytes
- nucleus and other organelles gone
- seen only in thick skin
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Stratum Corneum
horny layer
- outermost layer
- 20-30 cell layers thick
- cells are dead and flattened
- full of keratin
- water resistant
- constanly being rubbed off
75
Psoriasis
- chronic skin disorder/ autoimmune disease
- dark red, scaly lesion, usually with well-defined edges
- thought to be due to accelerated keratinocyte turnover and/or hyperplasia
- mitosis happens so fast, not enough time to shed layers at the top, stratum conreum is weaker
- can use UV, drugs, or supplement therapy (anti-inflammation)
76
Melanocytes
- in stratum basale
- derived from neuroectoderm (neutral crest)
- mature associated with keratinocytes
- precursors around hair bulb
- appear with elongated nuclei and clear cytoplasm - sometimes hard to see with H&E
- produce melanin, the pigment that protects the skin from UV damage
77
Skin Pigmentation
| Two types of pigments
Carotene: orange-yellow pigment
-accumulates in epidermal cells and fatty tissues of the dermis
-can be converted to vitamin A
Melanin: yellow-brown (pheomelanin) brown (eumelanin)
-produced by melanocytes
-stored in transport vesicles (melanosomes)
-transferred to keratinocytes
-skin colour depends on melanin production, not the number of melanocytes
-degredation of melanin is faster in light skinned people
78
Skin Cancer
Basal Cell Carcinoma - from outer root sheath keratinocytes, slow growing easier to detect and treat
Squamous Cell Carcinoma - painless patch surrounded by inflamed area, many treatments depending on location - Moh's surgery
Malignant Melanoma - very aggressive unless treated early, from melanocytes
79
Langerhans Cells
- also called epidermal dendritic cells - WBCs
- macrophages that migrated from bone marrow, can enter and leave tissue, first line of immunological surveillance - presents antigen to educate other immune cells
- in the three deepest layers of epidermis
- usually need special stains to see
80
Merkel Cells
- have both neural and epidermal markers
- cells with clear cytoplasm is stratum basal
- synapses with an afferent neurone (Merkel's corpuscles)
- acute sensory perception, like fingertips
- mechanoreceptors for light touch
81
Dermis
-the dermis is the connective tissue layer under the epidermis
-has nerves, blood supply to feed epidermis
-made largely of dense, irregular CT
-type 1 collagen and elstin predominant
Cell: fibroblasts and macrophages
Layers: Papillary and Reticular Dermis
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Papillary Dermis
-narrow region
-areolar CT
-has egg carton interface to contribute to adhesion
Epidermal Ridges - folds of epidermis going down
Dermal Papillae - folds of dermis going up
83
Dermatitis
- an inflammation of the papillary layer
- caused by infection, radiation, mechanical irritation or chemical
- characterized by itch or pain
- contact dermititis is any allergic reaction that has above characteristics from coming into contact with something toxic - like poison ivy
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Reticular Dermis
- deepest layer
- more dense irregular CT
- contains nerves, blood vessels and glands
85
Cutaneous Blood Supply
Cutaneous Plexuses- rete cutaneum, deep plexuses, b/w the hypodermic and reticular dermis
Subpapillary Plexus - rete subpapillare, superficial plexus, b/w the reticular dermis and the papillary dermis
-the superficial dermis gives capillary branches that form beds in each dermal papilla
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Arteriovenous Anastamoses
- direct connection b/w arteries and veins that bypass capillary beds
- required for thermoregulation
- can be gated to control blood flow to skin by ANS
87
Cutaneous Innervation
-sensory (afferent) receptors (SNS)
functionally they are mechanoreceptors that are triggered by mechanical force, thermoreceptors that are triggered by temperature, and nociceptors that are triggered by chemicals
-free nerve endings as well as encapsulated nerve endings
88
Free Nerve Endings
- have no associated schwann cells
- most numerous of all 3 functions
- they terminate in the stratum granulosum
- are involved in light touch such as hair movement and whisker movement
- a cell that are specialized synapses with neurones are called Merkel Cells or just corpuscles
89
Meissner's (Tactile) Corpuscle
- located in the dermal papillae
- mechanoreceptor for light touch
- flat schwann cell with helical neuron
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Pancinian (Lamellated) Corpuscles
- lie at dermal/hypodermal boarder
- mechanoreceptor for deep touch
- respond only when deep pressure is first applied
- also monitors high frequency vibrations, so a deep tissue massage would stimulate these receptors
91
Ruffini Corpuscles
- mechanoreceptor for tension
- fusiform shaped
- found mostly in collagen bundles
92
Hyodermis
-subcutaneous layer that is not part of the skin
-is the superficial fascia
-composed of adipose tissue and areolar connective tissue
functionally it stabilizes the skin, allows separate movement, has larger veins arteries and nerves passing cutaneously from inner body structures
-this is the site of subcutaneous injections using hypodermic needles
93
Hair characteristics
-the human body is covered with hair, except palmar and plantar surfaces, lips and portions of the external genitalia
-functionally the hair protects and insulates, guards openings against particles, is sensitive to very light touch
Two types of hair:
Vellus - fine hair that covers most of the body
Terminal Branches - heavily pigmented, heavy hair, covers head, eyebrows, eyelashes, axilla, pubic region and face
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Structural Hair
Root - everything that is not sticking out of the skin, root hair plexus surrounded by sensory nerves
Shaft- the part sticking out of the skin, not attached to skin. Layers of highly organized keratin
Bulb - active growing site
Arrector Pili - involuntary smooth muscle, causes hair to stand up, produces goose bumps
Sebbaceous Glands - lubricates hair and control bacteria
95
Hair Production
- the hair follicle is a tube created by a pocket of epidermis that extends down into hypodermis
- the hair papilla contains capillaries and nerves
- the hair bulb produces hair matrix, a layer of dividing basal cells, produces hair structures and pushes hair up and out of skin
- as hair is produced, it is keratinized. medulla contains flexible soft keratin, cortex and cuticle contain stiff hard keratin
96
The follicular Bulge
- region of the hair shaft b/w the sebaceous gland duct and the arrestor pili insertion
- ES cells that can make hair, and epidermis when the skin is wounded
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Hair Growth Cycle
-growing hair is firmly attached to the matrix
-grows in a cycle
-club hair pushed out by new hair growing under it
Anagen - growth
Catagen - transition
Telogen - rest
98
Sebaceous Glands
- simple acinar gland, pale staining
- holocrine
- outgrowth of hair follicle
- duct empties into hair shaft
- produce sebum - oil that helps waterproof the skin and prevent infection
- Ance is the infection of sebaceous glands
99
Eccrine Sweat Glands
- simple tubular exocrine
- secretory region is coiled and in reticular dermis having 3 cell types: clear, dark and myoepithelial cells
- excretory region goes to surface
- located everywhere but concentrated in the forehead, axillae, scalp, palms and soles
- secrete sweat that is important for temperature regulation
100
Apocrine Sweat Glands
- simple, tubular exocrine (actually use merocrine excretion), are very eosinophillic
- can sometimes see round cap on the cells that are shedding
- found in axillae, areola and nipple and in the circumanal region
- being functioning at puberty
- secrete a protein and fat rich substance that bacteria can use for nutrients in hair follicles or on to surface
- may function as a pheromone
- surrounded by myoepithelial sells that push secretion out in response to hormonal or nervous signal
101
Structure of nails
Nail Root - a deep epidermal fold near the bone where nail production occurs
Nail Body - the visible portion of the nail
Nail Bed - an extension of the stratum basal beneath the nail, covered by the nail body
Lateral nail grooves, lateral nail folds
Lacuna - the moon at the base of the nail where active nail growth from the nail matrix occurs
Hyponychium - skin beneath the distal free edge of the nail under nail
Eponychium - skin covering the site of emergence
102
Repair of Intugement
- mast cells initiate an inflammatory response at site of wound
- cells of stratum germanativum migrate along edge of wound, phagocytic cells are removing debris with more cells arriving to enhance circulation to area
- after one week the scab has been undermined by epidermal cells migrating over the scabby meshwork leaving fibroblast made layer
- fibroblast continue to make scar tissue that eventually elevates the overlying epidermis
103
Cartilage
specialize connective tissue
functionally it is cushioning, stress resistance, primary tissue in fetal skeleton, important for bone growth
Matrix - specialized, pliable with no blood vessels
Cells - chondrocytes
Types - Hyaline, elastic and fibrocartilage
-is avascular and aneural
104
Cartilage Matrix
- keeps chondrocytes alive, chondrocytes secrete and maintain it
- gel-type ground substance proteins for shock absorption and protection
- permits diffusion of nutrients and removal of waste from edge of tissue- this means cartilage can only grow so wide
- many GAGs and type II collagen fibbers in matrix make it able to bear weight
- as long as chondrocytes are healthy, the matrix can remodel and respond to environmental change
105
Collagen in Cartilage
Type II, VI, IX, X, XI
106
Ground Substance Proteoglycans
3 kinds of GAGs: Hyaluronan, Chondroitin Sulfate, Keratin Sulfate
Aggrecan - proteoglycan monomer formed from many chondroitomn sulfates and keratin sulfates attached to a core protein
-aggrecan line up along large hyaluronan molecule to form spongy matrix, aggrecan-hyaluronan aggregates
-differences in staining have to do with differences in composition of the ground substance
107
Hyaline Cartilage
glassy cartilage
functions: stiff but flexible, reduces friction b/w two boney surfaces
Matrix: contains type II collgen, GAGs, proteoglycans and multiadhesive glycoproteins
Locations: articular surfaces, larynx, trachea, nasal septum, costal cartilage
108
Chondrocytes live in holes
- few cells in hyaline cartilage
- exist singly
- can exist in small clusters, isogenous group that is cells that are recently divided
- Lacunae is the nest or hole that these chondrocytes live in
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Isogenous Group organization
- recently divided
- capsular matrix that will have dense stain, highest concentration of GAGs and Type VI collagen
- territorial matrix - stains less dense and is type II and VI collagen
- interstitial matrix - lightest stain
110
Chondrocyte Characteristics
- immature chondrocytes are a nucleus in an empty lacunae
| - mature chondrocytes are big and fill the lacunae with a large nuclei may have some organelles
111
Perichondrium
- a type of dense CT with fibroblast like cells
- supports growth by: chondrogenic perichondrium and fibrous perichondrium
- absent in articular joint surfaces
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Chondrogenic Perichondrium
- location is near the cartilage (inner layer)
- cells are undifferentiated cells that can form chondroblast or chondrocytes
- matrix is chondroblast and type II collagen
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Fibrous Perichondrium
- location is the outmost layer
- cells are fibroblast that actively make collagen
- matrix is therefore containing type I collagen
114
Elastic Cartilage
functions: stiff but flexible support, allows for some distension and recoil
matrix: like hyaline, but with high concentration of elastin in fibbers and sheets
location: auricle of external ear, epiglottis, auditory canal, cuneiform cartilage of larynx
- has perichondrium
115
Fibrocartliage
functions: resists compression, allows for stability without bone-to-bone contact
matrix: contains type I and II collagen
- no true perichondrium, chondroblasts form small bundles
locations: menisci, pubic symphasis, intervertebral discs
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Chondrogenisis
- the growth of cartilage
- done by 2 mechanisms, interstitial growth and appositional growth
- these can happen simultaneously
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Chondroblasts
- chondrocyte precursor cells
- cartilage is made from mesenchyme
- Sox-9 (transcription factor) makes chondroblasts
- spacing makes chondrocytes
118
Interstitiall Growth
- forms new cartilage within the existing cartilage
- can do this because matrix is flexible
- matrix secretion helps push cells apart
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Appositional Growth
-forms new cartilage on the surface of existing cartilage
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Cartilage repairs poorly
- cartilage has limited capacity for repair
- has no blood supply (avascular)
- chondrocytes are immobile
- chondrocytes in matrix have a limited capacity to divide
- can only repair if the injury involves the perichondrium
- often healing triggers ossification
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Bone (Osseous Tissue)
- connective tissue
functions: support, protection, calcium and phosphate storage
- mineralization contains hydroapatite crystals
- type I and V collagen with trace of several others, this is a third of matrix and acts like rebar
- has specialized ground substance, only 10% feeds the cells, remainder is to promote and maintain calcification
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Bone Ground Substance
4 main groups of other proteins in substance:
Proteoglycan-binding growth factors, may inhibit mineralization
Multiadhesive glycoproteins:
Osteonectin-glue hydroxyapatite to collagen
Osteopontin-adheres osteocytes to bone
Sialoprotein I and II-start calcification
Bone specific proteins that require Vit K:
Osteocalcin-stimulates calcium uptake from blood and osteoclast activity
Growth factors/Cytokines:
Bone morphogenic proteins- induces bone growth
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Histological Preparation
acid treatment - dissolves organic matrix and preserves cells and organic matrix
heat treatment - removes cells and organic matrix, preserve inorganic matrix
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Periosteum
-covering of bone
functions: isolates bone from surrounding tissues, provides a route for circulatory and nervous supply, participates in bone growth and repair, contains arteries, veins and sensory nerves
Fibrous periosteum - resembles dense CT
Osteogenic Periosteum - contains osteoprogenitor cells that can become osteoblasts, this is absent in areas where it directly articulates with cartilage
Sharpeys fibers - fibbers of collagen that extend from periosteum into the bone itself to anchor the periosteum
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Endosteum
- the layer of cells facing the marrow cavities
- single cell thick covering
- made of endosteal cells, flattened with elongated shape
- also there are the osteoprogenitor cells
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Marrow
-fills the marrow cavity
-site of hematopoiesis
Red bone marrow: develops red blood cells, many blood cells undergoing hematopoiesis, reticular fiber matrix, amount does not increase with bone length, in adults to get the red from iliac crest and sternum
Yellow Bone Marrow: blood cell production that has decreased and the marrow has been replaced with unilocular adipose tissue
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Structure of Flat bone
- resembles a sandwich of spongy bone
- b/w two layers of compact bone
- still periosteum, endosteum and marrow, but in slightly different places
- within the cranium, the layer of spongy bone b/w the compact bone is called the dipole
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Spongy bone structure
similar to compact bone but bone is arranged with opening with fingers of bone
-trabeculae and spicules
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Blood Supply
- the major difference b/w bone and cartilage is that bone has blood
- nutrient foramina are holes that blood vessels enter into bones
- nutrient artery is the first arteries to migrate in to create the bone, often the bones major blood supply
- blood enters and leaves thru Volkmann's canals
- dispersed thru the central artery in the Haversian canal
- diffused via cell interaction thru canaliculi-little channels
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Osteoprogenitor Cells
- osteoblast processor cells
- derived from mesenchymal stem cells
- found on external and internal surfaces of bones, periosteal cells and endosteal cells
- squamous cells with lightly staining, elongated nuclei and a slightly coloured rim of cytoplasm
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Osteoblast Cells
- immature bone cells that secrete matrix compounds, type I collagen, BMPs and many matrix proteins
- Osteid-matrix produced by osteoblasts but not yet calcified to form bone
- cuboidal or polygonal shape
- tend to cluster on growing side
- basophillic cytoplasm
- can be surrounded by a thin, unstained area b/c of the osteoid
- osteoblasts surrounded by bone become osteocytes
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Osteocytes
- function: to maintain protein and mineral content of matrix, to help repair damaged bone
- live in lacunae, are between lamellae
- connect by cytoplasmic extensions thru canaliculi in lamellae
- do not divide
- if they die, triggers bone remodelling
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Osteoclasts
- giant, multinucleate cells
- derived from same precursors and granulocytes and monocytes (blood)
- dissolves bone matrix and release stored minerals (osteolysis), it has many lysosomes, inflammation can stimulate osteoclast mediated bone resorption
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Ossification Build Bone
ossification - the process of building bone
calcification - the process of depositing calcium salts
There are 2 process:
Intramembranous Ossification
Endochondral Ossification
Both are appositional growth - the differentiation of osteoprogenitor cells into osteoblasts that build the bony matrix
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Endochondral Ossification
- oddifies bone that originate as hyaline cartilage
- most bones
- are mediate by Fibroblast growth Factors and Bone Morphogenic Proteins
- mesenchymal cells make chondrocytes, these chondrocytes then die to make room for osteocytes
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Zones of Epiphyseal Cartilage
Zone of reserved cartilage - no active matrix production, looks like hyaline cartilage
Zone of proliferation - cells that stack, are bigger, produce collagen
Zone of Hypertrophy - cells enlarge due to glycogen buildup, secrete Type I and X collagen
Zone of Calcified Cartilage - chondrocytes and calcified cartilage becomes bones scaffold, matrix usually changes colour/density
Zone of Resorption - small blood vessels invade region left open by dying chondrocytes, bring osteoprogenitor cells that populate and create calcified bone
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Bone lengthening
- once ossification occurred, spongy bone regions are remodelled to form compact bone in the diaphysis
- not long after birth, secondary ossification centres form and begin to make bone at the epiphysis
- in b/w forms the cartilage epiphyseal growth plate
- cartilage in plates grow as bone grows and is remodelled to lengthen
- in adulthood, the epiphyseal plates ossify and close to make an epiphyseal line
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Zones of Articular cartilage
Superficial Zone - elongated chondrocytes
Intermediate Zone - round chondrocytes with less organized collagen, fluid exchange helps care for chondrocytes
Deep Zone - small chondrocytes in short stacks, fibbers and cells perpendicular to articular surface, interstitial growth happens here
Tidemark - line formed by calcification
Calcified Zone - calcified cartilage that lacks chondrocytes
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Synovial Joint Architechture
Joint Capsule - variable in thickness, correlates with stability
Stratum Fibrosum - outer portion of capsule comprised of dense irregular CT
transitions of fibrocartilage at insertion point on bones, poorly vascularized but richly innervated with proprioceptive nerve endings
Stratum Synovium - inner lining layer of capsule, intima consists of 1-3 layers of specialized fibroblasts known as synoviocytes, responsible for producing synovial fluid and removing debris, subsynovial layer is highly vascularized
Synovial Fluid - this fluid film that coats articular surfaces and the stratum synovium
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Bone Remodelling
-compact bone can be made by remodelling fetal spongy bone or deposited directly over adult compact bone
Internal remodelling - the process that makes new osteons
Resorption cavity - tunnel cut by osteoclasts that has dimensions of new osteon, blood vessels enter and new bone deposition begins
Bone remodelling units: Cutting Cone - advanding osteoclasts eating forward and out
Closing Cone - advancing capillary loop and pericytes, endothelial cells, and precursors that make osteoblasts deposit and walls of cavity to fill in, leaving Haversian canal for blood vessel
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Mineralization
-cell regulated extracellular event
-occurs in cartilage, bone and dentin, cememtun and enamal of teeth
Events:
-osteocalcin, sailoproteins that bind calcium
-Alkine phosphotase, osteoblasts secrete and it causes an increase in PO4 which causes an increase in Ca2+
-the high concentration of these two causes release of matrix vesicles by exocytosis into the ECM
-vesicles picp up Ca and cleave PO and CaPO4 crystals precipitate, these are the hydroxyapatite crystals
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Calcium and Bone Homeostasis
-blood calcium levels are critical to like, calcium is stored or mobilized into the blood from the skeletal system
-bone building and bone recycling must balance, more breakdown than building the bones become weak
exercise, weight bearing, causes osteoblasts to build bone and osteocytes to strengthen matrix in direction of applied stress
-effect of exercise, mineral recycling allows bones to adapt to stress, heavilty stressed bones become thicker and stronger, lamellae align and are modelled in direction of stress
-bones degenerate quickly
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Parathyroid Hormone
secreted by the parathyroid gland, raises the calcium levels to normal by taking calcium out of the blood, increases the osteoclast activity , also increases the dietary uptake of Ca from gut and slows excretion from the kidneys
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Calcitonin
secreted by the thyroid gland, increases the storage of calcium by increasing the activity of the osteoblasts
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Osteopenia
-begins b/w the ages of 30-40 moreso in women, losing they bone mass
-the epiphysis, vertebrae and jaws are most affected
usually caused by hormones and/or lifestyle that alter balance of factors going to osteoblasts and osteoclasts
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Osteoporosis
- severe bone loss
- over age 45 occurs more frequently in women
- fracture risk in all bones increase but spine and hips morbidity and mortalilty rates
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Paget's Disease
- usually people over 55, more common in men
- bones are larger in size but weaker in structure
- presumed to be caused by increased osteoclast activity
- osteoblasts go overboard wanting to repair the lost matrix
- repaired matrix is woven, instead of lamellar and weaker prone to fractures
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Osteosarcoma
- malignant tumor of osteoblast
- most common in children in the long bones at the knee
- osteoid does not mineralize completely and the legs bow at the knee
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Osteoid osteoma
- benign tumor of osteoblasts
- manifests itself as bony nodules forming on various bones
- osteoid becomes excessively mineralized in these areas
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Osteomalacia
- softening of the bones resulting in increased tendency to fracture
- osteoblasts are apparently normal
- failure to mineralize is a result of decreased serum calcium and phosphate
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Rickets
- essentially osteomalacia in children leading to permanent deformities
- typically the osteoid in the long leg bones mineralizes poorly
- failure to mineralize is often attributed to a Vit D defeciency
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Osteogenesis Imperfecta
- autosomal dominant genetic disorder that stops production of type 1 collagen
- bones are very brittle and breakable
- can have other symptoms depending on which type of OI and mechanism of pathology
- blue sclera in the eyes also common
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Blood as a part of the Cardiovascular System
-the cardiovascular system consists of the heart, vessels and blood
-blood is CT with formed elements and a fluid matrix
Functions: delivery of oxygen and nutrients, transports waste and carbon dioxide, delivery of hormones and other regulators, buffering pH and temp, coagulation, transportation of WBCs
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Components of WBC's
- Plasma is 46% to 63%, fluid consistinf of water, dossolved plasma proteins and other solutes
- formed elements is 37% to 54%, thrombocytes (Platelets) - clotting, Erythrocytes (RBCs) - transport oxygen, Leukocytes (WBCs) - immunity
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Physical Characteristics of Blood
- 38 degrees is normal temperature
- high viscosity
- slightly alkaline pH
- blood volume = 7% of body weight
- blood is made by hematopoesis from cells in bone marrow
- blood is analyzed using fractionalization with centrifuge
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Composition of Plasma
- makes up 50-60% of blood volume
- more than 90% of plasma in water
- Serum is the liquid part of the blood left over once the solids clot
- Extracelluler fluids, Interstitial fluid and plasma, Materials plasma and IF exchange across capillary walls (water, ions, small solutes)
- Plasma proteins: Albumin 60%, Globulins 35% and Fibrinogens 4%
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Functions fo Plasma Proteins
Albumins - transport substances such as fatty acids, thyroid hormones and steroid hormones
Globulins - antibodies, also called immunoglobulins
transport globulins
Fibrinogens - molecules that form clots and produce long insoluble strands of fibrin
Other Plasma Proteins - changing quantities of specialized plasma proteins, peptide hormones normally present in circulating blood, insulin prolactin and the glycoproteins thyroid stimulating hormone (TSH) follicle stimulating hormone, and lutenizing hormone
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Erythrocytes
-makes up 99% of the blood
-have no nucleus or organelles
-O2 and CO2 transport only, biconcave shape to maximize surface area
-lives 120 days
-Hemoglobin - pigment that binds O2
Carbonic Anhydrase - helps take up CO2 in tissue and drop it5 in the lungs
-shape is specialized and RBC form stacks called rouleaux
-discs bend and flex entering small capillaries
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RBC life cycle
-live for 120 days, 1% of ciculating RBC wear out per day, about 3 million per second
-RBC are considered old when their ion pumps are working poorly, this makes the RBC become swollen
-Hemoglobin monitoring in the liver, spleen and bone marrow, macrophages in these areas monitor the RBC by checking the transport protein functions and engulf if need be, hemolyze.
Recycling happens in the liver
-phagocytes break the hemoglobin into components creating globular AA and heme to biliverdin
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Hemoglobinuria
hemoglubin breakdown products in urine due to excess hemolysis in the bloodstream
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Hematuria
whole red blood cells in urine due to kidney or tissue damage
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Jaundice
is caused by bilirubin buildup, usually due to liver problems
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Leukocytes
-do not have hemoglobin
-have nuclei and other organelles
Functions: defend against pathogens, remove toxins and wastes, attack abnormal cells
-most WBCs are in CT, lymphatic system organs, blood
-Small number in blood so they have the greatest activity in the CT
Classifications: Granular - nuetrophil, eosinophils, basophils
Agranular - lymphocytes, monocytes
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Ciculating WBCs
- can migrate out of the bloodstream
- have ameboid movement
- attrached to chemical stimuli
- some are phagocytis - nuetrophils, eosinophils, and monocytes/macrophages
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Neutophils
-roughly 50-70% of the circulating WBCs
-multilobed nucleus
Pale Cytoplasm Granuoles with: Lysosomal Enzymes, Bactericides, High level of Glycogen b/c they are anaerobic.
Functions: very active, first to attack bacteria
are phagocytes (form pus)
Degranulation - removing granules from cytoplasm by releasing defensins that attack pathogen membranes
release prostaglandins and leukotrienes
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Eosinophils
-about 2-4% of circulating WBCs, multilobed nuclei, few organelles, acidophilic granules
Functions: phagocytic, affinity for antigen-antibody complexes
excrete toxic compounds: nitric oxide and cytotoxic enzymes
increase response to: parasitic diseases, allergic conditions, adverse drug reactions
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Basophils
-less than 0,5% of WBCs, multilobed nuclues, basophilic granules-contains heparin and histamine, IgE Ab surface receptors
Functions: related to mast cell functionally, accumulate in damaged tissue
In response to IgE binding- release histamine that dilates blood vessels, release heparin that prevents blood clotting
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Lymphocytes
-about 30% of circulating WBCs, smaller, dark round nuclei
Functions: they are adaptive immune system
3 different types. T cells - made in thymus, B cells - made in bone marrow, and Natural killer cells - detect and destroy abnormal tissue cells
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Monocytes / Macrophages
-mono 2-8% in of WBCs, are large, bean shaped, clear cytoplasm, enter peripheral tissue and become macrophages
Functions: phagocytosis or large particles and pathogens, secrete molecules that attract immune systems cells and fibrocytes
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Thrombocytes
-anucleate cells derived from megakaryocytes in bone marrow, may have other organelles, 2/3 circulate, 1/3 in spleen, 10 day circulation time
Functions: clot formation, temporary patch vessel walls, reduces size of wounds in vessel wall
Storage vesicles contain several clotting factors including: Platlet derived growth factors - promotes fibroblast and smooth muscle proliferation
Serotonin - a vasoconstrictor
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FOrmation of a CLot
Vascular phase: 0-30 minutes after injury, serotonin release causes vasoconstriction by smooth muscle cells, reduce blood loss from damaged vessels
Platelet Phase: begins 15 seconds after injury, damage endothelium exposes collagen and other wall components, circulating platlets use integrin proteinson their surfaces to adhere to these vascular wall components, integrins bind specifically to fibronectin proteins in the matrix
Platlet Aggregation, more platlets adhere to those already located at damaged site
Platlet Plug- eliminates further blood loss, these binding events cause secretory vesicles
PDGF release causes proliferation of smooth muscle and fibroblasts to help repair the damaged walls
Coagulation Phase: fibrinogen is converted to fibrin
the insolbule fibrin mass replaces the platlet plug
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Hematopoiesis
-the birth of RBC from the bone marrow
-Monophyletic theory of Hematopoiesis - a single mesenchymal precursor gives rise to all the formed elements in blood, blood is made from stem cells
Myeloid tissue- red bone marrow most peripheral blood cells, all WBCs mature in the bone marrow
Lymphoid tissue - spleen, thymus, lymph nodes finishing school for some white blood cells
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Stem cells
have potential to change their gene so they can become a completely different cell with a more specialized morphology and function
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Pluripotent stem cells
true stem cell
capable of making any kind of blood cells
does so by dividing and making multipotential stem cells
also self renews through mitotic division
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Multipotent Stem cells
a stem cell commited to one lineage of blood cells
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Hematopoietic Stem Cells (HSC)
stem cells in myeloid tissue divide to produce: Myeloid stem cells that become RBC some WBCs and platlets, express CFU-GEMM
Lyphoid stem cell become lymphocytes, express CFU-L
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Erythropoiesis
continuation of hematopoisesis to make RBCs, occurs only in myeloid tissue in adults
As they develop they decrease in size, increase their hemoglobin content, loose their organelles gradually, eject nucleus
Regulation: building requires AAs, Iron, Vitamins B12, B6 and folic adid
Erythroproteins/hormone - secreted when oxygen in peripheral tissues is low (hypoxia), due to disease or high altitude
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RBC Pathology
Polythemia - high RBC number in blood, found in blood doping and EPO supplementation in athletes
Anemia - low RBC level in blood, Pernicious anemia meaning low RBC production due to unavailability of Vit B12
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Granulopoiesis
extension of myelopoiesis to make granulocytes
| -develop cytoplasmic granules, shrink slightly, develop multi-lobed nuclei, granules change colors
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Lymphopoiesis
the production of lymphocytes
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Leukemia
-a liquid or non-solid tumor
-excessive proliferation of leukocytes or their precursors in bone marrow
-the precursors then populate the peripheral blood
-classified according to cell line involved
-impairs ability to fight infection and also to make new blood cells and form clots
Gleevac/Imatinib - a drug that is used to help leukemia
