Histo Block B

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Histo Block B
2012-10-31 23:33:29

histology block B
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  1. What is osteoid?
    initial unmineralized bone formed by osteoblasts
  2. what is the role of calcification of cartilage in the development of bone?
    inhibits diffusion of nutrients, causing death of the chondrocytes in the cartilage model
  3. what is the bony collar?
    an initial distinctive cuff of periosteal bone formed in the diaphysis of long bones during endochondral bone development
  4. what is the periosteal or osteogenic bud?
    • nonlamellar bone; immature bone formed in the fetus
    • stains more intensely due to increased ground substance (darker pink in decalcified prep)
    • contains woven bone
  5. what is an osteon?
    • same as Haversion system
    • surrounds a central Haversion canal
  6. what structures are contained within Haversian canals?
    vascular and nerve supply of the osteon
  7. how are volkmann's canals related to the nutrient foramina of Haversian canals? 
    they create cross connection between Haversian canals
  8. how to bones increase in length & width?
    appositional growth
  9. what hormones affect the development of the epiphyseal plate?
    • PTH: increases bone resorption; in pulses, increases bone formation
    • calcitonin: decreases bonoe resorption
    • gonadal steroids: decrease bone resorption & increase bone growth
    • thyroid hormone: increases bone resorption
  10. bone composition
    • bone tissue
    • other connective tissues
    • hematopoietic tissue
    • fat tissue
    • blood vessels
    • nerve
  11. bone classifications: shape
    • long
    • short
    • flat
    • irregular
  12. long bones
    • compact bone mainly in diaphysis
    • mainly spongy bone in the epiphyses
  13. short bones
    shell of compact bone with spongy bone & marrow in the center
  14. flat bones
    two layers of compact bone with spongy bone in between
  15. irregular bone
    ex. vertebrae
  16. periosteum
    • found on all bones EXCEPT on articular surfaces
    • composed of dense fibrous connective tissue
    • collagen fibers arranged parallel to surface of the bone
    • inner layer contains osteoprogenitor cells
  17. endosteum
    tissue lining the compact & spongy bone associated with the marrow cavity
  18. sharpey's fibers
    • where ligaments & tendons attach to a bone
    • the collage fibers of the periosteum extend into the circumferential lamellae
  19. bone matrix: inorganic
    • mainly crystalline mineral salts & calcium present in the hyrdoxapatite
    • matrix is laid down as unmineralized osteoid (secreted by osteoblasts)
    • mineralization begins with secretes alkaline phosphatase (starting point for calcium & phosphate deposition)
  20. bone matrix: organic
    • mainly type I collagen
    • synthesized intracellularly as tropocollagen & then exported
  21. bone tissue
    • connective tissue characterized by a highly mineralized matrix
    • contains mainly type I collagen
    • contains lacunae connected by canaliculi
  22. bone cells
    • osteoprogenitor cells: form new bone cells
    • osteoblasts: sit on free edge & make matrix; mature into osteocytes
    • osteoclasts: large & multinucleated
    • bone lining cells: osteocytes
  23. treatment for sprains
    • Rest
    • Ice
    • Compression
    • Elevation
  24. bone collagen arrangement
    • twisted
    • conveys extra strength; withstands stress better; gives bone flexibility
  25. origins of bone cells
    • osteoblasts: bone marrow derived mesenchymal progenitors
    • osteoclasts: bone marrow derived hematopoietic progenitors
  26. osteoprogenitor cells
    • derived from mesenchymal stem cells in the marrow
    • activated to become osteoblasts by CBFA1 transcription factor
    • found in the innermost layer of the periosteum & endosteum
  27. osteoblasts
    • capable of dividing
    • secretory cells that produce type I collagen + bone matrix proteins
    • respond to mechanicl stimuli to mediate bone growth & remodeling
  28. osteoid
    newly formed bone matrix
  29. osteocytes
    • mature cells of bone
    • surrounded by calcified extracellular matrix
    • have long processes that pass through canaliculi
    • "touch" other osteocytes via gap junctions
    • maintain the bone matrix
  30. osteoclasts
    • large, multinucleated cells
    • responsible for resorption of bone matrix
    • rest directly on bone tissue that is being removed
    • derived from fusion of mononuclear hemopoietic progenitor cells
    • form a syncitium
    • rest in Howship's lacuna
  31. Howship's lacuna
    shallow depression directly below an osteoclast
  32. ruffled border
    • the part of the cell in direct contact with bone matrix
    • numerous deep plasma membrane infoldings
  33. clear zone
    • adjacent to ruffled border of osteoclasts
    • site of resorption & degradation
  34. basolateral region
    exocytosis of digested material in osteoclasts
  35. osteoclast action
    • filled with lysosomes that contain hydrolytic enzymes
    • demineralize the matrix by secreting hydrogen ions into extracellular space
    • release carbonic anhydrase (converted into carbonic acid & hydrolytic enzymes like collagenase) to break down fibrous portion of bone
    • resorption releases calcium & phosphorous into blood circulation
    • after resorption is complete, osteoclasts undergo apoptosis (promoted by bisphosphonates & estrogen)
  36. function of osteoclasts
    • resorption of calcium & phosphorous into blood circulation
    • endocytosis: ruffled border has coated pits
    • bone remodeling in response to stress
  37. organization of compact bone
    • osteons: consist of concentric lamellae
    • Haversian/central canal: contain blood vessels & connective tissue
    • lacunae: contain osteocytes
    • canaliculi: connect osteocytes
    • Volkman's/ perforating canals: contain blood vessels that travel from one Haversian canal to the next
  38. PTH
    • parathyroid hormone
    • released when calcium levels are low
    • stimulates osteoclasts to degrade bone & release calcium into the blood
    • causes increased intestinal absorption of calcium
    • causes the kidneys to retain calcium
    • EXCEPTION - pulses of PTH increase bone formation
  39. circumferential lamellae
    • near the surface of compact bone
    • arranged parallel to the surface
  40. interstitial lamellae
    represent remnants of older Haversian systems which have been partially destroyed as the bone tissue is remodeled or reorganized
  41. hormones that increase bone resorption
    • parathyroid hormone
    • glucocorticoids
    • thyroid hormone
    • vitamin D metabolites (high doses)
  42. calcitonin
    • stimulates calcium salt deposition in bone
    • released in response to high levels of calcium
    • produced by thyroid gland
    • stimulates osteoblasts to incorporate calcium (from bloode) into newly formed bone
    • responsible for calcium storage
  43. hormones that decrease bone resorption
    • calcitonin
    • gonadal steroids
  44. hormones that increase bone formation
    • growth hormone
    • vitamin D metabolites (low doses)
    • gonadal steroids
  45. hormones that decrease bone formation
  46. effects of parathyroid hormone
    • efflux of calcium from bone
    • decreased loss of calcium in urine
    • enhanced absorption of calcium from intestine
    • increased concentration of calcium in blood
  47. endochondral bone formation
    • replacement of a hyaline cartilage model with bone tissue
    • ossification begins as blood vessels invade the cartilage model, bringing osteoprogenitor cells
    • a collar of bone is formed around the diaphysis (shaft)
    • the matrix begins to calcify replace it with bone
    • secondary ossification centers form in the epiphyses
  48. zone of proliferation
    cartilage cells undergo division & organize into distinct columns
  49. zone of hypertrophy
    • chondrocytes are metabolically active
    • secrete VEGF which initiates vascular invasion
    • cells become larger ("big & fluffy")
  50. zone of calcified cartilage
    hypertrophied cells begin to degenerate & cartilage matrix becomes calcified
  51. zone of resorption
    • calcified cartilage is resorbed & replaced with osteoprogenitor cells that differentiate into bone cells
    • KILLS off cartilage EXCEPT at growth plate
  52. epiphyseal plate
    • the cartilage zone left at each end of the marrow cavity
    • allows bones to continue to grow in length & width
    • when growth is complete, becomes the epiphyseal line
  53. intramembranous ossification
    • occurs in flat bones
    • embryonic mesenchyme condenses
    • ossification occurs in numerous sites simultaneously
    • both spongy & compact bone can arise via this mechanism
  54. growth of long bones
    • as bone grows, it is constantly resorbed and remodeled
    • osteoclasts eat away at center (cavity) as osteoblasts build diameter
    • don't want bones to be too thick (heavy) or too thin (fragile)
  55. growth of flat bones
    • intramembranous ossification
    • different random ossification centers eventually grow together to form a layer of bone
  56. appositional growth
    • growth in diameter
    • new bone is added to the outside of bone & osteoclasts remodel inside of bone
    • prevents bone from becoming too thick
  57. stages of bone remodeling
    • resorption
    • reversal
    • formation
    • resting
  58. bone remodeling
    • occurs all the time, especially in growth
    • osteoclasts resorb & osteoblast reform new bone
    • caused by mechanical stimulation
    • ex. orthodontic appliances
  59. stages of fracture repair
    • hematoma formation
    • fibrocartilage callus formation
    • bony callus formation
    • bone remodeling
  60. strength of bone
    • compressional strength: greater than reinforced steel
    • tensile strength: reinforced concrete
    • torsional strength: LOW strength to endure twisting
  61. fracture repair
    • after initial injury, neutrophils & macrophages begin to clean up site of damage
    • fibroblasts & capillaries proliferate and grow into site of injury
    • loose CT (granulation tissue) is formed & becomes dense
    • dense CT & cartilage cover bone at fracture site forming a callus
    • callus helps to stabilize & bind together the ends of fractured bone
    • osteoprogenitor cells within periosteum divide & differentiate into osteoblasts
    • original callus tissue is replaced with new bone (bony callus)
    • spongy bone is formed & some parts are replaced with compact bone
  62. bone density
    • ground reaction or impact forces like gymnastics & weight lifting have the highest effect on bone density
    • the mechanical stress of exercise puts stress on the bone & increases bone density
  63. osteoporosis
    • affects over 44 million people in the US
    • responsible for 1.3 millions fractures/year
    • low bone mass
    • deteriorationg of both inner (trabecular) and outer (cortical) parts of bone
    • 1 in 2 caucasion women will have an osteoporotic fracture
    • 20% of patients with hip fractures will die within one year due to complications
  64. consequences of osteoporosis
    • fractures of the vertebrae
    • decrease in height
    • scoliosis
    • hip fractures
    • minimal stress fractures
    • loss of bone in the jaw (loose teeth of movement of teeth)
  65. risk factors for osteoporosis
    • gender (females)
    • ethnicity (caucasian/asian)
    • hormone levels (post menopausal)
    • thin & small body frame
    • family history
    • lifestyle - smoker, alcohol consumption, lack of exercise, diet low in calcium
  66. role of estrogen in osteoporosis
    • reduced estrogen levels in postmenopausal women
    • low estrogen causes increased RANK-L expression
    • low estrogen causes increased osteoclast formation
    • low estrogen causes excessive bone resorption
    • NO SIGNAL for osteoclast apoptosis
  67. diagnosis of osteoporosis
    • risk factors
    • family history
    • DXA scan: dual energy x-ray absorptiometry scan
  68. treatment of osteoporosis
    • lifestyle changes - adequate calcium, weight bearing exercise, no smoking/drinking
    • medication that stops bone loss & increases bone strength (bisphosphonates, calcium, pulses of PTH)
  69. bisphosphonate
    • inhibit osteoclast activity & promote osteoclast apoptosis
    • released locally during bone resorption
    • concentrated under osteoclasts
    • may modulate signaling from osteoblasts to osteoclasts - decrease RANK-L expression, increase OPG expression
  70. bisphosphonates: mechanism of action
    • antiresorptive agents
    • bind to hydroxyapatite crystals in bone
    • directly or indirectly inhibit osteoclasts
    • inhibit bone mineralization (at sufficient doses)
    • pharmacologically active only while on exposed bone surfaces
    • remains bound in bone matrix for years
  71. hormonal therapies for osteoporosis
    • osteoprotegerin (OPG)
    • competitive inhibitor of RANK (binds to RANK-L)
    • prevents stimulation of osteoclastogenesis
  72. calcitonin: osteoporosis Rx
    • inhaled calcitonin
    • used daily (alternate nostrils)
    • few side effects
    • exhibits an optimum level, then loses efficacy
  73. anti-resorptive factors
    • things that cause new bone formation and/or inhibit bone resorption
    • ex. estrogens, calcitonin, BMP 2/4, TGF beta, TPO, IL-17, PDGF, calcium
  74. parathyroid hormone therapy
    • Rx for osteoporosis - Forteo
    • pulses of PTH increase bone formation
    • increased osteoblast differentiation & activity
    • decreased osteoblast apoptosis
    • daily injectable - problems with compliance
    • recombinant teriparatide
    • must be used before bisphosphonates are started
  75. denosumab
    • osteoporosis treatment designed to target RANK-L
    • fully human monoclonal antibody (IgG2) that binds to RANK-L with high affinity & specificity
    • blocks interaction of RANK-L and RANK
    • NO osteoclast formation
  76. bisphosphonates vs. denosumab
    • bisphosphonates: bind to bone mineral & disable osteoclasts (decrease RANK-L expression)
    • denosumab: blocks osteoclast formation
  77. gout
    • uric acid crystals in the joints
    • side effect of treatment with thiazide anti-hypertensive medication
    • predisposition - family history
  78. rheumatoid arthritis
    • chronic, systemic autoimmune disease
    • results in inflammation of synovial joint & destruction of cartilage and bone tissue
    • 2-3X more common in women
  79. osteoarthritis
    articular cartilage wears out
  80. acromegaly
    • uncommon hormonal disorder
    • develops when the pituitary gland produces too much growth hormone during adulthood
    • bones increase in size - especially hands, feet & face
    • affects middle aged adults
  81. osteogenesis imperfecta
    • autosomal dominant mode of inheritance
    • mutations affect the synthesis or structure of type I collagen
    • eight different types
    • weak bones, susceptible to fractures, short statures
    • blue tint to whites of eyes (blue sclera); multiple bone fractures; early hearing loss (deafness)
    • location of mutation determines severity
  82. histological presentation of osteogenesis imperfecta
    • bony spicules in metaphysis
    • poor ossification
  83. Paget's disease
    • causes bones to grow larger and weaker than normal
    • most common in spine, pelvis, skull & legs
    • might affect one or several bones, but not entire skeleton
    • more common in men than women
    • common in older people
    • symptoms - pain, enlarged bones, broken bones, damaged cartilage in joints
  84. peripheral blood functions
    • conveyance of nutrients, wastes, regulatory molecules, humoral agents & cells
    • homeostasis via thermoregulation & its buffering capacity
    • related functionally, developmentally & genetically to connective tissue
    • biochemically similar to lymph & interstitial fluid (plasma)
  85. peripheral blood components
    • formed elements: cells & cell fragments
    • unformed elements: plasma (slightly alkaline, 90% water)
  86. hematocrit
    % volume of packed erythrocytes (RBCs)
  87. buffy coat
    layer of leukocytes (WBCs) & platelets
  88. relative volumes of formed elements in the blood
    • more agranulocytes than granulocytes
    • lymphocytes are more numerous than monocytes
    • neutrophils > eosinophils > basophils
  89. plasma
    • anticoagulant (heparin or sodium citrate)
    • prevents clot formation
    • predominant components - albumin, fibrinogen, immunoglobulins, lipids (lipoproteins), hormones, vitamins & salts
  90. serum
    • NO anticoagulant
    • blood left to clot
    • a protein-rich fluid lacking fibrinogen but containing albumin, immunoglobulins, & other components
    • plasma LACKING fibrinogen
  91. clot
    • combination of soluble proteins that become insoluble under certain conditions
    • formed elements trapped in fibrin
    • a fibrin-containing network trapping blood cells
  92. composition of blood plasma
    • 90% water
    • 8% protein (albumin, globulin, fibrinogen)
    • 2% other solutes (electrolytes, nutrients, blood gases, etc.)
  93. formed elements
    • erythrocytes
    • leukocytes (agranulocytes & granulocytes)
    • platelets
  94. cell counts: formed elements
    • total erythrocyte count
    • total leukocyte count
    • differential leukocyte count
  95. total leukocyte count
    • normal distribution of cells - 5000 to 9000/mm3
    • number increases with infection (>10,000)
  96. differential leukocyte count
    • 5 identified types of WBCs
    • unique function in each individual case
    • numbers/changes in numbers compared to normal distribution
    • neutrophils: indicate bacterial infections
    • eosinophils: indicate parasitic/skin infections; long term chronic infection
  97. erythrocytes
    • red blood cells
    • anucleated
    • specialized for oxygen transport
    • terminally differentiated cell
    • 120 day life span
    • replenished via hemopoiesis (blood cell production)
  98. rouloux
    scanning electron micrograph of stack of RBCs
  99. composition of erythrocytes
    • 66% water
    • 33% hemoglobin
    • 1% lipids (carbohydrates & other proteins)
  100. hemoglobin
    • each molecule is composed of 4 protein subunits (2 pairs of identical subunits)
    • subunits consist of 4 main types of chains - alpha, beta, gamma, delta
    • each subunit has a heme molecule
    • trapped within heme is iron molecule (chelating agent)
    • when oxygen is trapped on heme, iron turns red
  101. types of hemoglobin in normal adults
    • HbA: 96% (2 alpha, 2 beta chains)
    • HbA2: 2% (2 alpha, 2 delta chains)
    • HbF: 2% (2 alpha, 2 gamma chains)
  102. horseshoe crab
    • Limulus polyphemus
    • has NO IRON in blood
    • copper is chelating agent
    • blood is blue/green
  103. sickle cell anemia
    • position 6 on beta chain of hemoglobin has valine substituted for glutamic acid
    • HbS: 2 alpha chains & 2 altered beta chains
    • altered cell shape at low oxygen concentrations
    • RBCs only last 30-40 days in circulation
  104. fixative
    cross linking molecule prevents further breakdown of tissue sample
  105. tissue section
    • removal of water from tissue to use stain (soluble in organic solvents)
    • tends to shrink tissue
  106. microcyte
    RBC of less than 6um
  107. macrocyte
    RBC of greater than 9um
  108. erythrocyte morphology
    • ~8um diameter
    • deformable, biconcave disc
    • shape add 20-30% surface area
    • total RBC surface area = 2000X exterior body area
    • decreases diffusion distance for oxygen
  109. hemolysis
    rupture of erythrocyte membrane caused by hypotonicity of plasma (injection of water into cells) or hemolytic agents
  110. crenation
    • "spiky or spiny" appearance
    • results from change/decrease in ATP concentration or fatty acid content
    • NOT caused by hypertonicity of plasma
  111. surface antigens & blood typing
    • ABO blood group: A, B, AB, O
    • Rh blood group: Rh (D+) or Rh (D-)
  112. erythroblastosis fetalis
    • Rh (D+) mom develops antibodies against Rh (D-) baby
    • anti-D immunoglobins
  113. spectrin
    • surface antigen that lies on inside of RBC plasma membrane
    • accessory protein for actin
    • provides internal bracing for RBC membrane ("chain link fence")
    • deficiencies/defects cause deleterious RBC morphological alterations (hereditary ellipsocytosis or spherocytosis)
  114. ankyrin
    • links IM protein band 3 to network of spectrin molecules
    • anchor
  115. band 3
    • faciliates carbon dioxide exchanges
    • anion transporter channel
  116. glycophorin
    • anion transporter
    • major transmembrane protein exposed on outer surface of RBC
  117. anisocytosis
    • any change in RBC size
  118. poikilocytosis
    change in RBC shape
  119. hypochromia
    decrease in hemoglobin content
  120. hyperchromia
    increase in hemoglobin content
  121. anemia
    • decrease in hemoglobin content that results in inadequate oxygen provision to tissues
    • primary anemia: RBC count down
    • secondary anemia: RBC count constant, [Hb] down
    • macrocytic anemia: RBC count down, RBC size up
    • sickle cell anemia: change in Hb type, altered RBC shape (sickle)
    • hereditary ellipsocytosis: RBC shape altered (elipse)
    • hereditary spherocytosis: RBC shape altered (ball)
  122. agranulocytes
    • lymphocytes & monocytes
    • DO have primary granules (lysosomes)
  123. granulocytes
    • neutrophils, eosinophils, & basophils
    • collectively referred to as microphages
    • categorized via staining characteristics of secondary (specific) granules
    • terminally differentiated
    • non-mitotic
    • heterochromatic nuclei
  124. leukocytes
    • white blood cells
    • all terminally differentiated in peripheral blood
    • non-mitotic
    • nucleated
    • NO hemoglobin
    • arise, function & die within CT
    • divided into agranulocytes & granulocytes
  125. leukocytosis
    pathological increase in WBCs
  126. leukopenia
    pathological decrease in WBCs
  127. lymphocytes
    • agranulocyte
    • circulating immunocompetent cells
    • small lymphocytes: 6-8um; 90% of LMCs
    • large lymphocytes: 18um in CT
    • comprise 30% of circulating WBCs
    • circulate in blood ~8 hrs, go to CT sites & recirculate
    • exposure to antigens stimulates mitosis
    • produce effector & memory cells
  128. lymphocyte morphology
    • spherical, heterochromatic nucleus
    • cytoplasm - basophilic
    • usually have a few primary granules
  129. B lymphocyte
    • 15% of circulating lymphocytes
    • variable life span
    • responsible for humoral immune response
    • has immunoglobin receptors in membrane
    • differentiates into plasma cell in CT
  130. T lymphocyte
    • 80% of circulating lymphocytes
    • responsible for cell mediated immunity
    • memory cells - long lived
    • effector cells
  131. monocyte morphology
    • 9-15um
    • indented, moderately heterochromatic nucleus
    • "foamy" nucleoplasm
    • vacuolar cytoplasm (less basophilic)
    • has primary granules (lysosomes)
  132. monocyte derivatives
    • macrophage: connective & lymphoid tissue
    • osteoclast: modified monocyte in bone
    • alveolar macrophage: lung; pick up dust
    • Kupffer cell: liver; move in & out of circulation
  133. monocyte function
    • bacterial phagocytosis
    • bacterial inactivation via respiratory burst activity
    • cytokine production to recruit helpers
    • antigen processing & presentation
    • foreign body giant cell formation
  134. neutrophils
    • 60-70% of circulating WBCs (most prevalent)
    • 8 hrs in circulation, days in CT
    • polymorphonuclear: lobed nucleus
    • Barr body: female; extra X chromosome
    • Stab form: immature neutrophil indicating severe infection
  135. cytoplasmic granules
    • primary: azure; lysosomes (contain peroxidase, acid phosphatase); develop first, work last; clean up
    • secondary: specific; contain antimicrobial agents (lysozome, alkaline phosphatase, bactericides, opsonins); kill bacteria
    • tertiary: specific; contain gelatinase & plasmalemma glycoproteins; facilitate contact with & phagocytosis of bacteria; destroy membranes
  136. inflammation: sequence of events
    • release of contents of tertiary granules
    • digestion of basal lamina, priming of secondary granules
    • release of antimicrobial agents from secondary granules
    • phagocytosis, fusion of endosome with primary granules
    • form reactive compounds (superoxide, peroxide); respiratory burst activity
    • leukotrine synthesis (recruitment)
  137. inflammation: sequence of participating cells
    • neutrophils
    • monocytes
    • fibroblasts
    • basophils, eosinophils & lymphocytes (accumulate in chronic inflammatory reactions)
  138. eosinophil
    • 2-4% of circulating WBCs
    • 10-14um
    • bilobed nucleus
    • eosinophilic cytoplasmic granules
  139. granules of eosinophils
    • primary granules: azure
    • specific granules: acidophilic (RED)
    • major basic protein: active in antiparasitic functions
    • lysosomal enzymes
    • histaminases: antihistamine, counteracts basophil histamine
    • aryl sulfatase: counteracts slow reacting substance of anaphylaxis (from basophils)
  140. eosinophil functions
    • increased in allergic reactions, parasitic & skin infections
    • diurnal rhythm
    • good at phagocytizing antigen-antibody complexes
    • inefficient at bacterial phagocytosis
    • respond chemotactically to basophils & mast cells
    • counteract effects of basophil & mast cell degranulation
  141. basophils
    • 0.5-1% of circulating WBCs - RARE
    • related functionally to mast cells
    • 8-10um in diameter
    • lobed nucleus - can be hidden by dark granules
  142. basophil granules
    • primary (azure)
    • basophilic specific granules due to heparan sulfate content
    • hydrolytic enzymes
    • histamine: vasodilator, increases vascular permeability
    • slow reacting substance: anaphylaxis (also vasodilator)
    • eosinophil & neutrophil chemotactic factors
  143. basophil functions
    • degranulation
    • Fc portion of IgE binds to membrane IgE receptor on mast cells & basophils (sensitization)
    • on re-exposure, antigen binds bound IgE
    • results in mast cell & basophil degranulation
    • release of leukotrines & vasoactive substances counteracted by eosinophils
  144. asthma
    localized response of some vasoconstriction
  145. anaphylaxis
    systemic response, global vasoconstriction
  146. platelets
    • circulation time is 10 days
    • cell fragments derived from megakaryocyte
    • biconvex disc
    • granulomere & hyalomere
  147. hyalomere
    • peripheral region
    • contains microtubules for shape maintenance
    • microfilaments for clot contraction
  148. granulomere
    • central region; granules & membranous organelles
    • alpha fibrinogen, clotting factors
    • gamma ADP, ATP, serotonin, histamine - facilitate adhesion
    • lambda  hydrolytic enzymes - function in clot resorption
    • dense tubular system: similar to sER, sequesters calcium
    • surface connected open canalicular system receives active components
  149. platelet function
    • degranulation: occurs on contact with collagen
    • conversion of thromboplastin - prothrombin - thrombin
    • thrombin catalyzes the conversion of fibrinogen to fibrin
    • involved in clotting reaction
    • white thrombus: platelets only
    • red thrombus: platelets + fibrin
  150. types of hemopoiesis
    • general classification for all blood cell development
    • erythropoiesis:  erythrocyte development
    • leukopoiesis: granulopoiesis & lymphopoiesis
    • granulopoiesis: granulocyte development
    • lymphopoiesis: lymphocyte development
    • thrombopoiesis: platelet development
  151. phases of hemopoietic development
    • Yolk sac phase
    • liver phase
    • splenic phase (concurrent with liver phase)
    • adult phase
  152. yolk sac phase of hemopoiesis
    • 0-12 weeks
    • cells from embryonic mesoderm (blood islands)
    • seeds numerous colony forming units (CFUs)
    • erythrocytes nucleated
  153. liver phase of hemopoiesis
    • 4 weeks - 9 months
    • liver hemopoietic
    • produces nucleated RBCs
  154. splenic phase of hemopoiesis
    • 3-7 months
    • concurrent with liver phase
    • spleen hemopoietic
    • lymphopoiesis continues postnatally
  155. adult phase of hemopoiesis
    • 4 months - adult
    • primarily bone marrow performs hemopoiesis
  156. adult hemopoietic loci
    • myeloid tissue: tissue supporting RBC & WBC development (marrow)
    • lymphoid tissue: tissue supporting lymphocyte development (lymphoid organs - ex. thymus, gut associated lymphatic tissue, lymph nodes)
  157. hemopoietic theory
    • monophyletic / unitarian theory
    • all blood cells arise from common stem cell (hemopoieic stem cell/HSC)
  158. CFU
    • colony forming unit
    • hemocytoblast: cells capable of mitosis
    • derived from mesenchymal reticular tissue
    • potency variable
    • small lymphocyte-like cell
    • produces more differentiated stem cells responsive to different stimuli
  159. potency
    • potential of what a given cell can differentiate into
    • greater potency = greater number of potential developmental outcomes
    • potency decreases as cells become more differentiated (also mitotic ability decreases)
  160. overview of hemopoiesis stem cells
    • hematopoietic/pluripotent stem cell: from which all other blood cell types are derived
    • multipotential hematopoietic stem cell: myeloid; found in bone marrow & lymphatic tissues
    • progenitor cells: unipotential & self renewing; CFU
    • precursor cell: unipotential; not self renewing
    • mature blood cell
  161. colony stimulating factors
    • erythropoietin
    • granulocyte-monocyte colony stimulating factor (GM-CSF)
    • granulocyte colony stimulating factor (G-CSF)
    • monocyte colony stimulating factor (M-CSF)
  162. erythropoietin
    • produced in interstitium of kidney
    • hormone that stimulates production of CFU cells that give rise to RBCs
  163. GM-CSF
    • granulocyte-macrophage colony stimulating factor
    • source: T cells, endothelial cells, fibroblasts
    • target: CMP, ErP, GMP, EoP, BaP, MKP, all granulocytes, erthryocytes
  164. G-CSF
    • granulocyte colony stimulating factor
    • source: endothelial cells, monocytes
    • target: ErP, GMP, EoP, BaP, MKP
  165. M-CSF
    • monocyte colony stimulating factor
    • source: monocytes, macrophages, endothelial and adventitial cells
    • target: GMP, MoP, monocytes, macrophages, osteoclasts
  166. EPO
    • erythropoietin
    • source: kidney, liver
    • target: CMP, MEP, ErP
  167. TPO
    • thrombopoietin
    • source: bone marrow
    • target: MKP, megakaryocytes
  168. site of normal adult hemopoiesis
    • medullary cavities of bone
    • red marrow: hemopoietically active
    • yellow marrow: reduced hemopoietic activity; adipocytes dominate
  169. marrow: connective tissues
    • stroma & free blood cells
    • fibers: collagen & reticular fibers; some elastin
    • fixed cells: fibroblasts, reticular cells, macrophages, adipocytes, osteoblasts, endothelial cells, etc.
    • transient cells: developing blood cells in interstices of fixed cells & fibers
  170. life cycle of a granulocyte
    • development time - 14 days
    • 6-10 hrs in circulation
    • 1-2 days in connective tissue
    • granulocytes more numerous than erythrocytes in marrow (shorter life span, longer developmental time)
  171. decreased peripheral white count causes:
    • increased WBC release from marrow
    • increased differentiation of WBCs from specific CFUs
  172. common changes in granulopoiesis
    • decrease in cell size & cytoplasmic basophilia
    • increase in nuclear heterochromatiin & specific granule content
    • increase in deformability & adhesiveness (sticky)
    • increase in phagocytic activity & motility
  173. common terminology of granulopoiesis
    • myeloblast
    • promyelocyte
    • myelocyte
    • metamyelocyte
    • mature granulocyte
  174. microcytotic anemia
    lack of iron
  175. pernicious anemia
    lack of vitamin B12
  176. substances that induce erythropoiesis
    • iron
    • vitamin B12
  177. regulation of erythropoiesis
    • feedback loop
    • increased peripheral RBC count decreases erythropoietin synthesis
  178. hypoxia
    decrease of oxygen in periphery/tissue increases production of erythropoietin (which increased CFU-E production to stimulate RBC production
  179. monocytopoiesis developmental sequence
    • granulocyte/monocyte progenitor
    • monocyte progenitor
    • monocyte
    • macrophage in lung, liver, bone or loose CT
  180. results of lymphopoiesis
    • NK cell: cell mediated immunity
    • T cell: cell mediated immunity
    • B cell/ plasma cell: humoral immunity
  181. erythropoiesis developmental sequence
    • proerythroblast
    • basophilic erythroblast
    • polychromatophilic erythroblast
    • orthochromatophilic erythroblast
    • polychromatophilic erythrocyte/ reticulocyte
    • erythrocyte
  182. thrombopoiesis developmental sequence
    • megakaryocyte/erythrocyte progenitor
    • megakaryocyte progenitor
    • megakaryoblast
    • megakaryocyte (stays in marrow)
    • platelets
  183. megakaryocytes
    • largest cells in marrow
    • lobed polyploid nucleus (32-64N generated by endomitosis)
    • demarcation channels form in cytoplasm to define platelet boundaries
    • cytoplasm protrudes into marrow channels & sheds platelets
  184. autoimmune disorders
    • Lupus erythematosus: targets healthy cells of all body systems
    • Hemolytic anemia: targets healthy RBCs
    • Diabetes mellitus Type I: targets healthy beta cells of pancreas
    • Hasimoto's thyroiditis: targets thryoid follicles
  185. lymphatic system
    • group of cells, tissues, & organs that monitor body surfaces & internal fluid compartments
    • react to potentially harmful substances
    • lymphocyte: definitive cell of lymphatic system
  186. components of lymphatic system
    • lymphocytes
    • bone marrow
    • diffuse lymphatic tissue (MALT)
    • thymus
    • lymphatic nodules
    • lymph nodes
    • spleen
    • tonsils
  187. primary lymphatic organs
    • bone marrow
    • diffuse lymphatic tissue (MALT)
    • thymus
    • site of antigen-independent proliferation & differentiation of immunicompetent cells ready to enter circulation
  188. secondary lymphatic organs
    • lymphatic nodules
    • lymph nodes
    • spleen
    • tonsils
    • site of antigen-dependent activation of effector lymphocytes & memory cells
  189. function of lymphatic system
    lymphocytes process antigens and decide whether or not to mount an immune response
  190. innate immunity
    • nonspecific
    • physical barriers prevent entry of pathogens (skin)
    • chemical defenses destroy pathogens (low pH of stomach)
    • secretory substances neutralize pathogens (lysozymes of saliva)
    • phagocytic cells eliminate pathogens (macrophages)
  191. adaptive immunity
    • specific: directed response towards specific invaders
    • activation of immune effector cells results in immune "memory"
    • humoral response: secretion of antibodies and subsequent destruction by immune cells
    • cellular immune response: direct destruction of transformed cells by immune cells
  192. lymphocytes
    • T cells: T lymphocytes
    • B cells: B lymphocytes
    • NK cells: natural killer lymphocytes
  193. CD markers
    • cluster of differentiation markers
    • unique cell surface molecules used to identify hematopoietic cells
    • CD4 & CD8
  194. supporting cells of the lymphatic system
    • reticular cells
    • monocytes
    • granulocytes - basophils & eosinophils
    • macrophages
    • dendritic cells
    • follicular dendritic cells
    • Langerhans' cells - middle layer of epidermis
    • epithelioreticular cells - thymus
  195. function of lymphocytes
    • immunosurveillance
    • immune response
  196. circulating lymphocytes
    • 70% of lymphocytes
    • long lived
    • mature
    • immunocompetent
    • constantly in motion
    • hop out, check tissue, hop back in
  197. non-circulating lymphocytes
    • short lived
    • migrate directly to tissue
    • immature cells that have been activated/recruited
    • complete their job then undergo apoptosis
  198. T cells
    • named for thymus, site of differentiation and "education"
    • long lifespand
    • 60-80% of circulating lymphocytes
    • involved in cell-mediaetd immunity
    • express T cell receptors - either CD4+ or CD8+
  199. helper T cells
    • express CD4
    • subclassed based on secretion of cytokines
    • TH1 or TH2 cells
  200. interleukins
    particular type of cytokine
  201. function of cytokines
    • affect function of lymphocytes & leukocytes
    • autocrine: act on cell of origin
    • paracrine: act on neighboring cells
    • mimic hormones
  202. TH1 cells
    • helper CD4+ T lymphocytes
    • secrete IL-2, IFN-gamma, & TNF-alpha
    • interact with cytotoxic CD8+ T cells, NK cells & macrophages
    • cell-mediated immune response activated by intracellular pathogens 
  203. TH2 cells
    • helper CD4+ T lymphocytes
    • secrete IL-4, IL-5, IL-10, & IL-13
    • interact with B lymphocytes
    • antibody mediated immune response activated by extracellular pathogens
  204. cytotoxic T cells
    • express CD8
    • kill target cells (virus infected, bacterial infected, cancer cells, & transplanted cells) by releasing perforins to degrade target cell membrane
  205. suppressor T cells
    • originate in thymus
    • downregulate immune response to foreign & self-antigen
    • suppress proliferation of T cells & B cells
    • suppress antibody production
    • inhibit cell-mediated response of T lymphocytes
    • Rx: autoimmune disorders & transplant patients
  206. gamma/delta T lymphocytes
    • express ONLY T lymphocyte receptor
    • neither CD4 or CD8
    • develop in thymus
    • migrate to epithelial tissue & remain there
    • first line of defense: attack antigens before they enter the body
  207. B cells
    • named for bursa of Fabricus (bone marrow & MALT equivalent)
    • variable lifespan based on function
    • 20-30% of circulating lymphocytes
    • produce & secrete immunoglobulins
    • associated with humoral immunity
    • express B cell receptors: membrane bound immunoglobulins
    • express MHC II
  208. B cell receptors
    • IgM: immature B cells
    • IgD: mature B cells
  209. NK cells
    • named for ability to kill certain targets
    • 5-10% of circulating lymphocytes
    • do NOT mature in thymus
    • recognize transformed cells (virus, cancer, etc.)
    • release perforins & granzymes (like cytotoxic T cells)
  210. primary specific immune response
    • first contact with particular antigen
    • lag in response time
    • lack of circulating B lymphocytes able to response initially
    • subsequently, greater number of "memory B cells" remain in circulation for more rapid response
  211. secondary specific immune response
    • more rapid response
    • due to presence of "memory cells"
    • basis for immunization & hypersensitivity reactions
  212. immunization
    Even dead viruses cause immune reaction to allow B cells to develop memory cells
  213. hypersensitivity reactions
    • antibody mediated discharge of histamines from mast cells organism-wide
    • eosinophils neutralize effects
  214. humoral immunity
    mediated by antibodies produced by B lymphocytes or plasma cells
  215. cell-mediated immunity
    • mediated T lymphocytes
    • protects against transformed and foreign cells
  216. MHC
    • major histocompatability complex
    • transmembrane proteins
    • display short peptides on surface of cell (bound internally then transported to surface)
    • MHC I & II
  217. MHC I
    • on surface of all nucleated cells & platelets (NOT RBCs)
    • display fragments of all peptides actively synthesized in cell
    • allow for elimination of abnormal host cells
    • recognition of exogenous vs. endogenous cells
    • present peptides to cytotoxic T cells (MHC I restricted)
  218. MHC II
    • only on surface of antigen presenting cells
    • display fragments of endocytosed foreing peptides
    • present peptides to helper T  cells (MHC II restricted)
  219. antigen presenting cells
    • macrophages
    • Kupffer cells - perisinusoidal macrophages of liver
    • dendritic cells
    • Langerhans' cells
    • B lymphocytes
    • type II & III epithelioreticular cells - thymus
  220. lymphatic vessels
    • means of passage back to blood for cells and large molecules from tissue spaces
    • more permeable walls than blood capillaries
    • blind capillaries in loose CT (epithelium of skin & mucous membranes)
    • pass lymph through lymph nodes for entrapment, inspection & possible initiation of response
  221. movement of lymph & lymphocytes
    • lymphocytes move from one part of the body to the other
    • via afferent lymphatics to node
    • via efferent lymphatics from node ultimately to right lymphatic trunk or thoracic duct
    • via blod to node through high endothelial venules (postcapillary venules)
  222. diffuse lymphatic tissue
    • NOT enclosed by a capsule
    • MALT: alimentary canal (GALT) or bronchial tree (BALT)
    • contain large numbers of plasma cells & eosinophils
    • found in subepithelial tissue (lamina propria)
    • after contact with antigens, lymphocytes migrate to lymph nodes, undergo proliferation & differentiation, return as effector T and B cells
  223. lymphatic nodules
    • localized concentrations of non-encapsulated lymphocytes within a reticular meshwork
    • found in same areas as diffuse lymphatic tissue (subepithelial MALT)
    • lack afferent vessels
    • primary or secondary nodules
  224. primary lymphatic nodules
    • uniform staining nodule without germinal center
    • RARE
  225. secondary lymphatic nodules
    • germinal center
    • mantle zone (corona)
  226. germinal center
    • sign of lymphatic tissue response
    • contains activated lymphocytes and follicular dendritic cells
    • lighter staining - presence of lymphoblasts
    • highly mitotic
  227. lymphoblasts
    large immature lymphocytes
  228. mantle zone
    contains small lymphocytes
  229. aggregations ot lymphatic nodules
    • palatine tonsils
    • pharyngeal tonsils (adenoids)
    • lingual tonsils
    • Peyer's patches - ilium
    • vermiform appendix
  230. palatine tonsil features
    • tonsilar crypts
    • non-keratinized stratified squamous epithelium
    • incomplete CT capsule
    • secondary lymphatic nodules
  231. pharyngeal tonsils
    • adenoids
    • surface folds
    • pseudostratified columnar epithelium
    • lymphatic nodules
  232. lingual tonsils
    • skeletal muscle of tongue visible
    • non-keratinized stratified squamous epithelium
    • crypts
  233. Peyer's patches
    • collection of B & T lymphocyte rich nodule
    • in ileum
    • may also find solitary lymphatic nodules along rest of small & large intestine
  234. vermiform appendix
    • non-encapsulated lymphatic nodules
    • lamina propria infiltrated by nodules & lymphocytes
    • may be functionally associated with bursa of Fabricius (equivalent organs - bone marrow & MALT)
    • amount of lymphatic tissue decrease with age
  235. lymph nodes
    • small bean shaped organs
    • present along lymphatic vessels everywhere in body (esp. axilla, groin, messenteries)
  236. lymphatic vessel connection of lymph nodes
    • afferent lymphatic vessels: transport lymph to node & can enter anywhere of the convex surface
    • efferent lymphatic vessels: transport lymph away from node & exit at hilum
  237. lymph node supporting elements
    • capsule: dense connective tissue surrounding the node
    • trabeculae: dense CT extending into the node
    • reticular tissue: supporting meshwork throughout the node mainly composed of reticular cells & fibers
  238. reticular cells
    • indistinguishable from normal fibroblast
    • produce type III collagen - forms reticular fibers
    • have elongated cytoplasmic processes that wrap around the reticular fibers (isolate them from lymphocytes)
    • attract B cells, T cells & dendritic cells
  239. supporting cells within reticular meshwork of lymph nodes
    • dendritic cells
    • macrophages
    • follicular dendritic cells
  240. dendritic cells
    • bone marrow derived
    • antigen presenting cells
    • monitor local environment for foreign substances
    • have very high levels of MHC II
    • very efficient antigen presentation to T cells
  241. macrophages within reticular meshwork
    • phagocytic
    • antigen presenting cells
    • express MHC I & II
    • not as efficient antigen presentation to T cells
  242. follicular dendritic cells
    • multiple thin cytoplasmic processes that express Fc receptors
    • bind antibody-antigen complexes: retain these complexes on the surface for long time
    • are NOT antigen presenting cells
    • lack MHC II molecules
  243. lymph node structure
    • cortex: outer portion of the node (exception - hilum)
    • medulla: inner part of node
    • lymphatic channels: sinuses
    • high endothelial venules: postcapillary venules
  244. cortex of lymph node
    • outer portion of the node (exception - hilum)
    • dense mass of lymphatic tissue, lymphatic sinuses & lymph channels
    • superficial cortex: contains primary & secondary lymph nodules
    • deep cortex: free of nodules, rich in T cells
  245. superficial cortex of lymph nodes
    • nodular
    • contains primary & secondary lymphatic nodules
  246. deep cortex of lymph node
    • paracortex
    • thymus-dependent cortex
    • free of nodules
    • rich in T cells
  247. medulla
    • inner part of the node
    • consists of cords of lymphatic tissue, reticular cells & fibers and lymphocytes (mainly B), macrophages, dendritic cells & plasma cells
  248. lymphatic channels
    • supscapular (cortical) sinus: afferent lymphatic vessel drainage
    • trabecular sinus: originate from subscapular sinus & connect to medullary sinus
    • medullary sinus
    • continuous endothelium adjacent to connective tissue
    • discontinuous epithelium close to lymphatic parenchyma (not an open space)
    • often contain pseudopods from macrophages to monitor lymph
  249. high endothelial venules
    • postcapillary venules lined by cuboidal or columnar epithelial cells in the deep cortex
    • 90% of lymphocytes enter node - special receptos for antigen primed lymphocytes
    • diapedesis: cause B & T cells to leave
    • concentrate lymph through fluid & electrolyte gradients
  250. thymus
    • bilobed organ of superior mediastinum
    • from 3/4th pharyngeal pouch
    • derived from endoderm & mesenchymal mesoderm
    • fully formed at birth - remains large until puberty
    • gradually replaced by fat
  251. structure of thymus
    • CT capsule & trabeculae
    • thymic cortex
    • thymic medulla
    • blood vessels
  252. thymic CT capsule & trabeculae
    • fibroblasts & collagen fibers
    • plasma cels, lymphocytes, mast cells, adipose cells & macrophages
    • blood vessels, efferent lymphatic vessels & nerves
    • from thymic lobes - cortical caps over inner medullary tissue
  253. thymic cortex
    • basophilic
    • thymocytes: T lymphocytes
    • macrophages: phagocytose all the T cells that fail thymic education
    • epithelioreticular cells: type I, II, III
  254. thymic medulla
    • large lymphocytes
    • epithelioreticular cells: type IV, V, VI
  255. blood vessels of thymus
    • enter from the deeper part of the trabeculae
    • carry a perivascular CT sheath containing reticular fibers, fibroblasts, macrophages, plasma cells
  256. epithelioreticular cells
    • provide the framework for the developing T cells
    • similar function to reticular cells & reticular fibers (NOT found in thymus)
    • have characteristics of epithelia (intercellular junctions, intermediate filaments)
    • 6 types
  257. type I epithelioreticular cells
    • located at boundary of cortex & capsule or trabeculae or blood vessel
    • tight junction: border between the thymic parenchyma & CT
    • prevents developing T cells to move into the CT
    • do NOT express MHC II
  258. type II epithelioreticular cell
    • located within the thymic cortex
    • connect to other type II cells via desmosomes
    • rich in intermediate filaments
    • compartmentalize thymic cortex
    • express MHC I & II
  259. type III epithelioreticular cell
    • located at the border of the cortex & medulla
    • form a functional barrier between cortex & medulla
    • express MHC I & II
  260. type IV epithelioreticular cell
    • located at the border of the cortex & medulla
    • form a functional barrier between cortex & medulla (with type III)
  261. type V epithelioreticular cell
    • located within thymic medulla
    • connect to other type V cells over desmosomes
    • compartmentalize thymic medulla
  262. type VI epithelioreticular cell
    form Hassall's corpuscle
  263. Hassall's corpuscle
    • most characteristic feature of the thymus
    • isolated mass of concentrically arranged type VI cells
    • contains keratinhyalin granules, intermediate filaments & lipid droplets
    • center can contain keratin
  264. T cell education
    • multipotent lymphatic stem cell migrates to thymic cortex
    • maturation: expression of T cell receptors, CD4 or CD8
    • positive selection: exposed to type II & III epithelioreticular cells; must recognize MHC complexes or undergo apoptosis
    • surviving cells migrate to thymic medulla
    • negative selection: exposed to type V epithelioreticular cell and self MHC complexes; survive if NO immune response is shown
    • leave thymus as helper T cells (CD4+) or cytotoxic T cells (CD8+)
  265. blood-thymus barrier
    • protects lymphocytes from exposure to antigens
    • endothelium: major structural component; highly impermeable occluding junctions; basal lamina & pericytes
    • macrophages: catch the antigenic molecules escaping the parenchyma
    • type I epithelioreticular cells: occluding junctions & basal lamina
  266. spleen
    • largest lymphatic organ (fist size)
    • found in upper left quadrant of the abdominal cavity
    • filters blood & lymph
    • white pulp: immune system functions
    • red pulp: hematopoietic functions
    • "nonessential" organ
  267. immune system function of spleen
    • antigen presentation by dendritic cells & macrophages
    • activation & proliferation of B & T cells
    • production of antibodies against antigens in blood
    • removal of macromolecular antigens from blood
  268. hematopoietic function of spleen
    • removal & destruction of old/damaged/abnormal RBCs and platelets
    • retrieval of iron from hemoglobin
    • formation of RBCs during early fetal life
    • blood storage (NOT in humans)
  269. structure of spleen
    • capsule: dense CT
    • trabeculae: dense CT extending into parenchyma of spleen
    • myofibroblasts: contractile cell that produces CT fibers
    • hilum: site where splenic artery & vein, nerves & lymphatic vessels enter
    • splenic pulp: white & red based on functions
  270. splenic white pulp
    • consist of mostly lymphocytes
    • branches of the splenic artery enter the white pulp (central artery)
    • lymphocytes accumulate around central artery forming the periarterial lymphatic sheath
    • contain mostly B cells in nodule
    • T cells in area surrounding the nodule
  271. splenic red pulp
    • contains large number of RBCs
    • splenic sinuses
    • splenic cords (of Billroth) - connect splenic sinuses
  272. splenic sinuses
    • lined by very long endothelial cells
    • few contact points between the cells
    • no continuous basal lamina - wrap around endothelial cells
    • large intercellular spaces allow RBCs to pass through
  273. splenic cords
    • cords of Billroth
    • connect splenic sinuses
    • consist of loose network of reticular cells & fibers
    • contain RBCs, macrophages, lymphocytes, dendritic cells, plasma cells & granulocytes
  274. open splenic circulation
    • splenic atery enters into white pulp via the trabeculae
    • sends branches into white pulp & sinuses at perimeter (marginal sinuses)
    • splenic artery continues into red pulp
    • branches into penicillar arterioles
    • continue as arterial capillaries (sheathed by macrophages)
    • empty into reticular meshwork of splenic cords
    • blood cells re-enter circulation via splenic sinuses
    • leave spleen via trabecular veins & ultimately splenic vein
  275. development of the eye
    • optic vesicle: invagination of neuroectoderm
    • optic vesicle induces surface ectoderm to thicken and form lens placode
    • optic cup develops two layers
    • outer layer of optic cup: nonneural retina (pigmented cells)
    • inner layer of optic cup: neural retina (retinal cells)
  276. basic layers of the eye
    • corneoscleral coat: cornea & sclera
    • uvea: iris, ciliary body, choroid & lens
    • retina: fovea centralis with macula lutea & optic disc
  277. corneoscleral coat
    • outer fibrous layer, mostly connective tissue
    • sclera: posterior 5/6 of covering of the eye (white)
    • cornea: transparent anterior covering of 1/6 of eye
  278. ora serrata
    point of transition from nonvisual part of retina to visual part of retina
  279. uvea
    • choroid: highly pigmented, vascular layer
    • ciliary body: ring shaped swelling responsible for accomodation of lens
    • iris: controls light
    • lens
  280. chambers of the eye
    • anterior chamber: anterior to iris, posterior to cornea, communicates with posterior chamber
    • posterior chamber: small space behind iris, naterior to lens
    • vitreous chamber: space between posterior surface of the lens & neural retina
  281. aqueous humor
    isotonic protein-filled fluid that flows between anterior & posterior chamber
  282. vitreous humor
    • gelatinous media that fills vitreous chamber
    • high in hyaluronic acid & collagen
  283. function of cornea
    bends light to focus on lens
  284. layers of cornea
    • corneal epithelium: nonkeratinized stratified squamous; innervated by unmyelinated V1 free nerve endings; will regenerated
    • Bowman's membrane: where epithelium rests, nonregenerative
    • corneal stroma: highly arranged perpendicular collagen fibers; transparent; contains myelinated nerves of V1
    • Descemet's membrane: supports corneal endothelium; robust regeneration
    • corneal endothelium: simple squamous; nonregenerative; mediates metabolic activity of cornea (hydration)
  285. corneoscleral limbus
    • point of transition from cornea to sclera
    • corneal epithelium thicks & provides a source of stem cells (regenerative properties of corneal epithelium)
    • Bowman's membrane disappears
    • episcleral vessels appear
  286. layers of sclera
    • suprachoroid lamina (lamina fusca): closely associated with choroid
    • substantia propria (Tenon's capsule): most pronouced part; important in providing socket for prosthetic eyes
    • episcleral layer: close to fat
  287. drainage of aqueous humor
    • uvea: key for draingage
    • nonpigmented epithelium of ciliary processes produce aqueous humor
    • released into posterior chamber
    • drains to anterior chamber
    • drains to iridocorneal angle
    • filters into trabecular meshwork/ spaces of Fontana
    • drains into canal of Schlemm
    • empties into episcleral veins, then superior & inferior opthalmic veins
  288. ciliary channel
    • space between outer & inner layers of optic cup before fusion
    • separates pigmented & nonpigmented epithlial cells of ciliary processes
    • apical portions of cells are FACING EACH OTHER
    • basal lamina on OUTSIDE of nonpigmented epithelial cells anchors zonula fibers
  289. nonpigmented epithelium of ciliary processes
    • produces aqueous humor
    • basal portion of cells associated with zonula fibers (connect to lens)
  290. pigmented epithelial cells of ciliary processes
    associated with stroma of ciliary body (vasculature)
  291. glaucoma
    • blocked canal of Schlemm
    • increases intraocular pressure
    • can damage optic nerve
    • impedes flow of light through cornea
  292. parasympathetic stimulation of iris
    CONSTRICTS - constrictor pupillae m.
  293. sympathetic stimulation of iris
    DILATES - dilator pupillae m.
  294. constrictor pupillae m.
    • parasympathetic control of iris
    • shrink iris/ decrease pupil diameter
    • CN III carries preganglionic parasympathetic fibers
    • ciliary ganglion sends postganglionic parasympathetic fibers
  295. dilator pupillae m.
    • longitudinal muscle of iris
    • sympathetic control
    • dilates iris/ increase pupil diameter
    • preganglionic sympathetic fibers from IMLCC of T1-T5
    • superior cervical ganglion sends postganglionic sympathetic fibers (travels through long & short ciliary nerves)
  296. components of iris
    • constrictor pupillae m.
    • dilator pupillae m.
    • anterior pigmented myoepithelium
    • posterior pigment epithelium
    • stromal cells, fibroblasts, vasculature
  297. epithelium of iris
    • anterior pigmented myoepithelium: from outer layer of optic cup; some contractile properties associated with dilator pupillae m.
    • posterior pigmented epithelium: from inner layer of optic cup
  298. layers of lens
    • thick basal lamina (lens capsule): acts like basement membrane; where zonula fibers from ciliary processes insert
    • supscapular epithelium: simple cuboidal OR squamous arrangement; divides in germinal zone
    • lens fibers: at equatorial region, epithelial cells elongate & lose nucleus to become lens fibers
  299. lens fibers
    • specific cytoplasmic proteins filensin and crystallin
    • with aging - proteins accumulate & cloud or turn yellow
  300. cataract
    • aqeuous humor bathes lens & supplies nutrients to it under normal circumstances
    • inadequate nutrients cause lens to become opaque (formation of cataracts)
    • Rx - artificial lens
  301. function of ciliary body
    control shape of lens (accomodation)
  302. parts of ciliary body
    • largely smooth muscle - ciliary muscle (under parasympathetic control)
    • 3 indistinguishable layers
    • ciliary processes: nonpigmented & pigmented epithelium
    • ciliary epithelium communicate via gap junctions, held together tightly by desmosomes
  303. accomodation of lens: near vision
    • ciliary muscle contracts
    • ciliary body with inserted zonular fibers moves closer to lens
    • tension in zonular fibers reduced
    • lens relaxes/ becomes more round
  304. accomodation of lens: far vision
    • ciliary muscle relaxes
    • ciliary body moves away from lens
    • tension on zonular fibers increases
    • lens flattens
  305. layers of choroid
    • Bruch's membrane: separates chroid from retina
    • choriocapillaries: smallest capillary bed closest to retina
    • choroid: extensive vasculature, fibroblasts & immune cells, pigment cells, etc.
  306. Bruch's membrane
    • lamina vitrae
    • border of uvea (choroid) & retina
  307. age- related macular degeneration
    • accumulation of pigment between Bruch's membrane and RPE
    • may lead to retinal degeneration
  308. symptoms of macular degeneration of retina
    • thickening of Bruch's membrane
    • drusen - accumulation of pigment
    • atrophy of retina
    • depigmentation of retinal pigmented epithelium
    • obliteration of capillaries
    • ruptured blood vessels
  309. drusen
    • yellowish pigment that accumulates between Bruch's membrane & RPE
    • cause of macular degeneration & possible retinal detachment
  310. subdivisions of retina
    • non-neural retina: posterior pigmented cells of the iris & nonpigmented epithelial cells associated with the ciliary processes
    • neural retina: cells that actually detect the photons of light & transmit information to the brain
  311. layers of retina
    • retinal pigmented epithelium
    • layers of rods & cones
    • outer limiting membrane
    • outer nuclear layer
    • outer plexiform layer
    • inner nuclear layer
    • inner plexiform layer
    • ganglion cell layer
    • layer of optic nerve fibers
    • inner limiting membrane
  312. layer of rods & cones
    detect photons of light
  313. cones
    • minority photoreceptor type
    • lower sensitivity to light, higher acuity
    • 3 photopigments: red, green, blue
    • highest density towards fovea centralis
    • responsible for photopic or daytime vision
    • discs where photons reside are continuous with plasma membrane
  314. rods
    • predominant photoreceptor type
    • high sensitivity to light
    • 1 photopigment: grey
    • decreased density towards fovea centralis
    • associated with scotopic vision (nighttime/low light)
    • associated with peripheral vision
    • discs that hold photopigments are enclosed within a membrane separate from the plasma membrane
  315. cone photopigments
    • red-sensitive:  ~560 nm
    • green-senstive:  ~530 nm
    • blue-sensitive: ~420nm
  316. visual pigments
    • opsin + Vitamin A chromophore
    • cones: iodopsin
    • rods: rhodopsin (scotopsin + retinal)
  317. color blindness
    • inability to distinguish the differences between certain colors
    • results from absence of color-sensitive pigment in the cone cells of the retina
    • most problems are inherited & present at birth
    • red-green color blindness: most common type; red & green seen as same color
  318. bipolar cells
    • receive input from photoreceptors
    • 3 rod photoreceptors to 1 bipolar cell
    • 1 cone photoreceptor to 1 bipolar cell
    • leads to higher acuity in cone
  319. Muller's cells
    • form the scaffolding for the retina; span nearly the entire length
    • outer limiting membrane: apical end of cell
    • inner limiting membrane: basal end of cell
  320. retinal support cells
    • horizontal cells: modulate signals between bipolar & photoreceptors
    • amacrine cells: module signals between bipolar cells & ganglion cells
    • inner plexiform cells: send signals from inner plexiform layer to outer plexiform layer
  321. specialized areas of the retina
    • fovea centralis: high concentration of cones for visual acuity; tilted outer layers permit light to reach photoreceptors directly
    • macula lutea: around fovea
    • optic disc: blind spot
  322. layers of fovea centralis
    • RPE
    • layer of cones ONLY
    • outer nuclear layer
    • outer plexiform layer
    • NO inner retinal layers
  323. optic disc
    • blind spot of eye: devoid of photoreceptors
    • central retinal artery: branch of opthalmic artery supplying retina
    • optic nerve fibers go back towards CNS through lamina cribosa (fenestrations in sclera)
  324. lamina cribosa
    • area of transition between retina & optic disc
    • sclera has fenestrations to allow axons to leave optic disc
  325. conjunctiva
    • bulbar & palpebral parts
    • both parts have stratified columnar epithelium with goblet cells
  326. structures of eyelid
    • conjunctiva
    • orbicularis oculi m.
    • levator palpebrae superioris m.
    • tarsal glands
    • sebaceous glands
    • apocrine glands
    • accessory lacrimal glands
    • eyelash
  327. tarsal/meibomian glands of eyelid
    • located within tarsal plate (CT of stroma)
    • pronounced duct system
    • secrete "oily" tear into eye
  328. sebaceous glands of eyelid
    • common sweat glands associated with eyelashes
    • similar morphology to tarsal/Meibomian glands
  329. apocrine glands of eyelid
    • large cavity
    • eosinophilic cell types
  330. accessory lacrimal glands
    • located on superior part of eyelid
    • basophilic cells with simple cuboidal arrangement
  331. integument
    • skin & derivatives
    • forms external covering of the body
    • largest organ of the body
    • constitutes 16-20% of total mass
  332. derivatives of integument
    • hair & nails
    • glands - sweat, sebaceous, mammary
    • variations found in animal world - NOT normally found in humans
  333. variations of integument in animal world
    • blubber
    • feathers, beaks, claws
    • quills
    • horns, dermal plates
    • horse hooves
    • skin folds
  334. functions of skin
    • protective barrier: pathogenic organisms, dessication/hydration, UV light (some chemicals can be absorbed)
    • regulation of body temperature: sweating through evaporation & insulation through vasoconstriction
    • excretory: sweat glands
    • sensory: brings information about external environment to individual
    • endocrine: converts precursor molecules into hormonally active molecules (ex. Vitamin D)
    • diagnostic information: color, patterning
    • dermatoglyphics: personal ID through fingerprints & footprints
  335. skin: diagnostic information
    • yellow: jaundice, liver problem
    • blue (cyanosis): respiration or circulatory distress
    • dry/cracked skin/ rashes: many different problems
  336. skin proper
    • epidermis
    • dermis
  337. epidermis
    • keratinized stratified squamous epithelium
    • ectodermal origin
    • avascular
  338. dermis
    • irregular fibroelastic CT
    • mesenchymal in origin
    • vascular
  339. hypodermis
    • subcutaenous CT - more loose than dermis
    • superficial fascia
    • contains variable amounts of adipose tissue
    • allows for mobility
    • epidermis invaginates into dermis & hypodermis
  340. thick skin
    • in areas of most abrasion
    • palm of hand, soles of feet, fingertips, toes
    • hairless
    • abundant sweat glands
    • thick keratinized layer - epidermis is thicker than thin skin
  341. where is skin thickest?
    upper portion of the back (thick dermis)
  342. layers of thin skin
    • stratum corneum
    • stratum granulosum
    • stratum spinosum
    • stratum basale (germinativum)
  343. layers of thick skin
    • stratum corneum
    • stratum lucidum
    • stratum granulosum
    • stratum spinosum
    • stratum basale (germinativum)
  344. stratum corneum
    • most superficial layer
    • consists of squamous, dead, anucleated keratinocytes filled with keratin
    • forms a protective barrier
  345. stratum lucidum
    • only found in THICK skin
    • highly refractile
    • cannot see any cells
    • process of keratinization is well advanced
  346. stratum granulosum
    • from one to several layers thick
    • cells contain basophilic keratohyalin granules
  347. stratum spinosum
    • thickest layer
    • composed of cells with numerous spinous process connected by desmosomes
    • prickle cells: image due to artifact of fixation
  348. stratum basale (germinativum)
    • single layer of cells resting on a basal lamina
    • stem cells (keratinocytes) arise by mitosis
    • proliferation of keratinocytes must keep pace with the rate of desquamination
    • contains varying amounts of melanin
  349. cells of the epidermis
    • keratinocytes
    • melanocytes
    • langerhans' cells
    • merkel's cells
  350. keratinocytes
    • predominant cell type of epidermis
    • produces keratin - 85% of total volume of fully differentiated cell
    • keratin filaments aggregate into tonofilaments
    • bundles of tonofilaments form tonofibrils
    • as cells approach the surface, they begin to form keratohyalin granules
    • apoptosis begins & soft keratin is formed
  351. keratohyalin granules
    • contain filaggrin & trichohyalin
    • promotes formation of tonofibrils (keratinization)
  352. pH gradient of keratinocytes
    allows enzymatic breakdown of desmosomes holding keratinocytes together
  353. formation of water barrier
    • cells of stratum spinosum form lamellar bodies
    • lamellar bodies secrete their contents (sphingolipids, ceramides, & other lipids) through exocytosis onto the cell surface between stratum granulosum & corneum
    • lipid envelope: barrier to fluids
    • envelop maintains as cells approach the surface
  354. formation of melanin
    •  tyrosinse - DOPA - melanin
    • enzyme: tyrosinase
  355. melanocytes
    • premelanocytes formed in golgi
    • content of melanin increases with chemical transformation of tyrosine to DOPA and then to melanin
    • melanosomes migrate to tips of processes of melanocytes
    • melanosomes bud off & are phagocytized by keratinocytes
    • pigment donation
    • cytocrine secretion
  356. # melanocytes: light skin vs. dark skin
    • number of melanocytes in light skin is the same as in dark skin
    • light skin: melanin is degraded rapidly by lysosome activity; found only in basal layer of the skin
    • dark skin: melanin is distributed throughout the epidermis
  357. Langerhan's cells
    • cannot be seen in routine sections
    • function as antigen-presenting cells - involved in delayed hypersensitivity reactions (allergic dermatitis)
    • contain HIV - relatively resistant to effects of HIV; serve as reservoir for virus
    • contain birbeck granules
    • part of mononuclear phagocytic system
  358. Merkel's cells
    • not easily seen in routine sections
    • situated primarily in fingertips, oral mucosa, and base of hair follicles
    • processes extend up between keratinocytes
    • unmyelinated nerve fibers form merkel cell-neurite complexes that function as mechanoreceptors (sense light touch)
    • merkel cell carcinoma: extremely aggressive
  359. layers of dermis
    • papillary layer
    • reticular layer
  360. papillary layer of dermis
    • immediately under the epidermis
    • loose CT
    • loose network of collagen, reticular & elastic fibers
    • cell types - fibroblasts, macrophages, etc.
    • thin layer
  361. reticular layer of dermis
    • varying thickness
    • irregular dense CT
    • bundles of collagen fibers
    • fewer cells than papillary layer
    • langer's lines: bundles of collagen fibers that allow minimal scarring (surgical importance)
  362. epidermis - dermis interface
    • dermal papillae: projections into epidermis
    • epidermal ridges (rete ridges): projections of epidermis into dermis
    • projections are more numerous in thick skin than in thin skin
    • hemidesmosomes: link intermediate filaments of the cytoskeleton to fibers in the papillary layer (anchoring filaments)
  363. integument nerve supply
    • free nerve endings: in epidermis around hair follicles (fine touch, pain, heat & cold)
    • merkel's cell: merkel's cell-neurite complex (light touch)
    • pacinian corpuscle: deep dermis, hypodermis (pressure & vibration)
    • meissner's corpuscle: papillary layer of dermis under hairless skin (touch)
    • ruffini's corpuscle: displacement of collagen bundles
    • Krause's end bulb: papillary layer (pressure)
  364. partial list of skin diseases
    • infections (fungal & bacterial)
    • infestations
    • pigmentary disorders
    • drugs & chemicals
    • tumors
    • weedwacker's dermatitis
  365. wound healing
    • antimicrobial peptides
    • inflammation
    • re-epithelialization: mitosis & mobilization of keratinocytes
    • subsequent repair of the underlying tissues
    • deeper wounds require involvement of hair follicles
  366. burns
    • first degree: surface of skin is damaged, but epidermis is still intact
    • second degree: burn extends through epidermis into dermis; blisters variable
    • third degree: both epidermis & dermis are destroyed; grafting likely necessary
  367. appendages of the skin
    • eccrine sweat glands
    • apocrine sweat glands
    • hair follicles & hair
    • sebaceous glands
    • nails
  368. function of eccrine sweat glands
    • helps regulate body temperature
    • secretions similar to ultrafiltrate of blood
    • sodium & water resorbed in the duct - hypotonic secretion
    • excretory function: sweat contains sodium chloride, urea, uric acid & ammonia
    • thermoregulatory sweating: cholinergic innervation; loss of water & electrolytes (K+ and Mg2+) can be excessive
    • emotional sweating: adrenergic innervation; sympathetic stimulation
  369. morphology of eccrine sweat glands: secretory portion
    • secretory segment: extremely tortuous
    • clear cells: secrete a watery component containing glycogen which reaches lumen via intercellular canaliculi
    • dark cells: secrete a proteinaceous solution
    • myoepithelial cells: help expel secreteion from the gland
  370. morphology of eccrine sweat glands: duct segment
    • stratified cuboidal epithelium
    • cells smaller & darker than secretory portion
    • cells end when duct enters the epithelium & epithelial cells form duct wall
  371. apocrine sweat glands
    • large lumen, coiled tubular glands (may branch)
    • found in axilla, areola, nipple of mammary glands & genital area
    • secretory portion: simple cuboidal cells found with myoepithelial cells
    • duct: stratified cuboidal cells (2-3 cells thick); no resorption of fluid takes place
    • secretory function: linked to sex hormones (secrete pheromones)
  372. hair
    • hair grows in cycles
    • hair is formed by the hair follicle
    • attached to each follicle is a sebaceous gland & a bundle of smooth muscle (arrector pili m.)
    • dermal papilla: tuft of loose CT with vessels & nerves at the bottom of the follicle
    • matrix cells: surround papilla; form germinative layer from which hair arises; cells increase in number & hair grows
  373. hair follicle layers
    • glassy membrane
    • external root sheath
    • internal root sheath - henle's layer, huxley's layer, cuticle
    • hair - cortex & medulla
  374. arrector pili m. & sebaceous glands
    • muscle & gland attached to same side of the hair follicle
    • muscle aids in secretory process; its contraction makes hair stand up & causes goose bumps
    • gland produces sebum (oily substance that coats the hair & skin)
    • holocrine secretion: cell accumulates secretion & ultimately dies & entire cell is secreted
  375. color & texture of hair
    • essentially controlled by genetics and ethnicity
    • black, brown, blonde - varying amount of pigments
    • gray & white (loss of melanins)
    • eumelanin: black-brown pigment
    • pheomelanin: red pigment
    • round hair - straight
    • flat, elliptical hair - curly
  376. hair growth cycle
    • anagen: active growth (90% involved) 3-7 years or longer
    • catagen: growth stops; 1-2 weeks (1-2% involved)
    • telogen: no more growth; club hair; 3 months (10-14% involved)
    • eyebrows have shorter times
  377. alopecia
    hair loss
  378. types of alopecia
    • androgenetic alopecia: male patterned hair loss; genetic control of hair pattern
    • alopecia areata: unexplained loss of hair
    • alopecia universalis: total loss
    • chemical alopecia: exposure to chemicals (chemotherapy)
  379. nails
    • hard keratin
    • rests on nail matrix (bed)
    • eponychium: cuticle
    • hyponychium: skin under tip of nails
  380. crown
    • covered in enamel & dentin
    • clinical crown: part of tooth visible, not covered by gingiva
    • anatomical crown: extends down to where enamel ends & cementum begins on the root of the tooth
  381. root
    structure covered in dentin
  382. cementum
    surrounds root and dentin at root of tooth
  383. components of teeth
    • crown
    • root
    • cementum
    • pulp & pulp chamber
    • apical foramen
    • peridontium
    • periodontal ligament
    • alveolar bone
  384. pulp
    • central soft core of the tooth
    • coronal portion: pulp chamber
    • radicular portion: root canal & lateral canals
  385. apical foramen
    • where blood vessels and nerves enter the tooth
    • pathway between peridontium and the pulp
  386. peridontium
    • periodontal ligament: holds tooth in place; extends from cementum to alveolar bone
    • alveolar bone: bone that tooth sits in
  387. names of teeth
    • central incisor
    • lateral incisor
    • canine
    • 1st premolar
    • 2nd premolar
    • 1st, 2nd, 3rd molars
    • 32 teeth in total
  388. cell types of teeth
    • ameloblasts
    • odontoblasts
    • cementoblasts
    • cementocytes
    • CT cells (fibroblasts, cells of the pulp)
  389. ameloblasts
    • formation of enamel
    • originally from ectoderm
    • sloughed off when tooth erupts - new enamel is not formed
  390. odontoblasts
    • formation & maintenance of dentin
    • exist after eruption to maintain dentin layer
    • decrease in number with age
  391. cementoblasts
    • formation of cementum
    • secrete cementum until they become incorporated in the matrix
    • become cementocytes (cells within cementum containing canaliculi)
  392. tooth development
    • lateral lamina: downgrowths from maxillary and mandibular cavities
    • successional lamina: projection off of bud that will form permanent tooth; begins to grow before birth
    • dentin forms first (from mesenchymal tissue)
    • enamel forms over dentin (from ectoderm)
  393. characteristics of enamel
    • extremely hard
    • brittle - maintained by underlying resilient dentin; easily fractured with destruction of dentin
    • translucent: color from light yellow to grayish white
    • varying thickness
    • mineralized tissue - 96% mineral (hydroxyapatite), 4% organic & water
    • NO collagen
  394. dental caries
    • progressive destruction of bone
    • result from dissolution of hydroxyapatite crystal in enamel
  395. enamel: age changes
    • no regeneration: non-vital tissue
    • wears progressively with age
    • increased discoloration: increased organic deposition; change in color of underlying dentin
    • reduced permeability: decrease in pore size, increase in crystal size, reduced water content
    • increase in fluoride content
  396. characteristics of dentin
    • 70% inorganic - hydroxyapatite crystals
    • 20% collagen fibers & other proteins
    • 10% water
    • softer than enamel but harder than bone
    • slightly elastic: protection for enamel
    • contains tubules
    • yellowish
  397. structure of dentin
    • contains densely packed dentinal tubules - from pulp to DEJ/DCJ
    • odontoblastic process: like an osteocyte process
    • encased in mineral
    • odontoblasts line pulp cavity
    • dentin conforms to general shape of the tooth
  398. amelogenesis
    • formation of enamel
    • amelioblasts differentiate from ectoderm in long, vertical cell lines
    • Tome's process: covers enamel
    • direct secretion & calcification of enamel completed by amelioblasts
  399. enamel developmental defects
    • febrile diseases
    • tetracycline-induced: incorporated into enamel; may present as brown band; may also cause enamel hypoplasia
    • fluorosis: above 5ppm will cause enamel mottling
  400. dentinogenesis
    • odontoblasts secrete dentin
    • odontoblasts have a process which extends from the cell body to the DEJ
    • these processes reside in dentinal tubules
    • the process usually occupies 1/3 of the length of the tubule
    • odontoblasts secrete dentin throughout the life of a tooth - do NOT die after eruption; pulp cavity deminishes in size
  401. predentin
    • before dentin calcifies
    • "mantle" dentin
  402. cementum
    • surrounds the root of the tooth
    • two types - acellular and cellular
    • acellular: predominant cementum
    • cellular: located at base of the root
    • secreted by cementoblasts in lacunae and have canaliculi which project towards the periodontal ligament
    • 45-50% hydroxyapatite
    • 50% collagen
  403. periodontium
    • composed of three basic components
    • periodontal ligament (membrane): comprised of collagen fibers, very dense, runs from cementum of root to alveolar bone (attached by Sharpey's fibers)
    • cementum: surrounds the root
    • alveolar bone: alveolar process
  404. pulp cells
    • odontoblasts
    • fibroblasts
    • undifferentiated ectomesenchymal cells
    • macrophages & lymphocytes
  405. pulp matrix
    • fibers: collagen type I & type II
    • ground substance: glycosaminoglycans & glycoproteins
    • water
  406. theories of dentin sensitivity
    • nerves travel in dentinal tubules & are stimulated by occurances in the enamel
    • odontoblasts act as receptor for stimulus
    • hydrodynamics - movement of fluids in canal upsets odontoblasts
  407. oral mucosa
    • lines the oral cavity
    • mostly stratified squamous non-keratinized epithelia
    • underlying lamina propria
    • submucosa
  408. degrees of keratinization
    • orthokeratinized: apical cells full of keratin, no nuclei (skin)
    • non-keratinized: apical cells retain nuclei, wet surface (esophagus)
    • parakeratinized: moderate keratin, apical cells with picnotic nuclei; wet surface (gingiva)
  409. oral mucosal types
    • lining mucosa: non-keratinized, soft palate, cheek, lips, ventral tongue
    • masticatory mucosa: parakaratinized & orthokeratinized;  hard palate & gingiva
    • specialized mucosa: keratinized papillae; dorsum of tongue
  410. regions of the oral mucosa
    • lips
    • cheeks - lining mucosa with sebaceous glands
    • alveolar mucosa - lining mucosa; mucogingival junction with gingiva
    • gingiva - masticatory mucosa
    • hard palate - masticatory mucosa
    • soft palate - lining mucosa
  411. lips
    • vermillion border: red area of lips
    • transition between skin & oral mucosa
    • Fordyce's spots: white spots; sebaceous glands within oral cavity
  412. mucosa
    epithelial cells + lamina propria
  413. types of epithelial cells
    • keratinocytes
    • melanocytes
    • Langerhans cells
    • Merkel cells
  414. layers of lamina propria
    • papillary layer: loose connective tissue underlies epithelia
    • reticular layer: deep dense irregular connective tissue
  415. tongue
    • papilla: filiform, fungiform, foliate, circumvalate
    • taste buds
    • salivary glands
  416. tongue musculature
    • extrinsic: muscles originate outside tongue; moves tongue in and out
    • intrinsic: muscles originate in the tongue & insert in the tongue; alters shape of the tongue
  417. cell types of taste buds
    • basal cells (type IV)
    • dark cells (type I)
    • light cells (type II)
    • intermediate cells (type III)
  418. structure of taste buds
    • four cell types: basal, dark, light, intermediate
    • cells have long microvilli that project into tast pore
    • receptors on microvilli
    • taste is actually dependent more on smell
    • accessory cells: neuroepithelial cells, supporting cells & basal cells
  419. function of saliva
    • protection: lubricant, mucous protects epithelia of oral mucosa, clearance of sugars from mouth, form salivary pellicle on enamel
    • buffering: maintains pH
    • digestion: salivary amylase breaks down starch, lipase breaks down fat; dilutes gastric chime prior to entering GI tract
    • taste: dissolves food; mediates taste through saliva; gustin aids growth & maturation of taste buds
    • antimicrobial: histatin, lysozyme, lactoferrin, antibodies
    • maintenance of tooth integrity: remineralization through calcium binding proteins & saturation of calcium and phosphate ions
  420. antimicrobial function of saliva
    • histatin: antibacterial protein
    • lysozyme: hydrolysis of bacterial cell walls
    • lactoferrin: binds free iron, required by some bacteria for growth
    • antibodies: secretory IgA; agglutinate microorganisms; prevents adhesion to oral tissues
  421. salivary glands
    • parotid
    • submandibular
    • sublingual
    • minor salivary glands
    • Fordyce's spots
  422. parotid gland
    • largest salivary gland
    • between ear & ramus of mandible
    • peripheral branches of CN VII facial
    • duct opens near maxillary second molar
  423. submandibular gland
    • posterior part of the floor of the mouth
    • tucked up against medial aspect of the mandible
    • duct opens beneath tongue, lateral to lingual frenulum
  424. sublingual gland
    • floor of the mouth - between tongue & teeth
    • ducts open into raised sublingual folds
    • often intermingles with submandibular gland ducts
  425. minor salivary glands
    • between 600-1000
    • small discrete masses throughout oral mucosa
    • except within the gingiva & anterior hard palate
    • mucus glands except serous glands of von Ebner (circumvallate papilla)
    • NONE in gingiva
    • protective effect on enamel - help form the acquired pellicle
    • important for lubrication of oral cavity
  426. Fordyce's spots
    sebaceous glands on inside of lip
  427. structure of salivary glands
    • compound tubuloalveolar (acinar) glands: excretory duct, striated duct, intercalated ducts
    • terminal acinar: tubules secrete mucus; acini secrete serous fluid; serous demilunes present
    • cell types: mucous cells, serous cells, myoepithelial cells
  428. serous demilunes
    • artifact of preparation/fixation
    • serous cells capping over serous-mucus cells
    • inner acinus of mucus cells (light by H&E)
    • outer layer of serous cells (dark by H&E)
  429. CT of salivary glands
    • forms capsule
    • projects into the gland
    • subdivides gland into lobules
    • cells - mainly fibroblasts; numerous plasma cells that contribute antibodies to saliva
  430. cells of terminal acini
    • serous cell: secretes proteins, intensely stained by H&E, prominent Golgi apparatus
    • mucous cell: secretes mucin, stains lightly
    • myoepithelial cells
  431. nerve supply of oral cavity
    • minor mucosal glands have slow continuous secretion
    • major serous glands have stimulated secretion
    • B-adrenergic (sympathetic) stimulation: protein secretion
    • L-adrenergic & cholinergic stimulation (parasympathetic): water & electrolyte release
  432. age changes of salivary glands
    • reduced salivary output with age: fatty degeneration, fibrosis, lymphocyte accumulation, reduced productive epithelial cells
    • oncocytes: granular, acidophilic epithelial cells; increase with age; may give rise to neoplasms
  433. major salivary gland features
    • parotid gland: 100% seromucous
    • submandibular gland: 80% seromucous; 20% mixed serous demilunes
    • sublingual gland: mostly mucus acini; some mixed serous demilunes
  434. intercalated ducts
    • small diameter
    • connected to the acini
    • myoepithelial cells
    • short cuboidal cells
    • similar in staining to acini
    • prominent in parotid gland (serous)
    • secrete bicarbonate
    • absorb chloride
  435. striated ducts
    • columnar cells
    • central nuclei
    • eosinophilic
    • prominent striation in basal region
    • prominent basal lateral infoldings
    • removes Na+ from salivary secretions
    • secrete bicarbonate
    • makes saliva hypotonic
    • flow rate
  436. terminal excretory ducts
    • transitions from simple columnar to stratified columnar
    • pseudostratified intermediary
    • makes saliva more hypotonic
  437. 3 main divisions of the ear
    • outer ear: auricle & external acoustic meatus
    • middle ear: converts sound waves to mechanical vibrations
    • inner ear: functions in equilibrium
  438. function of auricle
    collect & slightly amplify sound; localize sound in vertical direction
  439. auricle
    • pinna
    • external component of the ear
    • shape attributed to elastic cartilage
    • lined with thin skin, hair follicles, sweat glands & sebaceous glands
  440. function of external acoustic meatus
    conduct sound to the tympanic membrane
  441. external auditory meatus
    • air filled space leading from auricle to tympanic membrane/ eardrum
    • lateral 1/3: S-shaped elastic cartilage continuous w/ that of the auricle; contains hair follicles, sebaceous glands & ceruminous glands
    • medial 2/3: thin skin atop petrous portion of temporal bone; fewer hair cells & glands
  442. cerumen
    • ear wax = sebum from sebaceous glands + desquaminated epithelial cells from skin
    • function: lubricate ear & impede entry of foreign particles
    • may prevent otitis media (inflammation/infection of outer ear)
  443. function of middle ear
    converts sound waves from outer ear to mechanical vibrations in inner ear
  444. middle ear
    • air filled space called tympanic cavity within temporal bone
    • lateral boundary: tympanic membrane
    • medial boundary: bony wall of inner ear
  445. tympanic membrane
    • separates outer ear from middle ear
    • outer layer: keratinized stratified squamous epithelium (EAC)
    • middle layer: radial & circumferential CT fibers (except at pars flaccida)
    • inner layer: mucous membrane covered in simple cuboidal epithelium (continuous w/ auditory tube & mastoid antrum; becomes respiratory epithelium)
  446. auditory ossicles
    • malleus, incus & stapes
    • manubrium of malleus is embedded in the tympanic membrane
    • freely moveable synovial joints b/w malleus & incus and b/w incus & stapes
    • stapes acts as a piston attached to oval window
  447. otosclerosis
    auditory ossicles can become ossified and fracture; which leads to conductive hearing loss
  448. direction of sound from external ear to internal ear
    outer ear - tympanic membrane - malleus - incus - stapes - oval window
  449. muscles of the middle ear
    • tensor tympani: increases tension on tympanic membrane (CN V3 innervation)
    • stapedius: dampens movement of stapes at oval window (CN VII innervation)
  450. contents of internal ear
    • bony labyrinth
    • membranous labyrinth
    • vestibulocochlear nerve (CN VIII)
    • facial nerve (CN VII)
  451. bony labyrinth
    three connected spaces (vestibule, semicircular canals, cochlea) within petrous portion of temporal bone bathed by perilymph
  452. vestibule
    • central oval space of bony labyrinth connected to semicircular canals & cochlea
    • vestibular ganglion: vestibular portion of CN VIII
    • contains oval window
    • contains utricle & saccule of membranous labyrinth
  453. vestibular system
    vestibule + semicircular canals
  454. oval window
    attachment of stapes; transmits vibratory motion of airwaves into fluid waves within inner ear
  455. round window
    compensatory mechanism to dissipate energy from motion of fluid
  456. semicircular canals
    • extend from the vestibule anterior at right angles to each other
    • lateral: detects angular acceleration in horizontal plane
    • anterior & posterior: detect vertical acceleration
    • ampulla: swelling at end of semicircular canal closest to vestibule
  457. cochlear system
    • anterior spiral extension from the vestibule; cochlea
    • contains round window
    • cavity of spiral - cochlear duct
    • spiral ganglion: cochlear portion of CN VIII
  458. membranous labyrinth
    • lies within the bony labyrinth
    • divided into the cochlear & vestibular labyrinth
    • bathed by endolymph
  459. vestibular labyrinth
    • function: equilibrium & balance
    • semicircular ducts: lie inside the semicircular canals
    • utricle: continous w/ semicircular duct
  460. endolymph
    • fluid produced by stria vascularis
    • contained w/in membranous labyrinth
    • high in K+
  461. perilymph
    • fluid contained w/in bony labyrinth
    • similar to extracellular fluid in content
  462. cochlear membranous labyrinth
    • function: hearing
    • cochlear duct: cavity of spiral; lies inside cochlea
    • contains spiral ganglion (cochlear portion of CN VIII)
    • saccule: continuous w/ cochlear duct
  463. neuroepithelium of ear
    hair cells: modified columnar epithelial cells grouped by innervation (type I & II)
  464. macula
    patches of hair cells in the utricle & saccule that detect gravity & linear acceleration
  465. components of macula
    • stereocilia: large microvilli; multiple tightly packed groups of actin per hair cell
    • kinocilium: one large cilium (9+2 arrangement) per hair cell on UTRICLE (vestibular system only)
    • otoconia: calcium carbonate crystals embedded on gelatinous membrane (otolithic membrane) that add weight & impact gravitational movement of hair cells
  466. mechanism of hair cells in ear
    • hair cells act as stretch receptors
    • stereocilia bend according to change in gravity (directional response)
    • cell membrane is stretched
    • K+ channels are opened, allow K+ to flow into cell
    • K+ stimulates increase in Ca2+ concentration
    • release of neurotransmitters may be followed by action potential in nerve
  467. cristae ampullaris
    patches of hair cells in the ampulla of semicircular canals that detect angular acceleration
  468. components of cristae ampullaris
    • stereocilia: large microvilli made of actin; multiple per hair cell
    • kinocilium: one large cilium (9+2 arrangement) per hair cell
    • cupula: gelatinous fluid in duct causes cupula to drag behind and bend hair cells due to inertia
    • NO otoconia
  469. spiral organ of Corti
    • one long continuous ribbon of hair cells within cochlear labyrinth
    • NO kinocilium
    • inner row: 1 hair cell (with microvilli)
    • tunnel of Corti: contains cortilymph
    • outer row: 3-5 hair cells
    • supported by pharyngeal cells
  470. vertigo
    • sense of rotation without equilibrium
    • signifies dysfunction of vestibular system
    • causes may include viral infection, drugs & tumors
  471. motion sickness
    caused by excessive stimulation of utricle
  472. Meniere's syndrome
    • caused by blockage of cochlear aqueduct
    • increase in endolymphatic pressure causes dizziness & ringing in ears
  473. cochlea
    • detects sound, not movement
    • 2 & 3/4 turns
    • high frequencies detected at base
    • low frequencies detected at apex
  474. tunnel of Corti
    • separates rows of hair cells of spiral organ of Corti
    • formed by pillar cells
    • bathed in cortilymph
  475. tectorial membrane
    • arises from spiral limbus
    • sits on top of hair cells
    • causes deflection of hair cells when sound is detected - NOT directionally dependent
  476. modiolus
    • spiral bony part of cochlea
    • contains vestibular portion of CN VIII branches as they exit osseous lamina to form spiral ganglia
  477. cochlear canal
    • scala vestibuli: bony labyrinth filled w/ perilymph; separated from scala media by vestibular/Reisser's membrane
    • scala media: membranous labyrinth filled with endolymph; cochlear duct
    • scala tympani: bony labyrinth filled with perilymph; separated from scala media by basilar membrane
  478. vestibular/Reissner's membrane
    separates scala vestibuli & scala media
  479. basilar membrane
    separates scala media & scala tympani
  480. stria vascularis
    • ONLY vascularized endothelium in the body
    • sits on the outer wall of the scala media; opposite from entrance of nerve fibers
    • supported by spiral ligament
    • produces endolymph & functions in K+ transport
  481. helicotrema
    connection between scala vestibuli & scala tympani
  482. compensatory mechanisms to increase sound wave magnitude
    • area of tympanic membrane is 17X larger than oval window
    • cone shape of tympanic membrane (center - umbo)
    • mechanical advantage of levers created by auditory ossicles