The flashcards below were created by user EleanorN1130 on FreezingBlue Flashcards.

  1. Total thickness of cornea
  2. Tissue type of corneal epithelium
    Stratified squamous, non-keratinized epithelial tissue (5-7 cell layers thick)
  3. Functions of corneal epith
    • 1. barrier to pathogens
    • 2. excess uptake of fluid from tears
    • 3. UV filter
    • 4. surface for tear film distribution
    • 5. Transmission of O2, CO2 and metabolites**
    • 6. optical refractive surface (with tear film)
  4. What percentage of refractive power comes from the cornea?
    70% (~47D)
  5. Cell layers of K epith
    • 1. Basal Layer
    • 2. Wing Cells
    • 3. Squamous cell layers
  6. What does basal layer of K epith arise from?
    limbal stem cells
  7. Cell shape of K epith basal layer
    more columnar than cuboidal (shape depends on source of info)
  8. Basal layer of K Epith
    • 1. highly mitotic (many mitochondria)
    • 2. Produce basal lamina (40-60 nm thick)
    • -thinner than bowman's
  9. How do cells attach to basal lamina
  10. Describe devision of basal cells
    divide from stem cells (at limbus) and migrate inwardly
  11. Basal lamina contains
    • type 7 and 4 collagen and cell adhesion molec (CAMs)
    • involved in gross adhesion of basal cells to the basal lamina
  12. CAMs
    • 1. laminin and heparin sulfate
    • 2. integrins
    • 3. fibronectin
  13. Which corneal dystrophy does not occur early in life?
    Fuchs endothelial dystrophy (bw ages 40-50)
  14. Hereditary K dystrophy that is a disorder of basal epith cells
    Meesman's K dystrophy

    (non-progressive, fine dot-like glycogen containing opacities)
  15. Epithelial basement membrane disease characterized by bilateral cysts, dots or lines
    Epithelial basement membrane dystrophy (EBMD)
  16. EBMD
    • 1. most common cause of recurrent K erosion
    • 2. look for negative staining
    • 3. fibrillin material accumulates bw basal lamina and bowman's causing and incr in thickness
  17. Wing cells make up how many layers of K epith and what begins here
    1-3 layers; apoptosis (no mitosis happens here)
  18. What makes up most superficial 2 layers of epith?
    Squamous cell layers
  19. What happens in the squamous cell layers of epith?
    cells are starting to degenerate, loosing their RNA and chromatin
  20. What does most superficial layer of the squamous epith have between the cells?
    Zonula occludens; makes layer a semi-permeable membrane
  21. In the squamous cell layer why do some epith cells appear light?
    Light cells: are younger, smaller cells, that appear light due to their high level of microvilli
  22. How are K epith cells joined together?
    Cell-to-cell junctions
  23. Junctions that are found throughout the epith layers are...
    • Desmosomes (structural, cadherins)
    • and
    • gap junction (common in basal cell layer)
  24. Junctions that are only located in the most superficial, squamous layer of epith
    Zonula occludens
  25. How long does it take to haea new renewed corneal epith
    ~7-10 day (continues cycle)
  26. How do K basal cells migrate on the cornea?
    Vortex patten, curved (Y-axis of centripetal migration)
  27. When medications/metabolic conditions have evident pattern of corneal migration...
    • Whorl keratopathy (medications: amiodarone or choloroquine)
    • Fabry's dx (metabolic)
  28. How do basal cells divide
    • mitotically, producing wing cells
    • ( migrate superficially as more wing cells are produced, becoming squamous cells, X-axis of prolif)
    • become less cuboidal and more squamous as move superficially
  29. When does apoptosis begin
    in wing cell layer, ending just before squamous cell desquamation into the tear filn (Z-axis cell loss)
  30. XYZ hypothesis
    • X=from deep to superficial
    • Y=limbus to center
    • Z= superficial to tear film
  31. How is K epith renewal mediated
    • May be mediated by the sympathetic nervous system, likely has a feedback control loop mechanis
    • (intense pain signal may speed up the regeneration process)
  32. Availability
    • o The amount of drug instilled into
    • the ocular surface
    • o The active concentration of a drug
    • is ½ that in the drop, as only about ½ gets to the site
    • Higher concentration = more of the drug to get to its destination
  33. Water and lipid solubility
  34. o Lipid soluble drugs perfuse through
    • the epithelium more easily
    • o Water soluble drugs perfuse through
    • the stroma more easily
  35. Epithelial integrity / permeability
    specific drugs that break down the epithelial junctions = increased permeability

    • o Many drugs have a detergent or
    • surfactant to increase permeability
  36. Duration of contact / rate of elimination / blink
    • By mode of drug instillation (ung or
    • gtts)
    • celluvisc
    • Closing eyes or punctal occlusion
    • can increase duration of contact
  37. Drug
    kinetics / ionization in cul-de-sac
    • Stability of drug affected by pH,
    • temperature, chemistry of drug
  38. Action
    of Zonula Occludens
    • Tight junctions provide a natural
    • barrier, however ions may pass intercellulaly
  39. Epithelial cells are permeable to lipophilic molecules
    • Lipophilic aka: hydrophobic, fat
    • soluble molecules, non-polar
    • o Nonionic molecules permeate
    • epithelial cells
    • o Ions have low diffusion permeability;
    • polar
  40. Stroma is permeable to...
    • to hydrophilic molecules because there is so much
    • water in the stroma
  41. Endothelial permeability
    • Since it is only 1 cell layer thick,
    • this will not limit permeability
    • o Determined by molecule size, as
    • junctional gaps, and macula Occludens allow ions and non-ions to pass
  42. Action of detergents
    • Detergents are surfactants that kill
    • bacteria by breaking down lipid membranes and junctions
  43. Examples of detergents
    BAK, Chlorohexidene, EDTA
  44. Detergents...
    break down junctions and cause sloughing off of outer cells; inhibit wound healing, break down lipids and cell to cell junctions; cell membr
  45. Benzalkonium Chloride (BAK) 0.01%
    (common preservative)
    • - Causes an immediate increased
    • permeability to NaFl by breaking down junctions
    • § Inhibits healing, so prolonged
    • contact is not indicated
    • · Repeated use of 0.02% may cause
    • irreversible corneal damage
    • § Bacteriostatic: breaks down cell
    • junctions and lipid bilayers
    • § Commonly used in the best hand sanitizers
  46. Chlorhexidene
  47. § Similar to BAK, but weaker
    • § Bactericidal; static: disrupts
    • membranes
  48. EDTA
    • § Also breaks down cell-to-cell
    • junctions but does this by chelating metal ions
    • § Chelates calcium which makes
    • bacteria unable to survive
    • · The calcium is also required for
    • maintenance of tight junctions
    • · Chelation is where a molecule binds
    • a metal ion so that it becomes unusable to other functions; sequestering
  49. Increased pH favors:
    lipid solubility
  50. Increased pH decreases:
  51. Toleration of pH ranges
    • - Tear pH of 7.3-7.7 is within the
    • comfort zone
    • § Tear pH of <6.6 and >7.8 will
    • cause discomfort
    • § Tear pH of <6.5 and >8.5
    • indicates that endothelial damage is possible
  52. Ideal drug
    • 1. Biphasic (stimuli sensitive)--see notes
    • 2 . Small molecules
    • 3. Increased contact time with cornea
    • 4. Vehicle with surfactant / detergent
    • to break up epithelial integrity
  53. Tear film and drops
  54. · The average drop is 50uL
    • · The cul-de-sac holds 20-30uL
    • · The volume of tear file is 7-9uL
    • · Excess drops will run over (50uL)
    • · Quick dilution with reflex tearing
    • · Inflamed / infected eye – increased
    • protein in tears will bind to drug and decrease bioavailability of the drug
  55. How does a CL affect K epith?
    long term EW can thin epith by up to 5.6%
  56. What provides structural strength to the K?
    corneal stroma
  57. Corneal stroma accounts for how much of K thickness
    90%, ~500um
  58. What percentage of stroma is water
  59. what makes up stromal dry weight?
    • 68% is
    • collagen, 9% is proteoglycans, 10% is keratocyts, and the remainder is
    • random ions, salts, and glycoproteins
  60. How is collagen organized in k stroma?
    • organized in lamellae
    • (perpendicular, stacked, oblique), as regular dense connective tissue
  61. What are Keratocytes and what are their function?
    • modified fibroblasts
    • Functions:
    • · Production and organization of collagen and proteoglycans
    • · Turnover of the extracellular matrix, which takes 12 months or more
    • o Matrix metalloproteinase, MMP, are
    • enzymes produced by keratocytes to degrade the extracellular material so that
    • it can be renewed
    • · Communication throughout the cornea
    • via keratocyte-to-keratocyte gap junctions
    • · Provision of energy
    • · Tethering of neighboring lamellae
    • · Stromal wound healing
  62. Where are keratocytes found?
    bw the collagenous lamellae of the stroma
  63. Why are keratocytes transparent
    • When developing, they are very active and have many organelles, but once the stroma is mature, they have
    • lost most of their organelles and are fairly transparent and less active.
    • -There are also enzymes (ALDH1 and TKT) and crystalline that helps keep them transparent. When there is a wound, keratocytes mobilize to heal it and stop production
    • of these enzymes and are therefore not transparent during healing.
    • They are also extremely flat and a very small percentage of stroma.
  64. What are flat cells with extensive processes that interconnect via gap junctions?
    • Keratocytes
    • They can extend up to 100um and don’t have many organelles in their processes; organelles in the processes are within nodules
  65. What is a water insoluble structural protien, common throughout the body and eye?
  66. Functions of collagen
    • 1. structural support
    • 2. an anchor for overlying epithelial tissues, & basal lamina
    • 3. bed for wound repair
    • 4. In the cornea, its arrangement aids
    • corneal transparency
  67. is collagen hydrophilic or phobic?
    • Since collagen is hydrophobic, this
    • prevents most interactions between molecules, with crosslinking being the
    • exception
    • · The collagen is staggered
    • which gives a banded appearance due to the gaps
    • o This occurs every 64um
  68. Corneal collagen is Type?
    mainly 1 , some types 5, 6, 7
  69. Refractive index of collagen
  70. Stromal collagen..
    • -organizes into lamellae, of which
    • there are 200 to 250 arranged parallel to one another in the stroma
    • -highly organized
    • -Each lamella is 2um thick, and runs from limbus to limbus

    -At the limbus, the lamellae turn toform a 1.5-2.0mm wide annulus running circularly around the limbus; this functions to maintain tension on the central cornea, controlling corneal curvature

    • - Lamellar structure of the stroma makes
    • a partial corneal transplants possible
  71. Loss of lamellae over time, Thinning disorder of cornea
  72. Collagen in stroma V sclera:
    • -Size: Stroma – 30nm diameter fibrils
    • (22-32nm); Sclera - ~120nm diameter fibrils (variable)

    -Arrangement: Stroma – form into parallel lamellae (sheets), very regular; Sclera – interwoven connections of various sized fibrils, makes sclera stronger than stroma

    • -Spacing: Stroma – 42-44nm between
    • fibrils; Sclera – variable spacing, larger than cornea
  73. This provides volume to the stroma
    • Proteoglycans
    • water-soluble glycoproteins that are composed of a single
    • protein core or chain, with glycosaminoglycan (GAG) side chains
  74. GAGs of corneal proteoglycans are?
    sulfated; negatively charges the proteoglycan
  75. sulfating corneal proteoglycans does what?
    • causing attraction of water and repulsion of nearby
    • collagen fibrils, accounting for the interfibrillary distance in the stroma
  76. Proteoglycans found posteriorly and centrally in the stroma
    KS proteoglycans
  77. Tpyes of KS proteoglycans
    • 1. Lumican, the most common, which regulates collagen fibril diameter and spacing; it also regulates production of collagen by inhibiting fibrillogenesis
    • · Essential for maintaining corneal
    • transparency
    • 2. Keratocan is found almost exclusively in the cornea
    • 3.Mimecan
  78. Which proteoglycans are found
    found more anteriorly and peripherally in the stroma
    • CD and DS proteoglycans
    • -They tend to be more negativelycharged than KS proteoglycans, so the interfibrillary distance is larger in the
    • periphery

    • -Decorin is a
    • CD/DS proteoglycan found in the cornea that is also involved in inhibition of fibrillogenesis
  79. Which proteoglycans occur more frequently during scarring
    CD and DS proteoglycans
  80. Proteoglycan content in sclera vs stroma
    • -Increase of CD in stroma
    • -Increase of DS in stroma

    -Decrease of KS (or none) in stroma
  81. Sclera vs stroma, which has more water content
  82. Sclera vs stroma?
    has larger fibrils, more widely spaced and poorly organized
  83. 3 most common inherited stromal dystrophies
    (inherited, bilateral)
    • 1. lattice
    • 2. granular
    • 3. macular
  84. Most anterior 10um of the stroma
    Bowman's layer (not a membrane)
  85. Where does bowman's
    layer come from?
    Comes from modified fibroblasts that are part ofthe first mesenchymal wave
  86. What type of
    collagen does Bowman's layer have?
    ◦ types 3, 5, 6, and 7 are more common in Bowman’s◦ -It does not have as much Type 1 collagen as therest of the stroma
  87. What K dystrophy is specific to bowman's layer?
    Reis-Buckler's dystrophy
  88. What is Bowman's
    layer composed of?
    • ◦ It is composed of interweaving(non-parallel)collagen fibrils that are attached to fibrils in the anterior◦ stroma◦
    • o The interweaving is irregular andthe fibrils haverandom termination◦
    • o This organization gives the layer toughness(tougher than the rest of stroma)
  89. Does Bowman's layer contain keratocytes? Is it acellular or cellular layer?
    NO; acellular
  90. An Algar brush automatically stops at what layer?
  91. How can corneal transparency be lost?
    • Altered structure
    • Altered refractive index
    • Energy transfer
    • Produces heat
    • Produces altered frequency
    • Produces broken bonds (photopigment)
    • Destructive interference
  92. Maurice's lattice theory
  93. Goldman and Benedek's theory
  94. A simple (single layer) epithelial tissue of
    regularly arranged polygonal (mostly
    hexagonal) cells
    Corneal endothelium
  95. This layer is leaky, allowing diffusion from aqueous into the stroma and pumps material out
  96. Thickness of endothelium
    4-6um thick from base to apex
  97. Cell shape of endothelial cells
    • polygonal; 70-75% are hexagonal which is preferential as it is thermodynamically very stable and
    • strong (think benzene rings!)
  98. Diameter of K endoth
  99. How many endothelial cells are in young cornea and what happens with age?
    500,000, decrease 0.6% per year
  100. Newborn cornea has a cell density=

    Adult cornea has a cell densit=
    (Remember cell density = cell/area)

    2500 to 3500cells/mm2
  101. Minimum cell density to maintain normal endothelial function is ?
    400-700 cells/mm2
  102. What do you need to look at besides cell density to determine endothelial health?
    • Variation of cell size and # of hexagonal cells
    • -Specular microscopy (looks at the reflected light and allows measurement of cell size and number)
  103. 2 stress indicators of endothelium:
    1. CV of normal endothelium is approximately 0.25 and any increase in this value indicates a more variable cell area, acondition called polymegathism

    2. In a healthy young cornea, 70-80% ofendothelial cells are hexagonal at their apices and a reduction in thispercentage indicates that endothelial cells are losing their shape, a conditioncalled pleomorphism
  104. Describe organelles of K endoth
    • have large nucleus, many mitochondrion (very active), many ER and Golgi (produces a
    • lot of protein)
  105. What happens when endoth cell dies
    Amitotic: cell not replaced, but cells spread out and cover that area
  106. Why is endoth tissue is amitotic?
    • § Less energy is required (can use for running
    • pumps)
    • § Less chance of mutations
    • § Would slough off endothelial cells like the
    • epithelial cells do and where would they go?
  107. Factors that cause alterations, both polymegathism and pleomorphism, in the K endothelial mosaic:
    • 1. Age
    • 2. Surgery (see details in notes)
    • 3. Keratoconus
    • 4. DM
    • 5. Ocular HTN (causes a decr in cell density)
    • 6. CL use
  108. Lateral linkage of endothelial cells is via ...
    interdigitations,Macula Occludens, and gap junctions
  109. How many Na+ to K is moved by na/k/atpase pumps?
    3 Na+ for every K+
  110. Besides Na and K what is also transported thru endoth pumps?
    • Hydrogen, bicarbonate, and water are also
    • transported
    • o Water follows along with the sodium, helping the corneal stroma to retain its dehydrated state
  111. What is the basal lamina of the Endoth?
    Descemet's membrane
  112. Thickness of Descemet's at birth
    3-4 um
  113. What is the anterior banded layer?
    • at birth, This
    • portion of Descemet’s is composed of collagen types 4 and 8, and remains distinct throughout life as the anterior
    • banded layer
  114. As a person ages, the endothelial cells continually
    add new material (at a rate of 1-2 um/decade; increases in width) to the
    posterior surface of Descemet’s, which forms the
    posterior un-banded layer
  115. thickness of entire Descemet's as an adult
    10-15 um
  116. Descemet’s is connected to stroma how?
    • anteriorly to the stroma via collagen fibrils that run between thelayers
    • § Posteriorly, it connects to the endothelial
    • cells via Fibronectin adhesion, NOT
    • hemi-desmosomes
  117. What is a normal finding in peripheral endothelium
    • Hassal-Henle bodies
    • § Small white hyaline outgrowths on Descemet’s membrane, on the inside surface of the
    • cornea in its periphery; normal aging change
    • § CL patients may present with them sooner than
    • normal
  118. Name 5 disorders of Descemet's membrane
    • 1. Guttata
    • 2. Fuch's dystrophy
    • 3. Posterior polymorphous dystrophy
    • 4. Descemetocele
    • 5. Descemet's rupture
  119. What happens as corneal hydration increases
    • interfibrillary distance increases, thickness
    • increases, and light scatter increases (the only factor that affects thickness is hydration)
    • stromal hydration increases linearly with stromal thickness
  120. What is normal hydration of the cornea
  121. Factors that support an increase in hydration:
    • · Tendency of stroma to imbibe water (take inwater) and swell
    • Structural capacity for swelling, based uponits extracellular natureo Sincethere are lots of fibers etc. (not completely cellular); there is space for itto swell·
    • IOP forces water from aqueous into the stroma (bulk flow)·
    • Homeostatic characteristic of stromao Waterheld into place due to the negative charge of GAG’s
  122. Factors that support a decrease in hydration
    • 1. Structural limits on swelling·
    • 2. Action of pumps·
    • 3. Tear film osmolarity has a slight effecto As thetear film evaporates, water is evaporating, and solutes are left behind à tear film is hypertonic and fluid leavesstroma to make the tear film isotonic again·
    • 4. Cell-to-cell barriers and junctions
  123. Swelling pressure is equal to ?
    the force necessary to prevent swelling at a given level of hydration
  124. What is equilibium point of swelling pressure?
    55-60 mmHg
  125. If you increase thickness/hydration what happens to swelling pressure?
    • decreases
    • (inverse relationship)
  126. What is a measure
    of hydration and can be thought of as the pressure that results from stromal water uptake or the pressure from just being more full (pushback pressure)?
    Imbibation pressure
Card Set
physiology test 2
Show Answers