OXYGEN

ATP
Def
Function

Formation

Constitue
nts

Currency of energy in the body

Provides energy for:
1. Normal cellular function
2. Active transport
3. Cellular reproduction
Formed by breakdown of glucose:
Aerobic
Glycolysis
Krebs cycle
ET chain
Oxidative phosphorylation
ATP is
1.
2.
3.

Anaerobic
Glycolysis
Pyruvate
Lactate
Cori cycle
Glucose

a combination of:
Adenine
Ribose
Three phosphoryl groups (ATP, ADP, AMP)
Two of these phosphate radicals are connected to each other by high
energy phosphoanhydride bonds
Amount of free energy in each of these high energy bonds per mol of
ATP = 8000cals

AEROBIC PROCESSES
Process in presence of oxygen: Aerobic
1. Glucose enters cells via Glut4
2. In cytoplasm: glucose converted to pyruvic acid
3. Pyruvate dehydrogenase in mitochondrion converts pyruvic acid to acetyl co-enzyme A
4. Acetyl coA enters Krebs cycle > converts acetyl coA into NADH and FADH 2
5. NADH and FADH2 supply electrons which enter electron transport chain (ETC
consists of four complexes of proteins)
6. ETC uses energy in electrons to pump protons (H +) from lumen into inter-membrane
spacing > proton gradient created
7. Proton gradient results in H+ ions passing through ATP synthetase, producing ATP
How carbohydrate forms ATP cells
1. Final products of carbohydrate digestion = glucose, fructose, galactose
2. Glucose in blood combines with carrier protein (GLUT4)
3. Entry of glucose into cytoplasm of cell via facilitated diffusion
Insulin plays major role in movement of glucose into cells
4. Phosphorylation: Upon entering cell, glucose combines with phosphate radical
In most tissues (except liver, renal tubules and intestinal epithelium),
phosphorylation captures monosaccharade
5. Once in cell, glucose can be used or stored as glycogen
Glycogenesis: glycogen formation
Glycogenolysis: breakdown of glycogen to reform glucose in liver
Glycolysis: splitting glycose into pyruvic acid
Gluconeogenesis: Pyruvate to glucose (in liver)
6. Complete oxidation of 1 gram-mole of glucose releases 686 000 cals
8000 cals needed to form 1 ATP gram-mole
During process of forming ATP, cells utilize successive step so that energy is
released in small packets to form 1 ATP at a time
38 moles of ATP for each mole of glucose utilized
Glucose breakdown forms:
1. 2 ATP in glycolysis

2. 2 ATP in pyruvate to Acetyl Co A

3. 34 ATP in oxidative phosphorylation
Summary of conversion of glucose to ATP
- Glucose enters the cells
- In cytoplasm: glucose is converted to pyruvic acid
- Pyruvic acid is converted into Acetyl co-enzyme A
- Acetyl co-enzyme enters the mitochondrion and Krebs cycle
- Acetyl co-enzyme A via Krebs cycle is converted into 16H atoms
- Electrons from the H enter the electron transport chain (ETC)
- ETC converts H + O2 into H2O and energy
- Energy pumps H ions into the inter-membrane space
- H ions pass through the ATP synthetase and produce ATP
Krebs cycle

Proton pump

Na-K pump

ANAEROBIC PROCESSES
Glycolysis end products:
1. Pyruvic acid
2. NADH and 2 ATP
Build up of end products:
Build up of excessive amounts of end products would stop glycolysis and ATP formation,
and forms lactic acid
Under anaerboci conditions, most of pyruvic acid is converted to lactic acid that
diffuses readily into extra-cellular fluids
Process allows for continued glycolysis (without it, lasts for only a few seconds)
Once O2 becomes available, lactic acid immediately reverses itself into pyruvic acid
Importance:
Epithelial swelling (CCC, Sattlers Veil)
Stromal swelling (Striae, folds)

Discuss why the epithelium swells in the absence of O2

Uptake of certain sugars and amino acids mediated by carrier transport
Cell membranes = selective barriers (only certain substances allowed, eg. Glucose)
To get through membrane, help is needed in form of Na-K pump
Human cells: high [Na] outside cell; low [Na] inside cell
To keep electrical neutrality: high [K] inside cell
To keep [Na] higher on outside of cell: cell pumps Na out = active transport process, thus requires energy
(ATP)
ATP absent = no Na pump = increased [Na] inside cell
Osmotic pressure goes up = Flow of water into cell = Swollen cell
Detail why the stroma swells in the absence of O 2
Results from epithelial hypoxia
Anaerobic conditions: enormous amounts of glucose consumed to provide ATP needed for normal metabolism
Less energy produced for each molecule of glucose = more glucose used to keep up with demand
Increased use of glucose = 2-4 fold increase in lactate production
Stroma = sink for lactate
Epithelial lactate extrudes into stroma
Hypoxia: lactate accumulation in stroma creates transiently hyperosmotic stroma
Water imbibition and oedema results
DECREASED OXYGEN SUPPLY
Decreased supply of oxygen causes problems:
1. CCC/Sattlers veil
2. Striae
3. Folds
4. SPK
5. Other changes (Blebs, vacuoles)
Describe the epithelial signs of physiological compromise
Infiltrates
- Accumulation of white blood cells in the cornea
- May be single or multiple in one or both eyes
- Inflammatory response
icrocyst
- Minute scattered gray dots
- Irregular shape
- Reversed illumination
Oedema
- Accumulation of fluid in the epithelium
- Non-reversed illumination
- Large and round
Bullae
- Transparent, flattened, cobblestone- like formations
- Non-reversed illumination
- Oval shape
- Coalesce into clusters
List 5 signs of metabolic compromise
1. microcysts
2. vacuoles
3. bullae
4. oedema
5. neovascularization
6. blebs
7. polymegathism
OXYGEN SUPPLY
In open eye
3 potential sources of oxygen:

Atmosphere
Aqueous

In closed
eye
Oxygen
consumption

Most of oxygen supplied here

155mmHg
Very small amounts
55mmHg
Only peripheral cornea

Limbal
vessels
Oxygen supplied by capillary plexus in conjunctiva (55mmHg)
Usually inadequate
Cornea 4-6% thicker than normal when awakening
Driving force of oxygen into cornea is attributed to:
1. Consumption of oxygen by component layers of cornea
2. Difference in partial pressure of oxygen in atmosphere vs aqueous
Component layers of cornea show different rates of aerobic
respiration. Relative consumption of different layers are:
1. Endothelium = 21%
2. Epithelium = 40%
3. Stroma = 39%

COR

Oxygen utilization on basis of volumes of oxygen per unit volume of

tissue:
1. Epithelium is 10x more than stroma
2. Epithelium is 0.2x that of endothelium
Critical oxygen requirement: Minimum partial pressure of O2 at
which cornea can survive indefinitely without any compromise in normal
function
Strategies to determine COR of corneal epithelium:
1. Glycogen
Reduced in absence of oxygen
levels
2. Lactate
Increased with decreased oxygen
3. Mitochondrial
function
4. Oxygen flux
5. Mitosis
Reduced mitosis with reduced oxygen
6. Thickness
Increased thickness with reduced oxygen
7. Touch
Decreased sensitivity with reduced oxygen
Stromal COR
Oedema response used to determine COR
Corneal thickness measured before and after hypoxia
Pachometry: decreased oxygen = increased thickness
Central and peripheral cornea have different CORs:
Central = 73mmHg; Periphery = 91mmHg
Minus lenses = less oxygen in periphery where lens is thickest

How to
assess
corneal
oxygen

Endothelial COR
Observation of endothelial blebs = basis for determining COR
Blebs = result of altered metabolism dt epithelial hypoxia
COR to prevent bleb formation = 123mmHg (in vitro = 67mmHg)
1. DK/L physics and lab
2. EOP in vivo and oxygen thirst
3. Swelling of cornea

supply:
Lens
thickness
and oxygen

1. As thickness changes, so does DK/L

2. Physiological impact of lens on cornea is function of overall thickness
profile of lens
3. Different methods of measuring DK give varying results

By means of a diagram show the distribution of O2 through the cornea with a static
contact lens on the eye
Corneal response in oxygen shortfall
O2 Distribution across cornea with static
units to DK/L levels over composite
contact lens
spectrum of
1.2 to 189x10-9 (cm/sec)(ml O2/ml mmHg)
Oxygen tension and percentage distributions
across corneal layers for central cornea
wearing contact lenses allowing (A) 15%, (B)
10%, (C) 5%, and (D) 0% oxygen to be
present

Calculated transcorneal oxygen tensions

Oxygen distribution across cornea

without CL
Oxygen tension and percentage distributions
across corneal layers for (A,C) central, and
(B,D) superior corneal sites under (A,B) open
eye, and (C,D) closed-eye conditions.

Corneal oxygen tensions of open eye

covered by CL

Corneal oxygen tensions of closed eye

covered by CL

CORNEAL SWELLING
To avoid
Cornea needs constant supply of:
Cornea needs to eliminate:
1. Oxygen
1. CO2
oedema:
2. Glucose
2. Lactate
3. Vitamins
3. Necrotic cellular matter
4. Amino acids
5. Minerals
Factors
1. CL
2. Decreased tear osmolarity
causing
3. Tear pH changes
corneal
4. Mechanical effects
swelling
Closed eye
Moderately influenced by lens thickness profile surrounding site at which
swelling
it is measured
Detection of
1. Pachometer (optical, ultrasound)
2. Slitlamp
oedema
Hard lens: central corneal clouding by sclerotic scatter
Soft lens: Striae, folds, haze
Number of striae and folds indicate amount of swelling
List the methods available to an optometrist to determine the oedema levels of a
cornea
- A variety of sophisticated clinical and laboratory techniques can be employed to
measure the amount of contact lens induced edema.
- Most popular
o Optical pachometry
o Ultrasonic recording
- Also slitlamp
o CCC by sclerotic scatter
o Striae, folds and haze optic section
o Striae = oedema more than 5%
o Folds = oedema more than 8%
o Haze = oedema more than 15%
- Confocal microscopy
- Femtosecond laser ranging
- Interferometry
- (last three measuring the corneal thickness)

CL SELECTION
Ocular considerations for daily wear vs extended wear
1. Corneal status
After 3 hours of wear
Overnight wear in the morning
48h later
One week
2. Risk factors
Corneal oedema
Decreased sensitivity
Adherence (hards)
Inflammation and infection
3. Central thickness
Rx CT vs average CT
Oxygen demands
4. Tear film
Dry eye
Debris
Excess lipid
5. Lid integrity
Papillae
Follicles
Redness
6. Environmental
Gas
factors
Fumes
Nature of work
7. Individual
characteristics
Ocular considerations for extended wear vs. daily wear
Corneal status
Risk factors vs. advantages of the contact lenses
Rx Ct vs. average Ct and oxygen demands
Tear film, dry eye, debris, excess lipid
Lid integrity, papillae, follicles
Environmental factors gas, fumes, nature of work etc
Individual characteristics
Daily

RGP

wear vs Extended wear

Compared to daily wear, EW increases risk of complications by 2-6x
Each additional consecutive night increases risks
15x more risk of ulceration with EW than DW

EW vs SCL EW
RGP EW 2x as safe as SCL EW
RGP EW as safe as SCL DW
RGP adherence occurs in 95% of EW users

Factors to consider when deciding on what type of lens to fit patient with
1. Corneal
health
2. Intended
1. Frequency of wear
2. Type of lens
usage
3. Maximum wearing time
4. Level of care required
5. Level of professional care
6. Costs
3. Refractive
1. Myopia
2. Hyperopia
issues
3. Astigmatism (type)
4. Aphakia
5. Keratoconus
6. Post sugery
4. Corneal
Curvature
topography
Astigmatism
Keratoconus
Average CL parameters
Parameters
BC
OZ
Diameter

Hard lens
7.8
>8
9.5

Soft lens
8.5
>8
14