PHYSIOLOGY OF AQUEOUS HUMORDR GAN

AQUEOUS HUMOR

Clear, colorless fluid that fills anterior and posterior chambers

PHYSIOLOGICAL PROPERTIES

Volume 0.31ml Refractive index 1.333 PH 7.2 Hyperosmotic Rate of formation 1.5 – 4.5ul/min

COMPOSITION

Water constitutes 99.9% of normal aqueous Protein (5-16mg/100ml) concentration in aqueous is

less than 1% of plasma concentration Glucose 75% of plasma concentration Electrolyte:

Na+: similar in plasma and aqueous Bicarbonate ion: concentration higher in PC & lower in AC Cl ion concentration higher than plasma and phosphate

concentration lower than plasma Ascorbic acid concentration very high in aqueous Various components of coagulation and anticoagulation

pathways may be present in human aqueous humor

FUNCTIONS OF AH

Brings oxygen and nutrients to cells of lens, cornea, iris

Removes product of metabolism and toxic substances from those structures

Provides optically clear medium for vision Inflates globe and provides mechanism for

maintaining IOP High ascorbate levels protect against UV-induced

oxidative products, eg: free radicals Facilitates cellular and humoral responses of eye

to inflammation and infection

THE BLOOD-AQUEOUS BARRIER

Barriers to movement of substances from the plasma to AH

In the ciliary body the barriers include Vascular endothelium Stroma Basement membrane Pigmented and non-pigmented epithelium

The blood-aqueous barrier is responsible for differences in chemical composition between plasma and aqueous humor

Breakdown of blood aqueous barrier In some situations (eg intraocular infection), a

breakdown of blood-aqueous barrier is clearly therapeutic

In other situations (eg some forms of uveitis and following trauma), the breakdown of barriers leads to complication

AQUEOUS HUMOR DYNAMICS

Secreted by ciliary epithelium lining ciliary processes Enters the posterior chamber It then flows around the lens and through the pupil into AC There is convention flow of aqueous in the AC due to

temperature gradiant It leaves the eye by two pathways at the anterior chamber

angle: Through the TM, across inner wall of Schlemm’s canal into its

lumen, and thence into collector channels, aqueous veins, and the episcleral venous circulation – trabecular or conventional route

Across the iris root, uveal meshwork, and the anterior face of ciliary muscle, through the connective tissues between the muscle bundles, the suprachoroidal space, and out through the sclera – uveoscleral or unconventional route

AQUEOUS HUMOR PRODUCTION

Produced from pars plicata along the crests of the ciliary processes.

Derived from plasma within capillary network of ciliary processes

3 physiologic processes contribute to the formation and chemical composition of the AH: Diffusion Ultrafiltration Active secretion

DIFFUSION

Movement of substance across a membrane along concentration gradient

As AH passes from PC to Schlemm’s canal, it is in contact with ciliary body, iris, lens, vitreous, cornea, and trabecular meshwork

There is diffusional exchange, so that AC AH resembles plasma.

ULTRAFILTRATION

The process by which fluid and its solutes cross semipermeable membrane under pressure gradient is called ultrafiltration

As blood passes through capillaries of ciliary processes, about 4% of plasma filters through capillary wall into the interstitial spaces between capillaries and ciliary epithelium

In the ciliary body, fluid movement is favored by the hydrostatic pressure difference between capillary pressure and the interstitial fluid pressure and is resisted by the difference between the oncotic pressure of the plasma and the aqueous humor

ACTIVE TRANSPORT

Energy-dependent process that selectively moves substance against its electrochemical gradient across a cell membrane

It is postulated that majority of AH formation depends on active transport

It is done by non-pigmented epithelial cells

BASIC PHYSIOLOGIC PROCESSES

Accumulation of plasma reservoir Most plasma substances pass easily from

capillaries of ciliary processes, across stroma, and between pigmented epithelial cells before accumulating behind the tight junctions of the nonpigmented epithelium

This movement takes place primarily by diffusion and ultrafiltration

TRANSPORT ACROSS BLOOD-AQUEOUS BARRIER

Active secretion is major contributor to AH formation

Selective transcellular movement of certain cations, anions, and other substances across the blood-aqueous barrier formed by the tight junctions between the nonpigmented epithelium

Aqueous humor secretion is mediated by transferring NaCl from ciliary body stroma to PC with water passively following.

Carbonic anhydrase mediates transport of bicarbonate across the ciliary epithelium through a rapid interconversion between HC)3 and CO2

Other transported substances include ascorbic acid, which is secreted against a large concentration gradient by the sodium-dependent vitamin C transporter 2

Osmotic Flow The osmotic gradient across ciliary epithelium,

results from active transport It favors the movement of other plasma

constituents by ultrafiltration and diffusion

BIOCHEMISTRY OF AQUEOUS HUMOR FORMATION

The structural basis for aqueous humor secretion is the bilayered ciliary epithelium (pigmented & nonpigmented epithelium)

The active process of aqueous secretion is mediated by 2 enzymes present in the NPE: Na-K-ATPase and carbonic anhydrase

AQUEOUS HUMOR OUTFLOW

AH leaves the eye at AC angle through TM, Schlemm’s canal, intrascleral channels, and episcleral and conjunctival veins

Referred as conventional/trabecular outflow In unconventional or uveoscleral outflow, AH

exits through root of iris, between ciliary muscle bundles, then through the suprachoroidal-scleral tissues

Trabecular outflow accounts for 70-95% of aqueous outflow

And remaining 5-30% by uveoscleral outflow

CELLULAR ORGANIZATION OF TRABECULAR OUTFLOW PATHWAY

Scleral spur- the posterior wall of scleral sulcus formed by a group of fibers, the scleral roll, which run parallel to the limbus and project inward to form scleral spur

Schwalbe line- anterior to the apical portion of the trabecular meshwork is a smooth area calledas zone S. The posterior borders is demarcated by a discontinuous elevation, called the Schwalbe line

Trabecular meshwork- the scleral sulcus is converted into a circular channel, called Schlemm’s canal, by the trabecular meshwork. It may be divided into 3 portion: (a) uveal meshwork; (b) corneoscleral meshwork; (c) juxtacanalicular tissue

Uveal Meshwork This innermost portion is adjacent to AH in AC and is arranged in ropelike trabeculae that extend from iris root and ciliary body to peripheral cornea

Corneoscleral Meshwork This portion extends from the scleral spur to the anterior wall of the scleral sulcus

Juxtacanalicular Tissue This structure has 3 layers. The inner trabecular endothelial layer is continuous with the endothelium of corneoscleral meshwork. The central connective tissue layer & outermost portion is the inner wall endothelium of the Schlemm canal

Episcleral and Conjunctival Veins The Schlemm canal is connected to episcleral and conjunctival veins by a complex system of intrascleral channels

2 systems of intrascleral channels have been identified: Direct system of large caliber vessels, with short

intrascleral course, drain into episcleral venous system Indirect system of more numerous, finer channels,

which form an intrascleral plexus before draining into episcleral venous system

PUMPING MODEL FOR TRABECULAR OUTFLOW

The aqueous outflow pump receives power from the transient increases in IOP such as occur in systole of the cardiac cycle, during blinking and during eye movement.

CELLULAR ORGANIZATION OF THE UVEOSCLERAL PATHWAY

2 unconventional pathways have been discriminated: (a) through anterior uvea at the iris root, uveoscleral pathway, and (b) through transfer of fluid into the iris vessels and vortex veins, which has been described as uveovortex outflow

The uveoscleral pathway is characterized as “pressure independent”

It is reduced by cholinergic aganists, aging, and is enhanced by prostaglandin drugs.

A potential explanation for the observed decline in uveoscleral outflow with the aging is thickening of elastic fibers in the ciliary muscles.

FACTORS EXERTING LONG-TERM INFLUENCE ON IOP

Genetics Age Gender Refractive error Ethnicity

FACTORS EXERTING SHORT-TERM INFLUENCE ON IOP

DIURNAL POSTURAL VARIATION EXERTIONAL INFLUENCE LID AND EYE MOVEMENT INTRAOCULAR CONDITION SYSTEMIC CONDITION ENVIRONMENT GA FOODS AND DRUGS

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