aqueous humour dynamics
TRANSCRIPT
AQUEOUS HUMOUR DYNAMICS
Dr Prasanta Kumar Sahoo
INTRODUCTION Flow of aqueous humour against resistance generates an IOP of about 15
mm Hg, which is necessary for the proper shape and optical properties of the globe.
Aqueous humour dynamics plays an important role in development of pathophysiological mechanism of Glaucoma.
AH- clear ,colourless , watery solution
Flows from posterior chamber to anterior chamber
Nutrition to lens, cornea and iris
Removes metabolically toxic products by active transport system.
Refractive index- 1.33
Inflates globe and maintains IOP
Ascorbate-antioxidant-UV protection
Facilitates cellular and humoral response of eye to inflammation and infection
PHYSIOLOGICAL PROPERTIES Volume 0.31ml
Refractive index 1.333
PH 7.2
Hyper osmotic
Rate of formation 2.0 to 2.5 µl/min
COMPOSITION Water constitutes 99.9% of Normal Aqueous Proteins (5-16mg/100ml) concentration in Aqueous, is less than 1% of its
fluid concentration 200 times less protein and 20 times more ascorbic acid than plasma. Glucose – 75% of the plasma concentration. Electrolytes:
Na+ similar in plasma and aqueous Bicarbonate ion: Concentration in PC & in AC Cl ion concentration than plasma and phosphate concentration than
plasma IgG is more than IgM and IgA Viscosity and density is slightly higher than water. Hyaluronic acid- protective against clogging of outflow tract. TGF-β – transformin Growth Factor plays an important role in glaucoma
pathogenesis.
DYNAMICS Aqueous humour dynamics
include:Anatomy of aqueous humour
formation and drainage structuresAqueous humour formationAqueous humour drainage.
ANATOMYPrimary ocular structures involved are
1. Cilliary body
2. Posterior chamber
3. Anterior chamber
4. Angle of anterior chamber
5. Aqueous outflow system
CILIARY BODY Seat of aqueous production
Triangular in shape
Outer side- line with sclera with a supra choroidal space in betweeen
Inner side of ciliary body has two parts-
a) Anteriorly pars plicata(finger like projections-ciliary process)
b) Posteriorly pars plana
Ciliary muscle- non striated muscle -3 parts
1. Longitudinal or meridional fibers- helps in aqueous outflow
2. Circular muscles- helps in accomodation
3. Radial or oblique fibers- helps in aqueous out flow
CILIARY PROCESSES 70-80 Whitish finger like projections Composed of central capillary network with fenestrated
thin endothelium and pericytes surrounded by stroma and two layers of epithelium and ILM.
Inner nonpigmented (NPE) and outer pigmented epithelium (PE)
Outer epithelium is continuation of RPE Inner epithelium is continuation of neurosensory retina. Outer PE- gap junction, desmosomes between cells. Inner NPE characterized by mitochondria, zonula
occludens (ZO)and lateral surface interdigitations The tight junctions(Zona occludens) contribute to the
blood aqueous barrier
BLOOD AQUEOUS BARRIER(BAB)• Barriers to the movement of substances from the plasma to the
aqueous humor.
• In the ciliary body the barriers include – Vascular endothelium– Stroma – Basement membrane– Pigmented and non-pigmented epithelium.
Zona occludens
The blood–aqueous barrier is responsible for differences in chemical composition between the plasma and the aqueous humor.
Breakdown of blood aqueous barrierIn some situations (e.g., intraocular infection)- a
breakdown of the blood–aqueous barrier is clearly therapeutic
In other situations (e.g., some forms of uveitis and following trauma), the breakdown of the barrier leads to complications.
ANTERIOR CHAMBER
2.5mm deep in centre, Contains 0.25ml aqueous Bounded
anteriorly-post surface of cornea, Posteriorly- anterior surface of ciliary body and iris Comunicates through the pupil with post. Chamber
Chamber volume decreases by 0.11μl/year of life Chamber depth decreases by 0.01mm/year of life Chamber depth is shallower in hypermtropic than myopic Chamber depth is slightly decrease during accommodation
partly by lens curvature and partly by forward translocation of lens.
ANGLE OF ANTERIOR CHAMBER
Formed by iris root, anterior part of ciliary body, scleral spur ,trabecular meshwork and Schwalbe’s line.
Anteriorly- schwalbe’s line
Posteriorly-iris
Major drainage pathway for aqueous humour.
Also known as filtration angle or iridocorneal angle.
Angle is wider in myopic eyes and narrow in hypermetropes.
AQUEOUS FORMATIONComplex pathwayCiliary processes are site of aqueous
humour productionMainly by thee mechanisms
1. Ultrafiltration-20%
2. Active secretion-70%
3. Diffusion-10%
DIFFUSION Diffusion is the movement of substance across a
membrane along concentration gradient.
As aqueous humor passes from the 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 the AC aqueous humor resembles plasma.
ULTRAFILTRATIONAlso known as relative dialysis.The process by which the fluid and
solutes cross through the semipermiable membrane.
Capillary blood flow-150 ml/min4% through fenestrationsFavoured by hydrostatic pressure
difference between capillary and interstitial pressure.
Enough to move fluid to stroma but further requiered active transport.
Leads to form stromal pool
Dialysis
Ultrafiltration
ACTIVE TRANSPORTActive transport is energy-dependent process that
selectively moves substance against its electrochemical gradient across a cell membrane.
It is postulated that majority of aqueous humor formation depends on active transport.
It is done by non-pigmented epithelial cells
Involves electrochemical and biochemical process.
Transport across Blood-Aqueous Barrier Active secretion is a major contributor to aqueous
humor 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 the transport of bicarbonate across the ciliary epithelium through a rapid interconversion between HCO-
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.(SVCT2)
BIOCHEMISTRY OF AH FORMATION The structural basis for aqueous humor secretion is the
bilayered ciliary epithelium.(pigmented epithelium & non-pigmented epithelium )
The active process of aqueous secretion is mediated by two enzymes present in the NPE: Na+-K+-ATPase and carbonic anhydrase.(CA)
ATP ADP+Pi
CO2 + H2O →I H2CO3 →II H+ + HCO3- I reaction is facilitated by CA
II reaction is spontaneous
ACTIVE SECRETION
MATHEMATICAL EQUATION OF A.H FORMATION MODIFIED GOLDMANN EQUATION
Pe- episcleral venous pressure
Fin –aqueous flow
Fu- Uveoscleral flow
Ctrab- Trabecular meshwork flow
PHARMACOLOGY AND REGULATION Sympathetic and parasympathetic nerve terminals are present in the ciliary body
and arise from branches of the long and short posterior ciliary nerves.
Parasympathetic fibers originate in the Edinger-Westphal nucleus of the third cranial nerve.
Sympathetic fibers synapse in the superior cervical ganglion and are distributed to the muscles and blood vessels of the ciliary body.
Sensory fibers arise from the ophthalmic division of the trigeminal nerve and enter the ciliary body.
Cholinergic or Parasympathetic Mechanisms- Not clear but species related.
Choloinergic- increase AHF( by vaso dilation, loss of tight junctions and breakdown of BAB, e.g pilocarpine)
Adrenergic mechanism
Adrenergic agonists increase AHF e.g epinephrine, salbutamol,isoproterenol (isoprenaline),and terbutaline.
β-adrenergic antagonists (β blocker) decrease AHF. e.g Timolol
AQUEOUS HUMOR OUTFLOW The aqueous humor leaves the eye at the anterior chamber
angle through trabecular meshwork, the Schlemm’s canal, intrascleral channels, and episcleral and conjunctival veins.
This pathway is referred to as the conventional or trabecular outflow.
In the unconventional or uveoscleral outflow, aqueous humor exits through the root of iris, between the ciliary muscle bundles, then through the suprachoroidal - scleral tissues.
Trabecular outflow accounts for 70% to 95% of the aqueous outflow .
And remaining 5% to 30% by uveoscleral outflow.
FACTORS REDUCE AH SECRETION
Age
Diurnal cycle
Exercise
Reduction in Blood pressure
Hypothermia
Acidosis
General Anaesthesia
Plasma hyperosmolality
Cyclic GMP
Spironolactone
Increased IOP(Pseudofacility)
Uveitis(specially Iridocyclitis)
β-Adrenoreceptor antagonists (e.g., timolol, betaxolol, levobunolol, carteolol, metipranolol).
Carbonic anhydrase inhibitors.
Nitrovasodilators; atrial natriuretic factor(ANF)
Calcium channel antagonists
DA2 agonists (e.g., pergolide, lergotrile, bromocriptine)
ACE inhibitors
Cardiac glycosides (e.g., ouabain, digoxin , Vanadate)
Cellular Organization of the Trabecular Outflow Pathway
Scleral Spur The posterior wall of the scleral sulcus formed by a group of fibers, the scleral roll, which run parallel to the limbus and project inward to form the scleral spur.
Schwalbe Line Anterior to the apical portion of the trabecular meshwork is a smooth area called as zone S. The posterior border is demarcated by a discontinuous elevation, called the Schwalbe line
Trabecular Meshwork :The scleral sulcus is converted into a circular channel, called the Schlemm canal, by the trabecular meshwork. It may be divided into three portions: (a) uveal meshwork; (b) corneoscleral meshwork; and (c) juxtacanalicular tissue
– Uveal Meshwork This innermost portion is adjacent to aqueous humor in the 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 three 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.
VACUOLATION THEORY OF AQUEOUS TRANSPORT ACROSS SCHLEMM’S CANAL
Vacuolation theory of aqueous transport across the inner wall of the Schlemm's canal:
1. Non-vacuolated stage.
2.Stage of early infolding of basal surface of the endothelial cell.
3. Stage of macrovacuolar structure formation.
4. Stage of vacuolar transcellular channel formation.
5.Stage of occlusion of the basal infolding
CELLULAR ORGANIZATION OF THE UVEOSCLERAL PATHWAY
Two unconventional pathways have been discriminated: (a) through the 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.
Uveoscleral Outflow
Studies have shown aqueous humor passes through the root of the iris and interstitial spaces of the ciliary muscle to reach the suprachoroidal space. From there it passes to episcleral tissue via scleral pores surrounding ciliary blood vessels and nerves, vessels of optic nerve membranes, or directly through the collagen substance of the sclera.
Uveovortex Outflow
Tracer studies in primates have also demonstrated unidirectional flow into the lumen of iris vessel by vesicular transport, which is not energy dependent. The tracer can penetrate vessels of the iris, ciliary muscle, and anterior choroid to eventually reach the vortex veins
The uveoscleral pathway is characterized as “pressure independent,”
It is reduced by cholinergic agonists, aging, and is enhanced by prostaglandin drugs.
A potential explanation for the observed decline in uveoscleral outflow with aging is thickening of elastic fibers in the ciliary muscles.
PHARMACOLOGY OF OUTFLOW
CHOLINERGIC MECHANISM
Cholinergic agonist decrease outflow resistance in TM outflow(iris- ciliary muscle contraction-leads to alteration in TM configuration)- Increase out flow-decrease IOP
In UVEOSCLERAL out flow- muscle contraction reduces space between muscle bundles cause reduction in outflow.
ADRENERGIC MECHANISM
Trabecular outflow facility increases in response to β-adrenergic agonists
Intracameral epinephrine increase outflow facility
Trabecular cells synthesize cyclic AMP in response to stimulation with β-adrenoceptor-selective agonists.
β-Adrenergic receptors are present in ciliary muscle, and their physiologic or pharmacologic stimulation relaxes the muscle and thereby more inter muscular space and increase UVEOSCLERAL OUTFLOW
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