Agents of Tissue Damage PDF

Agents of Tissue Damage Hypoxia Hypoxia: Reduced oxygen delivery to cells, impairing function. Ischemia: Reduced blood flow to tissues, leading to less oxygen and nutrients. Both hypoxia and ischemia cause tissue damage due to lack of oxygen and blood flow. Reduced Oxygen in the Eye ​ Struc...

Agents of Tissue Damage Hypoxia Hypoxia: Reduced oxygen delivery to cells, impairing function. Ischemia: Reduced blood flow to tissues, leading to less oxygen and nutrients. Both hypoxia and ischemia cause tissue damage due to lack of oxygen and blood flow. Reduced Oxygen in the Eye ​ Structure: Central retinal artery ​ Function: Supplies blood to the inner layers of retina ​ Dysfunction: ○​ Occlusion of the artery stops blood flow ○​ Damage to retinal structures (RNFL, ganglion cells) ○​ Inability to transmit visual signals, leading to vision loss. Physical Agents ​ Trauma: Physical injury to cells and tissues causing damage or death. ​ Temperature: Extreme temperatures (too hot or cold) disrupt cell function and can lead to death. ​ Light: High-energy light wavelengths can damage cellular structures and cause cell death. ​ Radiation: Strips electrons from atoms, damaging cells and DNA, impairing cell division. Trauma ​ Structure: Lenticular zonules ​ Function: Connect the lens to the ciliary body, aiding in accommodation ​ Dysfunction: ○​ Blunt trauma damages the zonules, causing lens subluxation ○​ Results in reduced vision and accommodation, or loss of refractive power if the lens is dislocated. Temperature ​ Structure: Cornea ​ Function: Provides most of the eye's refractive power ​ Dysfunction: ○​ Thermal burn (e.g., curling iron) damages corneal proteins, causing opacity and vision loss ○​ Extreme cold (cryotherapy) can treat retinal detachment by inducing scarring and adhesion Light ​ Structure: Lens ​ Function: Contributes to refractive power ​ Dysfunction: ○​ UV rays form free radicals in the lens ○​ Free radicals damage lens proteins, causing clumping and scattering of light ○​ Leads to cataract formation and loss of clarity, reducing vision. Radiation ​ Effect: Ionizing radiation can cause cataracts by damaging lens proteins. ​ Therapeutic Use: Proton beam therapy targets ocular melanomas with high-energy particles. ○​ Protons damage cancer cell structures, including DNA ○​ Cancer cells can't divide or grow, leading to their death. Chemicals ​ Acids ○​ Direct exposure causes necrosis of epithelial and stromal cells ○​ Damage to corneal epithelium and stroma leads to scarring and loss of corneal transparency ○​ Loss of transparency results in reduced visual acuity if the scar is in the visual axis ​ Bases ○​ Direct exposure causes necrosis and penetrates tissue more easily than acids ○​ Can lead to globe rupture, lens damage, and potential total vision loss or loss of the eye. Toxins ​ Toxins are poisonous substances from plants, animals, or bacteria. ​ Toxicity is dose-dependent. ​ Some medicines, like Botox, are toxic in large doses but helpful in small amounts. Hydroxychloroquine Maculopathy ​ Structure: Macula ​ Function: Provides central vision ​ Dysfunction: ○​ Hydroxychloroquine accumulates in the retina, causing: ​ RPE dysfunction ​ Disruption of photoreceptor outer segment recycling ​ Photoreceptor damage ​ Oxidative stress, leading to accumulation of Reactive Oxygen Species (ROS) in retinal cells, damaging lipids, proteins, and DNA ​ Lysosomal dysfunction, accumulating cellular waste ○​ Results in photoreceptor death and loss of central vision. Nutritional Deficiency ​ Structure: Optic nerve ​ Function: Transmits visual information to the brain ​ Dysfunction: ○​ Thiamine (Vitamin B1), a coenzyme essential for energy metabolism (part of the Krebs cycle!), is deficient, often due to alcohol abuse ○​ Impaired absorption, increased excretion, and inability to convert thiamine into its active form in the liver contribute to deficiency ○​ Reduced thiamine leads to lower ATP production, impairing nerve cell function ○​ Optic nerve dysfunction causes optic neuropathy, leading to reduced visual acuity, visual field defects, and color vision anomalies. Genetic Abnormalities Retinitis Pigmentosa ​ Structure: Retina ​ Function: Converts light into electrical impulses ​ Dysfunction: ○​ X-linked mutation causes abnormal protein which affects photoreceptor cilia, impairing molecule transport to outer segments. ○​ Rhodopsin accumulates in rod cells, causing oxidative stress and rod cell death ○​ Leads to impaired night vision, followed by cone cell loss and central vision loss, resulting in blindness. Immune Dysregulation ​ Autoimmune Disorders: Immune system mistakenly attacks the body's own cells as foreign. ​ Immunodeficiency Disorders: Immune system fails to fight infections, leading to tissue damage from pathogens. Sjogren’s Syndrome ​ Structure: Lacrimal gland ​ Function: Produces tears to maintain ocular surface health ​ Dysfunction: ○​ Abnormal antibodies attack lacrimal gland cells ○​ Chronic inflammation leads to fibrosis and scarring, impairing gland function ○​ Results in dry eye. Mechanism of Cell Death ​ Necrosis: Cell death due to injury from various agents. ​ Apoptosis: Programmed cell death, triggered by enzymes that break down cellular structures, such as DNA. ​ DNA damage and other mechanisms can trigger apoptosis. Sublethal Cell Injury ​ Occurs when a cell can still function after injury ​ Damage may be reversible ​ Mechanisms: Hydropic swelling, Atrophy, Hypertrophy, Metaplasia Hydropic Swelling ​ Loss of fluid/ionic balance causes cell swelling, disrupting tissue function ​ Structure: Lens ​ Dysfunction: ○​ Diabetes causes sorbitol accumulation in the lens, increasing osmotic pressure ○​ Water enters the lens, denaturing proteins and causing cataracts ○​ Results in reduced visual acuity and glare sensitivity. Atrophy ​ Decrease in cell size or number due to injury ​ Structure: Optic nerve ​ Dysfunction: ○​ Trauma to the optic nerve causes cell death, leading to optic atrophy ○​ Results in impaired vision and visual field defects. Hypertrophy ​ Increase in cell size (not number) ​ Structure: Retina ​ Dysfunction: ○​ Trauma to RPE cells causes enlargement to repair damage, leading to RPE hypertrophy ○​ Hypertrophy can also be congenital and benign. Metaplasia ​ Change from one tissue type to another due to injury or other stimuli ​ Structure: Conjunctiva ​ Dysfunction: ○​ Ectropion (outward-turning eyelid) causes chronic irritation ○​ Epithelial cells change to keratinized, stratified squamous epithelium (like skin). Cell and Tissue Repair ​ Healing: Tissues repair by replacing damaged cells. The process involves inflammation and remodeling where cells and structures are reorganized after proliferation. ​ Scarring: Tissues may not return to normal structure and function. Scarring occurs when collagen fibers formed during healing differ from the surrounding healthy tissue. ---------------------------------------------------------------------------------------------------------------------------- Cornea Repair ​ Injury: Caused by abrasions, foreign bodies, infections (e.g., keratitis), or surgery (e.g., transplantation). ​ Inflammatory Response: Epithelial defects heal through cell migration, while deeper injuries attract immune cells to clear debris. ​ Fibroblast Activation: Inflammation triggers fibroblasts (from keratocytes) to produce collagen. ​ Collagen Deposition: Collagen is laid down irregularly, disrupting tissue transparency. ​ Collagen Reorganization: Over time, collagen becomes more disorganized, forming opaque scars that reduce visual acuity. ​ Endothelial Cells: These enlarge to fill in lost cells, further affecting corneal clarity and function. Other corneal layers do not regenerate Retina ​ Injury: Retinal detachment triggers inflammation and RPE cell proliferation. ​ Fibrosis: Over-proliferation of RPE cells leads to fibrotic tissue and gliosis, replacing damaged nerve cells with glial cells. Inflammation Inflammation in the Eye Inflammation can occur within the various structures of the eye Examples include conditions such as uveitis (inflammation of the uvea possibly affecting the iris, ciliary body, and/or choroid), conjunctivitis (inflammation of the conjunctiva), or retinitis (inflammation of the retina) Ocular inflammation can result from infections, autoimmune diseases, or other underlying conditions Inflammation may be chronic or acute Granulomatous inflammation Granulomatous inflammation is a specific type of chronic inflammation characterized by the formation of granulomas Granulomas are organized structures composed of immune cells, predominantly macrophages, and sometimes other immune cells like lymphocytes and giant cells These structures form in response to persistent or poorly degradable substances, such as pathogens, foreign bodies, or certain antigens Non-granulomatous inflammation: Unlike granulomatous inflammation, non-granulomatous inflammation is typically characterized by a more diffuse and less organized response of immune cells to injury, infection, or other stimuli Granulomatous Inflammation: ​ Macrophage Activation: Macrophages become activated, fuse to form multinucleated giant cells within the granuloma. ​ Chronic Nature: Typically chronic, long-lasting, often unresolved inflammation. ​ Tissue Damage: Granulomas can cause tissue damage and scarring despite being part of the body's defense. ​ Examples: Associated with tuberculosis, sarcoidosis, Crohn's disease, and certain fungal infections. Non-granulomatous Inflammation ​ Absence of Granulomas: Lacks distinct granuloma structures found in granulomatous inflammation.  ​ Diffuse Immune Cell Infiltration: Immune cells (e.g., neutrophils, lymphocytes, macrophages) infiltrate the tissue in a scattered, diffuse pattern. ​ Acute or Chronic Nature: Can be acute (short-term) or chronic (long-term), depending on the cause and body’s response. ​ Examples: Conditions associated with non-granulomatous inflammation include infections, autoimmune diseases, and tissue injury. Inflammation in Response to Infection: ​ Cause: Triggered by exogenous material from infectious agents. ​ Types: Can be acute or chronic, granulomatous or non-granulomatous. ​ Causes: ○​ Bacterial infections ○​ Viral infections ○​ Fungal infections ○​ Protozoal and metazoal infections. Bacterial Infections ​ Pyogenic (Pus-Producing):​ ○​ Common Pathogens: Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae. ○​ Clinical Presentation: Rapid onset of redness, purulent discharge, irritation, and inflammation. ○​ Examples: Bacterial conjunctivitis, preseptal cellulitis, internal/external hordeola (styes). ​ Chronic Bacterial Infections:​ ○​ Example: Chlamydia trachomatis. ○​ Clinical Presentation: Slow-developing, persistent symptoms like follicular conjunctivitis, photophobia, tearing. ○​ Progression: Leads to scarring of the upper lid and cornea, resulting in vision loss (severe Trachoma). Viral Infections ​ Herpes Simplex Virus (HSV):​ ○​ Types: HSV-1 and HSV-2. ○​ Ocular Effects: Herpetic keratitis, dendritic ulcers, stromal keratitis, uveitis. ○​ Complications: Corneal scarring and vision loss if untreated.  ​ Herpes Zoster Virus (HZV):​ ○​ Cause: Varicella-Zoster Virus (VZV), responsible for chickenpox and shingles. ○​ Ocular Effects: Herpes zoster ophthalmicus (HZO), keratitis, uveitis, acute retinal necrosis (ARN), and progressive outer retinal necrosis (PORN). ○​ Complications: Rapid retinal damage and vision loss. Fungal Infections ​ Fungal Keratitis:​ ○​ Common Pathogens: Fusarium, Aspergillus, Candida. ○​ Clinical Presentation: Corneal infiltrates or ulcers, leading to scarring. ○​ Risk Factors: Contact lens wear, trauma, immunocompromised status. ​ Endophthalmitis:​ ○​ Clinical Presentation: Severe inflammation inside the eye, resulting in vision loss. ○​ Causative Agent: Candida species. Protozoal and Metazoal Infections ​ Acanthamoeba Keratitis:​ ○​ Causative Agent: Acanthamoeba, a free-living amoeba. ○​ Clinical Presentation: Severe keratitis with corneal ulceration, leading to scarring and vision impairment. ○​ Risk Factors: Improper contact lens hygiene, contaminated water exposure. ​ Toxoplasma gondii:​ ○​ Causative Agent: Toxoplasma gondii, an intracellular parasite. ○​ Clinical Presentation: Retinal scarring (inactive form), vitritis (active form), leading to vision loss. ○​ Transmission: Ingesting undercooked food, contact with cat feces, organ transplantation. ​ Toxocara canis:​ ○​ Causative Agent: Larvae of the dog roundworm (Toxocara canis). ○​ Clinical Presentation: Granulomatous inflammation, retinal scarring, and vision loss. ○​ Transmission: Ingestion of contaminated soil or contact with infected dogs. Autoimmune Diseases Affecting the Eye ​ Type 1 Autoimmune Response (Antibody-Mediated, Immediate): ○​ Example: Allergic conjunctivitis. ​ Type 2 Autoimmune Response (Antibody-Mediated): ○​ Example: Thyroid eye disease. ​ Type 3 Autoimmune Response (Immune Complex-Mediated): ○​ Examples: ​ Systemic lupus erythematosus. ​ Rheumatoid arthritis-associated eye disease. ​ Polyarteritis nodosa. ​ Polyangiitis with granulomatosis. ​ Type 4 Autoimmune Response (Cell-Mediated, Delayed): ○​ Examples: ​ Temporal arteritis (Giant cell arteritis). ​ Sympathetic ophthalmia. ​ Multi-type Autoimmune Diseases: ○​ Examples: ​ Sjogren’s syndrome. ​ Lens-induced uveitis. Allergic Conjunctivitis ​ Allergen Exposure:​ Allergic conjunctivitis begins when the eye is exposed to allergens like pollen, dust mites, pet dander, or chemicals. The immune system recognizes these as foreign invaders.​ ​ Immune Response:​ Mast cells in the conjunctiva release histamines and other mediators in response to the allergens, which initiate inflammation.​ ​ Inflammatory Cascade:​ Histamines cause blood vessels in the conjunctiva to dilate and become more permeable, increasing blood flow and allowing fluid leakage into surrounding tissues.​ Effect on Ocular Tissues ​ Conjunctival Redness (Rubor):​ Blood vessel dilation causes redness (conjunctival injection) in the eyes.  ​ Swelling and Edema:​ Increased permeability leads to fluid buildup in the conjunctival tissue, causing swelling (conjunctival chemosis).​ ​ Itching (Pruritus):​ Histamine release triggers itching, a hallmark symptom.​ ​ Tearing (Epiphora):​ Excess tears are produced as a response to irritation and inflammation, attempting to flush out allergens.​ ​ Mucous Discharge:​ Inflammation stimulates goblet cells to secrete excess mucus, resulting in stringy or mucous discharge.​ Thyroid Eye Disease: ​ Immune System Activation: In TED, the immune system produces autoantibodies ​ Targeting Thyroid and Ocular Tissue: These antibodies target receptors on thyroid cells and orbital tissues. ​ Ocular Involvement: The autoimmune response affects the orbital tissues, including the extraocular muscles and adipose tissue Effect on Ocular Tissues ​ Proptosis (Bulging Eyes):​ Inflammation and expansion of orbital fat and extraocular muscles push the eyes forward, causing proptosis, where the eyes appear to bulge.​ ​ Diplopia (Double Vision):​ Enlarged extraocular muscles may misalign the eyes, leading to double vision (strabismus).​ ​ Eyelid Retraction:​ Inflammation may cause the upper eyelids to retract, exposing more of the cornea.​ ​ Corneal Exposure and Dry Eye:​ Eyelid retraction and incomplete blinking lead to corneal exposure, causing dry eye symptoms and potential scarring.​  ​ Optic Neuropathy:​ Severe inflammation can compress the optic nerve due to the enlargement of orbital fat and muscles, leading to optic neuropathy and vision loss.​ Systemic Lupus Erythematosus (SLE) ​ Immune System Activation:​ The immune system produces autoantibodies against self-antigens like DNA and RNA.​ ​ Formation and Deposition of Immune Complexes:​ Autoantibodies form immune complexes that deposit in tissues, causing inflammation and damage.​ Effects on Ocular Tissues ​ Keratoconjunctivitis Sicca (Dry Eye):​ Inflammation affects lacrimal glands, reducing tear production and causing dry eye.​ ​ Corneal Complications:​ Dryness and inflammation lead to epithelial damage, ulcers, and infections.​ ​ Inflammation in Episclera, Sclera, and Uvea:​ Can cause episodes of episcleritis, scleritis, and uveitis, leading to tissue damage and vision loss.​ ​ Retinopathy:​ Lupus can cause microvascular changes in retinal vessels, impairing blood flow and causing ischemic damage to the retina.​ Rheumatoid Eye Disease ​ Immune System Activation:​ Autoantibodies attack joint tissues, leading to chronic inflammation in rheumatoid arthritis (RA). Effects on Ocular Tissues  ​ Keratoconjunctivitis Sicca (Dry Eye):​ Decreased tear production leads to dryness, discomfort, and blurred vision.​ ​ Corneal Complications:​ Inflammation can cause epithelial damage, ulcers, and infections.​ ​ Episcleritis, Scleritis, and Uveitis:​ These conditions cause pain, redness, and discomfort, with the potential for tissue damage and vision loss.​ ​ Scleral Nodules:​ Rheumatoid nodules may develop, leading to scleral thickening, thinning, or even perforation.​ Vasculitis ​ General Characteristics:​ Vasculitis involves inflammation and necrosis of blood vessel walls. Examples ​ Granulomatosis with Polyangiitis (GPA):​ Inflammation affects small and medium-sized vessels, causing ocular manifestations like scleritis, uveitis, and retinal vasculitis.​ ​ Temporal Arteritis:​ Inflammation of the temporal artery may lead to vision loss due to optic nerve ischemia.​ ​ Polyarteritis Nodosa (PAN):​ Affects small and medium arteries, with ocular involvement causing retinal vasculitis.​ Polyangiitis with Granulomatosis (GPA) ​ Pathophysiology:​ GPA involves immune-mediated inflammation with granuloma formation, impacting various organs, including the eyes. Ocular Effects  ​ Scleritis:​ GPA can cause scleritis, resulting in pain and redness.​ ​ Uveitis:​ Causes blurred vision, photophobia, and pain.​ ​ Retinal Vasculitis:​ Inflammation of retinal blood vessels can impair blood flow and cause ischemic damage to the retina.​ Temporal Arteritis ​ Pathophysiology:​ The autoimmune response leads to inflammation and thickening of the temporal artery. Ocular Effects ​ Amaurosis Fugax:​ Transient vision loss due to ocular artery involvement.​ ​ Optic Neuropathy:​ Reduced blood flow to the optic nerve head causes anterior ischemic optic neuropathy, leading to permanent vision loss.​ Sympathetic Ophthalmia ​ Triggering Event:​ Trauma or surgery in one eye exposes antigens, triggering an immune response in the unaffected eye.​ ​ Immune Activation:​ T-cells migrate to the unaffected eye, causing inflammation.​ Effects on Ocular Tissues ​ Bilateral Uveitis:​ Primarily affects the uveal tract, causing bilateral uveitis.​  ​ Vision Impairment:​ Inflammation leads to photophobia, blurred vision, pain, and potential vision loss.​ ​ Optic Nerve Involvement:​ Severe cases involve the optic nerve, leading to optic neuropathy.​ Sjögren’s Syndrome ​ Immune System Activation:​ Autoantibodies target exocrine glands, including lacrimal and salivary glands.​ ​ Glandular Destruction:​ Leads to reduced tear and saliva production.​ Effects on Ocular Tissues ​ Dry Eye Syndrome (Keratoconjunctivitis Sicca):​ Decreased tear production causes irritation and discomfort.​ ​ Conjunctival Inflammation:​ Chronic dryness leads to inflammation and redness.​ ​ Corneal Complications:​ Inadequate tear film can cause epithelial damage, ulcers, and scarring.​ Lens-Induced Uveitis ​ Immune Response to Lens Proteins:​ Exposure of normally sequestered lens proteins triggers an immune response. Effects on Ocular Tissues ​ Anterior Uveitis (Iritis):​ Inflammation of the iris and ciliary body causes pain, redness, and blurred vision.​ ​ Synechiae Formation:​ Chronic inflammation can cause adhesions between the iris and lens, impairing pupil function.​  ​ Glaucoma:​ Chronic uveitis can block the trabecular meshwork, increasing intraocular pressure and potentially causing optic neuropathy.​ Conclusion ​ Inflammation and Ocular Health:​ Inflammation profoundly affects ocular tissues and can lead to a variety of ocular conditions.​ ​ Ocular Effects of Inflammation:​ These can include dry eye, keratitis, scleritis, uveitis, retinal vasculitis, and optic neuropathy.​ ​ Importance to Optometrists:​ Understanding ocular inflammation is crucial for early diagnosis and treatment.​ ​ Preserving Vision:​ Prompt recognition and management of inflammation can help prevent severe complications like vision loss.​