The Orbit Eye is held in the orbit (a cavity w/in the skull) which is filled with muscle and fat …. The adiposites have TSH receptor giving ECM deposits? Proptosis Poping out/Bulging eye due to increase in ocular content. Autoimmune condition, with lymphocytic infiltration Graves disease: accumulation of extracellular matrix proteins FIBROSIS, and ENLARGEMENT of extraocular muscles. muscle-restriction, exposure problems (dry-eye) Axial proptosis seen in any meningal layer Tumors meningiomas in the dura optic gliomas. Cranial n
Retina (10 layers) is derived from the diencephalon and contains no Lymphatics Reaction to injury-gliosis. Retinal detachment: Separation of the neurosensory retina from the RPE. ?? Adult vitreous humor is avascular.?? Pt presents w: Blurry vision, Visual field loss, Photopsia -flashing lights * *
Rhegmatogenous: full-thickness retinal defect MC seen Posterior vitreous detachment
Non-rhegmatogenous without retinal break Seen w choroidal tumors & malignant HTN
RETINAL VASCULAR DISEASE Hypertension, Diabetes Mellitus Retinopathy of Prematurity (Retrolental Fibroplasia) Hypertensive retinopathy Grade 1 : focal narrowing of the arterioles, mild A-V nicking Grade 2: + copper wiring Grade 3: + silver wiring, flame shaped and dot blot hemorrhages, soft cotton wool spots and hard exudates present, disc normal Grade 4: + papilledema is present. Fundus in Hypertension: reduction in the diameter of arterioles and copper wire color of the blood columns bc less saturated …*** sclerotic arteriole crosses over and compresses vein *
Eyelid contains 2 sebacous glands: Meibomian glands and glands of zeis Chalazion - Granulomatous inflammation due to obstucion of meibonian gland of eyelid leads to lipid escape of lipid substance into the stroma giving you a into surrounding tissue provokes granulomatous reaction - lipogranulomatous inflammation . painful
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Stye – infection of the eyelid M.C due to S.aureus.
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Malignancy of the eyelid: Basal cell carcinoma –MC (MC in Skin) Squamous Melanoma Sebaceous cell carcinoma The Cornea: 2 types ofInflammation (Keratitis Uclers eroding the cornea: Noninfectious: trauma Infectious (MC) HSV VZV and Acanthamoeba (MC) in asso w contact lens use Respond to topical antibiotics and steroids. Complications: Descemetocele - due to melting away of stroma (supporting structures) causing thining of connea and protrustion. - Loss of visions due to infection spread anteriorly- Perforation leads to hypotonia. Invasion of infectious organisms into the globe and often loss of the eye. Intact corneal Epithelium with inflamation underneath:Stromal Ulcer : Inflammation with absent overlying epithelium .??? Risk factors : wearing contact lenses , debilitation and immunodeficient states. Clinical Symptoms: Foreign body sensation, severe ocular pain, photophobia and blurred vision even eye discharge Often pain is more severe than signs in early course of the disease Keratomalacia : Vitamin A deficiency helps in ?? Bacterial infection and ulceration of the cornea. Major cause of blindness in underdeveloped countries. Undernourished children. Xerosis, Bitot’s spot . Keratinization of mucous membrane epithelium. MC and earliest symptom: Night blindness -
Lens Cataract Opacities in the lens : Senile(Elderly) cataract - Most common effective Pt cannot see during the day glare, dec visual acuity during bight sunlight Drug induced: Posterior sub capsular cataracts (steroid use) autoimmune pt Acquired: DM, Galactosemia, Wilsons disease Treatment :Simple surgical procedure extra capsular lens extraction. Glaucoma: changes in the visual field & in the cup of the optic nerve Raised IOP in most cases sometimes can be normal(10-20 mmHg) to low tension Aqueous humor is produced by the ciliary body in the posterior chamber of the eye passes through pupil into anterior chamber into the main drainage system Trabecular meshwork(second is cannal of schleems)
Diabetic retinopathy: New Neovascularisation in the retinal layers Pre-proliferative Abnormalities of angiogenesis located within the retina Basement membrane of retinal blood vessels is thickened. Microaneurysms Macular edema Exudates- outer plexiform layer Proliferative Appearance of new vessels (excess angiogneissis) that sprout from existing vessels on the surface of either the optic nerve head or the surface of the r etina * * * *
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Retrolental fibroplasia seen in premature infants, surfractant is def (ARDS) so oxygen as a complication of the O2 therapy Retinal ischemia -upregulation of VEGF-retinal angiogenesis… Detachment can take place when the neovascular membrane contracts. Sickle cell retinopathy. Can be proliferative (w neovascularization) or non- proliferative. Retinal occlusions A( infarction of retina) V (VEGF-neovascularization, hemorrhage, edema) Age Related Macular Dengeration: major health prob w increasing longevity Disturbance in the Brusch membrane and choricapillaries causing problems w photoreceptors giving visual loss any component of the “unit’’- RPE Genes-CFH(Complement Factor H) genotype with H/O smoking 10pack years. 2 types: dry or wet. *
Retinitis pigmentosa: Mutatio Mutations ns in genes that regulate the photoreceptor cells or the RPE. Both rods & cones are lost to apoptosis- varying degrees. *
Retinoblastoma: MC primary intra-ocular malignancy of kids. Arises from neuronal cells.
40% of cases - inherited germline mutation of one RB one RB allele allele on chromosome 13 . May be bilateral “trilateral” assoc w pinealoblastoma. 60% sporadic where both RB allele are deleted asso with osteocarcoma Necrosis and dystrophic calcification Flexner-wintersteiner rosettes around vascular channels Small blue cells w that are hyperchormatic and scanty cytoplasm Retinal lymphoma Similar to primary large cell lymphoma of the brain. In older people mimics uveitis clinically. *
Open angle glaucoma dec aquous outflow due to blocking of trabecular meshwork by proteins pigment: leads to visual impairment & eventual blindness Angle closure glaucoma due to pupilary dialation the irus is closer to the lens narrowing the anterior chamber angle, there is retinal ischemia (cuasing upregulationof VEGF)this is an …EMERGENCY Can be caused by Necrotic retinoblastomas also -
Uvea: Cilliary Body, Iris, and Choroid -! Inflammation: Uveitis Infectious: Pneumocystis carinii. Sarcoidosis: inflammation resulting in “candle wax drippings” with Granulomas Confirmation of diagnosis: conjunctival biopsy-granulomatous inflammation. *
Sympathetic ophthalmi(autoimmune) Bilateral granulomatous inflammation causing Panuveitis …Develops after a penetraing injury to eye that exposes rential Ag in blood that are not recognized by immune system causing bilateral blindness effected eye and not C/F: floating spots, reduced vision, pain in both eyes and increased sensitivity to light Uveal Melenoma MC primary intra-ocular malignancy of adults (mc in skin 2 nd is uvea ) Large cells, vesicular nucleus; prominent eosinohoiolicnucleolus.?? Melanin pigment+ Most Common in the choroid…Iris melanoma usually presents as a pigmented mass My cause retinal detachment, macular edema *
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Optic nerve 1.Glioma (pilocytic astrocytoma) & Meningioma (commonest tumors) asso tumors) asso w NF1 2.Papilledema: sign 2.Papilledema: sign of raised ICP or compression of the N a) In CSF pressure around the nerve. b) Compression of the nerve by tumors.
Diseases of Neuromuscular Junction Myasthenia gravis Autoimmune autoantibodies against ACH receptors at NMJ postsynaptic deposits at the motor end plate resulting muscular weakness Associations: MC cause Thymic hyperplasia 85% , Thymoma Morphology: Type II fiber atrophy Muscular weakness; facial muscles Extraocular muscles weakness: Ptosis, diplopia Weakness worsens with repeated contractions Complication: Respiratory muscle weakness - Death Treatment: Anticholinesterase agents, steroids, thymectomy Eaton Lambert syndrome Autoantibodies against volatag e gated calcium channels on the presynaptic membrane inhibiting depolarization. No Ach release No post-synaptic activation MC presentation is apart of paraneoplastic syndrome of Small Cell Carcinoma of lung Clinically: Proximal muscular weakness improves with repeated contraction
Auto-Immune mediated demyelinating neuropathy Guillain-Barre Syndrome: Ascending paralysis: Acute onset weakness in the distal limbs rapidly prgressing proximal Absence of deep tendon reflexes Slowing down of nerve conduction velocity Endoneuroitis** and perivenular presence of lymphocytes, plasma cells and macrophages Endonurom lines the single lnerve fibers Fasicalles/biundels is by perinueium Outtermost is epinurimunm Pathogenesis: CD4 T-cell mediated response directed twd myelin asso protein 2/3 of cases are preceded by an acute, influenza-like illness Associated infections with hisotry of prior vaccination Campylobacter jejuni* Cytomegalovirus Epstein-Barr virus, Mycoplasma pneumoniae, Morphology: Inflammation of peripheral nerves Diagnosis: Nerve conduction studies CSF analysis: Albuminocytological dissociation Normal cell count Elevated proteins-albumin
Diseases of Skeletal Muscle Spinal Muscular Atrophy AR (Infantile) Progressive illness that selectively destroy the anterior horn cells in the spinal cord or cranial nerve! Motor Neuron Disease Mutation: affecting survival motor neuron 1 (SMN1) Histologic: panfascicular atrophy- total atrophy off all the muscle fibrils in the bundle w/in the fascicle Werdnig-Hoffmann disease (SMA type 1) severe hypotonia "floppiness of infants " distal muscle dorisfelxor of foot flexors of hands facial mucular atrophy Specific histological changes, normal creatinine kinase level Central core disease: AD " Nemaline myopathy: AD/AR " Myotubular myopathy: X Linked, AR/AD " •
Duchenne Muscular Dystrophy X-Linked DMD is one of the largest human genes MC and Severe form of muscular dystrophy deletion of the dystrophin gene total lack…. Mild form Beckers seen in late adulthood. Cytoplasmic protein located next to sarcolemmal membrane in myocytes allows for intracellular to extracellular connective tissue contraction by transferring the force
Cause of death: Respiratory failure involving the diapham so you mush put them on ventilator
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Pathogenesis Females carriers; asymptomatic but often have elevated serum creatine kinase Diagnosis: Muscle biopsy DNA analysis by PCR Western blot Clinical features: Normal at birth; Symptoms by 5 yrs progressive proximal muscle weakness: shoulders & pelvic girdles Trendlenberg gait Gower’s sign using hand when sitting! standing (use the distal muscles) Calf pseudohypertrophy various sizes of muscle fibers that are undergoing degeneration … your muscles are being replaced by fibrosis and adipocytes(fatty infiltration ) Heart failure arrhythmia Dilated Cardio Myopathy Respiratory insufficiency & pulmonary infections (M/C cause of death) Microscopy: Necrosis, degeneration, regeneration of fibers Proliferation of endomysial(what covers indavisual muscle fiber) connective tissue
Infectious Polyneuropathies Leprosy: Tuberculoid and Lepromatous (ulcers in joint) Both show symmetiric involvement of peripheral nerves in the cool extremities Mycobacterium leprae invades Schwann cells . The body tries to compensate by Segmental demyelination , remyelination and loss of axons– (onion-bulbs) Diphtheria releases exotoxin that causes paraesthesia and weakness Varicella Zoster Virus infections also cause infectious polyneuropathies once it effects the body it remains latent in the trigeminal ganglion if there is reactivation you will get singles there or thoracic dermatomes
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Herediatary Motor and Sensory Neuropathy Charcot-Marie-Tooth Disease (HMSN – I): AD Mutation in myelin asso protein PMP22 Demyelinating & hypertrophic neuropathy (Palpable peripheral nerves) Presentation: Childhood or early adulthood: calf atrophy, distal muscle weakness, peroneal (longis bervious) muscular atrophy, classical deformity of pes cavus(high arch and metarsle head and the toes will be curved upward)
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Myotonic Dystrophy: Myotonia ! sustained involuntary contraction of a group of muscles AD with Increased CTG repeats (normally ~ 25 there= 100s to 1000s) You have excess miss folded proteins in every cell in the body resulting in Cardiomyopathy, Cataract, Frontal balding, Gonadal atrophy Patients complain of ‘stiffness’ Patients find it difficult to release the grip Percussion of thenar eminence elicits a myotonia intrinsic hand muscle and distal leg muscle weakness when you ask them to grip you hand it will be so tight BUT they will not be able to open the door knob Microscopy: Ring fibers
Acquired Metabolic and Toxic Neuropathies Peripheral neuropathy in Adult onset DM: 50% o f DM pt… 80% if suffering for +15 yrs Invlovment of sensory, sensorimotor, autonomicSymmetric neuropathy that involves distal sensory and motor nerves Asymmetric neuropathy-mononuropathy single peripheral/cranial N(oculomotor) Pathogenesis: (sorbital causes defect in …) polyol pathway * nonenzymatic glycation of proteins invloves BV(arteriosclerosis) Clinical features: Non healing ulcers Autonomic neuropathay Postural hypotension Incomplete bladder emptying resulting in urinary stasis!recurrent infection Sexual dysfuction -
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Myopathies associated with inborn errors of metabolism Mitochondrial Myopathies (Oxidative Phosphorylation D" mutations nuclear and mito genes effecting type 1 muscle fiber There is high mutation rate for mtDNA (Maternal inheritance ) compared w nuclear DNA. Microscopy: Ragged red fibers – suggestive of irregular contour C/F: Proximal muscle weakness External ophthalmoplegia. Encephelomyopathy Lactic acidosis Dialated cardiomyopathy.
Metabolic and Nutritional Neuropathy Uremic pts suffer from axonal degeneration – uremic nephropathy Thiamine (Vit B1) deficiency causes Neuropathic beriberi – a type of axonal neuropathy Deficiencies of Vits B6, B12, & E (antioxidant) also cause axonal neuropathy Chronic liver diseases and chronic respiratory diseases also cause – peripheral neuropathies
Neuropathies Associated w Malignancy…a local spread or due to paraneoplastic syndrome… Apical tumors in the lung ! Brachial plexopathy " Obturator palsy ! pelvis " Polyradiculopathy – With manengiocarinomatosisi tumor metastasis to cauda equina giving prob rise to lower limbs …there will be lumboscar invlment ..baldder and rectal " Cranial nerve palsy!Intracranial tumors " P ar an eo pl as ti c e ff ec t o f d is tan t c ar ci no ma (s ma ll ce ll ca rc ino ma ) causes diffuse s ym me tr ic peripheral neuropathy,immunological mechanism is suggest (IgG antibodies againt the nevere protein) "
Traumatic neuropathies (avulsions and lacerations) lead to nerve injury Re-growth (a slow process) is possible if ends are close in proximity 1-2 cm apart " Carpal tunnel syndrome * Meandian N compression neuropathy-numbness and parastheisa over thenar muscles of thumb and fingers ) " Longterm dialysis gives you amyloidiosis : Beta 2 microglobulin, " Acromegally: you are getting ILGF or Sematomendin C leading to growth of soft tissue, bone ,cartilage, and mucles all undergo hypertophy giving pt compression " Pregnancy " Hypothyroidism, •
Ion Channel Myopathies : (induced by vigorous exercise, cold, or a high-carbohydrate meal) Familial disease accompanied by myotonia and relapsing episodes of hypotonic paralysis Hyperkalemic: Mutations in genes that encode sodium ion channels - SCN4A Hypokalemic voltage-gated L-type calcium channel ONLY WORRY ABOUT below Malignant hyperpyrexia (malignant hyperthermia) - genes encoding L-type voltagedependent calcium channel, notably the rynodine receptor (RyR1). Excess realse of ca form the SER giving you severe hyperpyrexia bc ther is used of ca in high amounts you can get Tetany, increased muscle metabolism, and excessive heat production
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Inflammatory myopathies myositis Non-infectious Myopathies immune mediated disorders resulting in injury and inflammation Dermatomyositis Inflammation involves skin and skeletal muscle Pathogenesis: Antibody and complement deposits in capillaries specifically from B and CD4+ T cells are involved Microscopy: Perimysial & vascular inflammatory/lymphocytic infiltrate Perifascicular fiber atrophy Skeletal muscle fiber degeneration & regeneration C/F: Lilac or heliotrope skin rash of upper eyelids associated with periorbital edema Scaling erythematous eruption /dusky red patches on elbows, knuckles, knees- gottrons lesion A juvenile variant : GIT invlovment abdominal symptoms, mucosal ulceration and perforation Children/ adults, bilateral symmetric proximal muscle weakness Dysphagia Increased risk of visceral cancers Polymyositis: Adults, bilateral proximal muscle weakness with no cutaneous involvement Pathogenesis: Skeletal muscle injury is mediated by CD8+ T cells asso w HLA class-I & II. Microscopy: Endomysial lymphocytic inflammation Inclusion body myositis: only muscle Adults> 50 yrs Asymmetrical distal muscle weakness Microscopy: Cytoplasmic vacuoles w basophilic granules containing amyloid.(congo-red)
Toxic myopathies Thyrotoxic Myopathy : hypoT Acute/chronic proximal muscle weakness (cramping/aching) Ethanol Myopathy – asso w binge drinking ! rhabdomyolysis and myoglobinuria which (manifest as hematuria only when you observe on microsobe you will see no RBC or Cast) Drug- induced myopathy – steroid (Type 2 muscle fibers), chloroquine and statins
