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
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 tissueprovokes granulomatous reaction - lipogranulomatous inflammation. painful
Stye infection of the eyelid M.C due to S.aureus.
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,
Bitots spot . Keratinization of mucous membrane epithelium.
MC and earliest symptom: Night blindnessLens
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)
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 2nd is uvea )
Large cells, vesicular nucleus; prominent eosinohoiolicnucleolus.??
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Melanin pigment+
Most Common in the choroidIris melanoma usually presents as a pigmented mass
My cause retinal detachment, macular edema

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. ??
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Adult vitreous humor is avascular.??
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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

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Hypertension, Diabetes Mellitus
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Retinopathy of Prematurity (Retrolental Fibroplasia)
Hypertensive retinopathy
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Grade 1 : focal narrowing of the arterioles, mild A-V nicking
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Grade 2: + copper wiring
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Grade 3: + silver wiring, flame shaped and dot blot hemorrhages, soft cotton
wool spots and hard exudates present, disc normal
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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
Diabetic retinopathy: New Neovascularisation in the retinal layers
Pre-proliferative Abnormalities of angiogenesis located within the retina
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Basement membrane of retinal blood vessels is thickened.
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Microaneurysms
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Macular edema
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Exudates- outer plexiform layer
Proliferative
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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 retina
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
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Genes-CFH(Complement Factor H) genotype with H/O smoking 10pack years.
2 types: dry or wet.
Retinitis pigmentosa: Mutations in genes that regulate the photoreceptor cells or the RPE.
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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 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
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Similar to primary large cell lymphoma of the brain.
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In older people mimics uveitis clinically.
Optic nerve
1.Glioma (pilocytic astrocytoma) & Meningioma (commonest tumors) asso w NF1
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 volatage 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
Inflammatory neuropathies:

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!
Cause of death: Respiratory failure involving the diapham so you mush put them on ventilator !
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
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)
Acquired Metabolic and Toxic Neuropathies
Peripheral neuropathy in Adult onset DM: 50% of 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

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 Malignancya 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
" Paraneoplastic effect of distant carcinoma(small cell carcinoma) causes diffuse symmetric
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

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

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Central core disease: AD
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Nemaline myopathy: AD/AR
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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
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
Gowers 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
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
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.
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 !