Systemic Disease Flashcards
Inflammation
Defense response that elimates the products of cellular injuries. Inflammation plays a role in the healing of injured cells bi diluting or destroying the agent responsible for injury.
Acute inflammation
Occurs in 1-2 minutes post injury. Leukocytes help clear up the injury site by invading bacteria and degrade necrotic byproducts of the damage. Acute inflammation is deterministic-it happens the same way every tine
What are the three major types of acute inflammation
- Vascular size changes (dilation) to facilitate increased blood flow
- Structural changes in the microvasculature (increased permeability) facilitate the arrival of plasma proteins and leukocytes from the circulation
- Immigration of neutrophils (PMNs) from circulation to the site of injury
What does acute inflammation generate
RUBOR (redness)
CALOR (heat)
DOLOR (pain)
TUMOR (swelling)
Also the presence of WBCs
Possible outcomes of acute inflammation
Complete resolution
Scarring of fibrosis
Abscess formation
Progression to chronic inflammation
Chronic inflammation
Last weeks to years. Active inflammation, tissue injury, and healing progress at the same rate.
Chronic inflammation is characterized by
- Infiltration with mononuclear cells (macrophages, lymphocytes, and plasma cells)
- Tissue destruction
- Repair involving new vessel proliferation (neovascularization) and fibrosis
Chronic inflammation will arise from
- Persistent infections (H. Pylori)
- Prolonged exposure to potential toxic agents (asbestos)
- AI disease (RA)
Presentation of chronic inflammation
Not all chronic inflammations are identical. In fact the body adjusts the response according to the type of injury. One type of chronic inflammation is granulomatous inflammation
Granulomatous inflammation
Is marked by collections of large, activated macrophages with a squamous cell-like appearance
Examples of granulomatous inflammation
Bacterial: TB, leprosy, syphilis
Fungal: histoplasmosis, blastomycosis
FB: suture, vascular graft
Unknown: sarcoidosis
Local factors that affect wound healing
Prolonged healing: local infection, decreased blood supply, and the inabilialty to form clots
Systemic factors that can prolong healing
Diabetes, immunocompromised states, decreased peripheral blood flow, systemic infection, malnutrition, and increases glucocorticoid production (stress)
Reversible cellular injury
Process is marked by decrease in blood supply to a cell and a corresponding decrease in oxygen supply (hypoxia)
Lack of oxygen to a cell will cause
- increase in glycolysis and anaerobic respiration-the lack of oxygen leads to increases lactic acid concentration and a decrease in tissue pH
- a decrease ATP production, which disrupts the Na and K gradient across the cell; this causes accumulation of intracellular Na and subsequent cellular edema
If oxygen is restored to a cell during injury
ATP increases, the Na-K pump is restored, and anaerobic respiration ceases. Persistent ischemia will lead to irreversible cell injury
Irreversible cell injury
- Insuffient ATP resutls in Na accumulation and the cell, in turn, becomes edematous, which disrupts the cell membrane. This causes crucial cellular components needed for the reconstruction of ATP to leak out, and thereby further facilitates the depletion of high energy phosphates
- lack of oxygen will ultimately increase ischemia, causing irreversible tissue necrosis.
The events leading to irreversible tissue necrosis from cell ischemia
- progressive loss of membrane phospholipids
- cytoskeleton abnormalities
- toxic oxygen radicals, which damage the cell membrane and other cell components
- lipid breakdown products, which accumulate in ischemic cells and result in phospholipid degradation
Necrosis is a result of
Irreversible cell death
The death of one or more cells as a result of irreversible damage
Necrosis
What are the two processes that occur with necrosis
- Enzymatic digestion of the cell
2. Desaturation of the proteins
What are the 4 types of necrosis
- Cogaulative necrosis
- Liquefactive necrosis
- Caseous necrosis
- Fat necrosis
Coagulative necrosis
The structural boundary of the coagulated cell, tissue, or vessel is maintained, but integral structural proteins are denatured. This type of necrosis often occurs following MIs
Liquefactive necrosis
Cell with a well-defined boundary remains, but is consists of dull, gray-white remains. This is seen with fungal infections and often occurs in the lungs
Fungal, lungs
Caseous necrosis
Most often seen in TB infections. The term casesou comes from “cheesy” because the central necrotic tissue appears white and cheesy
Fat necrosis
Death to adipose tissue. Small white lesions are formed
Apoptosis
Well organized self destruction of cells; commonly referred to as programmed cell death. It occurs during embryogenesis, endometrium shedding during the menstrual cycle, or cell depletion in tumors. Apoptosis is critical in fine-tuning the developing retina. Over 70% of ganglion cells die via this process during development
Apoptosis and the retina
Critical in fine-tuning the developing retina. Over 70% of ganglion cells die this way during development
What are the hypersensitivity reactions
Anaphylactic
cytotoxic
Immune complex
Delayed
Anaphylactic HS components
Type 1
IgE
Histamine
Anaphylactic HS
An allergen activates a B lymphocytes and IgE Abs are produced and bind to the surface of mast cells and basophils. A second exposure to the allergen causes cross linking of IgE, allowing calcium to enter and resulting in degranulation of the cell
Common causes of a type I HS
Peanuts, shellfish, drugs (PCNs), snake venom, and winged insects
Initial response of a type I hS
5-30m and resolves in 30-60m. Late phase response (4-6 hours later) can occur, resulting in tissue damage
Histamine and type I HS
Primary mediator released from mast cells and basophils during a type I allergic reaction
Symptoms of histamine during type I HS
Itching Redness Rhinitis Wheezing Hypotension (vasodilation) Tachycardia Nausea/vomiting HA, syncope, seizures Life threatening anaphylactic shock
Which HS is fast and first
Type I anaphylactic
Requires EpiPen
What are the players of a type 2 HS
IgG and IgM
Ex. Rheumatic fever
Destroy part of the body in attempt to destroy the toxic cells
What is type II HS facilitates by
Abs against antigens absorbed on various tissue components, such as cell surfaces. IgM and IgG Ab bind to antigen or enemy cell, which leads to its destruction
- transfusion reaction with the prime example being Rh disease. Maternal IgG ab capable of crossing the placenta attack fetal erythrocyte antigens.
- rheumatic fever is another example
Which HS reaction has no Ag/Ab
Delayed
Which HS reaction has two players
Cytotoxic
Which HS involves Ca2+ reentering the cell
Anaphylactic
Comments of type III HS
Ag/Ab complexes
RA/SLE
Immune complex mediated HS
Type III
- mediated by Ag/Ab complexes either in the systemic circulation of those formed at the location of antigen deposition
- these Ag/Ab complexes activate the complement response. This triggers the attack on neutrophils, which then release lysosomal enzymes
- SLE
- serum sickness is also an immune complex disorder in which Ab are formed due to the intake of large amounts of foreign proteins
Delayed HS Components
T cells (memory)
2-3 days
TB skin test example
Delayed or cell-mediated HS
Type IV
Sensitized T lymphocytes encounter an antigen and release leukokinin, leading to macrophage activation
-examples: TB skin test, contact dermatitis, and cornal transplant rejection, phlyctenules is
2-3 days
SLE
AI disease affects multiple systems including the skin, kidneys, joints, and heart. Female to male is 10:1 and often arises in the 2-3rd decades of life. Symptoms include a butterfly (malar rash), discoid lupus, photosensitivity, arthritis, renal disorders, neuro disorders, immunological disorders, and hemolytic anemia. SLE patients will produce ANA and 90% will have joint pain.
Ocular findings of SLE
Dry eye, recurrent episcleritis, peripheral keratitis, and photophobia
Neuroophthalmic implications of SLE
Disc edema and papilledema
RA
The most common systemic inflammatory disease classically causes systemic arthritis in multiple locations that leads to destruction of articular cartilage. Symptoms are often worse in the AM and can include pain in the hands, wrist, feet, and small joints. Women are affected mroe commonly than men, age 40-50. These patients will have a positive RF test. Appx 25% of patients with RA will have ocular manifestations
Ocular manifestations of RA
Keratoconjunctivitis sicca
Scleromalacia perforans
Choroiditis, retinal vasculitis
Papilledema is less common but possible
Scleritis in RA patients
Necrotizing without inflammation=scleromalacia perforans. No pain
JIA
Formerly known as JRA. Predilection for young females and can affect multiple joints, these patients will have a negative RF, but can have a positive ANA. Patients under the age of 6 with recent onset of the disease and positive ANA are at a higher risk of ocular manifestation
They usually just have one joint affected
What is the most common cause of uveitis in children
JIA q
Classic clinical picture of JIA
Female with asymptomatic, chronic, bilateral, non-granulomatous, anterior uveitis
Often present with a low grade fever
Sjögren’s syndrome
Affects females between 40-60. Classified as primary and secondary
Primary Sjogrens
Aqueous deficient dry eye
Dry mouth
Evidence of reduced salivary secretion, positive focus score on a minor salivary gland biopsy, and the presence of autoAb
Secondary Sjogrens
Primary Sjogrens AND an autoimmune CT disease (RA)
Dry eye, dry mouth, arthritis
Classic triad of secondary Sjogrens
Dry eyes
Dry mouth
RA
What are Sjogrens patietns at a risk of
Appx 5% of Sjogrens patients develop a malignant B cell lymphoma
- primary Sjogrens more likely
- mean development of it is 7 years
When should you evaluate someone for Sjogrens
Refractory dry eye disease
Patients with oncurrent symptoms of dry eye, dry mouth, and/or arthritis
Sarcoidosis
Idiopathic condition that classically affects middle aged AA females. Characterized by non-caseating granulomas and increased levels of serum angiotensin converting enzyme (ACE). Up to 40% of active cases of sarcoidosis can have normal ACE resutls. 90% of patients have lung invovlemt-a chest X ray is indicated if the disease is suspected. Patients are often asymptomatic, but can have complaints of breathing difficulties, dry cough, and unusual rashes. 25% of patients will have ocular manifestation
Ocular manifestations of Sarcodosis
- chonric dacryadenitits
- dry eye disease
- 19% of patients will have chronic, bilateral, anterior granulomatous uveitis
- CN VII palsy
- vasculitis, vitritis
- possible ON disease (unilateral disc edema, papilledema)
Ankylosing spondylitis
Chronic inflammatory condition of the spine with large joints that usually affects young males 10-30 years old. 90% of patients with be HLA-B27 positive
Manifestations of ankylosing spondylitis
- bamboo spine
- sacroiliitis causing lower back pain that IMPROVES with exercise and responds well to NSAIDs
- Acute anterior, unilateral (or alternating) non-granulomatous uveitis
- aortic regurgitation
Order a sacroiliac X ray
Most common cause of acute unilateral (or alternating) anterior non-granulomatous uveitis
Ankylosing spondylitis
Reactive arthritis
AKA reiters syndrome
- classic triad of urethritis, conjunctivitis, and/or anterior uveitis, and arthritis
- urinary symptoms will usually appear first. Low grade fevers, conjunctivis, and arthritis will then develop over the next several weeks
- affects young males more than females and is typically HLA-B27 positive
Can’t see, cant pee, cant climb a tree
Things that can cause episcleritis
RA
Lupus
UCRAP
Things that can cause anteiror nongranulomatous uveitis
UCRAP
JIA
Syphilis
Things that can cause anteiror granulomatous uveitis
TB
Sarcoidosis
Syphilis
AI things that can cause ONH disease
Sarcoidosis
Lupus
Psoriatic arthritis
Symmetrical, peripheral, small joint pain with accompanying psoriatic lesions found on the knees, elbows, and scalp. 7% of patients with psoriatic arthritis may develop anterior uveitis. These patients will have a positive HLA-B27 test. Treatment includes UV-B light exposure and methotrexate
What are the HLA-B27 conditions
UCRAP
- ulcerative colitis
- Crohns disease
- reactive arthritis
- ankylosing spondylitis
- psoriatic arthritis
Temporal arteritis (GCA)
Systemic vasculitis that affects the medium to large vessels including temporal artery. These patients are typically older than 55 years old and present with complaints of jaw claudication, jabbing neck pain, anorexia, scalp tenderness, temporal HA, and fever. A dialted and nodular temporal artery may also be present. 50% of patients with GCA may also develop polymayalgia rheumatica, which characterized by fatigue and morning stiffness in the hips and shoulders
Testing for GCA
STAT ESR
STAT CRP
STAT CBC with differential and platelets
Temporal artery biopsy (gold standard)
-can have false negatives due to skip lesions
Elevated ESR
> age/2 for men
>age +10/2 for women
Elevated CRP
> 2.45 mg/DL
Elevated platelets
> 400,000 cells/uL
What does the ESR/CRP look like in GCA patietns
90% will have an ESR>50 mm/hr. An elevated ESR and CRP is 97% specific for GCA
Eye problem and GCA
AION due to occlusion from the SPCA
Ischemic optic neuropathy may not be present for the first 24-48 hours after the onset of blindness
If GCA is suspected, what must you do
Begin therapy with prednisone immediately. Low dose aspirin (81mg) should also be considered to reduce the chance of visual loss or stroke
Granulomatosis with polyangitis (Wegner’s)
Systemic vasculitis involving the URT, lungs, kidneys. 60% have ocular invovlvement
Ocular complications of Wegner’s
Granulomatous sclerouveitis, retroorbital mass lesion with proptosis, conjunctivis, episcerlitis, scleritis, and ciliary vessel vasculitis
Peripheral sclerokeratitis may also occur and lead to corneal ulceration
Scleroderma
Multisystem disorder causing inflammation and vascular changes of the skin and internal organs. Ocular effects:
-dry eye and shrinkage of the areas of the skin, including the conjunctiva
Gout
- caused by the formation of monosodium urate crystals in joints in response to increased Uris acid levels
- occurs most frequently in the MTP joint of the big toe, which is called podagra
- more common in men. Presents with sudden onset of red, hot joints
What ocular complication can occur secondary to gout
Band K
What drug is used to reduce gout flare ups
Allopurinol: reduces incidence of gout flare ups by inhibiting xanthine oxidase
The most common causes of acute, anterior, non-granulomatous uveitis are
Ankylosing spondylitis (90%) IBD (85-90%) Reactive arthritis (60%)
Since they are all HLA-B27, ordering this test fails to differentiate between them if you suspect uveitits is due to an HLA-B27 disease
Diseases of immunodeficiency
May develop due to inherited defects in the development of the immune system or may be secondary to disease that affect the normal immune system. An ex alpine of inherited immunodeficny is immunoglobulin A deficiency
Deficiency of immunoglobulin A
- IgA deficiency is the most common of the primary immunodeficiency diseases
- IgA is the prominent immunoglobulin in external secretions, including the tear film; involved in mucosal defenses
- patient will show a significant decrease in IgA in both serum and secretions
- may be asymptomatic, or may suffer from recurrent respiratory infections, keratinization of the cornea, weight loss, and diarrhea
AIDS
Caused by HIV, and RNA virus that uses reverse transcriptase to make viral DNA within effected cells. AIDs is marked by severe immunosuppression and resulting opportunistic infections. The smog common way to acquire HIV is through sexual contact. The most common symptoms include fever, lymphadenopathy, sore throat, rash, myalgia/arthralgia, and HA. Prolonged duration of these vague symptoms with the presence of mucocutaneous ulcers is suggestive of the disease
What do all drugs for HIV target
Reverse transcriptase
What CD4 count do you have to reach to have AIDS
<200
Testing for HIV
ELISA test is used as the screening test for HIV. A western blot is then used to confirm the ELISA test. Collectively these tests have a 99.9% specificity rate. Although these tests are still recommended for testing saliva and dried spot blood samples, the CDC recommends new guidelines for testing blood samples for HIV that involves Ag/Ab immunoassay to detect HIV Ab and HIV Ag within the blood
The most common ocular infection and the leading cause of blindness in AIDS
CMV retinitis
-CD4 <200 at risk, <50 at high risk
Treatment for CMV retinitis
Gancyclovir
Foscarnet
What is the most common opportunistic infection in HIV
Pneumocystic pneumonia
Parasitic opportunistic infections in HIV
Toxoplasmosis
- papilledema
- CN palsies
Bacterial opportunistic infections of HIV
Mycobacterium TB
Viral opportunistic infections of HIV
CMV and herpes simplex
Kaposi’s sarcoma is a malignancy caused by HHV-8
Kaposi’s Sarcoma
Herpes virus 8
HIV
Malignant
Red/purple lesions on the lids or conj
Seborrheic keratitis
Crusty, plaque like tan lesions that have a classic elevated “Stuck on” appearance. These are found most commonly in males over 30. Seborrheic keratosis is usually not treated; for smaller lesions, shave excision or curretage is recommended; larger lesions rewuire complete surgical excision
Keratoacanthoma
Isolated, dome shaped nodules usually seen on the face and mimics SSC. It has a spontaneous remission over a period of several months
Papilloma
Common slow growing epithelial tumors (viral warts) that may be caused by HPV
- characterized by finger like or cauliflower like appearance (skin tag); usually elevated and multilobulated with a central vascular core
- treatment for papillomas can range from no intervention, to excision or snipping, chemical cauterization, surgical excision, or cryotherapy
Xanthelasma
Yellow, elevated, plaque like lesions that are typically bialteral, symmetric, and located within the medial portion of the eyelids
- associated with older age, female gender, and high cholesterol, although most patients with xanthelasma have normal cholesterol
- treatment includes full thickness surgical excision, carbon dioxide laser treatment, and chemical cauterization; recurrences after treatment are common
Molluscum contagiosum
- Chronic infection (direct contact) skin condition caused by DNA pox virus. The condition is common in kids and young adults in communities with poor hygiene.
- classic presentation is a single or multiple dome shaped waxy umbilicated nodules on the eyelid or eyelid margin. Patients are typically asymptomatic, but nodules can spontaneously open, resulting in a follicular conjunctivitis
- if multiple are presently, HIV should be considered
- treatment is incision, curretage, shaving excision, cauteriation, or cryotherapy
What causes follicles
CHAT
- chlamydia
- herpes
- adenovirus
- toxic (molluscum)
Acne rosacea
Syndrome of undertermined etiology that affects sebaceous glands of the face and eyelids. It is characterized by vascular abnormalities and papulopustular lesion on the cheeks and forehead. Classic signs include superficial telangiectasia, rhinophyma (late stage), and facial flushing. The latter is associated with triggers such as alcohol, spicy foods, caffeine, and increased sun exposure
Ocular findings of acne rosacea
Due to inflammation of the meibomian and zeiss glands
- inspissated meibomian glands
- blepharitis
- hordeola
- chalazia
- DED
- phlyctenules
- staph marginal keratitis
- SPK
- corneal neo
Allergic contact dermatitis
Delayed type 4 HS response of inflammation to any substance that comes in contact with the skin. Classically results from cosmetics, makeup, shampoo, hairspray, fingernail polish, perfume, jewelry, poison ivy, CL solution. Medications such as aminoglycosides, trifluridine, cyclo/myds, glaucoma meds, and preservatives
Ocular signs of contact dermatitis
Acute periorbital swelling
Conjunctival chemosis, redness, itching, and tearing
Impetigo
Gram + infection with classic honey colored crusted lesion
Very common in kids
HSV
HSV I and II. Both can cause ocular infections but type I is significantly more commonly (98%) of cases. Type I HSV usually occurs above the belt and is transmitted by close persons along contact. Type II HSV usually causes infections below the belt and is STD
What HSV is most common cause of ocular manifestations
Type I
Which HSV is the most common cause of herpetic keratitis in neonates
HSV II
90% of adults wtih HSV I obtain it from
Primary infection as a child
After initial infection of HSV
Virus hides in the trigeminal ganglion and can reoccur at any time
Reactivation of HSC can be triggered by
Physical and emotional stress, including sun exposure, hormonal changes, fever, trauma, and immunosupression
Primary ocular exposure of HSV
Blepharitis with focal vesicular lesion on the eyelids and periorbital skin
Acute unilateral follicular conjunctivitis with PAL
Recurrent HSV ocular manifestations
- dendritic keratitis
- marginal or GA ulcers
- neurotrophic Keratopathy
- interstitial keratitis
- disciform endotheliitis
- acute anterior unilateral non-granulomatous uveitits with trabeculitis
- acute retinal necrosis
After an inital corneal HSV epithelial infection, there is a ___ chance of having a recurrent.
25%
The risk increases to 40-45% after a 2nd episode
HZV
Initially presents at chicken pox. After the inital infection, the virus lays dormant in the nerve roots. HZV is the reactivation of VZV in the dermatome that was assocaited with the latent virus. 66% of patients are over the age of 50. Consider a medical evaluation in patients younger than 40 to determine if they are immunocompromised
HZO may involve the following
- blepharitis with vesicles on the eyelid margin
- acute follicular conjunctivitis on the affected side
- episcleritis
- pseudodendritic keratitis
- acute anterior unilateral non-granulomatous uveitis with trabeculitis
- acute retinal necrosis
- optic neuritis
- EOM palsies
- proptosis
Hutchinson’s sign
Vesicular rash on the tip of the nose. Indicates involvement of V1, which increases the risk of ocular involvement
Nasociliary
Behçet’s disease
Inflammtory disease causing multissytem complications. Recurrent oral aphthous ulcers and two of the following features are needed for diagnosis: genital ulcers, eye lesions, or skin lesions. Most commonly seen in Asian and middle eastern young adults. Ocular findings are
- acute recurrent hypopyon,
- iritis
- posterior and anterior uveitis
- retinal vasculitis
- vitritis
- secondary cataracts
- glaucoma
- neovascular lesions
What is the only systemic condition that presents with a hypopyon
Behçet’s disease
Malignant melanoma
- most common cancer of young women
- depth of invasion is the number one prognostic factor
- risk: age, skin color, fam Hx, an repeated irritation and sun exposure
- characteristics of suspicious skin lesions for malignant melanoma include ABCDE; asymmetry, border, color, diameter, and enlarging
Most common cancer of young women
Malignant melanoma
What is the number one prognostic factor for malignant melanoma
Depth of invasion
What is the most common variant of melanoma
Superficial spreading melanoma
-it has rapid growth and is classically found on non-exposed skin
BCC
- malignancy of the basal cell layer of the epidermis. Often appears as a shiny, firm, pearly nodule with superficial telangiectasia. Progression can lead to central ulceration (rodent ulcer)
- treatment is 5-FU or biopsy with surgical removal
SCC
Malignancy of the stratum spinosum layer of the epidermis. Non-healing ulcer that often appears an an erythematous plaque. It can arise from a pre cancerous lesion called actinic keratosis
Sturge Weber Syndrome
Rare congenital vascular disorder characterized by a facial capillary malformation (overabundance) known as a port wine stain. These patietns may have seizures, focal neurological deficits, or mental retardation. Ocular findings
- unilateral glaucoma due to increased EVP (obstruct outflow)
- vascular malformations of the conjunctiva, episclera, choroid, and retina
- iris heterochromia
Tuberous sclerosis
Multisystem genetic disease that causes benign tumors to grow in the brain and other organs. About 90% of these patietns with TSC have one of the characteristic skin lesions which include hypopigmented macules (ash leaf spots), shagreen patches, angiofibromas, and a distinctive brown fibrous plaque on the forehead. Ocular findings
- astrocytic hamartoma s or phakomas which are grey-ish or yellowish-white lesion in the retina. Astrocytic hamartoma calcify and can be seen on a CT scan
- choroioretinal depigmentation
- coloboma
- angiofibromas of the eyelid
- papilledmea ( from brain tumors)
AD disroders
Resutls from one abnormal dominant gene. If an affected heterozygous man (Aa) and an affected heterozygous woman (Aa) have kids, the rolling phenotypes are possible
- 75% of offspring will have the condition
- the remaining 25% will NOT have the condition
AR disorders
Result from two abnormal recessive genes. If a man (aa) and a carrier heterozygous woman (Aa) have kids, the following phenotypes are possible in their offspring
- 50% of their kids will have the condition
- the remaining 50% of the kids will NOT
X-linked disorders
Defective recessive genes on the X chromosome. A man is affected i he has an abnormal recessive gene on his X chromosome. A woman is affected i both X chromosomes have the abnormal recessive gene. If an affected nan (XdY) marries a carrier women (XDXd), the following phonetypes are possible
- half of their sons will have the condition
- half od their daughters will have the condition
What systemic diseases are associated with keratoconnus
TDOME Turners Down OI Marfans Ehlers-Danlos
Down syndrome (trisomy 21)
- most common chromosomal disorder
- caused by an extra 21st chromosome
- mental retardation, flat facial profile, prominent epicanthal folds, congenital cataracts, glaucoma, strab, simian crease in hands, congenital heart disease, and early onset of Alzheimer’s, keratoconnus
Klinefelters syndrome
XXY
- girly men
- most common cause of male primary hypogonadism
- an extra X chromosome (XXY) results in testicular atrophy, long extremities, gynecomastia, female hair distribution, and hypogonadism
Turners syndrome
X0
- absent X chromosome
- manly girls
- the only sex chromosome aneuploidy with established ocular findings; common ones include keratoconus, strab, amblyopia, reduced accommodation, and convergence insuffiency (turners=eye turn)
- affects 1 in 3000 females and is characterized by short stature, dysgenesis, webbing of the neck, and coarctation of the aorta
- most common cause of primary amenorrhea
Which genetic gender disorder affects the binocular vision
Turners
-strab and Amblyopia
Autosomal dominant disorders result from
Abnormal structural genes. They affect many generations and occur equally in males and females. They often present after puberty; one must consider fam Hx in dx. Examples of AD disroders include
- VHL
- NF1
- marfans
- Huntington’s Chorea
- FAP
VHL
AD
Benign and malignant tumors
Retinal agiomas that can hemorrhage if left untreated, leading to retina detachment, glaucoma, and loss of vision
NF1
AD Tumor forming nerve cells 1:3000 50% have no fam Hx Triad -cafe au lait spots, neurofibromas, and lisch nodules on the iris Optic nerve gliomas (can squeeze ON) Congenital glaucoma
Marfans
AD
CT disease
Tall ,long extremeitis, subluxating joints, and long fingers and toes
Causes cardio effects such as aortic incompetence, dissecting aortic aneurysms, and floppy mitral valve
Ocular effects
-subluxation of the lens (ST), RD, kone
Number one cause of lens subluxation
Truama
Huntington’s chorea
AD
Chromosome 4
Gradual onset and progression of chorea and dementia
30-50 years of age, with a 15-20 year survival rate
Abnormal eye movements will occur and include a delay in pursuits, voluntary saccades, and refixation (“Hunters pursuit”)
FAP
AD
Chromosome 5
Hundreds of polyps on the colon post puberty
100% of these patients get colon cancer
Gardners syndrome
-variant of FAP characterized by multi-focal CHRPE (4 or more)
-refer for colonoscopy
AR diseases
Sickle cell
Tay-Sachs
PKU
AR disorders are usually
Seen in 1 generation, as 25% of offspring from 2 carrier parents are affects. The disease are often more severe than the dominant disorders and will often present in childhood
Sickle cell anemia
- patients have painful crises (ischemia) due to sickle CHRPEs RBCs causing blockages within arteriole vessels; ultimately leading to organ failure I
- the most common form of sickle cell anemia is caused by a single base pair mutation in the beta globin gener where VALINE is substituted with GLUTAMIC ACID
- 1 in 400 AA are afflicted. 8% of AA population are carriers
- can occlude retinal arterioles, leading to ischemia and subsequent retinal neo (proliferative). The blood vessels are often called sea fan retinopathy because of their shape.
Labs for sickle cell
Decreased hemoglobin
Increased bilirubin
Increased reticulocytes
Blood smear shows sickling
What diseases cause proliferative retinopathy
DRVOS
- DM
- ROP
- vein Occlusions
- OIS
- sickle cell
PKU
- AR
- mutations in the enzyme phenylalanine hydroxylase; this is used in the AA conversion of phenylalanine’ to tyrosine. If not treated, it will result in mental retardation. All newborns are tested for PKU. If the patient responds as a positive carrier, then treatment with a diet low in phenylalanine is initiated. Phenylalanine is found in milk products, aspartame, meat, and chicken.
- occurs in 1/10,000 people
Tay-Sachs disease
AR
Eastern European Jews
progressive destruction of the nervous system. Ocular findings
- cherry red spot
-atrophy of the ON
Build up of ganliosides in the ganglion cells (none in the fovea)
What are two conditions that can cause a cherry red spot
CRAO
Taysaches disease
X linked conditions
Fabrys
Duchenne muscular dystrophy
Fabrys diseas
X linked
Abnormal lipid depositions in blood vessel walls throughout the body. Deficiency of the enzyme alpha galactosidase A allows lipids to build up to harmful levels in the eyes, kidneys, ANS, and cardiovascular system. It affects adolescent boys and is characterized by excruciating pains in the extremeities and abdomen. Areas of telangiectasia on the umbilicus, growing, elbows, and knees are diagnostic
Ocular findings
-light colored, whorl K
Duchenne muscular dystrophy
- AR
- deletion within the gene coding for dystrophin
- 1/3000 male infants afflictedm symtoms by age 5
- condition is characterized by muscle weakness that begins in the pelvic girls and progresses superiority
- walking and getting tired
Which of the keratonnus systemic diseases has messed up type 1 collagen
OME of “TDOME”
OI
Brittle bone disease
-host of genetic defects giving rise to abnormal collagen synthesis. Characterized by multiple fractures occurring with minimal trauma. Ocular findings are blue sclera, keratoconnus, and megalocornea
Mitochondrial disorders
Transmitted only through mother’s (maternal inheritance). All offspring of affected females may show the disease. An important mitochondrial disorders with ocualr results manifestations is LHON
LHON
rare recessive disorder that resutls in bilateral, asymmetric primary optic neuropathy. 85% of affected patients are males. The average age is late teens or early 20s. The condition may spontaneously improve in 35% of cases
ocular findings:
-early: optic disc hyperemia, and telangiectatic vessles
-late: progressive optic disc pallor with resulting loss of central vision (BCVA 20/200 to CF)
My Mother Leber Lost My Eyes
Most common type of anemia
Iron deficiency
More than 50% of anemia’s fit into this category
Anemia’s with decreased MCV (small cells)
Iron deficiency
Thalassemia
All have decreased Hgb
Anemia’s with normal MCV
Aplastic
CKD
Sickle cell
All have decreased Hgb
Anemia’s with increased MCV
Vit B12 deficiency
Folic acid deficiency
Alcoholism
Iron deficiency anemia
- most common anemia
- adutls=GI blood loss
- may also occur with malabsorption or increased need with decreases intake, such as in childhood or pregnancy
- iron defiance impairs cellular function and can cause brittle hair, nail spooning, and pica (eating weird things)
- treat with oral iron
Aplastic anemia
Pancytopenia characterized by severer anemia, neutropenia, and thrombocytopenia
-destroyed bone marrow
Causes of aplastic anemia
Infectious agents (viruses) Radiation (chemo) Drugs -chloramphenicol -acetazolamide -trimethoprim -methotrexate -pyrimethamine
Anemia of chronic kidney disease
Chronically damage kidneys synthesize inadequate amounts of erythropoietin (EPO), a hormone that normally stimulates RBC production in the bone marrow
Sickle cell anemia
Can cause proliferative retinopathy due to the crescent or sickle shaped cells occluding the retinal vessels
Vitamin B12 deficiency
Due to inadequate intake or malabsorption of vitamin B12; malabsorption is often caused by pernicious anemia
Pernicious anemia
Characterized by autoAB directed against parietal cells of the stomach, causing decreased production of intrinsic factors
Intrinsic factor and B 12
Intrinsic factors helps absorb B12. Decreased=decreased B12
Folic acid deficiency
- dietary deficiency is the leading cause and use especially common in alcoholics
- may also be drug induced (chemo, methotrexate), or from malabsorption syndromes
- folic acid deficiency in pregnancy increases the risk of neural tube defects (spina bifida)
Multiple myeloma
Neoplastic disorder of plasma cells
Proliferation of a malignant clone of plasma cells in the bone marrow. This often results in extensive skeletal bone destruction, unexplained anemia, hypercalcemia, and acute renal failure
Neoplastic disorders of the blood cells
Leukemia and lymphoma are malignant proliferative diseases involving leukocytes. Early cell growth and maturation are inhibited, causing “malignant clones” of these cells to accumulate. Death results because of substantial loss of normal cells, and also due to poor organ function owing to the increase in malignant cells
Lymphoma-lymph tumor
Proliferation of malignant lymphoid cells in solid tissues such as lymph nodes, spleen, and the GI tract. Initally the tumor is localized, but it may subsequently spread. There are two types of lymphomas
- Hodgkin
- Non-Hodgkins
Hodgkin’s lymphoma
40% of lymphoma
- tow peak age groups: 15-30 and then >50
- commonly presents with enlarged lymph nodes, fever, night sweats, and itching
- characterized by Reed-Sternberg cells (owl eye nucleus)
- prognosis is good is dx early enough
- 50% of cases are associated with EBV
Non-Hodgkins lymphoma
- 60% of lymphomas
- enlarged lymph nodes and GI tumors (with abdominal pain)
- heterogenous group of malignancies with variable prognoses depending on the type
- bone marrow biopsy is performed to determine T or B cell ropes
Reed sternberg cells
Hodgkin lymphomas
Which type of lymphoma is most common
Non-Hodgkin
Acute leukemia
This disease can affect all ages, but usually occurs in younger patients. The predominate cell type is Blast cells: >30% of marrow cells are blasts (immature cells). There are two major types of acute leukemia
- Acute myeloblastic leukemia (AML)
- Acute lymphocytic leukemia (ALL)
Acute myeloblastic leukemia (AML)
- infants and middle aged or older
- characterized by normal WBC count with excessive myeloblasts
- Auer Rods may be seen within leukemic cells in the blood
Auer rods
AML
Acute lymphoblastic leukemia (ALL)
- peak age 2-10
- normal WBC count with excessive lymphoblastic
- with treament, 75% of kids remain disease free > 5 years
ALL kids live long
A retinal hemorrhage with a white spot in the middle
Roth spot
Characteristic of leukemia and endocarditis
Chronic leukemia
Usually affects older adults. The predominant cells are mature cells of the bone marrow. Patients are often asymptomatic and may have anemia. There are two types
- Chronic myelocytic leukemia (CML)
- Chronic lymphocytic Leukemia (CLL)
Chronic myelocytic leukemia
- age of onset 25-60 years old. Poor prognosis, only 3 year survival rate
- characterized by WBC count of 50,000 to 300,000 with increased granulocytes in all states of maturation
- 90% have the Philadelphia chromosome
“Cut my life”
Philadelphia chromosome
CML
Chronic lymphocytic leukemia (CLL)
- onset >50
- male/female 2:1
- WBC count of 20,000-200,000 with a predominance of mature small lymphocytes
- 5-10 year survival rate
“Could live long”
Leukopenia
A decrease in the number of WBC
Due to bone marrow injury, bone marrow inactivation, drugs, or chemical suppression
Leukocytosis
Increase in the absolute number of WBCs
Can occur after surgery, or result from infections, illness, stress, or pregnancy
Neutrophilia
Increase in he absolute number of neutrophils
Typically reuslts from stress, exercise, pain, fear, or pathological infections
Thrombocytosis
Elevated platelet count
Causes include inflammation, kidney disease, or spleen removal
Pancytopenia
Decrease in the number of RBCs and WBCs and platelets
Thrombocytopenia
Decrease in platelets
Causes include infection, live failure, and bone marrow disorders
Edema
Increased intestinal fluid that can be non-inflammtory (yielding protein poor transudate) and inflammatory (yielding protein rich exudate) in etiology. Edema can be recognized on exam by increased swelling of the length due to subcutaneous edema, or shortness of breath due to pulmonary edema. Treatment includes diuretics and compression stockings
Non-inflammatory causes of edema
- Increased organ pressure: seen in CHF, liver cirrhosis, and venous obstruction or compression
- Reduced plasma osmotic pressure: protein-losing glomerulo-pathologies and malnutrition
- Lymphatic obstruction-post surgical or neoplastic
- Sodium retention: excessive salt intake with renal insuffiency
diabetic macular edema
Caused by macroaneurysms with dilation of capillary walls. Pericytes, endothelial foot-plates that surround the vessels, are damaged, allowing leakage of blood and fluid with resulting edema
Inflammatory causes of edema
Acute and chronic inflammation
Angiogenesis (after injury)
Hemorrhage
Leakage of blood due to a vessel injury that may be uncontained or enclosed within a tissue. Hemorrhage within a tissue are referred to as hematomas. All are grouped according to size
Petechiae
1-2mm hemorrhages on the skin
Purpura
Greater than 3mm hemorrhagehs associated with trauma, local vascular inflammation, and low platelet count
Ecchymoses
Greater than 1-2cm and include subcutaneous hematomas or bruises
Hemothorax/hemopericardium/hemoperitoneum
These are large accumulations of blood within body cavities
Thrombosis
Resutls from an inappropriate activation of blood clotting in an uninjured vein, or an occlusion of a vessel after a relatively minor injury. These can form anywhere in the circulatory system, may be arterial or venous, and may be non-occlusive. The most common location of thrombus formation is the deep venous system of the legs
Virchows triad
A major theory delineating the cause of a venous thromboembolism (VTE). It proposes that VTE occurs as a result of
- Alterations in blood flow STASIS
- Vascular endothelial INJURY
- Alterations in the constituents of the blood through an inherited or acquired HYPERCOAGULABLE STATE
Inherited hypercoagulable states
Factor V laden
Antothrombin 3 deficiency
Protein C and S deficiency
Prothrombin gene mutation
Acquired hypercoagulable states
BCP
Preg
Smoking
Malignancy
Venous thrombosis
Commonly occurs in either the superficial or deep legs of the veins. Those in the deep leg veins (typically above the knee) are mote likely to embolism to the heart or lungs
Leg to lungs=pulmonary embolism
Arterial thrombosis
These are commonly formed from atherosclerosis or a MI. They usually travel (embolism) to the brain, kidneys, and spleen
