Atchley Objectives Flashcards
Differentiate necrosis from apoptosis in terms of how controlled and mess each is
- necrosis: irreversible, often uncontrolled death of many cells. May produce exudate-mess, high protein fluid filled with neutrophils. May be aseptic due to blood loss
- apoptosis: programmed cell death, well organized self-destruction of cells. Apoptosis is critical in fine tuning the developing retina
Identify the 4 types of necrosis discussed in class
Coagulative necrosis, liquefactive necrosis, caseous necrosis, fat necrosis
Recognize the gross morphological features and general cause for each of the types of necrosis
a. Coagulative necrosis: the structural boundary of a coagulated cell, tissue or vessel is maintained by internal proteins are denatured. Due to ischemia or infarction: heart attack
b. Liquefactive necrosis: structural transformation of the tissue into a liquid viscous mass. Leave spurs and fluid remains, forms abscess. Associated with bacterial or fungal infections. EXCEPTION: in the brain, liquefactive necrosis is aseptic and due to ischemia.
c. Caseous necrosis: Cheesy proteinaceous dead cell mass. Most often observed in TB infections
d. Fat necrosis: death of adipose tissue, small white lesions formed. Usually in subcutaneous tissue because of trauma
Identify the type of necrosis that occurs in the brain due to ischemia vs other organs in the body.
In most places in the body, ischemia leads to coagulative necrosis, but in the brain it leads to aseptic liquefactive necrosis.
Identify the enzyme that initiates the arachidonic acid pathway and predict the impact of steroids on the COX and LOX pathways
a. Pal-2
b. Steroids hit PAL-2 and stops the whole cascade
Name the two arms of the COX pathway and explain why aspirin blocks one arm, but not the other.
a. COX goes into PGI2 and Thromboxane A2
b. Aspirin blocks thromboxane A2. It actually works on cyclooxygenase, but causes platelets to not regenerate TXA2. This is a way for it to work on the platelets without shutting down PGI2
How does the action of aspirin differ from that of other NSAIDS?
a. Aspirin is irreversible. It acetylates the platelets and neutralizes them. Other NSAIDs are reversible
List the cardinal signs of inflammation
Rubor, tumor, dolor, calor, functio laesa
Determine which of the signs are driven by histamine and which is activated by another facto
a. Histamine drives rubber, tumor, calor.
b. Dolor is from PGE2 and bradykinin
Recall which cell types play the leading role in a true inflammation vs chronic inflammation
a. Acute: neutrophils
b. Chronic: macrophages and lymphocytes, eosinophils, basophils/mast cell
Explain how circulating neutrophils can double in numbers without activating bone marrow.
- 50% aim circulating pool and 50% in marinating pool.
- When taking CBC, you are only getting a reading of the circulating pool, if trauma happens, the marginating neutrophils become detached and now you get a higher reading
Describe the cellular composition of a granuloma
Epithelioid macrophages (sometimes forming multinucleated giant cells) surrounded by lymphocytes, central necrosis commonly occurs in TB
Decipher the acronym ‘ACID’ as it pertains to the four types of hypersensitivities
a. Anaphylactic/atopic-type I
b. Cytotoxic-type II
c. Immune Complex-type III
d. Delayed (cell mediated)-type IV
Anaphylactic (type I)
i. Allergen activates B cells, IgM class switches to IgE, preformed IgE docks on mast cells (basophils). Subsequent allergen exposure crosslinks IgEs and causes degranulation.
ii. Late phase: infiltration of tissues with eso and segs (major basic protein). Splits arachidonic acid from cell membrane. Releases leukotrienes and prostaglandins
Cytotoxic type II
i. Ab bind to cell membrane causing cellular destruction, inflammation, or cellular dysfunction
ii. Opsonization leads to complement, NK cell killing, and inflammation
iii. Ab bind and cause abnormal blockade or activation
Immune complex type III
Circulating Ag-Ab (IgG/IgM) complexes lodge in vessels and on tissues and activate complement, producing tissue damage
Delayed type IV
i. Antigens bind to sensitized CD4 cells
ii. CD 4 cells release cytokines that activate macrophages and CD8 cells and cause tissue damage
iii. AB not involved
Which antibodies drive three of the 4 HS reactions?
Type I: IgE
Type II and III: IgG and IgM
Which cytokines drive production of IgE
IL-4 and IL-13
Explain why the biggest threat of an anaphylactic reaction doesn’t end with mast cell degranulation
a. The early phase ends with mast cell degranulation, the late phase causes release of prostaglandins and leukotrienes (1000X stronger than histamine)
b. The late phase is driven by leukotrienes which is 100X stronger than histamine, which is what early phase is driven by
Explain how IgE mediated killing of parasites differs from IgE mediated allergic reactions
a. For a parasite, IgE is generated to bind to the worm (FAB portion), FD left swinging in the breeze and eosinophils have FC epsilon receptors. They collide with the parasite with IgE on it. Once eosinophils have cross linking, they release MAJOR BASIC PROTEIN, killing the parasite and causing tissue damage.
b. Major basic protein
What is coombs serum
Anti human IgG serum from rabbit immunized with human IgG
Differentiate a direct from an indirect Coombs test and explain why DAT is frequently used to evaluate a person with jaundice
a. Direct (DAT) tests for Ab on RBCs
b. Indirect (IAT) tests for Ab in the blood that could potentially bind RBCs. Plasma antibodies
c. DAT To test for anemia
Differentiate an Arthus reaction from induration in terms of hypersensitivity type and mechanism.
a. Arthurs is localized and serum sickness if systemic
b. Both are type III
c. Arthus: arm turns red after getting immunization. Ab that you formed that are not IgE, red and inflamed. Due to immune complexes
d. Serum sickness: most commonly caused by oral drugs. Drugs form haptins, which binds to proteins and have formation of immune complexes. If they bind directly to the cells and cause lysis, that is a type II
Describe phlyctenulosis macroscopically.
a. Blistering-forming keratoconjunctivitis that occurs due to a type IV HS reaction to antigens of bacterial origin.
What is phlyctenulosis most common cause?
Secondary due to blephatritis due to staph aureus
What HS reaction is phlyctenular KC?
IV
Differentiate a macular, papule, vesicle, pustule, scale, and a crust.
a. Macule is a flat lesion less than 1 cm (freckle)
b. Papule is a raised solid skin lesion less than a 1 cm (mole)
c. Vesicle is a fluid filled blister less than 1 cm (shingles)
d. Pustule is a pus filled vesicle (pustular psoriasis)
e. Scale is flaking off of stratum corneum (eczema)
f. Crust is dry exudate (impetigo)
Interpret the signs and symptoms and labs of a case to determine which of the following autoimmune diseases is present: SLE, scleroderma, Sjogren.
SLE:
- Signs/symptoms: malar rash, arthritis, renal disorders, neuro disorders, hemolytic anemia, rashes
- Labs: ANA, Anti-dsDNA, Anti-Smith Ab
Scleroderma - Signs and symptoms: excessive fibrosis throughout the body, skin and pulmonary involvement
- Labs: ANA is positive in 95% of pts, diffuse/bad scleroderma: Anti-Scl-70 antibody positive, limited/bending scleroderma: anti-crentromere Ab
Sjogrens - Signs and symptoms: dry mouth, dry eyes, and arthritis
- Labs: ANA and RF positive
Why is ANA sensitive, but not specific
Shows up in several disorders, such as SLE, scleroderma, and sjogren
Explain the prognostic significant of discoid lupus and drug induced lupus in patients with SLE.
a. Discoid: Only 10% get it and it only effects the skin
b. Drug induced: only 10% get it, signs and symptoms stop upon cessation of drug
Explain the meaning behind CREST in patients it’s scleroderma.
a. It is in limited scleroderma
b. Calcinosis, raynauds, esophageal dysmotility, sclerodactyly, telangiectasia
c. Benign
Most common cause of arthritis
Osteoarthritis
Is RA or OR more likely to have systemic manifestations
RA
Which is more likely to have legatee ESR.CRP, OA or RA
RA
Recall the immunoglobulin class of rheumatoid factor (RF) and explain its significance in the pathogenisis of rheumatoid arthritis
a. IgM
b. Autoantibody specific to FC portion of IgG bound to cartilage collagen
Estimate the likelihood of ocular symptoms in patients with RA, identifying the most likely one and most severe one
a. 25%
b. Most likely would be keratoconjunctivitis sicca (decreases tear production)
c. Most severe would be scleromalacia perforans
What’s the difference between RA and JIA?
a. JIA is ANA polite, RD negative (50% of cases)
b. Targets young females (children)
Define a seronegative spondyloartheropathy and recall the significance of HLA-B27 in this grouped of conditions
a. Arthritis without rheumatoid factor (not anti-IgG antibody)
b. MHC-1
Interpret a case to determine which of the 4 spondyloarthropathies discussed in class causes a patient to develop uveitis
Reactive arthritis, psoriatic arthritis, ankylosing spondylitis
-Only one that does not is inflammatory bowel disease
Skin lesion associated with sarcoidosis
Non-caseating granulomas
Predict chest X ray of sarcoidosis
Pulmonary infiltrates
Hilar adenopathy
What is the most common ocular manifestation of sarcoidosis
Uveitis
