Apoptosis
- Noninflammatory cell death. Nuclear fragmentatoin and blebs forming
- Lupus may occur because of self reaction to apoptoti blebs
Intrinsic Pathway
- Loss of a growth factor or cellular injury leads to death of cell
- Increase in bax and decrease in BCL-2 leads to an increase in cyt c leakage from mitochondria leading to activation of caspaces
Extrinsic Pathway
FAS-L from T cells interacts with FAS on cell activating BAD and caspaces
-Also can be from perforin and granzyme that cause activation of caspaces
Ca
Increase in intracellular Ca causes activation of caspaces and cellular death
Necrosis
-Inflammatory process from irreversible cell damage
Gangrene
-Ischemic death. If not infected is considered dry, and if is infected, is considered wet
Fibrinoid Necrosis
-Occurs in vasulitis and in RA
Soponification
-Lipase digestion post infarct leads to Ca binding within dead tissue and decrease in plasma calcium
Irreversible Cell Injury
- Plasma Membran Ruptire
- Influx of Ca
- Lysosomal or mitochondrial Rupture
- Nuclear fragmentation
Brain areas vulnerable to ischemic injury
-Pyramidal cells of hipocampus and purkinje cells of cerebellum
Kidney
- Straight portion of the proximal tubule (medulla)
- Thick ascending limb of the loop of henle (medulla)
- Both have limited blood supply and increased metabolic demand
Shock
- Cardiogenic/hypovolemic: Increased TPR, decreased CO, cool clammy patient
- Septic: Vasodialtion leads to warm, red patient with decreased TPR and normal CO
Acute Inflammation
-Neutrophil, eosinophils, complement, Ab
Chronic
-Monocytes and lymphocytes predominate
Leukocyte extravasation
- Margination becuse of dilation and turbulent flow
- Rolling: P selectin from WP and E selectin, release due to IL-1 and IL-6 interact with sialyl lewis acid X on leukocytes
- Tight adhesion: ICAMs on endothelium and Integrins on leukocytes
- Tranmigration: Pecam, homotypic
- Chemotactic by: Bacterial products (LPS), IL-8, C5a, LTB4, Kalikrein
Free Radical Damage
- Lipid Peroxidation, protein damage, DNA damage
- Radiation, drugs, etc
- Eliminated by SOD, Catalase, Peroxidase, glutathione, ACE
Free Radical Diseases
- Retinopathy of prematurity, bronchopulmonary dysplasia
- Carbon tetrachloride, acetomenaphin cause liver damage
- Hemochromatosis causes liver cirrhosis
- Reperfusion injury
Wound Healing
- Initially Neutrophil, platelets, macrophages cause inflammation
- 3 days macrophages clear debris and granulation tissue with type 3 collagen begins to form
- 7 days granulation tissue replaced with type I collagen
- Wound healing delayed with Zn, Cu, Vit C deficencies
- Keloid is overexuberant produciton of granulation tissue (type 3 collagen)
- Hypertrophic scar is overprodcution of type 1 collagen
Granulomas
-Casseating: Mycobacteria and fungal, bartonella
-Also seen in:
RA (Rheumatoid Nodules), fibrinous necrosis also seen in joints
-Churgg Straus and Wegners
-Rheumatic Fever
-Chrons
-Trepnoma (Gummas)
-Sarcoidosis
-Foreign Body
-Listeria
-Schistosomiasis
Fe Poisoning
Common among children
- Acutely leads to GI ulceration and bleeding due to free radical damage mediated by peroxiadtion of membran lipids by Fe
- Chronically causes acidosis with anion gap
Amyloidosis
- Beta pleated sheets with apple green birefringence
- AL (Primary) multiple myeloma and can present systemically (Heart, bruising, renal, neuro)
- AA: SAA secondary to chronic inflammatory conditions (RA) has a systemic presentation
- Tissue Tranthyretin: slower onset and most commonly seen in heart and nerves. Mutation can lead to hereditery form, but more commonly is due to senile, or old age
- Alzheimers: APP
Neoplastic Progression
- Dysplasia leads to anaplasia and carcinoma in situ which is not through BM
- Loss of E Cadherin allows for spread
- Gain of collagenases and integins allow for spread to blood
- Proper “Soil” allows spread to other organs
Cachexia
Weight loss and fatigue with chronic illness
-TNF alpha, IL-6 and IFN y mediated
Tuberous Sclerosis
- AD mutation in TSG, incomplete penetrance
- Most common symptoms are siezures, hypopigmentation (ash leaf spots)
- Presence of harmatomas, most commonly giant cell astrocytoma in the brain (98%), also angiomyolipoma of the kidney and cardiac rhabdomyoma
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Neuro Path202
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Psych99
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Neuro Cards 182
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Micro Cards 12
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Repro Cards Q2
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General Path45
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Heme Once109
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Endocrine116
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GI Cards 12
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Endo Cards 11
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Reproductive239
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Renal Path126
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Cardio Path189
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Respiratory Path98
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MSI Path116
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Biochem 27
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Behavioral Science66
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Questions 5-1411
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Immunology109
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Pathology37
