Pathology Flashcards
Apoptosis What is it? What is required? Phys Inflammation Histo Clean up?
Programmed cell death
ATP required
Cytosolic caspases mediate cellular breakdown
No inflammation
Shrinkage, Pyknosis (nuc shrinkage), Basophilia, Blebbing, Nuclear Fragmentation (karyorrhexis), Apoptotic bodies
Phagocytosis
Intrinsic Apoptosis Pathway
What process is it involved with?
Mechanism
Mito involvement
Tissue remodeling in embryogenesis and after exposure to injurious stimuli
Growth factor withdrawn from proliferating cells
Changes in proportions of anti and pro apoptotic factors lead to ↑ mito permeability and ctyochrome c release
Extrinsic Apoptosis Pathways
Fas ligand binding to Fas Receptor (CD95)
Tc cells release Perforin and Granzyme B
Necrosis
What causes it?
Process?
Inflammation?
Exogenous injury
Enzymatic degradation and protein denaturation –> Intracellular components extravasate
Inflammation
Coagulative Necrosis
Heart, Liver, Kidney
Liquefactive Necrosis
Brain, Bacterial Abscess, Pleural Effusion
Caseous Necrosis
TB, Systemic Fungi
Fatty Necrosis
Peripancreatic fat (saponification via lipase)
Fibrinoid Necrosis
Blood vessels
Gangrenous Necrosis
Dry
Wet
Where?
Dry: Ischemic Coagulative
Wet: Bacteria
Limbs and GI tract
Reversible Cell Injury
What is required?
PathoPhys
Histo
Oxygen
↓ ATP synthesis, ↓ Glycogen
Swelling (impaired Na/K pump), Chromatic clumping, Fatty Change, Ribosomal detachment
Pro-apoptotic Mito protein
Bax
Anti-apoptotic Mito Protein
Bcl-2
Irreversible Cell Injury
Pathway
What happens to the cell?
Histo
Ca influx –> caspase activation
Plasma membrane damage, Lysosomal Rupture, Mito Permeability
Pyknosis, Karyolysis, Karyorrhexis
Location of Brain susceptible to ischemic injury
ACA/MCA/PCA boundary area
Location of Heart susceptible to ischemic injury
Subendocardium of LV
Location of Kidney susceptible to ischemic injury
Straight segment of PT in medulla
Thick Ascending Limb in medulla
Location of Liver susceptible to ischemic injury
Central Vein (zone III)
Location of Colon susceptible to ischemic injury
Splenic Flexure and Rectum
Red Infarcts What kind of infarct? What kind of tissue? Organs? When?
"Red = Reperfusion" Hemorrhagic Tissue with collaterals Liver, Lungs, Intestines Following reperfusion
Hypoxic Ischemic Encephalopathy affects what kind of cells?
Pyramidal Cells of Hippocampus and Purkinje cells
Pale Infarcts
What kind of tissue?
Organs?
Solid tissues with a single blood supply
Heart, Kidney, Spleen
Reperfusion injury is due to…
Free Radicals
Hypovolemic Shock
Output
TPR
Presentation
Low output
↑ TPR
Cold and Clammy
Cardiogenic Shock
Output
TPR
Presentation
Low output
↑ TPR
Cold and Clammy
Septic Shock Output TPR Vasculature Presentation
High output
↓ TPR
Dilated arterioles, High venous return
Hot
Atrophy
What is it?
Possible causes?
Reduction in size or # of cells
↓ hormones, innervation, blood flow nutrients
↑ pressure
Occlusion of secretory ducts
Characteristics of Inflammation
Redness, Heat, Swelling, Loss of Function
Vascular component of inflammation
↑ vascular permeability, vasodilation, endothelial injury
Cellular component of inflammation
Neutrophil mediated
Acute component of inflammation Mediators Onset Duration Possible outcomes
Neutrophils, Eosinophils, Abs
Seconds to minutes
Minute to days
Resolution, Abscess, Chronic inflammation
Chronic component of inflammation Mediators Characteristic Associated with... Outcomes
Mononuclear cells
Persistent destruction and repair
Blood vessel proliferation. Fibrosis
Scarring, Amyloidosis
Granuloma
Histo
Pathway
Nodular collection of Epithelioid Macrophages and Giant Cells
Th1 secretes IFNγ which activates Macs which secrete TNFα
Leukocyte Extravasation
Steps w/ mediators
1.Rolling:
Vasculature: E and P selectins. Leukocyte: Sialyl-Lewis
2. Tight Binding
V: ICAM. L: LFA1 (integrin)
3. Diapedesis (between endothelial cells)
V: PECAM. L: PECAM
4. Migration
Leukocyte (neutrophil) chemotactic factors
“CLIK”
C5a, LTB4, IL8, Kallikrein
How do free radicals damage cells?
Membrane lipid peroxidation
Protein modifications
DNA breakage
Free Radicals
What causes them?
How are they eliminated?
Radiation, Metabolism of drugs, Redox rxns, Nitric Oxide (NO), Transition metals, Leukocyte oxidative burst
Enzymes (Catalase, SOD, Glutathione Peroxidase), Decay, Antioxidants (A, C, E)
Free Radical Diseases
ROP, Bronchopulmonary Dysplasia, CCl4 –> liver necrosis (fatty change), Acetominophen OD, Hemochromatosis, Reperfusion
Would Healing Phases
Inflammatory, Proliferative, Remodeling
Would Healing Inflammatory Phase
When?
Mediators
What happens?
Immediate
Platelets, Neutrophils, Macrophages
Clot formation and ↑ permeability
Would Healing Proliferative Phase
When?
Mediators
What happens?
2-3 days after injury
Fibroblasts, Myofibroblasts, Endothelial cells, Keratinocytes, Macrophages
Deposition of granulation tissue and collagen. Angiogenesis, Epithelial cell proliferation, Dissolution of clot, Wound contraction (via myofibroblasts)
Would Healing Remodeling Phase
When?
Mediators
What happens?
1 week
Fibroblasts
Collagen III replaces Collagen I –> ↑ tensile strength of tissue
Granulomatous Diseases
TB
Fungal Infections (Histoplasmosis, Coccidioidomycosis)
Treponema Pallidum (Syphilis)
M Leprae (Leprosy)
Bartonella Henselae (cat scratch disease)
Sarcoidosis, Crohn’s Disease, Wegener’s, Churg Strauss
Berylliosis, Silicosis
Transudate Cellularity? Protein? Specific gravity Causes
Hypocellular
Low protein
Less than 1.012
↑ hydrostatic pressure, ↓ oncotic pressure, Na retention
Exudate Cellularity? Protein? Specific gravity Causes
Cellular
Protein rich
Greater than 1.02
Lymphatic obstruction or Inflammation
Iron Poisoning
MoA
Acute
Chronic
Peroxidation of membrane lipids
Acute gastric bleeding
Chronic: Metabolic acidosis, Scarring –> GI obstruction
Amyloidosis
What is it?
What does it cause?
Appearance of tissue?
Abnormal aggregation of proteins into β-pleated sheets
Cell damage and apoptosis
Waxy appearance
AL Amyloidosis
What kind of protein?
What disorders present with it?
Organ systems affected
Ig Light chains
Plasma cell disorder or Multiple Myeloma
Renal (nephrotic), Cardiac (failure, arrhythmia), Hematologic (easy bruising), Hepatomegaly, Neuropathy
AA Amyloidosis
What kind of protein?
What diseases?
Systems involved?
Amyloid A fibrils
RA, IBD, Spondyloarthropathy, Chronic Infections
Multiple systems like in AL
Dialysis Related Amyloidosis
What kind of protein?
What kind of pt?
Presentation
β2 microglobulin
ESRD on long term dialysis
Carpal tunnel syndrome and other joint issues
Heritable Amyloidosis
Genetics
Disease
Transthyretin (TTR or prealbumin) gene mutation
ATTR neurologic/cardiac amyloidosis
Age-Related (Senile) Amyloidosis
What kind of protein?
Organs affected
Progression
wt TTR
Systemic: deposited in myocardium and other sites
Slower progression of cardiac dysfunction vs AL
Organ Specific Amyloidosis
What is affected?
Example with protein
A single organ
Alzheimer’s Disease due to deposition of amyloid-β protein from APP
Anaplasia
Abnormal cells lacking differentiation
Desmoplasia
Fibrous tissue formation in response to neoplasm
Tumor Grade
Degree of cellular differentiation