pathology Flashcards
apoptosis
- programmed cell death; ATP required
- intrinsic or extrinsic pathway; both pathways–>activation of cytosolic caspases that mediate cellular breakdown
- no significant inflammation
- characterized by cell shrinkage, nuclear skrinkage (pyknosis) and basophilia, membrane blebbling nuclear fragmentation (karyorrhexis), and formation of apoptotic bodies, which are then phagocytosed
intrinsic pathway
- involved in tissue remodeling in embryogenesis
- occurs when a growth factor is withdrawn from a proliferating cell population (eg. dec IL-2 after a completed immune rxn–>apoptosis of proliferating effector cells)
- also occurs after exposure to injurious stimuli (eg. radiation, toxins, hypoxia)
- changes in proportion of anti- and pro-apoptotic factors lead to increased mitochondria permeability and cytochrome c release
extrinsic pathway
- 2 pathways:
- ligand receptor interactions (Fas ligand binding to Fas (CD95)
- immune cell (cytotoxic T cell release of perforin and granzyme B)
necrosis
- enzymatic degradtion and protein denaturation of cell resulting from exogenous injury.
- intracellular components extrasate
- inflammatory process (unlike apoptosis)
- types of necrosis:
- -coagulative–heart, liver, kidney
- -liquefactive–brain, bact abscess, pleural effusion
- -caseous–TB, systemic fungi
- -fatty–peripancreatic fat (saponification via lipase)
- -fibrinoid–blood vessels
- -gangrenous–dry (ischemic coagulative) or wet (with bacteria); common in limbs and in GI tract
cell injury:
- reversible with O2
- irreversible
- reversible with O2
- dec ATP synthesis
- Cellular swelling (no ATPimpaired Na+/K+ pump)
- nuclear chromatin clumping
- dec glycogen
- fatty change
- ribosomal detachment (dec protein synthesis) - irreversible
- nuclear pyknosis, karyolysis, karyorrhexis
- Ca2+ influxcaspase activation
- plasma membrane damage
- lysosomal rupture
- mitochondrial permeability
Ischemia: susceptible areas:Organ & location
- Brain
- heart
- kidney
- liver
- colon
- areas susceptible to hypoxia and ischemia/infarction
1. ACA/MCA/PCA boundary areas. Watershed areas receive dual blood supply from most distal branches of 2 arteries, which protects these areas from single-vessel focal blockage. However, these areas re susceptible to ischemia from systemic hypoperfusion. Hypoxic ischemic encephalopathy (HIE) affects pyramidal cells of hippocampus and Purkinjie cells
2. Subendocardium (LV)
3.Straight segment of proximal tubule (medulla)
Thick ascending limb (medulla)
- Area around central vein (zone III)
- Splenic flexure, rectum. Watershed areas receive dual blood supply from most distal branches of 2 arteries, which protects these areas from single-vessel focal blockage. However, these areas re susceptible to ischemia from systemic hypoperfusion. Hypoxic ischemic encephalopathy (HIE) affects pyramidal cells of hippocampus and Purkinjie cells.
Infarcts: red vs. pale
- Red (hemorrhagic) infarcts occur in loose tissues with collaterals, such as liver, lungs, or intestine, or following reperfusion
- pale infarcts occur in solid tissues with a single blood supply, such as heart, kidney, and spleen
- Red=perfusion
- Reperfusion injury is due to damage by free radicals
Shock:
- Hypovolemic/cardiogenic
- Septic
- Hypovolemic/cardiogenic
- Low-output failure
- Inc TPR
- Low cardiac output
- Cold, clammy patient (vasoconstriction) - Septic
- High-output failure
- Dec TPR
- Dilated arterioles, high venous return
- Hot patient (vasodilation)
Atrophy
- Reduction in the size or number of cells. Causes include:
- Dec hormones (uterus/vagina)
- Dec innervation (motor neuron damage)
- Dec blood flow
- Dec nutrients
- Inc pressure (nephrolithiasis)
- Occlusion of secretory ducts (cystic fibrosis)
Inflammation:
- vascular component
- cellular component
Characterized by rubor (redness), dolor (pain), calor (heat), tumor (swelling), and function lasesa (loss of function)
- vascular component–inc vascular permeability, vasodilation, endothelial injury
- cellular component–neutrophil extravasation from circulation to injured tissue to participate in inflammation through phagocytosis, degranulation, and inflammatory mediator release
Inflammation:
- Acute
- Chronic
- Acute- neutrophil,eosinophil, antibody mediated. Acute inflammation is rapid onset (second to minutes), lasts minutes to days. Outcomes include complete resolution, abscess formation, and progression to chronic inflammation
- Chronic–mononuclear cell mediated: characterized by persistent destruction and repair. Associated with blood vessel proliferation, fibrosis. Granuloma: nodular collections of epithelioid macrophages and giant cells. Outcomes include scarring and amyloidosis
Leukocyte extravasation in 4 steps
Neutrophils exit from blood vessels at sites of tissue injury and inflammation in 4 steps:
Step, vasculature/stroma, leukocyte
1.rollingE selectin, P-selectinSialyl-Lewis X
2.tight bindingICAM-1LFA-1 (integrin)
3.diapedesis-leukocyte travels btw endothelial cells and exit blood vesselPECAM-1-PECAM-1
4.Migration—leukocyte travels through interstitium to site of injury or infection guided by chemotactic signals-bacterial products: C5a, IL-8, LTB4, and Kallikrein (CILK)various
Free radical injury
-free radical damage cells via membrane lipid peroxidation, protein modification, and DNA breakage
-initiated via radiation exposure, metabolism of drugs (phase1), redox rxn, nitric oxide, transition metals, leukocyte oxidative burst
-free radicals can be eliminated by enzymes (catalase, superoxide dismutase, glutathione peroxidase), spontaneous decay, antioxidants (vits A, C, E)
Pathologies include:
1.Retinopathy of prematurity
2.Bronchopulmonary dysplasia
3.Carbon etrachloride, leading to liver necrosis (fatty change)
4.Acetaminophen overdose (fulminant hepatitis)
5.Iron overload (hemochromatosis)
6.Reperfusion after anoxia (eg superoxide), especially after thrombolytic therapy
Wound healing:
- Phase (3)
- mediators
- characteristics
- Inflammatory (immediate)–> platelets, neutrophils, macrophages–>clot formation, inc vessel permeability and neutrophil migration into tissue; macrophages clear debris 2 days later
- Proliferative (2-3 days after wound)–> fibroblasts, myofibroblasts , endothelial cells, keratinocytes, macrophages–> deposition of granulation tissue and collagen, angiogenesis, epithelial cell proliferation, dissolution of clot, and wound contraction (mediated by myofibroblasts)
- Remodeling (1wk after wound)–> fibroblasts–>type II collagen replaced by type I collagen inc tensile strength of tissue
Granulomatous disease
- Mycobacterium tuberculosis
- Fungal infections (eg histoplasmosis, coccidiodomycosis)
- Treponema pallidum (syphilis)
- M. leprae (leprosy)
- Bartonella henselae (cat scratch disease)
- Sarcoidosis
- Crohn’s dz
- Granulomatosis with polyangiitis (Wegener’s)
- Churg-Straus syndrome
- Berylliosis, silicosis
- Th1 cells secrete gamma interferon, activating macrophages.
- TNF alpha from macrophages induce and maintain granuloma formation.
- Anti-TNF drugs can, as a side effect, cause sequestering granulomas to breakdown, leading to disseminated disease