Ch.1 Cell injury, death, adaptation Flashcards
origin of a disease, including the underlying causes and modifying factors.
Etiology
Development of the disease. The HOW
Pathogenesis
Steady state
Homeostasis
Well cells indergo injurious stimulus so they ___ and achieve new steady state & preserve viability & fx.
Adapt
If injury is ___ homeostasis is restored
Reversible
If stress is persistent or severe this results in ____ injury
Irreversible
Oxgen deficiency
Hypoxia
Ischemia
Reduced blood supply
Most common cause of hypoxia and ischemia is
Blockage of an artery or inadequate oxygenation of blood.
Toxic agents in daily environment
Toxins
Infectious pathogens; viruses, bacteria, fungi, parasites that injure cells by diverse mechanisms.
Infectious Agents
Rxns that can result in cell injury and tissue injury;
ex. autoimmune rxns, excessive or common immune response to microbe
Immunologic reactions
Chromosomal abnormalities or mutations
Ex. Sickle cell anemia
Or even mutations that can result in decrease or increase in protein function.
Genetic Abnormalities
Protein-calorie insufficiency remains a major cause of cell injury, and specific vitamin deficiencies
Nutritional imbalances
Derangement of function and morphology that cells can recover from if the damaging stimulus is removed
Reversible Cell Injury
___ cell injury result in cell and organelle swelling which is main sign.
Reversible
____ ____ is another sign of reversible cell injury. Appearance of lipid vacuoles in cytoplasm. mostly occurs in organs that are involved in lipid metabolism ex. Liver
Fatty change
A cell becomes ____, turning redder due to injury. Becomes intensely basic.
Eosinophilic
4 signs of cell injury
-Blebbing (due to loss of surface microvilli)
-appearance of phospholipid rich densities
-dilation of ER-> detachment of ribosomes.
-Nuclear alteration. Myelin figures.
collections of phospholipids resembling myelin sheaths that are derived from damaged cellular membranes.
Myelin figures
When the cell passes the point of no return, excessive injury
Irreversible injury
1st Phenomena of irreversible injury
> inability to restore mitochondrial function= No Ox. Phosphorylation= NO ATP
2nd Phenomena of irreversible injury
Alt. structure & loss of function of the plasma membrane & intracellular membranes
3rd Phenomena of irreversible injury
Loss if structural integrity of DNA & chromatin
Inevitable end result of severe damage that is beyond salvage and is not thought to be regulated by specific signals or biochemical mechanisms
pathologic
Necrosis
pathway of cell death in which cells activate enzymes that degrade the cells’ own nuclear DNA and nuclear and cytoplasmic proteins. Req. ATP
physiologic
Apoptosis
Sign of Necrosis or apoptosis?
Swelling & adjacent  inflammation
Necrosis
Sign of Necrosis or apoptosis?
Shrinking
Apoptosis
Sign of Necrosis or apoptosis?
Pyknosis → karyorrhexis → karyolysis
Necrosis
Sign of Necrosis or apoptosis?
Fragmentation into nucleosome-sized fragments
Apoptosis
Sign of Necrosis or apoptosis?
Disrupted plasma membrane
Necrosis
Sign of Necrosis or apoptosis?
Intact plasma membrane, but orientation of lipids in altered
Apoptosis
Sign of Necrosis or apoptosis?
Enzymatic digestion, may leak out of cell
Necrosis
cellular function may be lost long before _________ occurs and that the morphologic changes of cell injury (or death) lag behind loss of function and viability
cell death
Myocardia cells become non-contractible after 1-2min of ischemia but don’t die until 20-30 min after ischemia has elapsed.
this Is an example that ____ ≠ ____
Loss of function ≠ non-viable
increased binding of eosin to denatured cytoplasmic proteins and in part to loss of basophilic ribonucleic acid (RNA) in the cytoplasm
Eosinophilia, sign of necrosis in cytoplasm.
____ is Characterized by nuclear shrinkage and increased basophilia; the DNA condenses into a dark, shrunken mass.
Pyknosis
Fragmentation of a pyknotic nucleus (shrunken)
karyorrhexis
basophilia fades due to digestion of deoxyribonucleic acid (DNA) by DNase.
Karyolysis
basophilia fades due to digestion of deoxyribonucleic acid (DNA) by DNase.
Karyolysis
No ATP results in loss of function of the Na+/K+ pump leaving more sodium in the cell resulting in
Cell swelling
Mitochondrial membrane damage allows ___ to Leak into the cytoplasm, this activates _____
Cytochrome C, apoptosis.
Lysosome membrane damage= hydrolytic enzymes leak into cytoplasm, becoming activated by _____
High intracellular calcium
Necrotic tissue retains its gross structure, cell shape, and organ structure. BUT nuclear structures are lost.
Coagulative Necrosis
Areas of necrosis caused by ischemia (no blood), leaving area pale.
Infarcts
When blood re-enters the loosely organized tissues.
Blood build up.
Seen in testicular, pulmonary.
Red infarction
Necrotic tissue liquified due to enzymatic lysis of cells and protein content.
ex. in accesses, proteolytic enzymes from neutrophil ___ tissue
Liquefactive Necrosis; liquify
Macrophage in CNS
Microglial Cell
Hallmark of ____ infarction are when proteolytic enzymes from microglial ells liquify the ___
Brain
Proteolytic enzymes from pancreas liquify surrounding parenchyma.
Pancreatitis
Liquefaction produces yellow substance
Pus
Localized collection of pus
abscess
When limb looses blood supply, has undergone coagulative necrosis of multiple. tissue layers. Mummified tissues. Limbs.
Gangrenous Necrosis
“cottage cheese like” due to presence of both coagulative & liquefactive necrosis. Tissue architecture destroyed.
Caseous Necrosis
_____ this disease causes caseous necrosis ion the lungs
Tuberculosis
Nodular inflammatory lesion
Granuloma
Necrosis of adipose tissues that results in chalky white appearance due to the build up of calcium in dead adipose tissue.
Fat Necrosis
When fatty acids or lipases attach to calcium.
Saponification
Enzymes leak out of damage pancreatic acing cells, digesting peritoneal fat cells + their content.
Released fatty acid + calcium = chalky lesions.
Acute Pancreatitis
When calcium deposits on necrotic tissues which acts as a collection point.
Normal serum calcium
Dystrophic calcification
When high serum calcium or phosphate levels lead to calcium deposition on normal tissues;
ex. Hyper-para-thyroidism
Metastatic Calcification
Necrotic damage to blood vessel wall, leaking of protein (fibrin) into blood vessel walls.
*youll see a ring of fibrin circumferential bright pink area of fibrin**
Fibrinoid Necrosis
2 causes of damage to blood vessels walls resulting in fibrinoid necrosis
- Malignant hypertension
- Vessel inflammation (vasculitis)
Leaking of what protein in cardiac muscle results in the detection of tissue specific necrosis unison blood or serum samples?
Troponin
Fragments of the plasma membrane that are altered, and recognized & phagocytose by macrophages. no inflammation
Apoptotic Bodiues
> Ex. Menstrual cycle -> (cells that have increased in # in preparation fertilization , not used, endometrial shedding.
> Ex. Resorption of cells and cellular cycle
> Ex. Bone remodeling in the mouth, bone cells flagged for being removed.
Physiologic Apoptosis
Exposure to radiation and cytotoxic drugs results in ____ apoptosis
Pathologic
Mitochondrial membrane becomes permeable due to Bcl2 is turned off , allowing Cytochrome C to leak into cytoplasm, triggers cause reaction by the cell itself.
mitochondrial (intrinsic) pathway
Explain the Bcl2 inactivation process in the intrinsic apoptosis.
BH3 -only proteins sense lack of survival signals or DNA/protien damage.
They activate effector molecules BAX, BAK which then demonetize to form a membrane channel. + a decrease in BCL-2 & BCL-X = cytochrome c leaks out.
> affected cell refuses to undergo apoptosis.
T cels recognize FAS(CD95) death receptor of affected cell
T-cells have the Fas ligand (FasL)
They go to the cell and cross link FasL with the FAS receptor. Binding adaptor proteins as well.
Recruit and activate Caspase-8.
Death-receptor (extrinsic) pathway of apoptosis via FAS Ligand
2 prototypic death receptors:
Type I TNF receptor & Fas (CD95)
What is an example of a situation where the FAS ligand pathway is used?
Elimination of self-reactive lymphocytes.
TNF binds to TNF receptor on target cell, cross linking & activating caspases.
Apoptosis
Death-receptor (extrinsic) pathway of apoptosis via TNF
Apoptosis pathway that has both intrinsic and extrinsic elements .
>perforins secreted by CD8+ T cells, Create holes in membrane of target cell, insert granzyme, activate capases. Kills viral infected cells.
Immune Pathway, cytotoxic T-cell mediated.
Activated Caspase-3 will fluoresce what color?
Red
Cellular damage induced by the accumulation of reactive oxygen species (ROS), a form of free radical.
Oxidative Stress
4 Effects of mitochondrial dysfunction & damage that lead to failure of oxidative phosphorylation and therefore no ATP.
- No sodium pumps= cell swelling cause Na+ accumulates inside cell.
- Increased aerobic glycolysis= lactic acid buildup= low pH= enzymes loose fxn.
- Structural disruption of RER, ribosomes detach= reduced protein synthesis
- Damage to mito & lysosomal membrane,
chemical species with a single unpaired electron in an outer orbital. Extremely unstable and can react with in & organic compounds. Attacking them!
Free Radicals
Incomplete reduction of O2 produces what three radical species?
- Superoxide O2
- Hydrogen Peroxide H2O2
- Hydroxyl Radicals OH-
Enzyme that will get rid of superoxide (O2-) converting it to H2O2
Superoxide Dismutase (SODs)
Enzyme that converts hydrogen peroxide H2O2 into O2
Catalase gluthione peroxidase
No enzyme to get rid of OH-, what do you do instead to convert it to H2O? They block formation of free radicals or scavenge them.
Endogenous or exogenous antioxidant
4 Diff. pathological ways free radicals are generated?
- Inflammation; NADPH oxidase generates O2- during oxygen dependent killing by neutrophils
2.Ionizing radiation causes H20 -> OH-
3.Fenton reaction (metals Fe2+) - Chemical compounds (medicine) broken down in liver P450, generating free radicals.
Combine and alter cellular structures by peroxidation of lipids and oxidation of DNA and proteins. (thus, DNA constant damage and repair by these ROS is implicated in aging & neoplasms)
Affect of free radical
Pt. comes in with infection, what can you tell them to do?
- take antioxidants (glucothianine, vitamin A,C,E) = reduce damage
- Anti- inflammatory = reduce amount to repair (NSAIDS)
3.Enzymes - Metal carrier proteins.
They are aspartate-specific cysteine proteases.
They breakdown cytoskeleton and activate endonucleases
Caspases
Return of blood (oxygen) to ischemic (oxygen deprived) tissue results in high influx of O2- derived free radicals (backed up breathing/electron transport), produces unstaggered production of ROS which further damages, to already STRESSED or INJURED tissue.
Ischemia Reperfusion Injury
Ex of Ischemia Reperfusion Injury
Continued increase of troponin in heart even after resolving ht blockage and reperfusion of infarcted myocardial tissue.
Misfolded protein deposits in extracellular space of tissues, causes tissue damage.
Systemic or localized deposition
Amyloid
Beta-pleated sheets, Congo red & apple green birefinginence when view microscopically cannot be removed
features of what?
an amyloid
systemic deposition of AL amyloid, which is derived from immunoglobulin light chain.
As. with plasma cell dyscrasias (e.g., multiple myeloma)
Primary Amyloidosis
systemic deposition of AA amyloid, which is derived from serum amyloid-associated protein (SAA).
As. w/chronic secretion.
Secondary Amyloidosis
Chronic inflammation (RF) and Familial Mediterranean Fever (FMF) are associated with
Secondly Amyloidosis (AA)
Genetic autosomal recessive dysfunction of neutrophils typically in med. region.
Symptoms: episodic fevers, sudden serial inflammation.
Familial Mediterranean fever (FMF),
4 different most SAA sensitive tissues w/symptoms
- Kidney/nephrotic syndrome (most common)
- Heart res. cardiomyopathy or arrhythmia
- Tongue enlargement, malabsorption, heptaosplenomegaly
affected organs must be transplanted, amyloid cannot be removed
