Parsa- Cell injury -2 Flashcards
Cell injury can occur due to abnormalities in:
- Decrease in ATP
- Mitochondrial damage
- Entry of Ca++
- Increase of ROS
- Membrane damage
- Protein misfolding, DNA damage
What are the major causes of ATP depletion
- Reduced supply of oxygen and nutrients
- mitochondrial damage
- action of some toxins
What are drugs that can generate free radicals that are not ROS but have similar effects
- Carbon tetrachloride
2. acetaminophen
Inc intracellular Ca++ causes cell injury by several mechanisms
- In mitochondria it results in opening of the mitochondrial permeability transition pore and failure of ATP generation.
- In cytosol, Inc Ca++ activates a number of enzymes, with deletrious cellular effects.
- intracellular Ca++ results in the induction of apoptosis by direct activation of caspases and by inc mitochondrial permeability
What are the sequence of events in cell injury
- biochemical (funtional)
2. morphologic (structural)
What are features of reversible cell injury
- cellular swelling
- fatty change
- plasma membrane alterations; blebbing, blunting, and loss of microvilli
- dilation of the ER; detachment of polysomes
- mitochondrial changes
- nuclear alterations
What are features of irreversible cell injury
- denaturation of intracellular proteins
- enzymatic digestion of the lethally injured cell.
- Cell contents leak out
- increased esoinphilia
- loss of nuclei
- fragmentation of cells
Hypoxia (reduced oxygen availability)or mitochondrial damage results in inadequate ___ production
ATP
ischemia refers to:
reduced blood flow
what are proteins used in diagnosis of cell damage of cardiac muscle?
- Troponin
2. creatine kinase (MB isoform)
Ischemic injury is associated with _____. Neurons have the shortest endurance for surivival, while ____ have the longest endurance. Transient induction of ____ helps ischemia
inflammation; fibroblasts; hypothermia
Reperfussion can have negative consequences by generation of _____ , influx of neutrophils, and activation of ____ system and promote cell death
ROS; complement
_____ necrosis is a form of necrosis in which the architiecture of dead tissues is preserved for a span of a couple of days. The affected tissues typically exhibit a pale discoloration and firm texture called an _____. Usually occurs in solid organs; the kidney or spleen.
Coagulative; infarct
What enzymes are elevated if hepatocyte cells are damageed
- alanine transaminase (ALT)
2. Aspartate transaminase (AST)
what enzymes are elevated if striated muscle cells are damaged
Creatine kinase (MM isoform)
what enzyme is elevated if exocrine pancreas cells are damaged
Amylase
Release of cytochrome ___ initiates the suicide program of apoptosis. ___ family of proteins regulate apoptosis. This includes the intrinstic/mitochondrial pathway of apoptosis
c; Bcl
TNF receptor, ____ and FADD are included in the ____ pathway of apoptosis
Fas; extrinsic
____ protect damaged proteins from damage
chaperones
_____ remove old/ damaged proteins by acting as a cofactor for proteolysis
ubiquitins
A _____ necrosis occurs where venous blood vessel is obstructed. This usually occurs in lung
hemorrhagic
____necrosis usually occurs in heart and spleen. ____ necrosis usually occurs in ____ and genitalia. Liquefactive necrosis occurs in ____ and abscesses. ______necrosis occurs in ____ extrimiteis. ______ necrosis refers to tuberculosis. ____ is a type of necrosis that deals with syphillis
Coagulative; Hemorrhagic; lung brain Gangrenous Caseous Gumma
Enzymatic fat necrosis deals with ____ pancreas
acute
____ necrosis deals with pts that have deposition of immune complexes in vascular structures; deposits of these IC result in bright pink areas called fibrinoid.
fibrinoid
When bacterial infection is superimposed there is more liquefactive necrosis bc of the actions of degradative enzymes in the bacteria and the attracted leukocytes giving rise to _____ gangrene
wet
syphilitic Gummas are white gray and rubbery and are surrounded by _____cells
plasma
___necrosis is not a true necrosis but enzymatic destruction of fat bc of release of activated pancreatic lipases in pancreas and peritoneal cavity. Pt has history of alcoholism.
Fat
_____cell injury directly injure critical cell components and convert chemicals to reactive toxic metabolites.
Chemical
In chemical cell injury ____ binds to cell membrane proteins and increase permeability of GI and kidney. _____ inhibits mitochondrial oxidative phosphorylation
Mercury; cyanide
Carbon _____ was once used widely in the dry cleaning industry; gets converted by cytochrome P450 in the ER to the highly reactive free radical CCl3 which causes lipid _____and damages many cellular structures
Tetrachloride; peroxidation
Modification of acetaminophen occurs in ____ER and is mostly detoxified by _____ and _____ and interact with glutathione
smooth; sulfation; glucouronidation
Apoptosis is cell death without _____
inflammation
what are physiologic forms of apoptosis
- involution of hormone dependent tissues upon hormone withdrawal
- cell loss in proliferating cell populations
- elimination of potentially harmful self reactive lymphocytes
- death of host cells that have served their useful purpose
what are pathologic forms of apoptosis
- DNA damage
- Accumulation of misfolded proteins
- Cell death in certain infections
- pathologic atrophy
inappropriately low rate of apoptosis –> _______ of abnormal cells.. Ex include cancer and autoimmune disorder
survival
inappropriately high rate of apoptosis –> exessive cell _____. Ex include neurodegeneartive diseases, ishemic injury and virus induced lymphocyte delpletion, or accumulation of misfloded proteins
death
alpha 1 antitrypsin deficiency refers to mutation significantly slowing down ____ folding
protein
What is ER stress
when cell is unable to cope with the load of misfolded proteins
What are mechanisms of intracellular accumulations
- Normal endogenous substance produced excessively or removed inadequately
- Abnormal endogenous substance defects in protein folding or degrading
- Normal endogenous substance, defects in metabolic enzymez (lysosomal)
- Abnormal exogenous substance (cells cant degrade it)
what is an ex of normal endogenous substance produced excessively or removed inadequately
accumulation of lipids
Deficiency of lysosomal _____ cause cells to be filled with excessive lipids that cant be broken down.
sphingomyelinase; Nieman Pick Disease
what are ex of abnormal accumulation of proteins within cells
- Proteinuria: Protein in urine gets picked up by epithelial cells.
- alpha 1 antitrypsin deficiency
3.
_____change is a non specific marker of cell injury. Ex include abnormal intracellular/extracellular protein deposits seen in ____ bodies, or amyloidosis, abnormal or misfolded proteins best demonstrated by polarizing Congo red stain
Hyaline; mallory
Abnormal glycogen deposition occurs in diabetics due to increased ____ and abnormal glucose metabolism. Test by using PAS stain with and without _____
gluconeogenesis; diastase
Pigments can be ____ meaning synthesized within the body itself, or exogenous; coming from outside of the body
endogenous
Melanin is an endogenous brown black pigment formed when tyrosine is oxidized by _____. It occurs in melanocytes
tyrosinase
____ is a Hb derived golden yellow to brown pigment that serves as one of the major storage forms of ____
Hemosiderin; iron
What are the two types of pathologic calcification
- Dystrophic: occurs locally in dying tissues
- Metastatic; deposition of calcium salts occur in otherwise normal tissues due to hypercalcemia secondary to some disturbance in calcium metabolism
what are psammoma bodies
lamellated configurations that look like grains of sand. Mostly seen in thyroid cancer
What are four principal causes of hypercalcemia
- increased PTH
- malignant tumors
- vitamin D related disorders
- renal faillure
Cellular aging results from a combination of :
- accumulating cellular damage (free radicals)
- reduced capacity to divide (telomere shortening)
- reduced ability to repair damaged DNA
- defective protein homeostasis
