Test 1: lecture 3 cell injury Flashcards
when can you detect biochemical changes
seconds to minutes
when can you detect ultrastructural changes?
mins-hours
changes seen by an electron microscope
when can you detect microscopic changes
6-12 hours
when can you see gross changes from cell injury
hours-days
how does decreased ATP effect cell
Na/K pump fails and Na floods cell, water follows salt and cell swells
Calcium pump fails, too much calcium in the cell caused increased enzyme activity
cells switch to using glucose for energy (glycolysis), this causes an increase in lactic acid which decreases intracellular pH, decreases enzyme activity
ribosomes fall off → protein misfolding
what happens to mitochondria with decreased ATP
breakdown in membrane means no oxidative phosphorylation (no new ATP is made)
this leads to the release of cytochrome C which leads to apoptosis
an increase in intracellular Ca leads to
PLA (phospholipase A) activation (breaks down phospholipids in membranes which damages mitochondrial membrane
amino acid generation
ATPases
Proteases
endonucleases
ATP loss, ROS, increased intracellular Ca and PLAs will recruit ___ and cause ___
T cells, viruses and complement factors
cell membrane to become leaky and cause the loss of AST,ALT and CK which can be seen on blood tests
5 mechanisms of cell injury
Decrease ATP
- Mitochondrial damage
- Calcium influx
- ROS
- Membrane permeability
Loss of ATP leads to:
Plasma membrane ___ pump fails → leads to increase of ___ in the cell
Na + K+ ATPase
Sodium, water follows and cell swells
Ca pump failure causes ___ which will ___ enzyme activity
increased intracellular Ca
increased (can damage stuff, too active)
if ATP not available, cells will switch to ___ for energy. This produces ___ as a waste product which causes a ___ in intracellular pH which causes ___
glycogen (glycolysis)
lactic acid and inorganic phosphate
decrease (more acidic)
decreased activity of some enzymes
protein misfolding will cause the activation of ___ factors
proapoptotic
(ribosomes detach form the RER, which decreases protein synthesis)
breakdown of the mitochondrial membrane will cause the loss of what function and will cause the release of ___
oxidative phosphorylation (making ATP)
release of cytochrome C → apoptosis
increased Ca inside cell activates ___ which will cause damage to ___
phospholipase A
membranes (mitochondrial and other cell membranes)
increased Ca will also activate proteases, ATPases and endonucleases
___ degrade chromatin
endonucleases
increased Ca generates ___ which is a mediator of inflammation
arachidonic acid
The cell membrane is damaged by the above insults and direct injury by infectious agents, complement, ____ and physical and chemical agents
killer T cells,
Membrane damage allows cell contents to leak into the plasma - these can be detected in ___
blood samples.
ALT, AST ect
another name for cell swelling
hydropic degeneration
what are some things that can happen to a cell during hydropic degeneration
swells
mitochondria (swollen with little cristae)
membrane blebs
loss of microvilli
lipidosis
accumulation of fat in a non-adipose cell
lipidosis can be caused by
excessive dietary intake of fat
• increased mobilization of fat (due to ___)
• excessive intake of carbohydrates
• decreased fatty acid oxidation due to hepatocyte dysfunction
• decreased apoprotein synthesis with subsequent decreased export of lipoproteins (protein malnutrition)
• impaired secretion of lipoproteins (toxins)
starvation
liver
diffuse hepatic lipidosis
diffuse, enlarged, yellow, soft, friable liver with rounded edges (reticular pattern)
glycogen accumulation in the liver
orangish, rounded
steroid hypertrophy
cytoplasmic swelling and clearing
reversible cell injury caused by the use of steroids (either exogenous- pred or endogenous-cushings- too much cortisol)
glycogen accumulation from too much steroids
cytoplasmic swelling and clearing of hepatocytes
Some cells may retain evidence of previous injury in the
form of ___ accumulation after autophagocytosis
of damaged organelles.
lipofuscin
necrosis vs apoptosis
necrosis→ what happens to a cell after death → messy (inflammation)
apoptosis → programed cell death → highly regulated, doesn’t really cause a fuss
nuclear shrinkage and increased basophilic
pyknosis
pyknosis
step of necrosis→ nucleus shrinks and becomes more pink (basophilic)
___ is nuclear fragments
karyorrhexis
step in necrosis that usually follows pyknosis (shrinkage and increased basophilic)
___ is the fading of a nucleus
karyolysis
last step in necrosis
what are three things that happen to the nucleus during necrosis
Pyknosis: nuclear shrinkage and increased basophilic
Karyorrhexis: nucleus fragments (usually following pyknosis)
Karyolysis: fading or disappearance of the nucleus
what happens to mitochondria during necrosis
get big with little cristae
calcification is a step in necrosis or apoptosis
necrosis
karyorrhexis → nuclear fragments
if necrosis is multifocal it is usually caused by ___
infections
if necrosis is massive it is usually caused by ___
toxic or nutritional cause
if necrosis is zonal or regional it is usually caused by ___
usually toxic, hypoxic or metabolic
multifocal-random distribution of necrosis in the liver
severe
tan necrosis with black rim hemorrhagic tissue
___ necrosis preserves the cell outline and is usually caused by ___
coagulative
ischemia
___ necrosis breaksdown the cell outline and is usually caused by ___
liquefactive
bacteria
___ is cheeselike
caseous
___ is an example of fat necrosis
pancreatitis- enzymatic destruction of fat
coagulative necrosis
still have cell outline but no nucleus
gangrene is a type of ___ necrosis caused by ___
coagulative (dead- no nucleus but still has outline)
ischemia
liquefactive necrosis
liver- no cell wall→ necrotic wave→ bacterial
fat necrosis due to acute necrotizing pancreatitis
Fa t necrosis with mineralization (saponification→ make soap)
___(heat, cold, radiation, electric shock) may directly rupture cells, damage their blood supply, denature cell proteins, create free radicals, or damage DNA.
Physical agents
___ (viruses, prions, bacteria, rickettsiae, protozoan and metazoan parasites) can damage cells directly by invading the cells or producing toxins, or the damage may be due to the inflammatory reaction they induce.
Infectious agents
____failure to respond to infectious agents and other antigens as a result of congenital or acquired immunodeficiencies; autoimmune diseases; hypersensitivity reactions.
Immunologic dysfunction
___ (mutations) cause a wide spectrum of abnormalities, from gross defects that are incompatible with life, to subtle variations in susceptibility to other diseases and include inborn errors of metabolism (storage diseases).
Genetic derangements
___ include decreased food intake (starvation), excessive ingestion of calories leading to obesity, and deficiencies or excessive intake (toxicity) of vitamins and minerals.
Nutritional imbalances i
Normally free radicals are scavenged, but when there is an excess of production or decreased removal
then ___occurs.
oxidative stress
Once formed, free radicals damage tissues by: ___ of membranes (this can be autocatalytic or self-perpetuating); Oxidative modification of proteins; DNA damage.
Lipid peroxidation
___that scavenge free radicals
Antioxidants
Free radical-scavenging enzyme systems including catalase, superoxide dismutases, and ___peroxidase
glutathione
what are some ultrastructural changes during hydropic degeneration
membrane alterations: blebs, blunting, and loss of microvilli, myelin figures (whorls of detached membranes), and loss of intercellular junctions
mitochondrial swelling, rarefaction, and small amorphous dense deposits
dilation of the endoplasmic reticulum with detachment of ribosomes
clumping of nuclear chromatin
___ is the accumulation of fat in hepatocytes
hepatic lipidosis
___ refers to the spectrum of morphologic changes (gross, histologic, and ultrastructural) that follow cell death in a living tissue
Necrosis
____ refers to one group of pathways of cell death that are the result of a regulated intracellular program that activates intracellular enzymes to cause degradation of cell proteins and DNA, cell shrinkage, and death.
Apoptosis
Coagulative necrosis occurs most often with ____ and for a few days the cells maintain their basic outline.
ischemia or toxins
Eventually enzymatic action and entering leukocytes leads to proteolysis and loss of the cell outline. Ischemic necrosis of an extremity with subsequent coagulation necrosis is called dry gangrene. When the action of bacteria causes liquefaction of the gangrenous tissue it is called wet gangrene.
Eventually enzymatic action and entering leukocytes leads to proteolysis and loss of the cell outline. Ischemic necrosis of an extremity with subsequent coagulation necrosis is called ___ . When the action of bacteria causes liquefaction of the gangrenous tissue it is called ___
dry gangrene.
wet gangrene.
Liquefactive necrosis occurs most commonly with ___ and the cells are digested by their own enzymes, bacterial toxins, or the enzymes of leukocytes.
bacterial, fungal, or lytic viral infections
Cells are replaced by neutrophils and macrophages. Focal collections of white blood cells (pus) and cellular debris are termed abscesses.
during liquefactive necrosis, Cells are replaced by neutrophils and macrophages. Focal collections of white blood cells (pus) and cellular debris are termed ___
abscesses.
mineralization of fat
saponification
Mycobacterium tuberculosis in humans and Corynebacterium in sheep are examples of ___
caseous necrosis
4 steps of apoptosis
Cell shrinkage
Chromatin condensation
Membrane blebs and apoptotic bodies
Phagocytosis of apoptotic cells
apoptosis→ shrunking cell
autolysis
when tissue is not preserved and starts to breakdown after death
autoysis→ softening of tissues after death→ melting apart
autolysis → lungs, happened after death
rigor mortis
contraction of muscle
___ is the contraction of muscle
rigor mortis
livor mortis
gravational pooling of blood in lung
gravational pooling of blood in lung
livor mortis
imbibition
when things next to each other color each other → bile from gallbladder
___ is when bile changes the color of things near it
imbibition
___ – blood pigment that is digested by bacteria
Pseudomelanosis
Pseudomelanosis
blood pigment that is digested by bacteria
during the initiation phase of apoptosis ___ become active
. Caspases
Initiation Phase via either the extrinsic (death receptor-mediated) or intrinsic (mitochondrial) pathway
Caspases become catalytically active (caspases are a family of cysteine proteases that cleave the nuclear scaffold and cytoskeleton proteins)
execution phase of apoptosis
Caspases cleave cytoskeletal and nuclear membrane proteins, activate DNAase that induces internucleosomal cleavage of DNA
___is the degradation of a cell by its own enzymes after it has died
Autolysis
the gradual cooling of the cadaver
algor mortis
hypostatic congestion or gravitational pooling of blood
livor mortis
pyknosis
karyolysis
karyorrhexis
