Exam 2 Flashcards
Adaptive Response of a cell to_____ ________leads to an altered steady state
stimuli (stress)
If a cell is under stress for a short amount of time_____ injury happens and the cell _____
Reversible, adapts
If a cell is under stress for a long amount of time_____ injury happens and the cell _____
Irreversible, dies
In reversible injury, low ATP causes
- decreased oxi phos which leads to low ATP
- low ATP can be offset by glycolysis but it leads to low pH and low glycogen stores. this causes clumping of chromatin
- low ATP causes down regulation of Na+ which leads to an influx of water and sodium and a loss of potassium, this causes blebs and cellular swelling
- the other effects of low ATP are low protein synthesis, detachment of ribosomes and lipid deposition
In irreversible injury, low ATP causes
- membrane injury; loss of phospholipids, cytoskeletal alternation and lipid breakdown leads to enzymes leaving the cell and an influx of Ca+ which leads to increased Ca2+ in mitochondria
- low pH from glycolysis leads to the release of lysosomal enzyme which digests proteins and changed the nucleus
Leads to NECROSIS
Attributes of necrosis
- group of cells affected
- caused by injurious agents/events
-reversible events happen before it becomes irreversible - no ATP needed
- cells swell from H20 influx
-organelles and nuclear material is degraded by lysosomal enzymes (no longer organized)
-debris stimulates inflammatory cell response
Attributes of apoptosis
- programmed death
- affects single or a few cell
- irreversible
- Requires ATP
- Cells shrink as cytoskeleton is disassembled (like a building crumbling in on itself)
- organelles are membrane bound and organized
- molecules on vesicles membrane stimulare phagocytosis
- no inflammatory response
4 components in the inflammatory process
- vascularized connective tissue ( plasma, blood vessels)
- blood cells (neutrophils, monocytes, leukocytes as a whole )
- connective tissue cells (mast cells, fibroblasts, macrophages and lymphocytes)
- chemical mediators
whats the first step in leukocyte migration
- Margination
(Due to gaps in vascular wall from vasodilation, protein filled exudate flows out of the vessel, making the blood more viscous and pushing the RBC toward the center. the WBCs are pushed toward the edge of the blood vessel toward the gaps)
Irreversible cell injury is when the membrane is _____ and leads to ______
no longer intact, necrosis
What is the second step in leukocyte migration
Rolling
-cytokines cause the expression of adhesion molecules on the surface of both the endothelium (selectins) and the leukocyte (lewis); this slows down the leukocyte and prepares it for integrin activation and endothelial adhesion
What is the third step in leukocyte migration
Integrin activation and stable adhesion
Once the leukocyte is slow enough, the integrins on the leukocyte will bind with the Integrin ligand on the endothelial walls. these ligands are induced by proinflammatory cytokines. the integrins are now active and adhered to the endothelium wall of the blood vessel.
What is the fourth step in leukocyte migration
Transmigration (diapedesis)
PECAM-1 allows adhered leukocytes to through endothelial gaps in the tissue in a controlled manner.
What is the fifth and sixth steps in leukocyte migration
chemotaxis allows leukocytes to migrate (5th) to the infection site to begin phagocytosis (6th)
chemokines from bacteria, mast cells, and compliment proteins attract the leukocyte to the infection site. leukocytes recognize and kill pathogens via phagocytosis
What are the 3 major steps in phagocytosis
- recognition and attachment (opsonization)
- engulfment
- killing in an O2 dependent/independent manner
What is O2-dependent killing?
When something is phagocytosed, oxygen is engulfed with it. O2 is rapidly converted into O2* (reactive O2) via NADPH to NADP oxidation. O2* is made into H2O2. H2O2 can be converted into HOCl via myeloperoxidase (MPO) which degrades bacteria.
neutrophils have myeloperoxidase (MPO) granules in them
What is O2 independent killing
- bactericidal enzymes that degrade bacterial walls
- lysosomal enzymes that hydrolyze glycopeptide coats on bacteria
- lactoferrin
-cationic granular proteins
-defensins
The first step of inflammation in Lobar Pneumonia
Congestion- fluid in alveolar space
fibrin rich fluid spreads from alveoli to alveoli. this causes less gas exchange and a cough
The second step of inflammation in Lobar Pneumonia
Red Hepasitsation (airless lung and cough)
-neutrophils attack organisms and phagocytose them
The third step of inflammation in Lobar Pneumonia
Grey hepatisation (cough)
- macrophages come in and phagocytose dead neutrophils, bacteria, and fibrin (clotting factors)
The fourth step of inflammation in Lobar Pneumonia
Many routes from here;
-resolution, no scarring
-scar if immunocomp (fibrosis)
- abscess if it cant be cleared up
-spread to other parts of the body if it can be cleared up
-death if it can’t be cleared up
Histologically, what do the purple dots mean?
types of leukocytes/WBC present.
WBCs are not normally in the tissue, in inflammation they are
Chronic inflammation occurs from___
Non-resolution of acute inflammation
Histologically, how do chronic and acute look
acute: some inflammatory cells (neutrophils) in tissue. no fibroblasts
chronic: lots of chronic inflammatory cells, giant cells, lots of thick fibrous tissue, and organ function is impaired.
Purulent exudate is____
Pus, which is dead and dying white blood cells
Hypertrophy
increased cell size
Hyperplasia
amount of cells increased
Histologically, Necrosis looks like
-lots of WBC and cells but no nuclei in them
Acute Inflammation lasts for ____ whereas chronic inflammation lasts for ____
hours to days, days to weeks.
Granulation tissue is present in both acute and chronic inflammation
true
granulation tissue is full of blood vessel. What is this process called?
angiogenesis
- budding of capillaries from vessels near the damaged area
-areas between capillaries are occupied by leukocytes, fibroblast and loose connective tissue matrix
What is healing by 1st intention
- clean wound/surgical incision
- focal disruption of basement membrane
- death of few cells
-normal cell regeneration over fibrosis
-small scar
minimal wound contraction
What is healing by 2nd intention
-large cut/ sometimes with bacteria
- inflammation with large amount of necrotic tissue
-large amount of granulation tissue to fill gaps
large wound contraction by myofibroblasts
-accumulation of ECM
-scar formation
Wound contraction is in both 1st and 2nd intention healing
false, only in 2nd intention healing
Vessels made in angiogenesis are leaky
true
What is a keloid
a keloid is where healing and repair go beyond the original area of damage
Histologically chronic inflammation has lots of
- mononuclear cells (-lymphocytes
-plasma cells
-macrophages) - giant cells
- fibroblasts
- leaky vessels
What are the subtypes of chronic inflammation
-non-specific (arises from non-resolution acute inflammation, e.x. gout)
-specific (response to certain types of injurious agents, not preceded by acute inflammation)
-granulomatous (specific to certain agents, like talc, silica and asbestos)
Granulomas are_____
Clusters of epithelioid macrophages. also known as giant cells
Giant cells are a hallmark of ____
both immune and non immune chronic inflammation
Liquefactive necrosis
-liquid-filled masses from tissue -> abscess with pus
-characteristic of anoxic brain injury
coagulative necrosis
Breakdown of cell organelles. Architecture is still present but insides are fucked up
Caseous necrosis
often seen in TB
- cheesy white appearance of necrotic tissue
-loss of cellular detail
-enclosed within inflammatory boarder
Hemorrhagic necrosis
- caused by injury and stroke and leads to brain damage
-blood in brain tissue
Gout is caused by____
Hyper-uricemia (high levels of urate) in blood, which crystalises into tophi
Can gout tophi be phagocytosed?
no, it’s a foreign body and cannot be phagocytosed as it doesn’t have a cell wall.
Where do gout tophi usually end up?
In between joints in the toes/fingers
Why does gout cause inflammation?
the body recognizes the crystals and foreign and attempts to rid of them via phagocytosis. this process does not work as they aren’t bacteria and don’t have cell walls/can’t be degraded. The phagocytes then get lysed releasing the crystals and lysosomal enzymes back into the body.
What type of inflammation is gout?
chronic: non-resolution of acute inflammation
Replacement of cells with the same type of cell is called _____
regeneration
Replacement of cells by connective tissue and scarring is called_____
fibrosis
Connective tissue repair starts with___
granulation tissue
Fibrosis occurs when____
- there is substantial damage to the connective tissue framework
-there is the lack of ability to regenerate specialized cells
Metaplasia
Where one adult cell type is replaced by another
How do cells adapt to stress?
-Hyperplasia
-Metaplasia
-Hypertrophy
-Atrophy
How do cells adapt to stress?
-Hyperplasia
-Metaplasia
-Hypertrophy
-Atrophy
