How can we help?

You can also find more resources in our Help Center.

71 terms

BMS Exam 2: Cell injury, inflammation & tissue repair

BMS Exam 2
STUDY
PLAY
list possible etiologies of cell injury
hypoxia
physical agents
chemical agents & drugs
infectious agents
immunological reactions
genetic derangements
nutritional imbalances
list outcomes of cellular stress
- cellular adaptation: new altered steady state for cell
- cell injury: occurs when limits of cellular adaptation are exceeded
4 cellular systems & processes prone to injury
cell membrane integrity
aerobic respiration
enzyme & structural protein synthesis
nuclear integrity
4 important biochemical themes common to cell injury & cell death
Δs in membrane permeability
ATP depletion
O2 & O2-derived free radicals
Intracellular Ca+2 homeostasis
List cellular effects due to injury?
cellular swelling
abnormal lipid accumulation
hyperglycemia
abnormal pigment accumulation
hemosiderin
calcification
hyaline infiltration
cellular swelling
hypoxia → ↓ATP production 2° ↓Na-K ATPase pump activity
abnormal lipid accumulation
steatosis → abnormal parenchymal accumulations of → triglycerides or cholesterol (Esp. Liver)
Define Hyperglycemia & what tissues/organs does it commonly affect?
Occurs in abnormalities of glucose metabolism (e.g. Diabetes Mellitus)

Commonly affects: blood vessels, eyes, heart, kidneys, nervous tissue
abnormal pigment accumulations
-lipofuscin - atrophied/chronically injured cells
-- free radical & lipid peroxidation

- melanin: normal pigment turns bad
--melanoma --> local melanocyte change
--Addison's Dz --> diffuse melanocyte response to ↑[ACTH]
hemosiderin
- insoluble form of Fe in tissue
- abnormal accumulations (eg ↑ [Fe], impaired Fe utilization, hemolytic anemias) --> tissue staining
ex: bruise- Hb breakdown releases Fe bound in tissue by hemosiderin
calcification
Ca+2 may precipitate in:
areas of chronic inflammation
dead or degenerating tissue
hyaline infiltration
protein deposition secondary to long-standing HTN and DM
List morphologic changes due to injury
atrophy
hypertrophy
hyperplasia
dysplasia
metaplasia
anaplasia
neoplasia
atrophy
↓ cell size secondary -
↓ workload
↓ innervation
↓ blood supply
↓ nutrition or hormone stimulation

physiologic atrophy - 2° ↑ age

disuse atophy - ↓ use
hypertrophy
↑ cell size 2° to ↑ workload
hyperplasia
↑ tissue mass 2° ↑ # of cells
dysplasia
microscopic Δ in cell size or shape w/ loss of normal architecture

controlled reproduction of cells but may be related to malignant transformation
define metaplasia and give one example of this
- one cell 'type' replaced by another cell type
- usually a reversible Δ
- may be related to malignancy

ex: smokers - ciliated pseudostratified columnar epithelium replaced by stratified squamous epithelium in the larynx
anaplasia
- abnormal appearing cells lacking differentiation
- equated w/ undifferentiated malignant neoplasms
neoplasia
excessive uncontrolled clonal cell proliferation
list causes of anoxic cell injury/death
ischemia
thromosis
embolism
ischemia
- O2 requirement > O2 supply, tissue starving for O2
- reversible if blood flow restored
- atherosclerosis - most common cause
- may precede infarction or tissue death
thrombosis
- blood clot formations on intimal lining of blood vessels or heart
- most common cause: intimal disruption exposing subendothelial collagen
define embolism & identifiy sources
- free floating particle in blood stream lodges in blood vessel & occludes blood flow
- thrombus - most common source, it can get dislodged
- may also occur from: fat, heart valve vegetations or foreign bodies (FAT BAT)
Fat
Air
Thrombus
Bacteria
Amniotic Fluid
Tumor
define infarction, red (hemorrhagic) infarction, pale infarction
infarction: localized area of tissue 2° ↓ blood flow

red (hemorrhagic) infarction: occurs in loose tissues w/ blood collaterals (lung, intestines)

pale infarction: occurs in solid tissues w/ single blood supply (brain, heart, kidney, spleen)
define necrosis
cell or tissue death w/ morphologic evidence of death
define coagulative (fibrous) necrosis
coagulation occurs in infarcted area --> homogenous mass deprived of blood
liquefactive necrosis
liquefication of tissue due to autolysis or bacterial breakdown

characterized as wet, juice, slimy
gangrenous necrosis
"dry" gangrene - loss of blood supply
"wet" gangrene - liquefaction
"gas gangrene - spcefic type of necrosis due to Clostridia infections
apoptosis
-highly controlled, orderly process of cellular self-destruction
- involves coordinated destruction of intracellular structures by caspases
- celular stresses - activation of caspases
pathology of apoptosis
- caspase activation causes mitochondria to release cyctochrome c
- cytochrome c formation of an apoptosome
- apoptosome activates other caspases --> intracellular protease activity --> cell death
define acute inflammation & 4 cardinal signs

what is the hallmark of acute inflammation?
destroys, dilutes & walls off injurious agents
- major Δ = vasolidation
- ↑ blood flow → rubor & color
- ↑ vascular permeability → interstitial exudate

4 cardinal signs:
- rubor (redness)
- calor (heat)
- dolor (pain)
- tumor (swelling)
- (loss of function)

hallmark of acute inflammation: edema
** define exudation & exudate **
exudation: process where fluid, proteins & blood cells 'leak thru' vascular system to interstitial tissue

exudate: extravascular fluid that contains cellular debris & ↑ [protein]
specific gravity > 1.020
pus
purulent exudate with
↑ [WBC]
parenchymal cell debris
lymphatics
- lymph flow ↑ during inflammation
- also transport WBCs, cell debris, injuring agent
lymphangitis & "streaking"
lymphangitis - inflammation of lymph vessels

"streaking" - inflammation of lymph channel (see cell injury lecture pg 16)
lymphadenitis
inflammation of lymph nodes
what are the positive and negative factors of delivery of WBCs
positive factors:
- phaocytosis
- kills micrboes
- degrades necrotic tissue & foreign Ag

negative factors:
- prolongs → inflammation
- induces tissue damage (by attacking normal, healthy tissues)
process of WBC delivery
-margination, rolling, adhesions
- deapedesis
- migration toward chemotactic factors
- chemotaxis → WBCs migrate along chemical gradient
what are chemotactic factors for the delivery of WBCs
bacterial products
complement components
lipoxygenase products
cytokines
What are the predominant WBC types in the 1st 24 hours, and more than 24 hours
1st 24hours - neutrophils (first line of defense)
> 24 hours - monocytes
Recognition & attachment in Phagocytosis
- microogranisms are typically coated by opsonins (Fc fragment or C3b)
- opsonins bind to WBC receptors
- bacterial lipopolysaccharides (LPS) bind directly to WBC
oxidative & non oxidative mechanism of phagocytosis
oxidative mechanisms:
- O2-, H2O2, HOCl, -OH produced in phagolysosome via NADPH oxidase
- myeloperoxidase (MPO) produces hypochlorous acid (HOCl)

non-oxidative mechanisms:
-lysosomal enzymes
list the cell-derived chemical mediators that cause inflammatory response to occur
focus:
histamine
eicosanoids
cytokines
tumor necrosis factor

others:
serotonin
platelet activating factor
nitric oxide
many, many others
list plasma-derived mediators that cause inflammatory response to occur
Factor XII (Hageman Factor)
Bradykinin
Complement (C3a, C5a)
Histamine
cell-derived chemical mediator
- mostly found in mast cells and basophils
- performed & stored in granules

**physiological effects**
EDEMA
- vasodilation
- "leaky" capillaries
eicosanoids
cell-derived chemical mediator
- cell membrane derived phopholipids are converted inro arachidonic acid
- transformed via 2 main enzyme pathways:
-- cyclooxygenase
-- lipoxygenase

**can manipulate this pharmacologically
cyclooxygenase (COX) derivatives
prostaglandins (PG)
- PGI (prostacyclin) - vasodilates
- PGE series - vasodilates
- PGF series - vasoconstricts
- induces fever and pain

Thromboxane (TX)
- cause platelet aggregation & vasoconstriction
lipoxygenase derivatives
leukotrines (LT)
- causes vasoconstriction, bronchospasm & ↑ vascular permeability
- chemotactic for WBC
- major products: HPETE, HETE, Di-OH ETE, lipoxins
What therapeutic agents and target sites to inhibit eicosanoids
see cell injury lecture pg 21
- Aspirin Indomethacin: inhibit cycloxygenase pathway → ∅ prostaglandings → ∅ pain

- New pharmacological agents? "non-steroidal" Leukotriene modifiers or blockers: inhibit lipoxygenase pathway → ∅ leukotriene
--useful for asthma, or intense vasoconstriction

- corticosteroids - block parent molecule of making arachindonic acid → anti-inflammatory → ↓ production of other products in cyclooxygenase and lipoxygenase pathway
What inhibits Prostaglandins (PG) and Thromboxane (TX)?
steroids and NSAIDS
What inhibits Leukotrienes?
steroids & LT modifiers (Zafirlukast - Accolate)
cytokines
mediator of inflammation

cell signaling molecules produced by WBCs & endothelium

induces WBC aggregation & primes cells for inflammatory effects
Tumor necrosis factor (TNF)
- regulates immune cells & stimulates acute phase reaction
- usually produced by activated macrophages
- induces fever, apoptosis, sepsis & cachexia
what inhibits Tumor necrosis factors? (TNF)?
TNF inhibitor
infliximab, etanercept & others
used in CHRONIC (not acute) inflammatory Dz's (RA, IBD)
Factor XII (Hagemen Factor)
Mediator of Inflammation

activated by platelets or exposed collagen turns on 3 systems
- kinin
- coagulation
- fibrinolysis
Bradykinin (Kinin system)
mediator of inflammation

induces -
vasodilation
↑ capillary permeability
complement
mediator of inflammation

complement: blood proteins that help w/ opsonization, chemotaxis & formation of the membrane attack complex

also forms anaphylatoxins C3a & C5a
anaphylatoxin effects
anaphylatoxins (C4a, C3a, C5a) -->
- chemotactic, stimulate immune responses
- suppress immune responses
- bronchoconstriction
- vasoconstriction
- edema
inflammation acute phase reactions
- fever, ↓ appetite & ↑ catabolism
- severe cases - hemodynamic Δs
- ↑ hepatic synthesis of: C-reactive protein (CRP), complement, coagulation poteins
Inflammation peripheral WBC Δ
leukocytosis
↑ # immature PMNs -
- "shift to the left"
- "left shift"
- "bandemia"
list post-inflammation outcomes
- complete resolution
- fibrosis
- abscess formation
- chronic inflammation
complete resolution
return of normal tissue
usually occurs w/ small or short lived injuries
fibrosis
- healing by CT replacement
- occurs after substantial tissue destruction
also occurs -
- in tissues that DO NOT regenerate
- w/ excessive fibrinous exudate
abscess formation
occurs w/ pyogenic (pus-producing) infections
chronic inflammation
occurs when acute response cannot be resolved 2° to
- persistence of injuring agent
- interference in healing process
- duration: weeks → months w/ simultaneous tissue healing & destruction
- serves to contain & remove an agent or process w/in a tissue
- tissue macrophages are major cell involved in process
- HALLMARK: destruction of parenchymal cells & stromal framework
granulomatous inflammation
distinct type of chronic inflammation in response to indigestible substances

predominant cell types
- macrophage w/ epithelial cell-like appearance & produces a granuloma
where does granulomatous inflammation occur?
chronic immune Dz
certain infections (eg TB)
foreign body response
wound healing
restoration of tissue integrity after injury

wounds undergo:
contraction
formation of granulation tissue
-- angiogenesis
-- cell proliferation
new extracellular matrix
scar formation
tissue regeneration
wound healing methods
1° intention
- wounds have → apposed edges
- wound type: lacerations, surgical incisions
- thin scar
- color Δs red → white ~ 3 months

2° intention
- wounds have largely separated edges
- wound type: crush, gouges, infected or chronic wounds
- large amounts of fibrin, necrotic debris & exudate → intense inflammation & large scar
wound healing complications
- reopening of wound from various causes dehiscence (wound that falls apart)
- keloid: scar w/ ↑ collagen formation
exuberant granulation: excessive granulation tissue