Cell Injury and Inflammation Flashcards
1
Q
Causes of Cell Injury
A
- ischemia (lack of blood flow or oxygen to an area)
- infectious agents (bacteria and virus kill cells)
- immune reactions (immune system becomes too excited and causes hypersensitivities or autoimmune)
- genetic factors
- mechanical factors
- nutritional factors
- physical factors
- chemical factors
-psychosocial factors
2
Q
Factors Influencing healing
A
- physiological variables (age, growth factors, vascular sufficiency)
- general health of the individual, immunocompetency, psychological/emotional well being
- the presence of comorbidities (DM, decreased oxygen perfusion, hematologic disorders, cancer, incontinence, Alzheimers, neurologic impairment, immobility
- tobacco, alchohol, caffeine
- nutrition
- infections
- type of tissue
- medical treatment
3
Q
Secondary Injury
A
complications after intial injury; usually the result of hypoxic-ischemia (brain cant get oxygen) injury caused by cerebral edema (swelling of brain) or intracranial hematomas (bleeding in brain)
4
Q
Phases of healing
A
- hemostasis and degeneration
- inflammation
- proliferation and migration
- remodeling and maturation
5
Q
Adaptation
A
the extent to which the cell is able to alter mechanisms and regain homeostasis in the altered environment
6
Q
What does “reversible injury” depend on?
A
- mechanism of injury
- length of time the injury is present w/o intervention
- severity of the injury
7
Q
Mild injury
A
- leads to sublethal alterations-may be reversible
8
Q
Moderate or severe injury
A
- Leads to lethal alterations - likely irreversible - lead to cell death
9
Q
Describe the pathway of Ischemia, one of the causes of cell injury
A
blood flow is insufficient (partial = hypoxia, total = anoxia) causing lack of ATP to be made which causes a build up of ions and fluid intracellularly, causing the cell to swell
10
Q
Causes of Ischemia (what is it?) (know the condition names)
A
- obstruction of the respiratory tree (suffocation)
- inadequate transportation of O2 across the respiratory tract (pneumonia)
- arterial lumen obstruction and narrowing (atherosclerosis)
- intravascular clot (thrombus)
- inadequate transport of O2 in the blood (anemia)
- the inability of cell to use O2 (CO poisoning)
partial (hypoxia) or total (anoxia) reduction in O2 supply = loss of aerobic metabolism = reduction ATP synthesis = accumulation of ions and fluid = cells swell - comprised function
11
Q
Infectious agents
A
- bacteria, viruses and others
12
Q
immune reactions
A
overzealous in its activity, leading to hypersensitivities ranging from a mild allergy to life-threatening anaphylactic reactions or autoimmune disorders
13
Q
Chemical factors
A
two catagories:
1. substances that can injure cells directly (heavy metals)
2. substances that require metabolic transformation into the toxic agent (carbon tetrachloride)
Production of reactive oxygen species (ROS)
- formation of free radicals
14
Q
Free radicals
A
- natural by-product of using O2
- it is when a normal oxygen atom lose one of four paired electrons, becomes a chain rxn
- excessive amounts = oxidative stress = cell injury or death
15
Q
Oxidation
A
when a molecule loses an electron
oxidation as a by product of metabolism damages cell membranes, leading to intrinsic cellular damage, a part of the normal aging process
16
Q
Other causes for free radical formation
A
- exposure of toxic chemicals
-exposure to high level of oxygen - irradiation
- UV
- fluorescent light
- pollutants
- tobacco smoke
- pesticides
- drug overdose
- heat stress
-reperfusion injury - prolonged exercise
*intense or prolonged strenuous exercise leads to oxidative stress and may be harmful
17
Q
Antioxidants
A
- they neutralize the extra free radicals and stop chain reaction
- endogenous antioxidants; enzymatic (scavengers) and nonenzymatic defense mechanisms
- exogenous antioxidants; 200 have been identified in food or plant substances (found outside the body)
- *moderate PA and exercise strengthen the antioxidant defense system
18
Q
Genetic Factors
A
- alterations in the structure of number of chromsoomes that induce multiple abnormalities (down syndrome; 3rd chromosomes in the 21st pair)
- single mutations of genes cause changes in the amount or functions of proteins (sickle cell anemia, low-density lipoprotein receptor deficiency and a-antitrypsin deficiency)
- multiple gene mutations that interact with environmental factors to cause multifactorial disorders (hypertension and type 2 diabetes)
I would just remember structure/number alteration, single gene mutation, genes interacting with environment
19
Q
Mechanical Factors
A
physical stress theory says changes in physical stress should cause a predictable adaptive response in tissue
- tissue response to physical stress includes decreased stress tolerance (atrophy), maintenance, increased stress tolerance (hypertrophy), injury and death
- soft tissues are influenced by the history of recent physical stresses so that the accumulation of individual stresses can cause injury
- trauma (bone fracture or ligaments rupture)
- other causes; repeated episodes of moderate-magnitude force, slow degradation of tissues tolerance, low loads sustained over long time
20
Q
Nutritional Factors
A
imbalances in essential nutrients
- excessive nutrient intake, (leads to obesity)
- dietary deficiency (abnormal level or vitamins, kwashiorkor)
21
Q
Physical factors
A
- blunt or penertrating trauma (brain contusions, internal organ damage, blood loss, delayed death of infections or organ failure)
- extremes of physical agents (temp; burn or frostbite), radiation and electricity
22
Q
Psychosocial factors
A
feat, tension or anxiety may influence individual threshold values for tissue adaptation and injury
23
Q
Cellular aging
A
Aging changes can significantly influence homeostasis and the recovery process (Mitochondrial DNA is big target for age changes)
- LIPOFUSCIN (natural waste product) pigmant is most well described age-association change in postmitotic cells (found in high concentrations in OLDER cells, so often used as a marker of cellular agin)
24
Q
Theories of Cellular Again
A
- with aging, cells experience decreased capacity to respond to stress = progressive decline in homeostatic balance = pathology
*Pathologic changes associated with aging vary from person to person but usually consist of reduced functional reserve caused by atrophy of tissues or organs
- aerobic training can help improve function of mitochondria, cardiac and skeletal muscle cells
25
Acute Reversible Cell Injury (Mechanism)
- impairment of ion homeostasis in cell (increased NA and Ca)
- causes influx of interstitial fluid and cell swells
- reduced metabolism occurs causing more cellular damage
- cell forms plasma blebs that seal off and detach from cell surface
- ribosomes detach from rough ER causing reduced protein synthesis and cycle of damage continues
simple: blebs (swellings) form and ribosomes detach from ER in response to acute reversible injury to a cell, continuing cycle of damage
nucleus remains undamaged in cell, normal cell fxn can return after removal of the stressor or injurious stimulus
26
Cellular adaptations in chronic cell injury (reversible)
Cells adapt when injury occurs, common adaptation - atrophy, hypertrophy, hyperplasia metaplasia and dysplasia
(focus on atrophy); Bone loss, muscle wasting and brain cell loss are examples of tissue/organ atrophy associated with aging
(then if stressor is removed it can return to normal cell)
27
Reversible cell injury - intracellular accumulations or storage
fatty liver
- when liver is injured, accumulation of lipids occurs, because protein synthesis reduction (blebs and info above) means there are no protien vesicles to take lipids out of the cells
28
Irreversible cell Injury
CELL DEATH
occurs via apoptosis (programmed cell death) or neurosis (end point of pathological process, degradation)
29
Apoptosis
Cell Size
Nucleus
Plasma membrane
Cellular contents
Adjacent inflammation
Physiological or pathologic role
Cell Size: reduced/shrinks
Nucleus; fragmentation
Plasma membrane; intact
Cellular contents; intact
Adjacent inflammation; no
Physiological or pathologic role; often physiological
30
Necrosis:
Cell Size
Nucleus
Plasma membrane
Cellular contents
Adjacent inflammation
Physiological or pathologic role
Cell Size; enlarged (swelling)
Nucleus; pyknosis, karyorrhexis, karyolsis
Plasma membrane; disrupted
Cellular contents; enzymatic digestion
Adjacent inflammation; frequent
Physiological or pathologic role; invariably pathologic
31
What can trigger inflammation
- infections, tissue necrosis, foreign bodies and immune reactions
32
Clinical manifestations of acute inflammation
Erythema (redness) - vasodilation and increased blood flow
Heat - vasodilation and increased blood flow
Edema - fluid and cells leaking from local blood vessels
Pain - for direct trauma, chemicals like bradykinins, histamines, serotonin. For internal pressure, welling of nerve endings
33
Inflammation fxn
- process initiated after cell injury
- removal of injurious agent, cellular debris and initiation of the healing process
normally protective but can potentially damage adjacent tissue
34
Characteristics of acute inflammation
- Vasodilation (increased blood flow, redness and heat)
- Increased capillary permeability (permits passage of plasma proteins and WBCs to site of injury and causes loss of fluid, ultimately causing increased blood viscosity)
- CLOTTING of the fluid in the interstitial spaces because of increased fibrinogen and other proteins to wall off the invader
- migration of WBCs from the microcirculation (accumulation at injury site causing swelling)
35
Factors affecting bloodblow
- Histamine and bradykinins: Increase blood flow by dilating blood vessels.
- Serotonin: Decreases blood flow by constricting blood vessels.
- Anaphylatoxins: Increase blood flow by dilating blood vessels.
- Leukotrienes: Can either constrict or dilate blood vessels, depending on the context.
- Prostaglandins: Typically increase blood flow by dilating blood vessels.
BAPH dialtes
S constricts
L varies
36
Acute inflammation cellular infiltrate
platelets
neutrophils
monocyte/macrophages
fibrocytes/fibroblasts
endothelial cells
37
Chronic inflammation cellular infiltrate
monocytes/macrophages
lymphocytes**
plasma cells
fibrocytes/fibroblasts
endothelial cells
38
difference between acute vs chronic inflammation cellular infiltrate
lymphocytes in chronic
39
Edema Vs Effusion
edema - fluid and cells leaking from local blood vessels into the extravascular spaces
effusion - (leakage into body cavity or joints) general term for escape of fluid, can be transudate (fluid with low protein content) or an exudate (fluid with high protein content)
40
Hemorrhagic; sanguineous Exudate
bright red or bloody, RBC
bloody, sang
41
Serosanguineous Exudate
blood-tinged yellow or pink, RBCs
sang - blood, but not straight up blood
42
Serous Exudate
thin clean yellow or straw colored, albumin and immunoglobins
S for Straw (yellow)
43
Purulent Exudate
- viscous, cloudy pus, cellular debris from necrotic cells and dying neutrophils
P for Pus (cloudy bc cellular debris)
44
Catarrhal Exudate
thin clear mucus
C for Clear
45
Leukocyte Accumulation (characteristic of acute inflammation response)
- WBS (leukocytes, neutrophils, mono/macrophages)
- remove or eliminate injurious stimulus by releasing enzymes and toxic substances that kill, inactive, and degrade microbial agents, foreign antigens or necrotic tissue
- neutrophils rapidly die out within 24 hrs
- monocytic/macrophage cells are responsible for cleaning cellular debris
MARGINATION, ADHESION, DIAPEDESIS, CHEMOTAXIS
46
How do the WBCs get to injury cite?
chemotaxis (chemical signals)
47
Chemical Mediators of inflammation
multifunctional, responsible for vascular and leukocyte responses in an acute inflammatory response
cell-derived and plasma derived
cell derived; histamine, platelets, arachnoid acid derivatives, cytokines
48
Histamine
- in mast cells, basophils, platelets (stored in granules = fast response)
- causes endothelial contraction, forming gaps and increasing blood vessel permeability, allowing blood cells to exit the interstitial spaces (vascular leak)
- can also be a vasodilator and bronchoconstrictor
-
49
Name the three inflammatory mediators derived from phospholipids
- PFA
- prostaglandins
- leukotrienes
50
Platelet-activation factor (PFA) and Arachidonic acid derivatives
- involved in pain response of inflammation
- PFA can increase strength of other inflammatory mediators
- arachidonic acid derivatives are in the pathway that produces prostaglandins (cause pain) and leukotrienes (cause inflammation)
-
51
What do aspirin and corticosteroids do to stop pain and inflammation
inhibit pathways in the phospholipid mediators (arachnoid/prosoglandins) to stop pain and inflammation
52
Cytokines
- polypeptide substances produced by leukocytes
- Systemic hormonal inflammatory effects
- autocrine affect (hormones impact themselves)
- paracrine affect (other cells)
ex; IL-I causes fever and TNF indice IL-I
so if you see those in the vlood, patient probably has fever and pain
53
What are examples of phagocytes and what do they do
neutrophils, monocytes and macrophages
inactive and remove inflammatory stimulus to begin healing
54
Factors affecting blood flow
Histamine
Serotonin
Bradykinins
Anaphylatoxins
Leukotrienes/prostaglandins
55
Diagnosing inflammatory process
- leukocyte counts
- increased WBCs is an indication of active inflammatory reaction (typically to an infection or tissue injury)
- decreased WBC is indicator of severe infections (sepsis)
