Cell injury Flashcards
1
Q
A
Histopathologic features of reversible cell injury
- Cell swelling
- Blebs on cell surface and microvilli
- Myelin figures
- Swollen mitochondria
- Darker staining
- cells switch from aerobic respiration to anaerobic glycolysis
- depletion of ATP
- glycogen depletion
- lactic acid accumulation
2
Q
A
Histopathologic features of irreversible cell injury
- loss of nuclei
- severe vacuolization of mitochdondria
- swollen lysosomes
- Massive Ca2+ influx causing protein denaturation and coagulative necrosis via phospholipases, proteases, and endonucleases
- loss of phospholipids
- lipid breakdown products
- cytoskeletal alterations
- Saponification due to accumulation of Ca2+
3
Q
Types of necrosis
A
- Coagulative necrosis: necrosis of solid tissue (heart, spleen, kidney), coagulated cells, proteins of cells are denatured however cell shape and size preserved
- cause: ischemia - Fat necrosis: chalky-cheese appearance; divided into non-traumatic and traumatic, Ex. pancreas (from lab)
- Liquefactive necrosis: occurs in brain (only type) and lungs
- cause: hydrolytic enzymes & bacteria - Caseous necrosis: cheesy-milk, eosinophilia, granulomas (dead macrophage), Ex lung (from lab)
- cause: only TB - Gangrenous necrosis: combination of ischemic coagulative necrosis & wet gangrene, clot in arteries causing hypoxia in limbs and heart
- cause: ischemia
4
Q
Intracell accumulation of lipids
A
- liver & heart are best examples, but any tissue can be affected
- fatty change often has little or mild functional effects; Exception is CCl4 change in lipid accumulation
- Fatty change in heart usually secondary to prolonged hypoxia or diptheric myocarditis
- Xanthoma: cholesterol-filled macrophages
5
Q
Hypertrophy
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- increase in size of cell accompanied by augmented functional capacity
- causes: increased functional demand
- Ex. LVH in hypertension
- Ex2. muscle hypertrophy in athletes
- Ex3. sex organs at puberty
6
Q
Hyperplasia
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- increase in number of cells
- Causes: increased functional demand
- Ex. polycythemia vera in high altitudes
- Ex2. endometrium in early phase of menstrual cycle
- Ex3. skin in calluses
- Ex4. Benign Prostatic Hyperplasia/Hypertrophy (BPH:) urethral compressed by many nodules
Ex5. Physiologically, hyperplasia in breasts during pregnancy and lactation
7
Q
Metaplasia
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- conversion of one cell type to another
- Ex1. bronchial ciliated columnar to squamous metaplasia in smokers
- Ex2. vagina/cervix (Cuboid to S; squamous metaplasia),
- Ex3. gall bladder (transitional to squamous metaplasia)
- Ex4. urinary bladder (transitional to squamous metaplasia)
- Ex5. GERD (squamous to columnar cell metaplasia)
- Ex6. Keratomalacia
- Ex7. Myositis ossificans
8
Q
Dysplasia
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- alteration in size, shape, and organisation of cell components including nuclei
- pre-neoplastic lesion
- Cause: persistent injury
- Ex. dysplasias in bronchial epithelium, cervical epithelium (CID), uterine epithelium
- dyplasias are graded
9
Q
Exudate
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- rich in proteins and cells
- specific gravity > 1.02
- classify inflammation based on contents of exudate ex. bacteria
10
Q
Pus
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- exudate of PMN, cell debris, and lysosomal enzymes
11
Q
Transudate
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- outpouring of fluid w/ low protein
- specific gravity <1.012
12
Q
Changes in vascular flow & calibre: Triple response of Lewis
A
- pale line along area of stroke
- Flare
- Swelling w/ blanching
w/ time-lapse
- Transient vasoconstriction of arterioles
- vasodilatation
- permeability changes w/ exudation:
- As blood flows more slowly and becomes more viscous, cell events begin to take place
13
Q
Endothelial cells capable of secreting:
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- prostaglandins
- coagulant factor VIII
- collagens
- anticoagulants (plasminogen activator)
14
Q
5 mechanisms by which the endothelium becomes leaky during inflammation
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- Immediate transient response: Leaky endothelium due to histamine inducing endothelial muscle contraction -> vasodilation -> and widening the space b/w endothelial cells.
- Junctional retraction: cytokine mediated, reorganization of cytoskeleton, disruption of endothelial cells, occurs 4-6 h post-injury, lasts > 24 h, demonstrated w/ TNF and IL-1 experimentally
- Direct endothelial injury w/ endothelial cell necrosis and detachment: endothelial detachment secondary to platelet adhesion and thrombosis, can either be immediate sustained or delayed prolonged leakage
- Leukocyte dependent endothelial injury: involves toxic O2 species and endothelial cell detachment occuring mostly in venules and pulm. capillaries
- Increased transcytosis: occurs in presence of VEGF, increase venular permeability
15
Q
Migration of Leukocytes (Exudation) sequence of events
A
- margination: WBC (smaller) pushed to periphery
- pavement & rolling: interaction of CAM on leukocyte (L-selectin) and endothelial cell surfaces (P-selectin & E-selectin)
- adhesion & emigration: mediated by endothelial adhesion molecules binding to integrins, ICAM-1 & VCAM (both upregulated) w/ LFA-1 (CD11a/18) & Mac1 (CD11b/18) and VLA-4, respectively
- chemotaxis & activation: bacterial products, C5a, LTB4, chemokines
16
Q
Phagocytosis involves 3 steps
A
- Recognition & attachment: involves opsonisation and attachment to 2 receptors on PMN or macrophages. Properties of macrophages:
- highly motile
- receptor for IgG and C3b
- activation by external stimuli - Engulfment: process involving pseudopods, phagolysosome, Ca2+, Mg2+
- Killing and/or degradation: 2 types of bactericidal mechanisms
a. O2-dependent mechanisms:
- H202-myeloperoxidase-haide system; mechanism deficient in Pt w/ chronic granulomatous disease; final reactive radical is HOCl
- MPO-independent killing; OH free radical
b. O2-independent bactericidal mechanisms
- decreased pH from lactate, carbonic anhydase actiivty, acid hydrolases w/in phagolysosome
17
Q
During phagocytosis, leukocytes release products extracell. in 3 ways
A
- Regurgitation during feeding
- Reverse endocytosis (frustrated phagocytosis)
- Cytotoxic release (following cell death)
18
Q
Neurogenic mechanisms
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- brief vasoconstriction in very early phaes of inflammtory rxn
- blocked by anesthesia
- followed by antidromic reflex w/ inhibition of vasoconstriction leading to vasodilation
- absence of innervation does not prevent inflammation
19
Q
Chemical mediators of inflammation: cell-derived
A
a. arachidonic acid metabolites: Prostaglandins & Leukotrienes
b. PAF: vasodilator, increases permeability, platelet aggregation; generated by all inflammatory cells, endothelial cells, and damaged cells.
c. vasoactive amines: 5HT (present on platelets only) & histamine -> vasodilates, increases venule permeability
20
Q
Agents responsible for release of histamine
A
- physical: trauma, cold
- immunologic (via IgE receptors)
- C3a and C5a (anaphylatoxins)
- histamine releasing factors from PMN, monocytes, and platelets
- IL-1
Note: degranulation mediated by cAMP and stimulated by platelet contact w/ collagen, thrombin, AFP, and Ag-Ab
21
Q
Chemical mediators of inflammation: plasma derived vasoactive mediators
A
3 different but interrelated systems:
- complement system
- clotting system
- kinin system: Bradykinin increases vascular permeability, produces smooth muscle contraction, vasodilation, and pain.
22
Q
Acute & chronic inflammation
A
- no sharp line
- Acute: 5 cardinal signs, vascular and exudative, characterized by presence of PMN
- Chronic: great amount of cell proliferation and CT, while less exudation; arbitrarily set at 2- 4 wks clinically
- Histopath of chronic inflammation: Ex. chronic inflammation of kidney; tubules far apart
- Chronic inflammation can occur from:
- persistent acute inflammation that is not resolved: Ex. PUD
- de novo inflammation: Ex. TB
- Chronic subdivided into 2 forms:
- Non-specific chronic inflammation: characterized by mononuclear cells & CT cells (fibroblasts)
- Granulomotous inflammation: characteristic tissue reactions in some infections (TB, syphillis, cat-scratch disease, fungal; protozoan), persistent forgein body inflammations, rheumatic fever (Aschoff body); rheumatoid arthritis, sarcoidosis, granuloma annular of skin
- Hallmark: epithelioid histiocyte surrounded by Giant cells
23
Q
Serous inflammation
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- albumin-containing exudate
- serosal mesothelial cells (peritoneal, pleural, pericardial, synovial)
- causes pitting edema
- Ex. blister from burns of skin; pulmonary TB
24
Q
Fibrinous inflammation
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- severe inflammations -> vessels permitting passage of large size molecule: fibrinogen)
- Ex. rheumatic fever (bread & butter pericarditis) and in pneumococcal pneumonias
- In tissues: easily identifiable b/c the ppt fibrin is deeply acidophilic
25
Suppurative or purulent inflammation
* a type of liquefactive necrosis
* characteristically seen in pyogenic infections by: staphylococcus, pneumococcus, miningococcus, gonococcus, E. coli, some non-haemolytic strep
* Ex. acute appendicitis
* In tissue: recognized by pools of numerous polyps (viable and dead)
26
Sanguinous inflammation
* exudate containing a large number of RBCs
* Ex. often seen in TB (sanguinous pleuritis)
* Ex2. inflammations as reactions to tumor invasion (sanguinous pericarditis)
* Ex3. Can also result from frost bites
27
Abscess
* caused by great intensity irritant (staph, turpentine)
* localised collection of pus caused by suppuration
* hole in tissue due to trypsin digestion, many PMN
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Erysipelas
- facial rash
29
Paronychia
- infections of fingernail
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Felon
- infection of distal phalanx
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Empyema
- collection of pus in pleural cavity
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Ulcer
* epithelium defect or excavation
* produced by sloughing of inflammatory necrotic tissue on surface
33
Pseudomembranous inflammation
* inflammation produced by powerful necrotizing toxin such as diphtheria
* false membrane consists of ppt fibrin, necrotic epithelium, and WBC
* pharynx, larynx, GI tract
34
Defects in leukocyte migration and chemotaxis
a. intrinsic corpuscular abnormality: Chediak-Higashi syndrome, diabetes
b. extrinsic
* defect in production of chemotactic factors (C5 deficiency)
* serum chemotactic inhibitors (C5 inactivators, especially in cirrhosis, sarcoidosis)
* inhibitors of leukocyte locomotion
* drugs
* factors in malignancy
* rheumatoid arthritis
35
Defects in microbicidal activity
* impaired H2O2 production: CGD
* MPO deficiency
* severe G6PD deficiency
36
Mechanisms involved in regen & repair: control of cell proliferation
1. stimulatory hormones & growth factors
2. inhibitory factors (chalones): lost of epidermal, granulocyte, lymphocyte chalones during injury
3. cell-cell interactions
4. cell-matrix interactions: integrin family (fibronectin-R, platelet surface-R, CAM)
37
Mechanisms involved in would healing: Fibronectins
* most important in wound healing; binds to both ECM components and cell surfaces -\> crazy glue or bridge
* seen in cell surfaces, BM, pericell matrices
* facilitate migraiton of new epithelium, chemotactic for monocytes and fibroblasts
* glycoprotein
* produced by fibroblasts, monocytes, endothelial cells
38
Collagenization & wound strength
1. angiogenesis: VEGF & b-FGF
2. Fibrosis: proliferation of site fibroblasts and deposition of ECM
3. Maturation and organisation of scar: collagen and other ECM degraded by metalloproteinases (zinc dependent)
39
Skin wound healing
1. Crust formation: provisional closure
2. Removal of dead tissue: w/ line of zone of demarcation
3. Replacement of lost cell and tissues: new tissue containing proliferating cellular and ECM termed Granulation tissue (tiny pink granules)
40
Stages of wound closure
* latent period: size of wound does not change
* period of contraction: shrinkage of granulation tissue -\> edges are pulled together
* epidermization
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* granulomatous inflammation
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Types of collagen
* adult skin: Collagen type I
* Granulation tissue: type III
* Cicatrisation: type III to I leading to wound retraction
* 5 major types of collagen:
* Types I, II, & III: fibrillary
* Types IV & V: amorphous and are found in basement membrane
* Keloid is type III collagen
* T1: bONE
* T2: cart2lage
* T3: pliability (embryonic tissue)
