Pathology - Inflammation Ppt Notes

Front 1

What are the morphologic hallmarks of all acute inflammations ?

Back 1

1) dilation of small blood vessels
2) slowing of blood flow
3) accumulation of WBC and fluid in the extra vascular tissue

Front 2

Chart the morphologic changes in Myocardial Infarction

Back 2

Reversible injury
0-0.5 hr: EM changes (Relaxation of fibrils; glycogen loss; mitochondrial swelling)
Irreversible injury
0.5-4 hr: waviness
4-12 hr: beginning coagulation necrosis.
12-24 hr: beginning PMN
1-3 d: intense PMN
3-7 d: beginning mononuclear  phagocytosis
10-14 d: granulation tissue
2 months: scar

Front 3

Histamine is released by mast cell degranulation in response to?

Back 3

1) physical injury trauma, cold, heat
2) antibodies, allergic reactions
3) anaphylatoxins (C3a and C5a)
4) histamine-releasing proteins
5) neuropeptides (substance P)
6) cytokines (IL-1, IL-8)

Front 4

What are the cyclooxygenase inhibitors

Back 4

aspirin, NSAIDs.

Front 5

What are the Lipoxygenase inhibitors

Back 5

Zileuton; Montelukast

Front 6

What are Broad-spectrum inhibitors

Back 6

steroids

Front 7

What are other ways of inhibiting the synthesis of eicosanoid (2)?

Back 7

1) Reducing the transcription of genes encoding COX-2, phospholipase A2, IL-1, TNF, iNOS.
2) Modify the intake and content of dietary lipids by increasing the consumption of fish oil.

Front 8

What ROS are produced within cells?

Back 8

Superoxide anion, hydrogen peroxide (H2O2), and hydroxyl radical (•OH)

Front 9

What are the actions of ROS?

Back 9

1) Induce endothelial cell damage, increased vascular permeability, injury to other cell types.
2) Inactivation of antiproteases, such as α1-antitrypsin, with increased destruction of extracellular matrix.

Front 10

List Antioxidant mechanisms (5)

Back 10

1) Superoxide dismutase.
2) Catalase.
3) Glutathione peroxidase.
4) copper-containing serum protein ceruloplasmin.
5) iron-free fraction of serum transferrin.

Front 11

Acid proteases degrade what?

Back 11

bacteria within the phagosomes.

Front 12

Neutral proteases degrade what?

Back 12

- extracellular components, resulting in the tissue destruction
- cleave C3 , C5, anaphylatoxins, and releases kinin

Front 13

The destructive effects of lysosomal enzymes, are held in check by what?

Back 13

a system of antiproteases (α1-antitrypsin α2-Macroglobulin).

Front 14

Neuropeptides are secreted by..?

Back 14

sensory nerves and WBC

Front 15

Role of substance P and neurokinin A

Back 15

the transmission of pain, regulation of BP, and increasing vascular permeability.

Front 16

What are the most important plasma proteases (activated by the complement,kinin,clotting systems) in vivo?

Back 16

Bradykinin, C3a, and C5a (vascular permeability); C5a (chemotaxis); thrombin (endothelial cells, other cell types

Front 17

What are the outcomes of acute inflammation?

Back 17

1) Complete resolution Eliminating of the stimulus, the injury is limited, little tissue destruction, removal of debris, regeneration.
2) Healing by connective tissue replacement (fibrosis). substantial tissue destruction, tissues that are incapable of regeneration, or when there is abundant fibrin exudation In all these situations, organization by CT.
3) Progression to chronic inflammation Follow acute inflammation, or chronic from the onset. Acute to chronic transition occurs when the acute inflammatory response cannot be resolved, the persistence of the injurious agent or some interference with the normal process of healing.

Front 18

Chronic inflammation is characterized by?

Back 18

- Infiltration with mononuclear cells, which include macrophages, lymphocytes, and plasma cells
- Tissue destruction, induced by the persistent offending agent and by the inflammatory cells
- Attempts at healing by connective tissue replacement of damaged tissue, accomplished by proliferation of small BV (angiogenesis) and, in particular, fibrosis

Front 19

Examples of diseases with granulomatous inflammation

Back 19

TB ,Sarcoidosis, Syphilis, mycotic infections, berylliosis, cancer, autoimmune diseases

Front 20

What are the 2 types of granulomas

Back 20

1 - Foreign body granulomas - incited by relatively inert foreign bodies (talc)
2 - Immune granulomas - caused by a agent that is poorly degradable and capable of inducing a cell-mediated immune response.

Front 21

What are the 3 general patterns of arteriosclerosis?

Back 21

1. Arteriolosclerosis - affects small arteries and arterioles, may cause ischemic injury. ( eg HTN).
2. Mönckeberg medial sclerosis - characterized by calcific deposits (bone) in muscular arteries in older than age 50. Usually not clinically significant.
3. Atherosclerosis

Front 22

What characterizes atherosclerosis?

Back 22

1. atheromas (atherosclerotic plaques) – intimal lesions
2. raised lesion with a soft, yellow, grumous core of lipid (mainly cholesterol and cholesterol esters) covered by a white fibrous cap.
3. mechanically obstructing blood, possible thrombis, aneurysm formation
4. weakening of the underlying media

Front 23

Risk factors for CHD?

Back 23

1. Hypercholesterolemia
2. Hypertension
3. Cigarette smoking
4. Diabetes mellitus

Front 24

Nonmodifiabale risk factors for AS

Back 24

- Inc. age
- Male gender
- Family history
- Genetic abnormalities

Front 25

Modifiable risk factors for AS

Back 25

- Hyperlipidemia
- Diabetes
- Hypertension
- Cigarette smoking
- C-reactive protein/inflammation

Front 26

What is C-reactive protein, what is its role

Back 26

• CRP is an acute-phase reactant synthesized by the liver.
• Plays a role in the innate immune response by opsonizing bacteria and activating complement.

Front 27

Where is CRP produced?

Back 27

- From cells in the AS intima

Front 28

What are Fatty Streaks composed of?

Back 28

- Lipid filled foamy macrophages

Front 29

What is the avg. size of AS plaques?

Back 29

- Size - 0.3 to 1.5 cm

Front 30

In descending order what are the most extensively involved in AS plaques

Back 30

- lower abdominal aorta > coronary arteries > popliteal arteries > the internal carotid arteries > circle of Willis.

Front 31

Which blood vessels are typically spared of plaques?

Back 31

- upper extremities are spare
- mesenteric and renal arteries, except at their ostia.

Front 32

What are the 3 components of AS plaques?

Back 32

In varying proportions
(1) cells, including SMC, MØ , and T cells.
(2) ECM, including collagen, elastic fibers, and PG
(3) intracellular and extra cellular lipid

Front 33

What are the morphology-characteristics of AS plaques?

Back 33

- Superficial fibrous cap composed of SMC & collagen.
- The "shoulder" is a cellular area at the periphery.
- Necrotic core containing lipid (cholesterol , esters, clefts), debris from dead cells, foam cells (lipid-laden SMC, MØ ), fibrin, variably organized thrombus.
- Neovascularization (proliferating small blood vessels)

Front 34

How to plaques typically evolve?

Back 34

- progressively enlarge due to cell death and degeneration, synthesis of ECM, and organization of thrombus & calcification

Front 35

What are some plaque complications?

Back 35

1. Rupture, ulceration, or erosion induce thrombosis. The clot may become organized and incorporated into the growing plaque.
2. Hemorrhage into a plaque. Rupture of the overlying fibrous cap, or of the thin-walled neovascularization, can cause an hematoma may expand the plaque or induce plaque rupture.
3. Atheroembolism - rupture can discharge microemboli.
4. Aneurysm formation. Atherosclerosis-induced pressure or ischemic atrophy of the underlying media.

Front 36

What is the AHA classification of atherosclerosis?

Back 36

Type I: Initial lesions: Isolated macrophage foam cells
Type II: Fatty Streak lesion: Mainly intracellular lipid accumulation
Type III: Intermediate lesion: Type II changes and small extracellular lipid pools
Type IV: Atheroma lesion: Type II changes and core of extracellular lipid
Type V: Fibroatheroma lesion: Lipid core and fibrotic layer, or multiple lipid cores and fibrotic layers , or mainly cacific, or many fibrotic
Type VI: Complicated lesion: Surface defect, hematoma-hemorrhage, thrombus

Note Type IV can directly progess to type VI, bypassing type V

Front 37

What is the main growth mechanism of Type 1-4 lesions?

Back 37

- Mainly by lipid accumulation

Front 38

What is the main growth mechanism of type V lesions?

Back 38

Accelerated SM and collagen increase

Front 39

What is the main growth mechanism of type VI lesions?

Back 39

Thrombus, hematoma

Front 40

Which growth promoters regular the migratory and proliferative activities of smooth muscle cells?

Back 40

- PDGF endothelin-1
- Thrombin
- FGF
- IFN-γ
- IL-1
- inhibitors - heparan sulfates, NO, and TGF-β

Front 41

What is a stereotypical response to blood vessel injury?

Back 41

Intimal thickening - SM migration from media or circulating precursors and proliferation within the intima, ECM synthesis

Front 42

How are neointimal SM cells different from medial SM cells

Back 42

- do not contract but have the capacity to divide.

Front 43

From where are intimal SM cells derived?

Back 43

- Derived from de-differentiation of media SM, and in part from circulating precursor cells.

Front 44

Described the pathogenesis of atherosclerosis?

Back 44

1) Chronic endothelial injury
2) Endothelial dysfunction – inc. permeability, leukocyte adhesion, monocyte adhesions and emigration
3) SM emigration from media to intimal. Macrophage activation
4) Macrophages and SMC engulf lipid
5) SM proliferation, collagen and other ECM deposition, extracellular lipid

Front 45

What are the two most important causes of endothelial dysfunction?

Back 45

1) hemodynamic disturbances
2) hypercholesterolemia. (other RF)

Front 46

Where to plaques tend to occur?

Back 46

- at ostia of BVs, along the posterior wall of the abdominal aorta, where there are disturbed flow patterns

Front 47

What are the mechanisms by which hyperlipidemia contributes to atherogenesis?

Back 47

1. Impairing endothelial cell function by increasing local oxygen free radical production.
2. Lipoproteins accumulate within the intima, are oxidized by oxygen free radicals locally generated by macrophages or endothelial cells.
3. Oxidized LDL is ingested by macrophages through a scavenger receptor, and accumulates in phagocytes, which are then called foam cells.
4. Oxidized LDL stimulates the release of growth factors, cytokines, and chemokines by endothelial cells and MØ that increase monocyte recruitment into lesions.
5. Oxidized LDL is cytotoxic to endothelial cells and smooth muscle cells and can induce endothelial cell dysfunction.