General Concepts In Pathology

Front 1

Define pathology

Back 1

The study of suffering, or the study of functional changes in cells, tissues, and organs that underlie disease

Front 2

Define homeostasis

Back 2

State of internal equilibrium at which normal physiologic demands of a cell are met; pathophysiology results when stimuli (cell injury) sufficiently disrupt homeostasis.

Front 3

What are some mechanisms of cell injury?

Back 3

Altered physiological stimuli; reduced oxygen supply; microbial infection; metabolic alteration; cumulative aging

Front 4

What are the ways that cells adapt to stress?

Back 4

Hyperplasia; hypertrophy; atrophy; metaplasia.

Front 5

Define hyperplasia

Back 5

An increase in number of cells as an adaptive response to stress, usually resulting in increased volume of an organ or tissue. Cells must be capable of mitotic division (EG prostate)

Front 6

Define hypertrophy

Back 6

An increase in cell size due to synthesis of cellular structural components as an adaptive response to stress, usually resulting in increased size of an organ or tissue. Does not require mitotic division (eg myocardium)

Front 7

Define atrophy

Back 7

Reduction of cell size due to loss of structural components of the cell. An attempt by the cell to reduce demand to match reduced supply. The entire tissue/organ diminishes in size when enough cells are involved.

Front 8

Give examples of physiologic atrophy

Back 8

Loss of certain embryologic structures (e.g., digit web space, umbilicus); uterus returning to nongravid state after parturition

Front 9

What are some causes of pathologic atrophy?

Back 9

Hypoxia, loss of innervation, disuse, and aging

Front 10

What is the process of reversible change that occurs when one adult cell type is replaced by another adult cell type?

Back 10

Metaplasia

Front 11

What are the hallmarks of reversible cell injury?

Back 11

Reduced oxidative phosphorylation, ATP depletion, cellular swelling, ion efflux, water influx

Front 12

When does irreversible cell injury occur?

Back 12

Highly variable and largely dependent on the cell/tissue type. Continued insult can eventually lead to irreversible cell injury but the threshold at which irreversible cell injury occurs is different in different tissue types. IRREVERSIBLY INJURED CELLS INVARIABLY UNDERGO CELL DEATH.

Front 13

Define karyolysis

Back 13

Karyolysis is dissolution of the nucleus

Front 14

Define karyorrhexis

Back 14

Karyorrhexis is nuclear fragmentation

Front 15

Define pyknosis

Back 15

Pyknosis is nuclear shrinkage and condensation

Front 16

What are the two main types of cell death?

Back 16

Apoptosis and necrosis

Front 17

Define apoptosis

Back 17

Apoptosis is a process of cell death by which a cell activates enzymes (caspases) that degrade the cell's own DNA and proteins (programmed cell death) while maintaining an intact plasma membrane. The entire cell is then phagocytized.

Front 18

Define necrosis

Back 18

A process of cell death by lysosomal enzymatic digestion and loss of plasma membrane integrity.

Front 19

What are the key differences between apoptosis and necrosis?

Back 19

Apoptosis may be physiologic or pathologic whereas necrosis is always pathologic; due to loss of plasma membrane integrity, necrosis often elicits inflammation in adjacent tissue; in necrosis, lysosomal enzymes may come from the dead cells (autolysis) or from leukocytes.

Front 20

Describe the steps of apoptosis

Back 20

Cell shrinkage, chromatin condensation and fragmentation, formation of apoptotic bodies, phagocytosis by macrophages.

Front 21

What are the three pathways which may initiate apoptosis?

Back 21

1. Intrinsic (mitochondrial) pathway
2. Extrinsic (death-receptor initiated) pathway
3. CTL mediated pathway; all three converge on executioner caspases to initiate the execution phase of apoptosis.

Front 22

What are the examples of triggers of apoptosis via the intrinsic pathway?

Back 22

Lack of hormonal or growth factor stimulation, DNA damage leading to p53 activation.

Front 23

What are the examples of triggers of apoptosis via the extrinsic pathway?

Back 23

TNF receptor ligands (TNF-a), FAS receptor ligands (FasL)

Front 24

What are the key steps in the intrinsic pathway of apoptosis?

Back 24

Loss of anti-apoptotic molecules (Bcl-2) and gain of pro-apoptotic molecules (Bak, Bax, Bim) in the mitochondrial membrane, increased mitochondrial membrane permeability and release of cytochrome c, activation of caspase-9.

Front 25

What are the key steps in the extrinsic pathway of apoptosis?

Back 25

Creation of a death domain by ligand binding of TNFR1 or FAS and adaptor proteins. The death domain then cleaves and activates pro-caspase 8 (creating caspase 8).

Front 26

What are the key steps in the CTL-mediated pathway of apoptosis?

Back 26

CTLs secrete perforin allowing entry of granzyme B and activation of executioner caspases. CTLs also secrete Fas ligand to initiate the extrinsic apoptotic pathway.

Front 27

What are the key steps in the execution phase of apoptosis?

Back 27

Activated caspase-9 or activated caspase-8 lead to cascade and activation of caspase-3 and/or caspase-6 (executioner caspases), disruption of cytoskeletal components or cell replication machinery, and changes to cell surface molecules which facilitates phagocytosis.

Front 28

What are the histologic features of necrosis?

Back 28

Increased cytoplasmic eosinophilia, vacuolated cytoplasm, nuclear changes, (karyolysis, pyknosis, or karyorrhexis), calcification, and inflammation in adjacent tissue.

Front 29

Give examples of histologic patterns of necrosis

Back 29

Liquefactive necrosis, coagulative necrosis, and caseous necrosis.

Front 30

In which type of necrosis is normal tissue architecture rapidly transformed into a liquid mass due to autolysis and heterolysis?

Back 30

Liquefactive necrosis

Front 31

Give examples of liquefactive necrosis

Back 31

Pancreatitis, bacterial abscess, CNS infarction, gastric ulcer, fungal infection

Front 32

What is the common pattern of necrosis observed in ischemic and infarcted tissue?

Back 32

Coagulative necrosis, except for CNS ischemia/infarction.

Front 33

Describe the appearance of coagulative necrosis

Back 33

The tissue has a firm texture, general tissue architecture is maintained, and "ghost" outlines of necrotic, anucleated cells may be present for weeks before undergoing phagocytosis.

Front 34

Describe the appearance of caseous necrosis

Back 34

The tissue has a soft "cheesy" appearance, general tissue architecture is obliterated, and "ghost" outlines of anucleated cells may be present.

Front 35

When is caseous necrosis most likely?

Back 35

Tuberculosis or fungal infection and at the center of malignant tumors.

Front 36

Define fat necrosis

Back 36

Fat degradation with possible saponification most commonly due to release of enzymes from the pancreas.

Front 37

When does one see fat necrosis?

Back 37

Acute pancreatitis, ruptured ulcer, penetrating trauma, and subcutaneous infection

Front 38

What is surgical necrosis?

Back 38

A synonym of gangrenous necrosis which is generally used to describe a limb which has lost blood supply and undergone coagulative necrosis.

Front 39

Define dystrophic calcification

Back 39

Local deposition of predominately calcium salts in injured or necrotic tissue in the setting of otherwise normal calcium levels.

Front 40

Define metastatic calcification

Back 40

Local or wide deposition of predominately calcium salts in otherwise normal tissues in the setting of hypercalcemia.

Front 41

What are the histologic features of dystrophic and metastatic calcification?

Back 41

Amorphous, basophilic granules in intracellular, extracellular, or in both locations. Over time, ossification may occur at sites of dystrophic calcification.

Front 42

Define hypoxia

Back 42

A state of reduced oxygen availability (poor hemoglobin saturation, inadequate ventilation, hemolysis)

Front 43

Define ischemia

Back 43

A state of significantly reduced blood flow (thrombolytic occlusion, trauma) which leads to tissue damage if not reversed

Front 44

What are the early consequences of ischemic injury?

Back 44

Transient shift to anaerobic glycolysis; disturbed ionic and fluid balance; inhibited beta-oxidation of fatty acids.

Front 45

What are the late consequences of ischemic injury?

Back 45

Lysosomal activation; leakage of proteins into serum (CK, troponin, myoglobin, cellular enzymes)

Front 46

Which injures tissues faster, ischemia or hypoxia?

Back 46

Ischemia. In hypoxic tissues, anaerobic glycolysis can continue whereas in ischemic tissues anaerobic glycolysis stops when substrates are depleted or when there is accumulation of excessive waste products due to the impaired blood flow.

Front 47

Why does reperfusion injury occur?

Back 47

When blood flow is restored, cells that survived the initial ischemia may now be damaged or irreversibly injured by processes initiated by oxygen free radicals, inflammatory cells, or activation of the complement pathway.

Front 48

What is the process by which lysosomes digest material from the extracellular environment?

Back 48

Heterophagy

Front 49

What is autophagy?

Back 49

Lysosomal digestion of a cell's own components.

Front 50

What are the three types of intracellular accumulations?

Back 50

1. Excess of a normal cellular constituent
2. Abnormal substance
3. Pigments (exogenous or endogenous)

Front 51

How do intracellular accumulations of protein appear?

Back 51

Generally as discrete eosinophilic cytoplasmic droplets, vacuoles, or aggregates.

Front 52

Which cell type scavenges for exogenous pigments?

Back 52

Macrophages

Front 53

What is th most common exogenous pigment?

Back 53

Carbon or coal

Front 54

When a person gets a tattoo, where does the pigment go?

Back 54

The pigment is ingested by dermal macrophages, usually without an inflammatory response.

Front 55

Give examples of endogenous pigments

Back 55

Lipofuscin, hemosiderin, melanin, hematin, bilirubin

Front 56

Iron is stored in cells in the form of which pigment?

Back 56

Hemosiderin

Front 57

What color does hemosiderin stain?

Back 57

Blue with the Prussian blue histochemical stain and yellow-brown with hematoxylin-eosin (H&E) stain.

Front 58

What pigment is derived from hemoglobin but contains no iron?

Back 58

Bilirubin

Front 59

Define jaundice

Back 59

Excess of bilirubin within cells and tissues

Front 60

What is the only endogenous brown-black pigment and how is it formed?

Back 60

Melanin; it is formed during the oxidation of tyrosine to dihydroxyphenylalanine (DOPA) by tyrosinase in melanocytes

Front 61

Define inflammation

Back 61

Biologic response to a perceived injurious agent that results in vascular changes which allow fluid and leukocytes into extravascular tissue.

Front 62

What is acute inflammation?

Back 62

Early and immediate response to injury lasting for a short duration.

Front 63

What features and cell type typically characterize the acute phase of inflammation?

Back 63

Hyperemia (rubor), pain (dolor), heat (calor), edema/swelling (tumor), polymorphonuclear (PMN) leukocytes.

Front 64

What is edema?

Back 64

Excess transudative or exudative fluid in the interstitial space or a body cavity.

Front 65

Define transudate

Back 65

A clear, extravascular, low-protein, low-cellularity fluid usually due to changes in hydrostatic or osmotic pressure. Specific gravity is <1.012.

Front 66

Define exudate

Back 66

A clear to cloudy extravascular, high-protein, high-cellularity fluid usually due to changes in capillary permeability. Specific gravity is >1.012.

Front 67

What is the term for an exudate rich in neutrophils and parenchymal cell debris?

Back 67

Pus (purulent exudate)

Front 68

What is the term for an acute inflammatory process where there is an overlay of fibrin and debris on a mucous membrane?

Back 68

Pseudomembrane formation

Front 69

What are the key steps in acute inflammation?

Back 69

Vasodilation, increased vascular permeability and exudation into extravascular tissues, intravascular stasis, and leukocyte margination

Front 70

What causes vasodilation and increased vascular permeability in acute inflammation?

Back 70

Inflammatory mediators such as histamine, nitric oxide, bradykinin, IL-1, TNF, and INF-gamma

Front 71

Which two vasoactive amines are among the first mediators to be released in acute inflammation? Why?

Back 71

Histamine and serotonin. These are the first to be released because they are present in preformed stores in mast cells, basophils, and/or platelets.

Front 72

What are the steps of leukocyte extravasation?

Back 72

1. Margination, rolling, and adhesion to endothelium
2. Transmigration across endothelium (diapedesis)
3. Migration toward a chemotactic stimulus in tissues

Front 73

Which cell surface molecule families play a role in leukocyte adhesion?

Back 73

Selectins (P-selectin, E-selectin on endothelial cells, and L-selectin on leukocytes), immunoglobulins (ICAM-1 and VCAM-1 on endothelial cells), and integrins (on leukocytes)

Front 74

What are the common chemotactic agents?

Back 74

Bacterial products, complement (especially C5a), leukotrienes, cytokines (IL-8).

Front 75

What is the major pathway by which chemotactic agents cause leukocyte movement?

Back 75

Chemotactic agents bind seven-transmembrane GPCRs leading to activation of effector and second messenger molecules which ultimately induced cytoskeleton component polymerization and contraction.

Front 76

What are the three stages of phagocytosis?

Back 76

1. Recognition and attachment
2. Engulfment
3. Killing and degradation

Front 77

What enzymes or molecules are involved in O2-dependent phagocytosis?

Back 77

NADPH oxidase, H2O2 activity, superoxide radicals, NADPH oxygenase

Front 78

What enzymes or molecules are involved in O2-independent phagocytosis?

Back 78

BPI (bactericidal permeability increasing protein), lactoferrin, lysozyme, major basic proteins, defensins

Front 79

What is the role of the complement system in inflammation?

Back 79

The complement system is a part of the innate and adaptive immune system by contributing to mediation of vascular permeability and vasodilation, leukocyte adhesion and chemotaxis, and phagocytosis.

Front 80

Which complement cleavage product is a powerful chemoattractant?

Back 80

C5a

Front 81

Which two components of the complement system act as opsonins to coat bacteria?

Back 81

1. C3b
2. iC3b

Front 82

What is the role of the kinin system in inflammation?

Back 82

The kinin system serves to produce bradykinin which mediates vascular permeability and vasodilation.

Front 83

Which neutrophil storage structure may contain lactoferrin, lysozyme, and collagenase?

Back 83

Specific granules (think Specific are Smaller than azurophil)

Front 84

Which neutrophil storage structure may contain myeloperoxidase, defensins, and elastases?

Back 84

Azurophil granules

Front 85

What are the four patterns of acute inflammation?

Back 85

1. Serous inflammation
2. Fibrinous inflammation
3. Suppurative inflammation
4. Ulcerative inflammation

Front 86

What are the four possible outcomes of acute inflammation?

Back 86

1. Complete resolution
2. Fibrosis
3. Abscess formation
4. Chronic inflammation

Front 87

What is chronic inflammation?

Back 87

A complex process lasting weeks to months of variable degrees of concurrent active inflammation, tissue destruction, and attempts at tissue repair.

Front 88

What are some causes of chronic inflammation?

Back 88

Persistent infections, prolonged exposure to toxins, autoimmune diseases

Front 89

What cell types are present in chronic inflammation?

Back 89

Mononuclear cells predominate: macrophages/monocytes, lymphocytes, plasma cells

Front 90

How do macrophages accumulate at the site of chronic inflammation?

Back 90

1. Continued recruitment
2. Local proliferation
3. Immobilization at the target site by cytokines and oxidized lipids

Front 91

What is a focal collection of epitheliod-macrophages surrounded by a rim of lymphocytes and plasma cells?

Back 91

A granuloma

Front 92

Name two types of granulomas

Back 92

1. Foreign body granuloma
2. Immune granuloma

Front 93

Give an example of a foreign body granuloma

Back 93

A nonabsorbable suture left in the body over a long period of time

Front 94

What is the prototype of the immune granuloma?

Back 94

A granuloma with central caseous necrosis (Tb)

Front 95

What is granulomatous inflammation?

Back 95

A pattern of chronic inflammation defined by the presence of granulomas.

Front 96

What is granulation tissue?

Back 96

Specialized type of CT which replaces a fibrin clot during wound healing. Angiogenesis, fibroblasts producing EC matrix, and some inflammatory cells are present. Granulomas are not present in granulation tissue.

Front 97

What are mediators of angiogenesis?

Back 97

Basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), vascular permeability factor (VPF)

Front 98

What are the steps in wound healing and repair?

Back 98

Acute inflammation, formation of granulation tissue, re-epithelialization collagen accumulation, regression of vascular channels, replacement of granulation tissue with scar, and wound contraction

Front 99

How long does it take for an inflammatory exudate to be removed?

Back 99

36 hours to 3-4 weeks

Front 100

What is the sequence of scar formation?

Back 100

1. Acute inflammation and fibrin clot formation
2. Granulation tissue produced by fibroblasts and endothelial cells replaces fibrin clot.
3. Fibroblasts lay down vertically oriented collagen fibers at the wound margin.
4. Wound space is completely filled with granulation tissue.
5. Progressive re-epithelialization, devascularization, and collagen deposition over next 2-3 weeks results in a dense white scar.