Pathology Block 1 Vocab (1,2,3,4,7,11,12)

Front 1

Aging (senile atrophy).

Back 1

The aging process is associated with cell loss, typically seen in tissues containing permanent cells, particularly the brain and heart.

Front 2

agenesis

Back 2

<embryology> A condition in which a part of the body (such as an organ or a tissue) does not completely develop or fails to develop at all.

Front 3

anthracosis

Back 3

The most common exogenous pigment is carbon or coal dust, which is a ubiquitous air pollutant of urban life. When inhaled, it is picked up by macrophages within the alveoli and is then transported through lymphatic channels to the regional lymph nodes in the tracheobronchial region. Accumulations of this pigment blacken the tissues of the lungs (anthracosis) and the involved lymph nodes. In coal miners, the aggregates of carbon dust may induce a fibroblastic reaction or even emphysema and thus cause a serious lung disease known as coal worker's pneumoconiosis

Front 4

aplasia

Back 4

refers also to the absence of an organ but one owing to failure of development of the primordium.

Front 5

Apoptosis

Back 5

occurs when a cell dies through activation of an internally controlled suicide program. It is designed to eliminate unwanted cells during embryogenesis and in various physiologic processes, such as involution of hormone-responsive tissues upon withdrawal of the hormone. It also occurs in certain pathologic conditions, when cells are damaged beyond repair, and especially if the damage affects the cell's nuclear DNA.

Front 6

ATROPHY

Back 6

Shrinkage in the size of the cell by loss of cell substance is known as atrophy. It represents a form of adaptive response and may culminate in cell death. When a sufficient number of cells are involved, the entire tissue or organ diminishes in size, or becomes atrophic. Atrophy can be physiologic or pathologic.

Front 7

Autophagy

Back 7

refers to lysosomal digestion of the cell's own components. In this process, intracellular organelles and portions of cytosol are first sequestered from the cytoplasm in an autophagic vacuole formed from ribosome-free regions of the rough endoplasmic reticulum. The vacuole fuses with lysosomes or Golgi elements to form an autophagolysosome

Front 8

autolysis

Back 8

The morphologic appearance of necrosis is the result of denaturation of intracellular proteins and enzymatic digestion of the cell. The enzymes are derived either from the lysosomes of the dead cells themselves, in which case the enzymatic digestion is referred to as autolysis, or from the lysosomes of immigrant leukocytes, during inflammatory reactions.

Front 9

BAX

Back 9

BAX binds to and antagonizes the apoptosis-inhibiting protein BCL-2; thus, BAX promotes cell death.

Front 10

BCL 2

Back 10

This pathway of apoptosis is the result of increased mitochondrial permeability and release of pro-apoptotic molecules into the cytoplasm, without a role for death receptors. Growth factors and other survival signals stimulate the production of anti-apoptotic members of the Bcl-2 family of proteins

Front 11

bilirubin

Back 11

The original red-blue color of hemoglobin is transformed to varying shades of green-blue, comprising the local formation of biliverdin (green bile), then bilirubin (red bile), and thereafter the iron moiety of hemoglobin is deposited as golden yellow hemosiderin

Front 12

Caseous necrosis

Back 12

Caseous necrosis, a distinctive form of coagulative necrosis, is encountered most often in foci of tuberculous infection . The term caseous is derived from the cheesy white gross appearance of the area of necrosis . On microscopic examination, the necrotic focus appears as amorphous granular debris seemingly composed of fragmented, coagulated cells and amorphous granular debris enclosed within a distinctive inflammatory border known as a granulomatous reaction. Unlike coagulative necrosis, the tissue architecture is completely obliterated.

Front 13

Catalase

Back 13

present in peroxisomes, which decomposes H2 O2 (2 H2 O2 → O2 + 2 H2 O).

Front 14

Coagulative necrosis

Back 14

Necrosis that implies preservation of the basic outline of the coagulated cell for a span of at least some days. The affected tissues exhibit a firm texture. Presumably, the injury or the subsequent increasing intracellular acidosis denatures not only structural proteins but also enzymes and so blocks the proteolysis of the cell. The myocardial infarct is an excellent example in which acidophilic, coagulated, anucleate cells may persist for weeks. Ultimately, the necrotic myocardial cells are removed by fragmentation and phagocytosis of the cellular debris by scavenger leukocytes and by the action of proteolytic lysosomal enzymes brought in by the immigrant white cells.
The process of coagulative necrosis, with preservation of the general tissue architecture, is characteristic of hypoxic death of cells in all tissues except the brain.

Front 15

dystrophic calcification

Back 15

There are two forms of pathologic calcification. When the deposition occurs locally in dying tissues, it is known as dystrophic calcification; it occurs despite normal serum levels of calcium and in the absence of derangements in calcium metabolism.

Front 16

dysplasia

Back 16

<embryology> Abnormality of development, in pathology, alteration in size, shape and organisation of adult cells

Front 17

Fat necrosis

Back 17

a term that is well fixed in medical parlance but does not in reality denote a specific pattern of necrosis. Rather, it is descriptive of focal areas of fat destruction, typically occurring as a result of release of activated pancreatic lipases into the substance of the pancreas and the peritoneal cavity. This occurs in the calamitous abdominal emergency known as acute pancreatitis

Front 18

gangrenous necrosis

Back 18

Although gangrenous necrosis is not a distinctive pattern of cell death, the term is still commonly used in surgical clinical practice. It is usually applied to a limb, generally the lower leg, that has lost its blood supply and has undergone coagulation necrosis. When bacterial infection is superimposed, coagulative necrosis is modified by the liquefactive action of the bacteria and the attracted leukocytes (so-called wet gangrene).

Front 19

Glutathione

Back 19

Glutathione peroxidase protects against injury by catalyzing free radical breakdown (H2 O2 + 2 GSH → GSSG [glutathione homodimer] + 2 H2 O, or 2 OH + 2 GSH → GSSG + 2 H2 O). The intracellular ratio of oxidized glutathione (GSSG) to reduced glutathione (GSH) is a reflection of the oxidative state of the cell and is an important aspect of the cell's ability to detoxify reactive oxygen species

Front 20

heat-shock proteins

Back 20

Some chaperones are synthesized constitutively and affect normal intracellular protein trafficking, whereas others are induced by stress, such as heat (heat-shock proteins, e.g., hsp70, hsp90), and "rescue" shock-stressed proteins from misfolding. If the folding process is not successful, the chaperones facilitate degradation of the damaged protein. This degradative process often involves ubiquitin (also a heat-shock protein), which is added to the abnormal protein and marks it for degradation by the proteasome complex.

Front 21

Hemosiderin

Back 21

a hemoglobin-derived, golden yellow-to-brown, granular or crystalline pigment in which form iron is stored in cells. When there is a local or systemic excess of iron, ferritin forms hemosiderin granules, which are easily seen with the light microscope. Thus, hemosiderin pigment represents aggregates of ferritin micelles. Under normal conditions, small amounts of hemosiderin can be seen in the mononuclear phagocytes of the bone marrow, spleen, and liver, all actively engaged in red cell breakdown.

Front 22

hemosiderosis

Back 22

Whenever there are causes for systemic overload of iron, hemosiderin is deposited in many organs and tissues, a condition called hemosiderosis. It is seen with: (1) increased absorption of dietary iron, (2) impaired use of iron, (3) hemolytic anemias, and (4) transfusions because the transfused red cells constitute an exogenous load of iron.

Front 23

Heterophagy

Back 23

the process of lysosomal digestion of materials ingested from the extracellular environment. Extracellular materials are taken up by cells through the general process of endocytosis. Uptake of particulate matter is known is phagocytosis; uptake of soluble smaller macromolecules is called pinocytosis. Extracellular materials are endocytosed into vacuoles (endosomes or phagosomes), which eventually fuse with lysosomes to form phagolysosomes, where the engulfed material is digested. Heterophagy is most common in the "professional" phagocytes, such as neutrophils and macrophages, although it may also occur in other cell types.

Front 24

hyalin

Back 24

the Mallory body, or "alcoholic hyalin," is an eosinophilic intracytoplasmic inclusion in liver cells that is characteristic of alcoholic liver disease, although it can be present in other conditions. Such inclusions are composed predominantly of keratin intermediate filaments.

Front 25

hyperplasia,

Back 25

an increase in the number of cells

Front 26

hypertrophy

Back 26

an increase in the sizes of individual cells

Front 27

hypoplasia

Back 27

<embryology> The incomplete development or underdevelopment of an organ or tissue.

Front 28

Hypoxia

Back 28

a deficiency of oxygen, which causes cell injury by reducing aerobic oxidative respiration. Hypoxia is an extremely important and common cause of cell injury and cell death. It should be distinguished from ischemia ,which is a loss of blood supply from impeded arterial flow or reduced venous drainage in a tissue

Front 29

infarct

Back 29

an area of ischemic necrosis caused by occlusion of either the arterial supply or the venous drainage in a particular tissue. Although venous thrombosis may cause infarction, it more often merely induces venous obstruction and congestion. Infarcts caused by venous thrombosis are more likely in organs with a single venous outflow channel, such as the testis and ovary

Front 30

Ischemia-Reperfusion injury

Back 30

Depending on the intensity and duration of the ischemic insult, variable numbers of cells may proceed to die after blood flow resumes, by necrosis as well as by apoptosis. The affected tissues often show neutrophilic infiltrates. This ischemia-reperfusion injury is a clinically important process in such conditions as myocardial infarction and stroke and may be amenable to therapeutic interventions.

Front 31

karyolysis

Back 31

The basophilia of the chromatin may fade (karyolysis), a change that presumably reflects DNase activity

Front 32

pyknosis

Back 32

characterized by nuclear shrinkage and increased basophilia. Here the DNA apparently condenses into a solid, shrunken basophilic mass

Front 33

karyorrhexis

Back 33

the pyknotic or partially pyknotic nucleus undergoes fragmentation

Front 34

Lipofuscin

Back 34

an insoluble pigment, also known as lipochrome and wear-and-tear or aging pigment. Its importance lies in its being the telltale sign of free radical injury and lipid peroxidation. It is seen in cells undergoing slow, regressive changes and is particularly prominent in the liver and heart of aging patients or patients with severe malnutrition and cancer cachexia

Front 35

Liquefactive necrosis

Back 35

characteristic of focal bacterial or, occasionally, fungal infections, because microbes stimulate the accumulation of inflammatory cells. hypoxic death of cells within the central nervous system often evokes liquefactive necrosis. Whatever the pathogenesis, liquefaction completely digests the dead cells. The end result is transformation of the tissue into a liquid viscous mass.

Front 36

lysosomes

Back 36

Primary lysosomes are membrane-bound intracellular organelles that contain a variety of hydrolytic enzymes, including acid phosphatase, glucuronidase, sulfatase, ribonu-clease, and collagenase

Front 37

Metaplasia

Back 37

A reversible change in which one adult cell type (epithelial or mesenchymal) is replaced by another adult cell type. It may represent an adaptive substitution of cells that are sensitive to stress by cell types better able to withstand the adverse environment.

Front 38

metastatic calcification

Back 38

the deposition of calcium salts in otherwise normal tissues is known as metastatic calcification, and it almost always results from hypercalcemia secondary to some disturbance in calcium metabolism.

Front 39

Necrosis

Back 39

Necrosis refers to a spectrum of morphologic changes that follow cell death in living tissue, largely resulting from the progressive degradative action of enzymes on the lethally injured cell (cells placed immediately in fixative are dead but not necrotic). As commonly used, necrosis is the gross and histologic correlate of cell death occurring in the setting of irreversible exogenous injury. Necrotic cells are unable to maintain membrane integrity and their contents often leak out. This may elicit inflammation in the surrounding tissue.

Front 40

neoplasia

Back 40

Literally new growth, usually refers to abnormal new growth and thus means the same as tumour, which may be benign or malignant.
Unlike hyperplasia, neoplastic proliferation persists even in the absence of the original stimulus.

Front 41

progeria

Back 41

Accelerated aging syndrome in which most of the characteristic stages of human senescence are compressed into less than a decade. Defect probably in DNA repair.

Front 42

Steatosis (Fatty Change)

Back 42

The terms steatosis and fatty change describe abnormal accumulations of triglycerides within parenchymal cells. Fatty change is often seen in the liver because it is the major organ involved in fat metabolism, but it also occurs in heart muscle, and kidney. The cause of steatosis include toxins, protein malnutrition, diabetes mellitus, obesity, and anoxia. In industrialized nations, by far the most common cause of significant fatty change in the liver (fatty liver) is alcohol abuse.

Front 43

Superoxide dismutase

Back 43

found in many cell types and convert superoxide to H2 O2 (2 O2 - + 2 H → H2 O2 + O2 )

Front 44

Agenesis

Back 44

Complete absence of an organ or its anlage

Front 45

Atherosclerosis

Back 45

Accumulation of fat and connective tissue within the wall of arteries, often causing progressive narrowing of the lumen and decreased blood flow to tissues.

Front 46

Cirrhosis

Back 46

Liver disease characterized pathologically by loss of normal microscopic lobular architecture with fibrosis and nodular regeneration

Front 47

Cushing's syndrome

Back 47

A constellation of clinical findings caused by excessive blood levels of glucocorticosteroid hormones

Front 48

Denervation

Back 48

Disruption of normal neural supply, due to traumatic or degenerative damage to the peripheral nerve or central nervous system motor neurons.

Front 49

Edema

Back 49

Abnormal accumulation of fluid within the interstitium of an organ, tissue or body cavity. This often leads to an increase in tissue or organ volume and weight.

Front 50

Eosinophilic

Back 50

Areas of a cell or tissue that stain with eosin, a rose-colored dye. This dye usually stains the cytoplasm of a cell.

Front 51

Ferritin

Back 51

An iron-protein (apoferritin) complex. Chief form of intracellular iron storage present in many types of cells.

Front 52

Fibrinoid necrosis

Back 52

Conversion of necrotic tissue to an amorphous, fibrillar eosinophilic mass that resembles fibrin.

Front 53

"Dry" gangrene

Back 53

Tissue appears black grossly; not accompanied by bacterial infection.

Front 54

"Wet" gangrene

Back 54

Necrotic tissue secondarily invaded by bacteria, resulting in liquefactive necrosis.

Front 55

Hematoxyphilic

Back 55

Areas of a cell or tissue that stain with hematoxylin, a blue-purple crystalline stain. This stain usually stains the nucleus of a cell or leaked DNA

Front 56

Regeneration

Back 56

Regrowth of normal tissue. Only labile cells and stable cells regenerate; regeneration does not occur in permanent cells.

Front 57

Torsion

Back 57

A mobile organ twists obstructing its blood supply and/or drainage.

Front 58

Transferrin

Back 58

A serum glycoprotein that binds and transports iron (Fe).

Front 59

abscess

Back 59

a localized collection of neutrophils and necrotic debris (pus) in a cavity

Front 60

Acute inflammation

Back 60

immediate response to injury characterized by vasodilatation, increased capillary permeability, presence of an exudate and emigration of leukocytes (mostly neutrophils). Clinically: calor, rubor, turmor, dolor, and loss of function.

Front 61

Acute phase protein

Back 61

plasma proteins, mostly synthesized in the liver, whose synthesis increases several hundred-fold in response to inflammatory stimuli (e.g., cytokines such as IL6 and TNF). Best known: C-reactive protein (CRP), fibrinogen, and serum amyloid A (SAA). CRP and SAA bind to microbial cell walls, and may act as opsonins and fix complement. Also help clear necrotic cell nuclei and mobilize metabolic stores.

Front 62

aggregation

Back 62

a crowded mass of independent but similar units; a cluster.

Front 63

autocrine

Back 63

cells that respond to signaling substances produced by themselves

Front 64

Bradykinin

Back 64

Polypeptide produced by action of Hageman factor and kallikrein; increases vascular permeability; also causes pain.

Front 65

C3a

Back 65

a complement cleavage product (“byproduct” of cell attack sequence); increases vascular permeability. Also called “anaphylatoxin” because C3a stimulate histamine release from mast cells.

Front 66

C3b

Back 66

remains attached to cells, activates the cell attack sequence of complement which leads to cell lysis; also the most important opsonin.

Front 67

C5a

Back 67

a complement cleavage product; increases vascular permeability and is a strong chemoattractant for neutrophils. Also called “anaphylatoxin” because C5a stimulates histamine release from mast cells.

Front 68

Cachexia

Back 68

Physical wasting with loss of weight and muscle mass caused by disease. Patients with advanced cancer, AIDS, and some other major chronic progressive diseases may appear cachectic. Cachexia is a wasting syndrome that causes weakness and a loss of weight, fat, and muscle. Anorexia (lack of apppetite) and cachexia often occur together. Cachexia can occur in people who are eating enough, but who cannot absorb the nutrients. Cachexia is not the same as starvation. A healthy person's body can adjust to starvation by slowing down its use of nutrients, but in cachectic patients, the body does not make this adjustment.

Front 69

carbuncle

Back 69

deep-seated pyogenic infection of the skin and subcutaneous tissues, usually arising in several contiguous hair follicles, with formation of connecting sinuses

Front 70

cellulitis

Back 70

inflammation of subcutaneous, loose connective tissue (formerly called cellular tissue)

Front 71

Chediak-Higashi syndrome

Back 71

hereditary defect that impairs the acute inflammatory response; is a defect in neutrophils; characterized by neutropenia, albinism, cranial and peripheral neuropathy, and a tendency to develop repeated infections. Is marked by the presence of abnormal white blood cells.

Front 72

Chemotaxis

Back 72

the migration of a cell in response to a chemical compound; a compound causing chemotaxis is called a chemoattractant

Front 73

Granulomatous inflammation

Back 73

Granulomatous inflammation is a distinctive pattern of chronic inflammatory reaction characterized by focal accumulations of activated macrophages, which often develop an epithelial-like (epithelioid) appearance. It is encountered in a limited number of immunologically mediated, infectious and some noninfectious conditions. Tuberculosis is the prototype of the granulomatous diseases, but sarcoidosis, cat-scratch disease, lymphogranuloma inguinale, leprosy, brucellosis, syphilis, some mycotic infections, berylliosis, and reactions of irritant lipids are also included. Recognition of the granulomatous pattern in a biopsy specimen is important because of the limited number of possible conditions that cause it and the significance of the diagnoses associated with the lesions.

Front 74

Chronic inflammation

Back 74

inflammation of prolonged duration or slow progress marked histologically by an infiltration of mononuclear cells (lymphocytes, macrophages, and plasma cells), often with proliferation of fibroblasts and fibrosis.

Front 75

Cyclooxygenase

Back 75

An enzyme that is responsible for formation of important biological mediators called prostanoids (including prostaglandins, prostacyclin and thromboxane). Pharmacological inhibition of COX can provide relief from the symptoms of inflammation and pain; this is the method of action of well-known drugs such as aspirin and ibuprofen.

Front 76

Chronic Granulomatous disease

Back 76

Chronic granulomatous disease (CGD), an inherited disorder of phagocytic cells, results from an inability of phagocytes to undergo the respiratory burst necessary to kill certain types of bacteria and fungi. This leads to recurrent life-threatening bacterial and fungal infections.

Front 77

Cytokine

Back 77

a hormone-like mediator produced by inflammatory cells

Front 78

edema

Back 78

Excess fluid in the interstitial tissue or body cavities; may be either an exudates or a transudate

Front 79

effusion

Back 79

an exudate or transudate that has passed into a part or tissue

Front 80

emigration

Back 80

passage of white blood cells through the endothelium and wall of small blood vessels.

Front 81

endocrine

Back 81

secreting internally, most commonly into the systemic circulation; of or pertaining to such secretion.

Front 82

erosion

Back 82

focal, complete loss of epidermis

Front 83

Erythema

Back 83

Erythema – redness due to capillary dilation

Front 84

Exudate

Back 84

An inflammatory extravascular fluid that has a high protein concentration and cellular debris; sg above 1.020

Front 85

fibrinous

Back 85

containing amount of fibrin

Front 86

Fibrinous inflammation

Back 86

characterized with exudate rich in fibrin; usually found upon inflammation of serosal or mucosal surfaces

Front 87

granulation tissue

Back 87

so called because grossly, under the scab, it has a granular appearance; characterized by ingrowth of new blood vessels (angiogenesis) and scar tissue (myofibroblasts)

Front 88

granuloma

Back 88

a specific form of chronic inflammatory response to antigens that cannot be eliminated during the acute inflammatory response; characterized histologically by collections of modified macrophages called “epithelioid cells” because they resemble epithelieal cells, usually surrounded by a rim of lymphocytes

Front 89

Hageman factor

Back 89

factor XII in clotting cascade

Front 90

Histamine

Back 90

preformed inflammatory mediator; stored in mast cell and platelet granules, causes increased vascular permeability

Front 91

ICAM-1

Back 91

intercellular adhesion molecule 1; is an endothelial / leukocyte adhesion molecule; belongs to immunoglobulin family of proteins; major role is adhesion, arrest, and transmigration of all leukocytes; binds integrins on leukocytes

Front 92

inflammation

Back 92

the response of vascularized living tissue to injury

Front 93

Integrins

Back 93

family of cell membrane glycoproteins that are heterodimers composed of alpha and beta chain subunits. They serve as extracellular matrix glycoprotein receptors involved in cell adhesion, e.g., the mediation of adhesion of neutrophils to endothelial cells; bind to endothelial immunoglobulin-family adhesion proteins, e.g. LFA-1, MAC-1, and VLA-4

Front 94

Interleukin 1 (IL-1)

Back 94

produced by monocytes/macrophages, as well as many other cells; acts locally (chemotactic, stimulates macrophoages, stimulates T-cell IL-2 production, B-cell maturation) and systemically (induces fever, acute phase reactant proteins, and neutrophil release from bone marrow).

Front 95

kallikrein

Back 95

Kallikreins (tissue and plasma kallikrein) are serine proteases that liberate kinins (BK and KD) from the kininogens. Prekallikrein is the precursor of plasma kallikrein. It can only activate kinins after being activated itself by factor XII or other stimuli.

Front 96

keloid

Back 96

an exaggerated form of scar that protrudes upward from the skin. Characterized by the presence of dense connective tissue

Front 97

Leukocyte adhesion

Back 97

results from interaction between endothelial adhesion molecules and leukocyte receptors

Front 98

Leukocyte adhesion deficiency

Back 98

Leukocyte adhesion deficiency type I (LAD I) is a failure to express the CD18 (aMb2 and aLb2) integrin, which serves as the receptor for C3b on myeloid and lymphoid cells. Most patients with LAD I express no CD18 on lymphocytes, macrophages, and neutrophils

Front 99

Leukocyte rolling

Back 99

during inflammation there is increased permeability, which results in blood flow stasis allowing leukocytes to fall out of laminar flow and roll along endothelium

Front 100

Leukotriene

Back 100

produced as a breakdown product of cell phospholipids by lipoxygenase pathway (production not inhibited by aspirin). In inflammation, most potent at increasing vascular permeability, but active relatively late; also chemotactic for neutrophils

Front 101

Lipooxygenase

Back 101

An enzyme that plays a pivotal role in the synthesis of inflammatory mediators known as leukotrienes

Front 102

Lipoxins

Back 102

Lipoxins are a recent addition to the family of bioactive products generated from AA. The principal actions of lipoxins are to inhibit leukocyte recruitment and the cellular components of inflammation. They inhibit neutrophil chemotaxis and adhesion to endothelium. There is an inverse relationship between the amount of lipoxin and leukotrienes formed, suggesting that the lipoxins may be endogenous negative regulators of leukotriene action and may thus play a role in the resolution of inflammation

Front 103

margination

Back 103

accumulation of blood cells (neutrophils) along the endothelium

Front 104

Nitric oxide (a.k.a. endothelium-derived relaxing factor)

Back 104

produced by endothelial cells; stimulates relaxation of smooth muscle, thus playing a role in controlling vascular tone; inhibits platelet aggregation, contributing to endothelial thromboresistance

Front 105

oncotic pressure

Back 105

pressure resulting from or caused by edema or any swelling (oncosis)

Front 106

Opsonin

Back 106

a compound that attaches to a foreign cell, such as a bacterium, and makes it more susceptible to a phagocytic cell

Front 107

Oxidative burst

Back 107

The ultimate step in the elimination of infectious agents and necrotic cells is their killing and degradation within neutrophils and macrophages, which occur most efficiently after activation of the phagocytes.30 Microbial killing is accomplished largely by oxygen-dependent mechanisms. Phagocytosis stimulates a burst in oxygen consumption, glycogenolysis, increased glucose oxidation via the hexose-monophosphate shunt, and production of reactive oxygen intermediates (ROIs, also called reactive oxygen sepecies)

Front 108

paracrine

Back 108

relating to a kind of hormone function in which the effects of the hormone are restricted to the local environment

Front 109

pavementation

Back 109

In time, the endothelium can be virtually lined by white cells, an appearance called pavementing

Front 110

PECAM-1 (platelet endothelial cell adhesion molecule 1)

Back 110

also known as CD31, major role involves leukocyte transmigration through endothelium

Front 111

Phagolysosome

Back 111

a body formed by union of a phagosome or ingested particle with a lysosome having hydrolytic enzymes

Front 112

Phagocytosis

Back 112

the ingestion of particulate material (e.g., tissue debris, living or dead bacteria, other foreign cells) by phagocytic cells. Neutrophils and monocytes-macrohages are most important phagocytic cells

Front 113

phagosome (secondary lysosome)

Back 113

phagocytosis is characterized morphologically by internalization of the attached opsonized particle by pseduopodial extensions from the surface of the leukocyte, which enclose the foreign particle, forming an internalized vesicle, the phagosome The phagosomes then fuse with cytoplasmic lysosomes and form phagolysosomes.

Front 114

phlegmon

Back 114

-An inflammatory mass of the subcutaneous tissues that may progress to an abscess.
-Obsolete term for an acute suppurative inflammation of the subcutaneous connective tissue

Front 115

pinocytosis

Back 115

the cellular process of actively engulfing liquid, a phenomenon in which minute incuppings or invaginations are formed in the surface of the cell membrane and close to form fluid-filled vesicles; it resembles phagocytosis

Front 116

Platelet activating factor (PAF)

Back 116

a phospholipid released from inflammatory cells of various types; activates release of enzymes from polymorphonuclear cell. Also causes platelet aggregation

Front 117

Prostaglandin

Back 117

produced as a breakdown product of cell phospholipids by cyclooxygenase pathway (product inhibited by aspirin). In inflammation, causes pain, increases vascular permeability, and causes vasodilation, but not as potent as leukotrienes; contributes to fever

Front 118

proud flesh

Back 118

results from excessive repair; excessive granulation tissue (exuberant granulation or proud flesh) can protrude above the surrounding skin and block reepithelialization. Excessive collagen accumulation forms a raised hypertrophic scar; progression beyond the original area of injury without subsequent regression in termed a keloid

Front 119

purulent

Back 119

containing, consisting of, or forming pus; pattern in inflammation is characterized by production of purulent exudates (pus) consisting of leukocytes and necrotic cells. An abscess refers to a localized collection of purulent inflammatory tissue accompanied by liquefactive necrosis (e.g., staphylococcal abscess)

Front 120

pus

Back 120

A purulent inflammatory exudate rich in neutrophils and cell debris

Front 121

pyogenic

Back 121

producing pus

Front 122

Residual Body (myelin figure)

Back 122

-A rolled-up or scroll-like arrangement of a lipid bilayer within a cell, superficially resembling the myelin sheath of nerves; observed with the electron microscope in the cytoplasm or as inclusion in mitochondria and autophagic vacuoles where they may represent artifacts of lipid fixation.
-A cytoplasmic vacuole (lysosome) containing accumulated particulate products of metabolism

Front 123

Resolution

Back 123

. In a perfect world, all inflammatory reactions, once they have succeeded in neutralizing and eliminating the injurious stimulus, should end with restoration of the site of acute inflammation to normal. This is called resolution and is the usual outcome when the injury is limited or short-lived or when there has been little tissue destruction and the damaged parenchymal cells can regenerate. Resolution involves neutralization or spontaneous decay of the chemical mediators, with subsequent return of normal vascular permeability, cessation of leukocytic infiltration, death (largely by apoptosis) of neutrophils, and finally removal of edema fluid and protein, leukocytes, foreign agents, and necrotic debris from the site

Front 124

Selectin

Back 124

cell surface adhesion molecules playing important role in acute inflammation
induced by the cytokines interleukin-1 (IL-1) and tumor necrosis factor (TNF)
Types
L-selectins – expressed on neutrophils and bind to endothelial mucin-like molecules such as GlyCam-1.
E- and P-selectins – expressed on endothelial cells and bind to oligosaccharides such as sialyl-Lewis X on the surface of leukocytes. P-selectins, stored in endothelial Weibel-Palade bodies and platelet granules, relocate to the plasma membrane after stimulation by mediators such as histamine and thrombin

Front 125

serosanguineous

Back 125

denoting an exudate or a discharge composed of or containing serum and also blood

Front 126

serous

Back 126

of exudate: virtually devoid of inflammatory cells or fibrin; resembles the appearance of serum

Front 127

suppurative

Back 127

inflamed due to the formation of pus

Front 128

Serotonin

Back 128

Endogenous mediator / vasoactive amine similar to histamine;
Influences chemotaxis, vasomotor phenomena, vascular permeability, pain, and other aspects of the inflammatory process;
Derived from platelets
Liberated from platelets, along with histamine, during the release action

Front 129

Serous inflammation

Back 129

reflected by tissue fluid accumulation and indicates a modest increase in vascular permeability. In the peritoneal, pleural, and pericardial cavities, this is called an effusion, but it can occur elsewhere (e.g., skin burn blisters)

Front 130

Stasis

Back 130

in inflammation: occurs when fluid loss causes concentration of red cells and increased blood viscosity, slowing the blood flow. With stasis, white cells (mostly neutrophils) accumulate along the endothelium (margination) and begin to emigrate through vessel walls

Front 131

Substance P

Back 131

powerful mediator of vascular permeability, transmits pain signals, regulates blood pressure, and stimulates immune and endocrine cell secretion. Local substance P release leads to plasma influx and amplification of an initial inflammatory stimulus

Front 132

Suppurative inflammation

Back 132

(suppurative – forming pus) synonymous with purulent: containing, consisting of, or forming pus; pattern in inflammation is characterized by production of purulent exudates (pus) consisting of leukocytes and necrotic cells. An abscess refers to a localized collection of purulent inflammatory tissue accompanied by liquefactive necrosis (e.g., staphylococcal abscess)

Front 133

Thrombin

Back 133

The protease thrombin provides the main link between the coagulation system and inflammation. Activation of the clotting system results in the activation of thrombin (factor IIa) from precursor prothrombin (factor II). Thrombin is the enzyme that cleaves circulating soluble fibrinogen to generate an insoluble fibrin clot and is the major coagulation protease. It binds to receptors that are called protease-activated receptors (PARs) because they bind multiple trypsin-like serine proteases in addition to thrombin. These receptors are seven-transmembrane G protein-coupled receptors that are expressed on platelets, endothelial and smooth muscle cells, and many other cell types. Engagement of the so-called type 1 receptor (PAR-1) by proteases, particularly thrombin, triggers several responses that induce inflammation. They include mobilization of P-selectin, production of chemokines, and expression of endothelial adhesion molecules for leukocyte integrins; induction of cyclooxygenase-2 and production of prostaglandins; production of PAF and nitric oxide; and changes in endothelial shape. As we have seen, these responses promote the recruitment of leukocytes and many other reactions of inflammation

Front 134

Toll-like receptor (TLR)

Back 134

plays part in leukocyte activation; surface molecule involved in leukocyte activation that mediates innate leukocyte responses to different classes of microbes, various cytokine receptors, and receptors for complement fragments and immunoglobulin that promote phagocytosis

Front 135

Transforming growth factor-beta (TGF-B)

Back 135

regulates integrin expression; is a growth inhibitor for many cell types and may aid in modulating the repair process; it is also a chemotactic factor for macrophages and fibroblasts

Front 136

transudate

Back 136

An extravascular fluid with low protein content and sg below 1.012; essentially an ultrafiltrate of blood plasma resulting from elevated fluid pressures or diminished osmotic forces in the plasma

Front 137

Tumor necrosis factor-alpha (TNF-a)

Back 137

Along with interleukin 1 are major cytokines mediating inflammation; they are produced primarily by activated macrophages. Most important actions in inflammation include effects on endothelium, leukocytes, and induction of the systemic acute-phase reactions.
TNF-alpha also regulates body mass by promoting lipid and protein mobilization and by suppressing appetite.
Sustained TNF production contributes to cachexia, a pathologic state characterized by weight loss and anorexia that accompanies some infections and neoplasias

Front 138

ulcer

Back 138

a local tissue defect, or excavation involving the epithelial surface of an organ or tissue

Front 139

Ulceration

Back 139

lesion through the skin or a mucous membrane resulting from loss of tissue, usually with inflammation; can be caused by inadequate granulation tissue or collagen deposition and remodeling

Front 140

Vasoactive amine

Back 140

mediators in inflammation; they cause vasodilation and increased vascular permeability; histamine and serotonin are most notable

Front 141

VCAM-1

Back 141

vascular cell adhesion molecule 1; is an endothelial / leukocyte adhesion molecule; belongs to immunoglobulin family of proteins; major role is adhesion of eosinophils, monocytes, and lymphocytes; binds integrins on leukocytes

Front 142

Angiogenesis

Back 142

the physiological process involving the growth of new blood vessels from pre-existing vessels

Front 143

Autocrine signaling

Back 143

Cells respond to the signaling molecules that they themselves secrete, thus establishing an autocrine loop. Several polypeptide growth factors and cytokines act in this manner. Autocrine growth regulation plays a role in liver regeneration, proliferation of antigen-stimulated lymphocytes, and the growth of some tumors. Tumors frequently overproduce growth factors and their receptors, thus stimulating their own proliferation through an autocrine loop

Front 144

Basement membrane

Back 144

produced by epithelial and mesenchymal cells and are closely associated with the cell surface. They consist of a network of amorphous nonfibrillar collagen (mostly type IV), laminin, heparan sulfate, proteoglycan, and other glycoproteins

Front 145

Cell Adhesion Proteins

Back 145

Most adhesion proteins, also called CAMs (cell adhesion molecules), can be classified into four main families: immunoglobulin family CAMs, cadherins, integrins, and selectins. These proteins are located in the cell membrane, where they function as receptors, or they are stored in the cytoplasm. As receptors, CAMs can bind to similar or different molecules in other cells, providing for interaction between the same cells (homotypic interaction) or different cell types (heterotypic interaction). Cadherins are generally involved in calcium-dependent homotypic interactions, while immunoglobulin family CAMs, because of the types of ligands they can bind, participate in both homotypic and heterotypic cell-to-cell interactions. The integrins have broader ligand specificity and are responsible for many events involving cell adhesion

Front 146

Chemotaxis

Back 146

After extravasation, leukocytes emigrate in tissues toward the site of injury by a process called chemotaxis, defined most simply as locomotion oriented along a chemical gradient. All granulocytes, monocytes and, to a lesser extent, lymphocytes respond to chemotactic stimuli with varying rates of speed

Front 147

Collagen

Back 147

Fibrillar collagens form a major portion of the connective tissue in repair sites and are important for the development of strength in healing wounds. Net collagen accumulation, however, depends not only on increased collagen synthesis but also on decreased degradation. Ultimately, the granulation tissue scaffolding is converted into a scar composed of spindle-shaped fibroblasts, dense collagen, fragments of elastic tissue, and other ECM components. Degradation of collagen and other ECM proteins is achieved by a family of matrix metalloproteinases (MMPs), which are dependent on zinc ions for their activity

Front 148

Cicatrix

Back 148

The formation of new tissue in the process of wound healing

Front 149

Contact inhibition

Back 149

Cell-to-cell interactions mediated by cadherins and catenins play a major role in regulating cell motility, proliferation, and differentiation and account for the inhibition of cell proliferation that occurs when cultured normal cells contact each other ("contact inhibition").

Front 150

Dehiscence

Back 150

Inadequate formation of granulation tissue or assembly of a scar can lead to two types of complications: wound dehiscence and ulceration. Dehiscence or rupture of a wound is most common after abdominal surgery and is due to increased abdominal pressure. This mechanical stress on the abdominal wound can be generated by vomiting, coughing, or ileus

Front 151

Elastin

Back 151

Tissues such as blood vessels, skin, uterus, and lung require elasticity for their function. Although tensile strength is provided by the proteins of the collagen family, the ability of these tissues to recoil is provided by elastic fibers. These fibers can stretch to several times their length and then return to their original size after release of the tension. Morphologically, elastic fibers consist of a central core made of elastin, surrounded by a peripheral network of microfibrils. Substantial amounts of elastin are found in the walls of large blood vessels, such as the aorta, and in the uterus, skin, and ligaments

Front 152

Endocrine signaling

Back 152

Endocrine signaling: Hormones are synthesized by cells of endocrine organs and act on target cells distant from their site of synthesis, being usually carried by the blood. Growth factors may also circulate and act at distant sites, as is the case for HGF. Several cytokines, such as those associated with the systemic aspects of inflammation discussed in Chapter 2, also act as endocrine agents

Front 153

Epidermal Growth Factor (EGF)

Back 153

EGF is mitogenic for a variety of epithelial cells, hepatocytes, and fibroblasts. It is widely distributed in tissue secretions and fluids, such as sweat, saliva, urine, and intestinal contents. In healing wounds of the skin, EGF is produced by keratinocytes, macrophages, and other inflammatory cells that migrate into the area. EGF binds to a receptor (EGFR) with intrinsic tyrosine kinase activity

Front 154

Transforming Growth Factor-α (TGF-α)

Back 154

TGF-α was originally extracted from sarcoma virus-transformed cells and is involved in epithelial cell proliferation in embryos and adults and malignant transformation of normal cells to cancer. TGF-α has homology with EGF, binds to EGFR, and produces most of the biologic activities of EGF

Front 155

Extracellular matrix

Back 155

The ECM is secreted locally and assembles into a network in the spaces surrounding cells. It forms a significant proportion of the volume of any tissue. The ECM serves many functions. For example, matrix proteins sequester water that provides turgor to soft tissues and minerals that give rigidity to skeletal tissues. They also function as a reservoir for growth factors controlling cell proliferation. ECM is important for cell-to-cell interactions and provides a substratum for cells to adhere, migrate, and proliferate, directly modulating cell form and function. Synthesis and degradation of ECM accompanies morphogenesis, wound healing, and chronic fibrotic processes, as well as tumor invasion and metastasis. Three groups of macromolecules, which are often physically associated, constitute the ECM: (1) fibrous structural proteins, such as the collagens and elastins; (2) a diverse group of adhesive glycoproteins; and (3) proteoglycans and hyaluronic acid

Front 156

Fibroblast Growth Factor (FGF)

Back 156

This is a family of growth factors containing more than 10 members, of which acidic FGF (aFGF, or FGF-1) and basic FGF (bFGF, or FGF-2) are the best characterized. Released FGFs associate with heparan sulfate in the ECM, which can serve as a reservoir for storing inactive factors. FGFs are recognized by a family of cell-surface receptors that have intrinsic tyrosine kinase activity. A large number of functions are attributed to FGFs, including angiogenesis, wound repair, development of skeletal musckle and lung maturation, and hematopoiesis

Front 157

Fibrosis

Back 157

the formation or development of excess fibrous connective tissue in an organ or tissue as a reparative or reactive process, as opposed to formation of fibrous tissue as a normal constituent of an organ or tissue

Front 158

G0, G1, S, G2 stages of the cell cycle

Back 158

The cell cycle consists of G1 (presynthetic), S (DNA synthesis), G2 (premitotic), and M (mitotic) phases. Quiescent cells are in a physiologic state called G0. Tissues may be composed primarily of quiescent cells in G0, but most mature tissues contain some combination of continuously dividing cells, terminally differentiated cells, stem cells, and quiescent cells that occasionally enter into the cell cycle.

Front 159

Granulation tissue

Back 159

Granulation tissue contains numerous newly formed blood vessels. VEGF promotes angiogenesis but is also responsible for a marked increase in vascular permeability (VEGF was first named vascular permeability factor). The latter activity leads to exudation and deposition of plasma proteins, such as fibrinogen and plasma fibronectin, in the ECM and provides a provisional stroma for fibroblast and endothelial cell ingrowth. Migration of fibroblasts to the site of injury and their subsequent proliferation are triggered by multiple growth factors, including TGF-β, PDGF, EGF, FGF, and the cytokines IL-1 and TNF

Front 160

Healing by first intention

Back 160

The least complicated example of wound repair is the healing of a clean, uninfected surgical incision approximated by surgical sutures. Such healing is referred to as primary union or healing by first intention. The incision causes death of a limited number of epithelial and connective tissue cells as well as disruption of epithelial basement membrane continuity. The narrow incisional space immediately fills with clotted blood containing fibrin and blood cells; dehydration of the surface clot forms the well-known scab that covers the wound

Front 161

Healing by second intention

Back 161

When there is more extensive loss of cells and tissue, as in surface wounds that create large defects, the reparative process is more complicated. Regeneration of parenchymal cells cannot completely restore the original architecture, and hence abundant granulation tissue grows in from the margin to complete the repair. This form of healing is referred to as secondary union or healing by second intention. • Perhaps the feature that most clearly differentiates primary from secondary healing is the phenomenon of wound contraction, which occurs in large surface wounds

Front 162

Hepatocyte Growth Factor (HGF)

Back 162

Has mitogenic effects in most epithelial cells, including hepatocytes and cells of the biliary epithelium in the liver, and epithelial cells of the lungs, mammary gland, skin, and other tissues. Besides its mitogenic effects, HGF acts as a morphogen in embryonic development and promotes cell scattering and migration. This factor is produced by fibroblasts, endothelial cells, and liver nonparenchymal cells

Front 163

Hyaluronic Acid

Back 163

HA is a polysaccharide of the GAG family found in the ECM of many tissues. It is a huge molecule that consists of many repeats of a simple disaccharide stretched end-to-end. It binds a large amount of water, forming a viscous hydrated gel that gives connective tissue the ability to resist compression forces. HA helps provide resilience and lubrication to many types of connective tissue, notably for the cartilage in joints. HA is also found in the matrix of migrating and proliferating cells, where it inhibits cell-to-cell adhesion and facilitates cell motility. CD44, a surface glycoprotein expressed by leukocytes, binds HA. Through such binding, T cells may be retained in tissues and remain bound to endothelium at sites of inflammation

Front 164

Insulin-like growth factors

Back 164

polypeptides with high sequence similarity to insulin. IGFs are part of a complex system that cells use to communicate with their physiologic environment. This complex system (often referred to as the IGF "axis") consists of two cell-surface receptors (IGF1R and IGF2R), two ligands (IGF-I and IGF-II), a family of six high-affinity IGF binding proteins (IGFBP 1-6), as well as associated IGFBP degrading enzymes, referred to collectivly as proteases

Front 165

Integrins

Back 165

Most adhesion proteins, also called CAMs (cell adhesion molecules), can be classified into four main families: immunoglobulin family CAMs, cadherins, integrins, and selectins. The integrins have broader ligand specificity and are responsible for many events involving cell adhesion. Integrins bind both to matrix proteins such as fibronectin and laminin, mediating adhesiveness between cells and ECM, as well as to adhesive proteins in other cells, establishing cell-to-cell contacts

Front 166

Interleukins

Back 166

A variety of naturally occuring polypeptides that are members of the family of cytokines which affect functions of specific cell types and are found in small quantities. They are secreted regulatory proteins produced by lymphocytes, monocytes and various other cell types and are released by cells in response to antigenic and non-antigenic stimuli. Interleukins are of the larger class of T-cell products, lymphokines which are now more frequently considered as cytokines. The interleukins, of which there are 12 identified to date, modulate inflammation and immunity by regulating growth, mobility and differentiation of lymphoid and other cells. Included among the cytokines are cachectin and lymphotoxin which are now known as tumor necrosis factor-alpha and tumor necrosis factor-beta, respectively. Interleukin-1 inhibitors are the first well-described proteins involved in the feedback regulation of interleukin activities

Front 167

Interferons

Back 167

A family of glycoproteins derived from human cells which normally has a role in fighting viral infections by preventing virus multiplication in cells. They are secreted by vertebrate cells in response to a wide variety of inducers and confer resistance against many different viruses, inhibit proliferation of normal and malignant cells, impede multiplication of intracellular parasites, enhance macrophage and granulocyte phagocytosis, augment natural killer cell activity, and show several other immunomodulatory functions

Front 168

Keloid

Back 168

The accumulation of excessive amounts of collagen may give rise to a raised scar known as a hypertrophic scar; if the scar tissue grows beyond the boundaries of the original wound and does not regress, it is called a keloid. Keloid formation appears to be an individual predisposition, and for unknown reasons this aberration is somewhat more common in African-Americans. The mechanisms of keloid formation are still unknown

Front 169

Labile cells

Back 169

In continuously dividing tissues (also called labile tissues) cells proliferate throughout life, replacing those that are destroyed. These tissues include surface epithelia, such as stratified squamous surfaces of the skin, oral cavity, vagina, and cervix; the lining mucosa of all the excretory ducts of the glands of the body (e.g., salivary glands, pancreas, biliary tract); the columnar epithelium of the gastrointestinal tract and uterus; the transitional epithelium of the urinary tract, and cells of the bone marrow and hematopoietic tissues. In most of these tissues, mature cells are derived from stem cells

Front 170

Laminin

Back 170

Laminin is the most abundant glycoprotein in the basement membrane and has binding domains for both ECM and cell-surface receptors. In the BM, polymers of laminin and collagen type IV form tightly bound networks. Laminin can also mediate the attachment of cells to connective tissue substrates

Front 171

Paracrine signaling

Back 171

One cell type produces the ligand, which then acts on adjacent target cells that express the appropriate receptors. The responding cells are in close proximity to the ligand-producing cell and are generally of a different type. Paracrine stimulation is common in connective tissue repair of healing wounds, in which a factor produced by one cell type (e.g., a macrophage) has its growth effect on adjacent cells (e.g., a fibroblast).

Front 172

Permanent cells

Back 172

Nondividing (permanent) tissues contain cells that have left the cell cycle and cannot undergo mitotic division in postnatal life. To this group belong neurons and skeletal and cardiac muscle cells. If neurons in the central nervous system are destroyed, the tissue is generally replaced by the proliferation of the central nervous system supportive elements, the glial cells

Front 173

Platelet derived growth factor (PDGF)

Back 173

PDGF is a family of several closely related proteins, each consisting of two chains designated A and B. All three isoforms of PDGF (AA, AB, and BB) are secreted and are biologically active. PDGF is stored in platelet α granules and is released on platelet activation. It can also be produced by a variety of other cells, including activated macrophages, endothelial cells, smooth muscle cells, and many tumor cells. PDGF causes migration and proliferation of fibroblasts, smooth muscle cells, and monocytes

Front 174

Polarity

Back 174

ECM scaffolds are essential for wound healing because they provide the framework for cell migration and maintain the correct cell polarity. In epithelial cells, the polarity meant is between apical and baso lateral regions, in moving cells, having a distinct front and rear

Front 175

Proteoglycan

Back 175

Proteoglycans and hyaluronic acid (HA, hyaluronan or hyaluronate) make up the third type of component in the ECM, besides the fibrous structural proteins and cell adhesion proteins. Proteoglycans consist of a core protein linked to one or more polysaccharides called glycosaminoglycans (GAGs). These are long repeating polymers of specific disaccharides in which one (or both) contains a sulfate residue

Front 176

RGD motif

Back 176

Several integrins bind to Arg-Gly-Asp (RGD) sequences in the fibronectin and vitronectin molecules

Front 177

Regeneration

Back 177

Regeneration refers to growth of cells and tissues to replace lost structures, such as the growth of an amputated limb in amphibians. In mammals, whole organs and complex tissues rarely regenerate after healing, and the term is usually applied to processes such as liver and kidney growth after, respectively, partial hepatectomy and unilateral nephrectomy. These processes consist of compensatory growth rather than true regeneration

Front 178

Repair

Back 178

The goal of the repair process is to restore the tissue to its original state. The inflammatory reaction set in motion by the injury contains the damage, eliminates the damaging stimulus, removes injured tissue, and initiates the deposition of ECM components in the area of injury. Some tissues can be completely reconstituted after injury, such as the repair of bone after a fracture or the regeneration of the surface epithelium in a cutaneous wound. For tissues that are incapable of regeneration, repair is accomplished by connective tissue deposition, producing a scar. This term is most often used in connection to wound healing in the skin, but it is also used to describe the replacement of parenchymal cells by connective tissue, as in the heart after myocardial infarction. If damage persists, inflammation becomes chronic, and tissue damage and repair may occur concurrently. Connective tissue deposition in these conditions is usually referred to as fibrosis

Front 179

Scar

Back 179

Healing consists of variable proportions of two distinct processes-regeneration, and the laying down of fibrous tissue, or scar formation. Superficial wounds, such as a cutaneous wound that only damages the epithelium, can heal by epithelial regeneration. Incisional and excisional skin wounds that damage the dermis heal through the formation of a collagen scar

Front 180

Stable Cells

Back 180

Quiescent (or stable) tissues normally have a low level of replication; however, cells from these tissues can undergo rapid division in response to stimuli and are thus capable of reconstituting the tissue of origin. They are considered to be in the G0 stage of the cell cycle but can be stimulated to enter G1

Front 181

Stricture

Back 181

A narrowing, especially of a tube or canal, due to scar tissue or tumour

Front 182

TGF-β

Back 182

Active TGF-β binds to two cell surface receptors (types I and II) with serine/threonine kinase activity and triggers the phosphorylation of cytoplasmic transcription factors called Smads. TGF-β has multiple and often opposing effects depending on the tissue and the type of injury. Agents that have multiple effects are called pleiotropic

Front 183

Tumor Necrosis Factor (TNF)

Back 183

A polypeptide hormone, produced by endotoxin-activated macrophages, which has the ability to modulate adipocyte metabolism, lyse tumor cells in vitro, and induce hemorrhagic necrosis of certain transplantable tumors in vivo
The cytokines TNF and IL-6 are implicated in the G0/G1 transition and the growth factors HGF and TGF-α are involved in cell-cycle progression after the cells reach G1.

Front 184

Vascular Endothelial Growth Factor (VEGF)

Back 184

VEGF is a potent inducer of blood vessel formation in early development (vasculogenesis) and has a central role in the growth of new blood vessels (angiogenesis) in adults. It promotes angiogenesis in tumors, chronic inflammation, and healing of wounds

Front 185

Atherosclerosis

Back 185

Accumulation of fat and connective tissue within the intima of arteries, often causing progressive narrowing of the lumen and decreased blood flow to tissues

Front 186

Congestion

Back 186

Accumulation of blood within an organ due to venous stasis.

Front 187

Deep vein thrombosis

Back 187

Typically occurs in the deep veins. These thrombi are usually loosely attached and thus easily dislodged

Front 188

Edema

Back 188

The accumulation of excess fluid in the intercellular (interstitial) tissue spaces or body cavities

Front 189

Embolus

Back 189

A detached mass within the blood stream that travels from its site of origin to lodge in a distant vessel. These may be solid (thrombo emboli, bone marrow emboli, fat emboli), liquid (amniotic fluid), or gaseous (air embolism, decompression nitrogen emboli).

Front 190

Heart failure

Back 190

Inability of the heart to produce a high enough cardiac output to meet the body's needs. Right heart failure leads to edema and congestion in tissues drained by the vena cava (liver, spleen, & lower extremities). Left heart failure leads to edema and congestion in the lungs

Front 191

Heart failure cells

Back 191

Hemosiderin-containing macrophages within alveolar spaces caused by microscopic or macroscopic hemorrhage

Front 192

Hyperemia

Back 192

Accumulation of blood within dilated arteries

Front 193

Infarct or infarction

Back 193

A localized area of ischemic necrosis resulting from obstruction of the arterial supply (or less commonly venous drainage). White (anemic) infarcts develop mostly in solid organs that do not have collateral circulation (spleen, heart, kidney) following an acute arterial occlusion. Red (hemorrhagic) infarcts develop in organs whose vasculature is in a pedicle, where venous compression can occur due to twisting (gonads, intestine), organs with a dual blood supply (lung), organs that contain great amount of loose tissue and previously congested organs that undergo ischemia of arterial origin. A brain infarct is a special case. The typical brain infarct is first an anemic infarct, that later undergoes liquefaction. When the occluded vessel reopens (re-perfusion), a hemorrhagic infarct ensues

Front 194

Lines of Zahn

Back 194

Laminations of platelets and fibrin in a thrombus. Easier to visualize in arterial thrombus than in venous thrombus

Front 195

Mural thrombus

Back 195

A non-occlusive thrombus, usually occurring in the heart or a large artery

Front 196

Organization

Back 196

the process of repair and granulation tissue formation within a thrombus

Front 197

Propagation of thrombus

Back 197

increase in size of an already formed thrombus.

Front 198

Recanalization

Back 198

Reestablishment of a lumen, through organization, in a vessel previously obstructed by a thrombus

Front 199

Stroke

Back 199

the lay term used to describe the sudden onset of signs and symptoms in a patient with a cerebral infarct

Front 200

Thrombus

Back 200

An intravascular blood clot that develops and attaches to the wall of an artery or vein. Arterial or myocardial thrombi are usually "white thrombi" because the rapid blood flow washes red cells away, leaving only platelets and fibrin. Venous thrombi are usually "red thrombi" because sluggish flow allows the thrombi to contain all normal blood constituents. Thrombus can be differentiated from postmortem clotted blood by the presence of fibrin/platelet/red blood cell laminations (lines of Zahn). Postmortem clotted blood contains a gelatin-like mass of red cells (currant jelly) overlaid by coagulated "chicken fat"-like plasma

Front 201

Transudate

Back 201

An ultrafiltrate of blood plasma that has passed from within blood vessels into tissues due to a change in hydrostatic pressure (low protein concentration)

Front 202

Volvulus

Back 202

A twisting of the intestine about the axis of its mesentery or around an abnormal fibrous band (often a postsurgical adhesion).

Front 203

Adenosine diphosphate

Back 203

Platelets adhere to exposed extracellular matrix (ECM) via von Willebrand factor (vWF) and are activated, undergoing a shape change and granule release; released adenosine diphosphate (ADP) and thromboxane A2 (TxA2) lead to further platelet aggregation to form the primary hemostatic plug

Front 204

Air embolism

Back 204

Embolism due to air bubbles entering the blood vessels after trauma, surgical procedures, or changes in atmospheric pressure

Front 205

Albumin

Back 205

Reduced plasma osmotic pressure can result from excessive loss or reduced synthesis of albumin, the serum protein most responsible for maintaining colloid osmotic pressure. An important cause of albumin loss is the nephrotic syndrome, characterized by a leaky glomerular capillary wall and generalized edema. Reduced albumin synthesis occurs in the setting of diffuse liver pathology (e.g., cirrhosis) or as a consequence of protein malnutrition. In each case, reduced plasma osmotic pressure leads to a net movement of fluid into the interstitial tissues and a resultant plasma volume contraction. Predictably, with reduced intravascular volume, renal hypoperfusion with secondary aldosteronism follows. The retained salt and water cannot correct the plasma volume deficit because the primary defect of low serum proteins persists. As with congestive heart failure, edema precipitated by hypoproteinemia is exacerbated by secondary salt and fluid retention.

Front 206

Anasarca

Back 206

Anasarca is a severe and generalized edema with profound subcutaneous tissue swelling

Front 207

Antithrombin

Back 207

Iinhibit the activity of thrombin and other serine proteases-factors IXa, Xa, XIa, and XIIa. Antithrombin III is activated by binding to heparin-like molecules on endothelial cells; hence the clinical usefulness of administering heparin to minimize thrombosis

Front 208

ascites

Back 208

Abnormal accumulation of serous fluid in the spaces between tissues and organs in the cavity of the abdomen. Also called hydroperitoneum

Front 209

Cardiac cirrhosis

Back 209

In severe, long-standing hepatic congestion (most commonly associated with heart failure), there may even be grossly evident hepatic fibrosis (cardiac cirrhosis

Front 210

coagulation

Back 210

a change to a viscous, jellylike, or solid state; especially : a change from a liquid to a thickened curdlike state not by evaporation but by chemical reaction

Front 211

Coagulation cascade

Back 211

The coagulation cascade constitutes the third component of the hemostatic process and is a major contributor to thrombosis.
The coagulation cascade is essentially a series of enzymatic conversions, turning inactive proenzymes into activated enzymes and culminating in the formation of thrombin.Thrombin then converts the soluble plasma protein fibrinogen precursor into the insoluble fibrous protein fibrin.
Each reaction in the pathway results from the assembly of a complex composed of an enzyme (activated coagulation factor), a substrate (proenzyme form of coagulation factor), and a cofactor (reaction accelerator). These components are typically assembled on a phospholipid complex and held together by calcium ions. Thus, clotting tends to remain localized to sites where such assembly can occur (e.g., on the surface of activated platelets or endothelium).

Front 212

Intrinsic pathway

Back 212

Coagulation cascade initiated by the activation of Hageman factor (XII)

Front 213

Extrinsic pathway

Back 213

Coagulation cascade activated by tissue factor, a cellular lipoprotein exposed at sites of tissue injury

Front 214

Congestion

Back 214

an excessive accumulation especially of blood or mucus

Front 215

Congestive heart failure

Back 215

Heart failure in which the heart is unable to maintain adequate circulation of blood in the tissues of the body or to pump out the venous blood returned to it by the venous circulation

Front 216

Decompression sickness

Back 216

a sometimes fatal disorder that is marked by neuralgic pains and paralysis, distress in breathing, and often collapse and that is caused by the release of gas bubbles (as of nitrogen) in tissue upon too rapid decrease in air pressure after a stay in a compressed atmosphere -- called also bends, caisson disease, decompression illness, decompression syndrome

Front 217

Dense bodies

Back 217

Gamma granules in platelets. They contain ADP, ionized calcium, histamine, serotonin, and epinephrine

Front 218

Disseminated intravascular coagulation (DIC)

Back 218

the sudden or insidious onset of widespread fibrin thrombi in the microcirculation – screws up kidneys, heart, brain, lungs

Front 219

Ecchymosis

Back 219

the escape of blood into the tissues from ruptured blood vessels marked by a livid black-and-blue or purple spot or area; also : the discoloration so caused -- > 1cm to 2 cm subcutaneous hematoma

Front 220

Inflammatory edema

Back 220

Because of increased vascular permeability, inflammatory edema is a protein-rich exudate, with a specific gravity usually over 1.02

Front 221

Edema

Back 221

Formerly known as dropsy or hydropsy. Swelling of any organ or tissue due to accumulation of excess lymph fluid, without an increase of the number of cells in the affected tissue. Edema can accumulate in almost any location in the body, but the most common sites are the feet and ankles

Front 222

Noninflammatory edema

Back 222

Caused by increased hydrostatic pressure, reduced plasma osmotic pressure, lymphatic obstruction, and sodium retention

Front 223

Effusion

Back 223

the escape of a fluid from anatomical vessels by rupture or exudation

Front 224

Embolism

Back 224

the sudden obstruction of a blood vessel by an embolus

Front 225

Embolus

Back 225

an abnormal particle (like a thrombus) circulating in the blood

Front 226

Endothelial prostacyclin (PGI2)

Back 226

Potent vasodilator – inhibits platelet aggregation – comes from endothelium – dukes it out with its nemesis TxA2 and wins in healthy status, but TxA2 dominates when injury is present which increases vasoconstriction and platelet aggregation

Front 227

Endothelin

Back 227

any of several polypeptides consisting of 21 amino acid residues that are produced in various cells and tissues, that play a role in regulating vasomotor activity, cell proliferation, and the production of hormones, and that have been implicated in the development of vascular disease

Front 228

Endotoxin / lipopolysaccharide

Back 228

a toxin of internal origin; specifically : a poisonous substance present in bacteria (as the causative agent of typhoid fever) but separable from the cell body only on its disintegration

Front 229

Fat embolism

Back 229

Fat from long bone marrow after a break, or occasionally tissue trauma becomes an embolus

Front 230

Fibrin

Back 230

a white insoluble fibrous protein formed from fibrinogen by the action of thrombin especially in the clotting of blood

Front 231

Fibrin split products

Back 231

Chemotactic agents from cleavage of fibrinogen – attracts neutrophils and monocytes – can also act as a weak anticoagulant after release from fibrin breakdown by plasmin (breaking up clot)

Front 232

Fibrinogen

Back 232

a plasma protein that is produced in the liver and is converted into fibrin during blood clot formation

Front 233

Glycoprotein Ib (GpIb)

Back 233

Platelet surface receptor – binds to vWF which in turn binds to exposed collagen at injury site. Deficiency causes Bernard-Soulier syndrome

Front 234

Heart failure cells

Back 234

macrophages in the lung during left heart failure that often carry large amounts of haemosiderin.

Front 235

Hematoma

Back 235

a mass of usually clotted blood that forms in a tissue, organ, or body space as a result of a broken blood vessel

Front 236

Hemorrhage

Back 236

a copious discharge of blood from the blood vessels

Front 237

Hemosiderin

Back 237

a yellowish brown granular pigment formed by breakdown of hemoglobin, found in phagocytes and in tissues especially in disturbances of iron metabolism (as in hemochromatosis, hemosiderosis, or some anemias), and composed essentially of colloidal ferric oxide

Front 238

Hemostasis

Back 238

1 : stoppage or sluggishness of blood flow
2 : the arrest of bleeding (as by a hemostatic agent)

Front 239

Hyperemia

Back 239

Active process – excess of blood in a body part (as from an increased flow of blood due to vasodilation) erythema results

Front 240

Congestion

Back 240

passive process caused by decreased outflow of blood from area – hypoxia results

Front 241

Infarct

Back 241

an area of necrosis in a tissue or organ resulting from obstruction of the local circulation by a thrombus or embolus

Front 242

Pale infarct

Back 242

anemic – in harder organs (spleen, kidney, heart) blood can’t flow outside of infarct area – turns pale

Front 243

Red infarct

Back 243

hemmorhagic – softer tissue (gut, ovaries, lungs) blood is able to hemmorhage outside of infarct area

Front 244

Lines of Zahn

Back 244

Laminations in a thrombus usually found in heart or aorta – not as likely in deep leg vein thrombosis

Front 245

Lymphedema

Back 245

edema due to faulty lymphatic drainage

Front 246

Organization

Back 246

Refers to ingrowth of endothelial cells, smooth muscle cells, & fibroblasts into the fibrin-rich thrombus to re-establish circulation – eventually to recanalize

Front 247

Nitric oxide

Back 247

Similar to PGI2 – acts as vasodilator & inhibitor of platelet aggregation

Front 248

Paradoxical embolism

Back 248

Rarely an embolism may pass through an interatrial or interventricular defect and get into systemic circulation

Front 249

Petechiae

Back 249

a minute reddish or purplish spot containing blood that appears in skin or mucous membrane as a result of localized hemorrhage – 1-2mm diameter

Front 250

Phlebothrombosis

Back 250

venous thrombosis accompanied by little or no inflammation

Front 251

Plasmin

Back 251

a proteolytic enzyme that dissolves the fibrin of blood clots

Front 252

Plasminogen activator inhibitors

Back 252

Endothelial cells produce PAIs to block fibrinolysis by decreasing t-PA binding to fibrin – a procoagulant

Front 253

Protein c

Back 253

Inhibits clotting by proteolytic cleavage factors Va and VIIIa, requires protein s, activated by thrombomodulin

Front 254

Protein s

Back 254

Synthesized by endothelial cells – cofactor to protein c to inhibit clotting

Front 255

Pulmonary embolism

Back 255

embolism of a pulmonary artery or one of its branches that is produced by foreign matter and most often a blood clot originating in a vein of the leg or pelvis and that is marked by labored breathing, chest pain, fainting, rapid heart rate, cyanosis, shock, and sometimes death -- abbreviation PE

Front 256

Purpura

Back 256

any of several hemorrhagic states characterized by patches of purplish discoloration resulting from extravasation of blood into the skin and mucous membranes - > 3mm in diameter

Front 257

Recanalization

Back 257

the process of restoring flow to or reuniting an interrupted channel of a bodily tube (as an artery or the vas deferens)

Front 258

Secondary aldosteronism

Back 258

Decreased CO triggers decreased renal perfusion, which spurs the renin – angiotensin – aldosterone axis which increases Na+ and H2O by the kidneys

Front 259

Shock

Back 259

systemic hypoperfusion caused by low CO or low effective blood volume

Front 260

Thrombin

Back 260

a proteolytic enzyme formed from prothrombin that facilitates the clotting of blood by catalyzing conversion of fibrinogen to fibrin and that is used in the form of a powder as a topical hemostatic agent

Front 261

Thrombocytopenia

Back 261

persistent decrease in the number of blood platelets that is often associated with hemorrhagic conditions

Front 262

Thrombocytosis

Back 262

increase and especially abnormal increase in the number of blood platelets

Front 263

Thrombophlebitis

Back 263

inflammation of a vein with formation of a thrombus

Front 264

Thrombosis

Back 264

the formation or presence of a blood clot within a blood vessel

Front 265

Thromboxane A2 (TXA2)

Back 265

(Thromboxane) any of several substances that are produced especially by platelets, are formed from endoperoxides, cause constriction of vascular and bronchial smooth muscle, and promote blood clotting & platelet aggregation & vasoconstriction

Front 266

Thrombus

Back 266

a clot of blood formed within a blood vessel and remaining attached to its place of origin

Front 267

Tissue factor

Back 267

membrane bound pro-coagulant factor synthesized by endothelium – acts in conjunction with secreted platelet factors to activate coagulation cascade, which activates thrombin

Front 268

Tissue plasminogen activator (t-PA)

Back 268

Counter regulatory mechanism to limit the hemostatic process to the injury site – promotes fibrinolytic activity to clear fibrin deposits from endothelial surfaces

Front 269

Trousseau syndrome

Back 269

Increased thrombosis, migratory thrombophlebitis

Front 270

Virchow triad

Back 270

3 influences that predispose to thrombus formation 1. endothelial injury 2. stasis or turbulence of blood flow 3. blood hypercoagulability

Front 271

Von willebrand factor (vWF)

Back 271

a protein secreted especially by endothelial cells that circulates in blood plasma as a large variable aggregation consisting usually of repeating dimers, that mediates platelet adhesion to collagen in subendothelial tissue at injury sites, that is often found complexed to factor VIII in plasma where it serves to protect it from degradation, and that is deficient or defective in individuals affected with von Willebrand's disease -- called also VW factor

Front 272

ABL gene/BCR-ABL hybrid gene

Back 272

The Philadelphia (Ph)chromosome, characteristic of chronic myeloid leukemia and a subset of acute lymphoblastic leukemias, provides the prototypic example of an oncogene formed by fusion of two separate genes. In these cases, a reciprocal translocation between chromosomes 9 and 22 relocates a truncated portion of the protooncogene c-ABL (from chromosome 9) to the BCR (break point cluster region) on chromosome 22. The hybrid fusion gene BCR-ABL encodes a chimeric protein that has constitutive tyrosine kinase activity. BCR-ABL tyrosine kinase has served as a target for leukemia therapy, with remarkable success so far

Front 273

Adenocarcinoma

Back 273

a carcinoma with a glandular growth pattern – it is common to specify the organ of origin, eg renal cell

Front 274

Adenoma

Back 274

a benign neoplasia made up of cells forming glands

Front 275

Adenomatous polyposis coli (APC) gene

Back 275

APC is a component of the WNT signaling pathway, which has a major role in controlling cell fate, adhesion, and cell polarity during embryonic development. WNT signaling is also required for self-renewal of hematopoietic stem cells. WNT signals through a family of cell-surface receptors called frizzled (FRZ), and stimulates several pathways, the central one involving β-catenin and APC.
An important function of the APC protein is to down-regulate β-catenin. In the absence of WNT-signaling APC causes degradation of β-catenin, preventing its accumulation in the cytoplasm. It does so by forming a macromolecular complex with β-catenin, which results in the degradation of β-catenin

Front 276

Aflatoxin

Back 276

Aflatoxin B1 (produced by the fungus Aspergillus flavus) is a potent hepatocarcinogen in animals and believed to be a factor in the high incidence of liver cancer in Africa. Grows on moldy grains and peanuts.

Front 277

anaplasia

Back 277

Lack of differentiation, or anaplasia, is considered a hallmark of malignant transformation, and is marked by a number of morphologic changes.
• Pleomorphism. Both the cells and the nuclei characteristically display pleomorphism-variation in size and shape (Fig. 7-8).
• Abnormal nuclear morphology. Characteristically the nuclei contain an abundance of DNA and are extremely dark staining (hyperchromatic). The nuclei are disproportionately large for the cell, and the nucleus-to-cytoplasm ratio may approach 1:1 instead of the normal 1:4 or 1:6.
• Mitoses. The presence of mitoses, however, does not necessarily indicate that a tumor is malignant or that the tissue is neoplastic.
• Loss of polarity. In addition to the cytologic abnormalities, the orientation of anaplastic cells is markedly disturbed (i.e., they lose normal polarity).
• formation of tumor giant cells, and in many anaplastic tumors, large central areas undergo ischemic necrosis

Front 278

angiogenesis

Back 278

Tumors stimulate the growth of host blood vessels, a process called angiogenesis, which is essential for supplying nutrients to the tumor. Even with genetic abnormalities that dysregulate growth and survival of individual cells, tumors cannot enlarge beyond 1 to 2 mm in diameter or thickness unless they are vascularized. Angiogenesis is a requisite not only for continued tumor growth, but also for metastasis. Without access to the vasculature, the tumor cells cannot readily spread to distant sites

Front 279

Balanced translocation

Back 279

In a translocation, a segment of one chromosome is transferred to another (see Fig. 5-26). In one form, called balanced reciprocal translocation, there are single breaks in each of two chromosomes, with exchange of material. Such a translocation might not be disclosed without banding techniques

Front 280

Basic fibroblast growth factor (bFGF)

Back 280

bFGF, a member of the fibroblast growth factor family, is expressed in human melanomas but not in normal melanocytes

Front 281

BCL-2

Back 281

Removal of BCL-2 from its normal controls leads to increased transcription and overexpression of the BCL-2 protein. As discussed in Chapter 1, BCL-2 protects cells from apoptosis by the mitochondrial pathway. Thus, there is a steady accumulation of B lymphocytes (the cells in which the translocation typically occurs as the immunoglobulin locus is open), resulting in lymphadenopathy and marrow infiltration. Because lymphomas that overexpress BCL-2 arise in large part from reduced cell death rather than explosive cell proliferation, they tend to be indolent (slow growing) compared with many other lymphomas.

Front 282

benign

Back 282

not cancerous

Front 283

Benzoylpyrene

Back 283

Dietary carcinogen and mutagen

Front 284

Bloom syndrome/ataxia-telangectasia/Fanconi anemia

Back 284

A group of autosomal recessive disorders
• are characterized by hypersensitivity to other DNA-damaging agents, such as ionizing radiation (ataxia-telangiectasia and Bloom syndrome), or DNA cross-linking agents (Fanconi anemia).
• These syndromes include, in addition to predisposition to cancer, other features such as neural symptoms (ataxia-telangiectasia), anemia (Fanconi anemia), and developmental defects and a predisposition to a very broad sprectrum of tumors(Bloom syndrome).
• The defective gene is located on chromosome 15 and encodes a helicase (BLM helicase), which participates in DNA repair by homologous recombination.

Front 285

borderline malignancy

Back 285

Borderline malignant neoplasms have some, but not all, of the features of a fully malignant neoplasm

Front 286

BRCA1 gene/BRCA2 gene

Back 286

• BRCA-1 and BRCA-2 are two genes associated with the occurrence of breast and several other cancers. As with tumor suppressor genes, individuals who inherit mutations of BRCA-1 or BRCA-2 are highly susceptible to the development of breast cancer. Thus, in contrast to other tumor suppressor genes (RB, p53, NF-1, VHL) that are associated with heritable cancer syndromes, mutations in either of the two BRCA genes are associated with the development of nonfamilial (sporadic) forms of breast cancer. Nevertheless, it is possible that alterations in the expression of genes related to BRCA-1 and BRCA-2 may be involved in non-hereditary breast cancer

Front 287

cachexia

Back 287

Patients with cancer commonly suffer progressive loss of body fat and lean body mass accompanied by profound weakness, anorexia, and anemia.
• The origins of cancer cachexia are obscure.
• not caused by the nutritional demands of the tumor.
• Current evidence indicates that cachexia results from the action of soluble factors such as cytokines produced by the tumor and by the host in response to the tumor.

Front 288

Cancer

Back 288

This is now a general term for more than 100 diseases that are characterized by uncontrolled, abnormal growth of cells. Cancer cells can spread locally or through the bloodstream and lymphatic system to other parts of the body

Front 289

Carcinoembryonic antigen (CEA)

Back 289

, normally produced in embryonic tissue of the gut, pancreas, and liver, is a complex glycoprotein that is elaborated by many different neoplasms. Depending on the serum level adopted as a significant elevation, it is variously reported to be positive in 60% to 90% of colorectal, 50% to 80% of pancreatic, and 25% to 50% of gastric and breast carcinomas.

Front 290

carcinogen

Back 290

A large number of agents cause genetic damage and induce neoplastic transformation of cells. They include (1) chemical carcinogens, (2) radiant energy, and (3) oncogenic viruses and some other microbes. Except for the few direct-acting alkylating and acylating agents that are intrinsically electrophilic, most chemical carcinogens require metabolic activation for conversion into ultimate carcinogens (Fig. 7-49). Other metabolic pathways may lead to the inactivation (detoxification) of the procarcinogen or its derivatives.
• the carcinogenic potency of a chemical is determined by the inherent reactivity of its electrophilic derivative but also by the balance between metabolic activation and inactivation reactions.

Front 291

carcinoid

Back 291

A slow-growing type of tumor usually found in the gastrointestinal system (most often in the appendix), and sometimes in the lungs or other sites. Carcinoid tumors may spread to the liver or other sites in the body, and they may secrete substances such as serotonin or prostaglandins, causing carcinoid syndrome

Front 292

carcinoma

Back 292

A malignant new growth that arises from epithelium, found in skin or, more commonly, the lining of body organs, for example: breast, prostate, lung, stomach or bowel. Carcinomas tend to infiltrate into adjacent tissue and spread (metastasize) to distant organs, for example: to bone, liver, lung or the brain

Front 293

carcinosarcoma

Back 293

A malignant neoplasm that contains elements of carcinoma and sarcoma so extensively intermixed as to indicate neoplasia of epithelial and mesenchymal tissue.

Front 294

Caspase

Back 294

• Proteolytic enzyme that mediates final phase (execution) of apoptosis
• mammalian homologues of the ced-3 gene in C. elegans.44
• The term caspase is based on two properties of this family of enzymes: the "c" refers to a cysteine protease (i.e., an enzyme with cysteine in its active site), and "aspase" refers to the unique ability of these enzymes to cleave after aspartic acid residues

Front 295

CD95 (Fas)

Back 295

The FAS ligand or FasL is a type II transmembrane protein that belongs to the tumor necrosis factor (TNF) family.

Some alternate names include Fas ligand, FasL, Apo1, apoptosis antigen ligand 1, CD95 ligand. It is a trimeric molecule.

FasL will bind to 3 monomers of FAS which are spanning the membrane of the "target" cell. This trimerization may lead to apoptosis, or cell death.

Defective Fas mediated apoptosis may lead to oncogenesis as well as drug resistance in existing tumors. Germline mutation of Fas is associated with autoimmune lymphoproliferative syndrome (ALPS), a childhood disorder of apoptosis

Front 296

CDKN2A/cyclin D/CDK4/RB

Back 296

Various growth factors promote the formation of the cyclin D-CDK4 complex. This complex (and to some extent cyclin E-CDK2) phosphorylates RB, changing it from an active (hypophosphorylated) to an inactive state (hyperphosphorylation). RB inactivation allows the cell to pass the G1/S restriction point. Growth inhibitors such as TGF-β and p53 and the Cip/Kip and INK4a (p16INK4a and p19ARF) cell-cycle inhibitors prevent RB activation. Transforming proteins of oncogenic viruses bind hypophosphorylated RB and cause its functional inactivation. Virtually all cancers show dysregulation of the cell cycle

Front 297

Chondroma

Back 297

Benign tumor of the connective tissue (cartilage)

Front 298

Chondrosarcoma

Back 298

Malignant tumor of the connective tissue (cartilage)

Front 299

choristoma

Back 299

• 1. Microscopically normal cells or tissues in abnormal locations. 2. An ectopic rest of normal tissue; for example, a rest of adrenal cells under the kidney capsule. Occasionally a pancreatic nodular rest in the mucosa of the small intestine may mimic a neoplasm, providing some partial justification for the use of a term that implies a tumor.

Front 300

Chromosome deletion

Back 300

A type of mutation where a segment of genetic information, DNA, is removed from the gene. Deletions can be as small as a single nucleotide or as large as entire chromosomes

Front 301

contact inhibition

Back 301

inhibition of cell proliferation that occurs when cultured normal cells contact each other

Front 302

Cyclin

Back 302

Cyclins are a family of proteins involved in the progression of cells through the cell cycle. A cyclin forms a complex with the cyclin-dependent kinase (Cdk), which activates the latter's protein kinase function. Cyclins are so named because their concentration varies in a cyclical fashion during the cell cycle; they are produced or degraded as needed in order to drive the cell through the different stages of the cell cycle. When its concentrations in the cell are low, cyclin detaches from Cdk, inhibiting the enzyme's activity, probably by causing a protein chain to block the enzymatic site

Front 303

cystadenocarcinomas

Back 303

A malignant epithelial neoplasm that forms in large cystic spaces

Front 304

Cystadenoma

Back 304

A benign epithelial neoplasm that forms in large cystic spaces

Front 305

dermoid

Back 305

Dermoid cyst – cystic teratoma, a cyst containing skin, or structures connected with skin, such as hair. Differentiates principally along ectodermal lines to create a cystic tumor lined by skin replete with hair, sebaceous glands, and tooth structures

Front 306

Desmoid/desmoplasia

Back 306

Stromal support of neoplasm where the parenchymal cells stimulate the formation of an abundant collagenous stroma. Also, Proliferation of normal fibrous tissue in response to growth factors produced by neoplastic cells

Front 307

differentiation

Back 307

Refers to the extent to which neoplastic cells resemble comparable normal cells, both morphologically and functionally; lack of differentiation is called anaplasia. Well-differentiated tumors are composed of cells resembling the mature normal cells of the tissue of origin of the neoplasm (Fig. 7-5). Poorly differentiated or undifferentiated tumors have primitive-appearing, unspecialized cells. In general, benign tumors are well differentiated (Fig. 7-6). Malignant neoplasms, in contrast, range from well
differentiated to undifferentiated.

Front 308

DNA repair gene

Back 308

DNA repair genes affect cell proliferation or survival indirectly by influencing the ability of the organism to repair nonlethal damage in other genes, including protooncogenes, tumor suppressor genes, and genes that regulate apoptosis.Disability in the DNA repair genes can predispose to mutations in the genome and hence to neoplastic transformation. With some exceptions, both alleles of DNA repair genes must be inactivated to induce such genomic instability; in this sense, DNA repair genes may also be considered as tumor suppressor genes

Front 309

dysplasia

Back 309

Encountered principally in epithelia. Characterized by a constellation of changes that include a loss in the uniformity of the individual cells as well as a loss in their architectural orientation. Cells exhibit considerable pleomorphisms, and often contain hyperchromatic nuclei that are abnormally large for the size of the cell. Mitotic figures are more abundant than usual, although almost invariably they conform to normal patterns.

Front 310

endophytic

Back 310

Referring to an infiltrative, invasive tumour

Front 311

Epithelial/mesenchymal

Back 311

In general, benign tumors are designated by attaching the suffix -oma to the cell of origin. Tumors of mesenchymal cells generally follow this rule. For example, a benign tumor arising from fibroblastic cells is called a fibroma, a cartilaginous tumor is a chondroma, and a tumor of osteoblasts is an osteoma. In contrast, nomenclature of benign epithelial tumors is more complex. Epithelial derived tissue= carcinoma; mesenchymal derived tissues= sarcoma

Front 312

Epstein-Barr virus (EBV)

Back 312

Member of herpesvirus family; Associated with: Burkitt lymphoma, nasopharyngeal cancer, B-cell lymphoma in immunosuppressed pts.; and some forms of Hodgkin’s disease

Front 313

exophytic

Back 313

Denoting a neoplasm or lesion that grows outward from an epithelial surface

Front 314

Familial cancer

Back 314

One occurring in families more frequently than would be expected by chance. Besides the inherited syndromes of cancer susceptibility, cancer may occur at higher frequency in certain families without a clearly defined pattern of transmission. Virtually all the common types of cancers that occur sporadically have also been reported to occur in familial forms. Examples include carcinomas of colon, breast, ovary, and brain, as well as melanomas. Features that characterize familial cancers include early age at onset, tumors arising in two or more close relatives of the index case, and sometimes, multiple or bilateral tumors. Familial cancers are NOT associated with specific marker phenotypes

Front 315

Fibroma

Back 315

Benign neoplasm that differentiates toward collagenous connective tissue

Front 316

Fibrosarcoma

Back 316

Malignant neoplasm that differentiates toward collagenous connective tissue

Front 317

Flow cytometry

Back 317

Measurement of the DNA content of tumor cells by flow cytometry is useful because with several tumors there is a relationship between abnormal DNA content and prognosis. Useful in detection of cell surface antigens in the diagnosis of leukemias and lymphomas. Separation, classification and quantitation of blood cells and antibodies which affect blood cells.

Front 318

Frozen section/fine needle aspiration (FNA)/cytologic smears

Back 318

Fine-needle aspiration procedure involves aspirating cells and attendant fluid from tumors or masses with a small-bore needle, followed by cytologic examination of the stained smear. Most commonly used for the assessment of readily palpable lesions in sites such as the breast, thyroid, and lymph nodes. Requesting "quick-frozen section" diagnosis is sometimes desirable, for example, in determining the nature of a mass lesion or in evaluating the margins of an excised cancer to ascertain that the entire neoplasm has been removed. This method permits histologic evaluation within minutes.

Front 319

Gene amplification

Back 319

Activation of protooncogenes associated with overexpression of their products may result from reduplication and amplification of their DNA sequences. May produce several hundred copies of the protooncogene in the tumor cell. The amplified genes can be readily detected by molecular hybridization with appropriate DNA probes. Amplification of C-MYC, L-MYC, and N-MYC correlates with disease progression in small cell cancer of the lung. Amplification of c-erb B2 gene in breast cancers

Front 320

Giant cells

Back 320

Feature of anaplasia is the formation of tumor giant cells, some possessing only a single huge polymorphic nucleus and others having two or more nuclei. Not to be confused with inflammatory Langhans or foreign body giant cells, which are derived from macrophages and contain many small, normal-appearing nuclei. In the cancer giant cell, the nuclei are hyperchromatic and large in relation to the cell. Although growing tumor cells obviously require a blood supply, often the vascular stroma is scant, and in many anaplastic tumors, large central areas undergo ischemic necrosis.

Front 321

Grade vs. Stage

Back 321

Staging has proved to be of greater clinical value than grading
The staging (large, invasive, metastatic) of cancers is based on the size of the primary lesion, its extent of spread to regional lymph nodes, and the presence or absence of blood-borne metastases. (UICC—TMN system; AJC I-IV system)
Grading of a cancer is based on the degree of differentiation (deviation from normal) of the tumor cells and the number of mitoses within the tumor as presumed correlates of the neoplasm's aggressiveness. (I-IV system. Useful prognostic indicator for most sarcomas and for some carcinomas. NOT a useful indicator for some very common carcinomas (breast, lung, colon). Imperfect because different parts of tumor may display different degrees of differentiation and grade of tumor may change as it grows

Front 322

Growth factors

Back 322

PDGF-B>>sis (protooncogen) overexpression  astrocytoma, osteosarcoma
Fibroblast GF>> hist-1 overexpression>>stomach cancer
Fibroblast GF >>int-2 amplificaiton>> bladder, breast cancer, melanoma

Front 323

Hamartoma

Back 323

Focal overgrowth of mature normal cells and tissues with an abnormal architectural pattern. Eg; a hamartomatous nodule in the lung may contain cartilage, bronchi, and blood vessels. Presence of multiple cell or tissue types usually distinguishes a hamartoma from monoclonal benign neoplasia

Front 324

Helicobacter pylori

Back 324

Linked to peptic ulcer, gastric lymphoma, and carcinoma. Induces reactive T cells that cause proliferation of polyclonal B-cell populations via cytokine secretion.

Front 325

Hematogenous spread

Back 325

Typical of sarcomas but is also seen with carcinomas. Arteries, with their thicker walls, are less readily penetrated than are veins. Arterial spread may occur, however, when tumor cells pass through the pulmonary capillary beds or pulmonary arteriovenous shunts or when pulmonary metastases themselves give rise to additional tumor emboli.

Front 326

Hepatitis B Virus/HCV

Back 326

Close association between HBV/HCV and liver cancer. By causing hepatocellular injury and resulting regenerative hyperplasia, pool of mitotically active cells subject to mutational damage is increased. HBV has HBx - increases transcriptional activation of several oncogenes + inactivates p53

Front 327

HER2 protein

Back 327

Also known as ERB B2 Gene. Member of EGF receptor family, is amplified in 25% of breast cancers and in human adenocarcinomas within ovary, lung, stomach, and salivary glands. Is the target of new therapeutic agents of monoclonal antibodies against the protein

Front 328

Hereditary nonpolyposis colon carcinoma

Back 328

Born with one defective copy of one of several DNA repair genes. Affected genes (hMSH2 and hMSH1) are involved in DNA mismatch repair. Leads to carcinomas of the cecum or proximal colon without a preneoplastic stage of an adenomatous polyp

Front 329

heterotopia

Back 329

Microscopically normal cells or tissues that are present in abnormal locations. Usually of little significance but may be clinically confused with true neoplasms

Front 330

Heterotopic rest

Back 330

Heterotopic rests of normal tissue may be present in the stomach, and are usually asymptomatic. With pancreatic heterotopia, nodules of essentially normal pancreatic tissue up to 1 cm in diameter may be present in the gastric submucosa, muscle wall, or at a subserosal location. When in the pylorus, localized inflammation may lead to pyloric obstruction. With gastric heterotopia, small patches of ectopic gastric mucosa in the duodenum or in more distal sites may present as perplexing sources of bleeding, due to peptic ulceration of adjacent mucosa.

Front 331

Human papillomavirus (HPV)

Back 331

Approximately 70 genetically distinct types of HPV have been identified. Some types cause benign squamous papillomas (warts) in humans. Implicated in the genesis of several cancers, including: squamous cell carcinoma of the cervix of the uterine cervix and anogenital region, and in some cases, to the causation of oral and laryngeal cancers; genital warts with low malignant potential are associated with distinct HPV types; Clonal integration of viral genome occurs in host cell DNA. Overexpression of E6 and E7 proteins of high-risk HPV disable p53 and Rb.

Front 332

Human T-cell leukemia virus type 1 (HTLV-1)

Back 332

Associated with a form of T-cell leukemia/lymphoma that is endemic in certain parts of Japan and the Caribbean basin but is found sporadically elsewhere, including the United States. Similar to the AIDS virus, HTLV-1 has tropism for CD4+ T cells, and hence this subset of T cells is the major target for neoplastic transformation. Human infection requires transmission of infected T cells via sexual intercourse, blood products, or breast-feeding. Leukemia develops in only 3% to 5% of the infected individuals after a long latent period of 40 to 60 years. Contains tax region – activates IL2 and IL2R (monoclonal T-cell tumor)

Front 333

Hyperchromatic

Back 333

Darkly stained nuclei that frequently contain prominent nucleoli. Charactierized as anaplastic, or poorly differentiated tumors

Front 334

Immunosurveillance

Back 334

Theory that tumors are suppressed by the immune system. Supported by increased frequency of cancers in immunodeficient persons. Refuted by idea that immunodeficient persons mainly get lymphomas, which is a consequence of abnormal immune system rather than a failure of immunosurveillance

Front 335

in situ

Back 335

In the natural or normal place, confined to the site of origin without invasion of neighbouring tissues

Front 336

Initiation

Back 336

Initiation results from exposure of cells to a sufficient dose of a carcinogenic agent (initiator); an initiated cell is altered, making it potentially capable of giving rise to a tumor . Initiation alone, however, is not sufficient for tumor formation. Initiation causes permanent DNA damage (mutations). It is therefore rapid and irreversible and has memory. Promoters can induce tumors in initiated cells, but they are nontumorigenic by themselves. Furthermore, tumors do not result when the promoting agent is applied before, rather than after, the initiating agent.

Front 337

Intraepithelial

Back 337

Within the layer of cells that forms the surface or lining of an organ.

Front 338

Invasion

Back 338

Tumor cells detach from each other because of reduced adhesiveness, and cells then attach to the basement membrane via the laminin receptors and secrete proteolytic enzymes, including type IV collagenase and plasminogen activator. Degradation of the basement membrane and tumor cell migration follow.

Front 339

Laminin

Back 339

Link proteins of basal lamina, binds to cells through specific receptors and to collagen type IV and heparin. Involved in cell attachment, locomotion, and growth

Front 340

Latent membrane protein 1 (LMP-1)

Back 340

Binds to and activates a signaling molecule that is normally activated by the CD40 receptor in B cells. Key recipient of helper T-cell signals, which are normally required for full B-cell responses. Mimicking CD40, LMP-1 activates the NFκB and JAK/STAT signaling pathways and promotes B-cell survival and proliferation, all of which are helper T cell-induced responses that occur in the absence of T cells (or any other signals) in EBV-infected B cells. Thus, the virus has efficiently co-opted a normal pathway of B-cell activation in order to increase the number of cells it can infect and inhabit.

Front 341

Leiomyoma

Back 341

Benign mesenchymal tumor with smooth muscle differentiation

Front 342

leukoplakia

Back 342

Circumscribed, firmly attached, thick white patches on the tongue and other mucous membranes (genitalia), often occurring as a pre-cancerous growth. Leukoplakia develops on the oral mucosa in response to chronic irritation (for example ill-fitting dentures, smoking, chewing tobacco).

Front 343

Li-Fraumeni syndrome

Back 343

Caused by an inherited mutant copy of the p53 gene (which prevents the propogation of genetically damaged cells). At high risk for malignant tumor by inactivation of the second normal allele

Front 344

Selected Tumor Suppressor Genes Involved in Human Neoplasms

Back 344

TGF-β receptor; E-cadherin; APC/β-catenin; RB; p53; WT-1; BRCA-1 and BRCA-2

Front 345

Loss of heterozygosity

Back 345

A child carrying an inherited mutant RB allele in all somatic cells is perfectly normal (except for the increased risk of developing cancer). Because such a child is heterozygous at the RB locus, it implies that heterozygosity for the RB gene does not affect cell behavior. Cancer develops when the cell becomes homozygous for the mutant allele or, put another way, when the cell loses heterozygosity for the normal RB gene (a condition known as LOH, for loss of heterozygosity). Because the RB gene is associated with cancer when both normal copies are lost, it is sometimes referred to as a recessive cancer gene

Front 346

Lymphatic spread

Back 346

Most common pathway for the initial dissemination of carcinomas; sarcomas may also use this route. Tumors do not contain functional lymphatics, but lymphatic vessels located at the tumor margins are apparently sufficient for the lymphatic spread of tumor cells. The emphasis on lymphatic spread for carcinomas and hematogenous spread for sarcomas is misleading because ultimately there are numerous interconnections between the vascular and the lymphatic systems. The pattern of lymph node involvement follows the natural routes of lymphatic drainage

Front 347

malignant

Back 347

Tending to become progressively worse and to result in death. Having the properties of anaplasia, invasion and metastasis, said of tumours.

Front 348

Metalloproteinase/collagenase

Back 348

Secreted by tumors to degrade the matrix components and create passageways for migration

Front 349

metastasis

Back 349

Cancer that started from cancer cells from another part of the body. For example: cancer that starts in the breast can spread to the lymph nodes and then be spread throughout the body.

Front 350

microinvasion

Back 350

Invasion of tissue immediately adjacent to a carcinoma in situ, the earliest stage of malignant neoplastic invasion.

Front 351

mixed tumor

Back 351

Divergent differentiation of single line of parenchymal cells into another tissue. Best example is mixed tumor of salivary gland origin (has islands of cartilage and bone in epithelial component)

Front 352

Monoclonal

Back 352

 A tumor is formed by the clonal expansion of a single precursor cell that has incurred the genetic damage

Front 353

Mucinous

Back 353

 High molecular weight glycoproteins which are altered in tumors and used for diagnostic markers and targets for therapy

Front 354

MYC gene

Back 354

Expressed in virtually all eukaryotic cells, belonging to immediate early response gene, rapidly induced to divide. Overexpression leads to sustained transcription of critical target genes and neoplastic formation

Front 355

neoplasia

Back 355

Literally new growth, usually refers to abnormal new growth and thus means the same as tumour, which may be benign or malignant.
Unlike hyperplasia, neoplastic proliferation persists even in the absence of the original stimulus.

Front 356

Nitrosamine

Back 356

Can be synthesized in the GI tract from ingested nitrites or derived from digested proteins. Carcinogen that may contribute to gastric cancer

Front 357

occult malignancy

Back 357

Obscure, concealed from observation, difficult to understand.

Front 358

oncogene

Back 358

Mutated and/or overexpressed version of a normal gene of animal cells (the proto-oncogene) that in a dominant fashion can release the cell from normal restraints on growth and thus alone or in concert with other changes, convert a cell into a tumour cell. Tumors have the capacity to proliferate without external stimuli, usually as a consequence of oncogene activation.

Front 359

Oncology

Back 359

The study of diseases that cause cancer.

Front 360

Oncoprotein

Back 360

Genes that promote autonomous cell growth in cancer cells are called oncogenes, and their normal cellular counterparts are called protooncogenes. Protooncogenes are physiologic regulators of cell proliferation and differentiation; oncogenes are characterized by the ability to promote cell growth in the absence of normal mitogenic signals. Oncogene products, called oncoproteins, resemble the normal products of protooncogenes with the exception that oncoproteins are devoid of important regulatory elements

Front 361

papilloma

Back 361

Benign epithelial neoplasia producing micro- or macroscopic finger like projections

Front 362

paraneoplastic syndrome

Back 362

Functional syndrome associated with the symptoms from the presence of a neoplasia that: cannot be simply explained by spread of the neoplasia; cannot be explained by local production of endogenous hormones. These occur in about 10% of patients with malignant disease. Despite their relative infrequency, paraneoplastic syndromes are important to recognize, for several reasons: They may represent the earliest manifestation of an occult neoplasm; In affected patients, they may represent significant clinical problems and may even be lethal; They may mimic metastatic disease and therefore confound treatment

Front 363

Paraneoplastic Syndromes

Back 363

Endocrinopathies (Cushing syndrome, hypercalcemia); Nerve and muscle syndromes (Myasthenia); Dermatologic disorders (Dermatomyositis)

Front 364

Parenchyma

Back 364

The distinguishing or specific cells of a gland or organ, contained in and supported by the connective tissue framework, or stroma.
Also, proliferating neoplastic cells that, along with supportive stroma (connective tissue + blood vessels) make up a tumor

Front 365

pleomorphism

Back 365

Having different forms at different stages of the life cycle. Nuclear and cellular pleomorphism – the wide variation in the shape and size of cells and nuclei – is a cytological feature of anaplastic tumors

Front 366

point mutation

Back 366

Mutation that causes the replacement of a single base pair with another pair.

Front 367

polyp

Back 367

A tumor projecting from the mucosa into the lumen of a hollow viscus (eg, stomach or colon)

Front 368

Poorly differentiated carcinoma

Back 368

Differentiation is the extent to which tumor cells resemble comparable normal cells. A well differentiated tumor is low grade, while an anaplastic, undifferentiated tumor is high grade. The more rapidly growing and the more anaplastic a tumor, the less likely it will be well-differentiated. Malignant tumors are poorly differentiated, and benign tumors are almost always well-differentiated

Front 369

progression

Back 369

Tumor progression is where tumors become progressively more aggressive and acquire greater malignant potential. Related to the sequential appearance within the tumor of cells that differ in invasiveness, rate of growth, ability to metastases, and evade immune surveillance.

Front 370

premalignant

Back 370

A premalignant condition is a disease, syndrome, or finding that, if left untreated, may lead to cancer. Examples of pre-malignant conditions include actinic keratosis and Barrett's esophagus.

Front 371

protooncogene

Back 371

The normal, cellular equivalent of an oncogene, thus usually a gene involved in the signaling or regulation of cell growth. In general, cellular proto-oncogenes are prefixed with a c, rather than their abnormal viral counterparts, that are prefixed with a v, for example c myc and v myc.

Front 372

RAS gene

Back 372

Induces cells to secrete growth factors and enables them to grow without anchorage to a normal substrate. Single most common abnormality of dominant oncogenes in human tumors. Activated in the GTP bound state>>recruits RAF + stimulates MAP-kinase pathway>>growth-promoting signals. Mutant RAS permanently activated. RAS is suppressed by NF-1, which can mutate to not work, leaving RAS on

Front 373

Retinoblastoma gene

Back 373

Regulates the advancement of cells from G1 to S. Cyclins D, E>>CDK>>>phosphorylates Rb>>E2F>>G1>>S. With mutations in the Rb gene, regulation of E2F is lost, and cells continue to cycle in the absence of stimulus

Front 374

Two-hit hypothesis

Back 374

In hereditary cases, one genetic change (“first hit”) is inherited from an affected parent and is therefore present in all somatic cells of the body, whereas the second mutation (“second hit”) occurs in one of the many retinal cells (which already carry the first mutation). In sporadic cases, however, both mutations (hits) occur somatically within a single retinal cell, whose progeny then form the tumor. Retinoblastoma serves as a paradigm for this hypothesis

Front 375

Sarcoma

Back 375

A malignant neoplasm arising from a mesenchymal tissue stem cell (“soft tissue or connective tissue”). The term is usually pre-fixed to indicate the type of differentiation, eg angiosarcoma – differentiates toward formation of vascular channels; chondrosarcoma – differentiates toward cartilage; fibrosarcoma differentiates toward collagenous connective tissue; rhabdomyosarcoma – differentiates toward striated muscle.

Front 376

Scirrhous

Back 376

Literally, scar-like. Describes tumors with a hard consistency due to the desmoplasia associated with malignant cells. Seen especially in breast cancers

Front 377

Seeding

Back 377

The process by which the distant spread of tumors moves into peritoneal, pericardial, and subarachnoid spaces

Front 378

Squamous cell carcinoma

Back 378

Carcinoma arising in any of the stratified squamous epithelia of the body – it is common practice to specify the organ of origin ( eg esophageal squamous cell carcinoma)

Front 379

Teratoma

Back 379

A neoplasm composed of a variety of parenchymal cell types representative of more than one germ layer and usually three. These tumors arise from totipotential cells and so are principally encountered in the gonads. Thought to originate from primordial germ cells or misplaced blastomeres that contains tissues derived from all three embryonic layers, such as bone, muscle, cartilage, nerve, tooth buds and various glands

Front 380

Totipotential cells

Back 380

An undifferentiated cell capable of developing into any type of body cell.

Front 381

tumor

Back 381

Literally, a swelling. Usually used as a synonym for a neoplasm of any type. It is a non-specific clinical term and can refer to an inflammatory mass.

Front 382

Tumor associated antigen

Back 382

Present on tumor cells and also on some normal cells

Front 383

Tumor progression

Back 383

Tumor progression is where tumors become progressively more aggressive and acquire greater malignant potential. Related to the sequential appearance within the tumor of cells that differ in invasiveness, rate of growth, ability to metastases and evade immune surveillance.

Front 384

Telomere/telomerase

Back 384

With each cell division there is some shortening of specialized structures, called telomeres, at the ends of chromosomes.116 Once the telomeres are shortened beyond a certain point, the loss of telomere function leads to activation of p53-dependent cell-cycle checkpoints, causing proliferative arrest or apoptosis (Fig. 7-40). Thus, telomere shortening functions as a clock that counts cell divisions. In germ cells, telomere shortening is prevented by the sustained function of the enzyme telomerase, thus explaining the ability of these cells to self-replicate extensively. This enzyme is absent from most somatic cells, and hence they suffer progressive loss of telomeres. Introduction of telomerase into normal human cells causes considerable extension of their life span,117 thus supporting the hypothesis that telomerase loss is causally associated with loss of replication ability. If loss of telomerase is the basis of the finite life span of cells, how do cancer cells continue to divide indefinitely? Cancer cells must find a way to prevent telomere shortening, and a mechanism that accomplishes this is the reactivation of telomerase activity

Front 385

Tumor specific antigen

Back 385

Present only on tumor cells and not on any normal cells

Front 386

tumor suppressor gene

Back 386

Genes that act to block the action of oncogenes. These genes are often lost or deleted during carcinogenesis. Examples include: TGF-B, APC, NF-1/2, Rb, p53, WT-1, BRCA-1/2

Front 387

Vascular endothelial growth factor (VEGF)

Back 387

Along with basic fibroblast growth factor (bFGF), it is the most important tumor angiogenic factor. Generally released from tumor cells or inflammatory cells that enter the tumor

Front 388

Xeroderma pigmentosum (XP)

Back 388

Disease involving mutations in the nucleotide excision repair genes required for correcting UV light-induced pyrimidine dimmer formation. Involves the development of skin cancers as a result of the mutagenic effects of UV light

Front 389

α-fetoprotein (AFP)

Back 389

Normally produced by fetal yolk sac and liver. Markedly elevated noted in cancers of the liver and testicular germ cells

Front 390

β-naphthylamine

Back 390

An aniline dye used in the rubber industries, was in the past responsible for bladder cancers

Front 391

Atypia (Atypical)

Back 391

This imprecise term is often used loosely to refer to any cell or growth pattern which is neoplastic, dysplastic or shows any features suggestive of a neoplastic or pre-neoplastic process - in diagnostic cytopathology it more precisely denotes cells which show features suggestive of dysplasia but which do not exhibit all of the specific criteria- pathologists sometimes call lesions with such cells borderline or worrisome.

Front 392

Benign

Back 392

Refers to lack of harm: a neoplasia lacking the ability to do damage by local invasion or metastasis.

Front 393

Borderline (worrisome) lesion

Back 393

Pathologists' term for a lesion that shows atypical cells or growth pattern suspicious of a dysplastic or neoplastic process

Front 394

Cancer

Back 394

Currently used as a lay and medical synonym for any malignant neoplasm. Previously used as a more specific medical synonym for carcinoma

Front 395

Carcinoid

Back 395

A neoplasm with neuroendocrine characteristics, usually arising from epithelium in the lung or GI tract, but can be found in other locations

Front 396

Carcinoma in situ

Back 396

A non-invasive proliferation of malignant epithelial cells which is within the confines of mucosa (i.e. has not penetrated the basement membrane).

Front 397

Choristoma

Back 397

Groupings of microscopically normal cells or tissues that are present in abnormal locations (e.g., a rest of pancreatic tissue found in the wall of the stomach or a rest of adrenal cells in the kidney).

Front 398

Cystadenoma

Back 398

A benign epithelial neoplasm that forms large cystic spaces

Front 399

Desmoplasia

Back 399

Proliferation of normal fibrous tissue in response to growth factors produced by neoplastic cells.

Front 400

Differentiation

Back 400

The extent to which neoplastic stem cells form mature progeny that resemble their normal counterparts morphologically and/or functionally

Front 401

Dysplasia

Back 401

A potentially reversible and probably polyclonal, pre-neoplastic condition in which the cell growth pattern is abnormal and some cytologic features are similar to those seen in neoplasia - in cervical carcinoma, dysplasia is often classified as cervical intraepithelial neoplasia types I-Ill or mild, moderate, severe. In other sites dysplasia is usually described as mild, moderate or severe.

Front 402

Ectopic hormone production

Back 402

Production by a neoplasm of a hormone that normally is not produced (other than trace amounts) by cells of the organ in which the neoplasia is found.

Front 403

CIN (cervical intraepithelial neoplasia)

Back 403

in cervical carcinoma, dysplasia is often classified as cervical intraepithelial neoplasia types I-Ill or mild, moderate, severe

Front 404

Grade

Back 404

The degree to which the cells of a malignant neoplasia deviate from their normal counterparts- the higher the number applied (scales of 1 to 3 or 4), the greater the deviation from normal- grade is a useful prognostic indicator for most sarcomas and for some carcinomas (e.g. prostate adenocarcinoma, bladder transitional cell carcinoma). Note that grade is not a useful indicator for some very common carcinomas: breast, lung, colon.

Front 405

Hamartoma

Back 405

- Focal overgrowth of mature normal cells and tissues with an abnormal architectural pattern. The presence of multiple cell or tissue types usually distinguishes a hamartoma from monoclonal benign neoplasia

Front 406

Hepatoma

Back 406

A malignant proliferation of cells with hepatocytic or choledochal differentiation

Front 407

Leiomyoma

Back 407

A benign mesenchymal tumor with smooth muscle differentiation

Front 408

Leiomyosarcoma

Back 408

A malignant tumor with differentiation toward smooth muscle cells

Front 409

Leukemia

Back 409

- A neoplasia derived from hematopoietic stem cells, in which the bulk of malignant cells are found circulating in the blood.

Front 410

Lipoma

Back 410

A benign mesenchymal tumor with adipose differentiation

Front 411

Liposarcoma

Back 411

A malignant mesenchymal tumor with differentiation toward fat cells.

Front 412

Lymphoma

Back 412

A neoplasia derived from hematopoietic stem cells with differentiation toward lymphocytes.

Front 413

Metastasis

Back 413

A secondary neoplastic growth in a tissue location disconnected from the primary.

Front 414

Neoplastic growth

Back 414

Frequently within a lymph node or distant organ. This reflects a clonal evolution from the primary growth. The metastatic growth often resembles the primary tumor histologically, but it may also be surprisingly more differentiated or less differentiated than the primary.

Front 415

Papilloma

Back 415

A benign epithelial neoplasia producing micro- or macroscopic finger-like projections.

Front 416

Paraneoplastic syndrome

Back 416

A functional syndrome associated with the presence of a neoplasia that: 1) cannot be simply explained by spread of the neoplasia and 2) that cannot be explained by local production of endogenous hormones.

Front 417

Pleomorphism

Back 417

Describes variation in the cytologic appearance of cells (size, shape, N::C ratio) or a complex pattern of neoplastic growth with various types of cellular differentiation

Front 418

Seminoma

Back 418

A malignant neoplasia of germ cell origin found in the testicle

Front 419

Scirrhous

Back 419

Scirrhous- Literally, scar-like. Describes tumors with a hard consistency due to the desmoplasia associated with malignant cells. Seen especially in breast cancers.

Front 420

Stage

Back 420

Denotes the clinically observed (Clinical Stage) or pathologically defined (Pathologic Stage) extent of spread of a malignant neoplasm from its primary site. The higher the number or letter, the greater the extent of spread. This is usually one of the best correlates with prognosis.

Front 421

Teratoma

Back 421

A neoplasm composed of a variety of parenchymal cell types representative of more than one germ layer and usually three. These tumors arise from totipotential cells and so are principally encountered in the gonads.

Front 422

Bland

Back 422

Refers to cell cytologic features or a growth pattern which does not differ significantly from the normal background

Front 423

Cellular

Back 423

Refers to abnormal crowding of cells

Front 424

Cribriform

Back 424

interweaving back to back pattern of neoplastic glands that lack stromal boundaries- indicative of malignancy

Front 425

Hyperchromasia

Back 425

Increased staining of nucleus related to increased DNA content

Front 426

Molding

Back 426

Cytopathologists' term for a change in configuration of neoplastic cell nuclei due to loss of membrane rigidity and compression by adjacent cells.

Front 427

Myxoid (stroma)

Back 427

Connective tissue product resembling mucus and associated with some soft tissue tumors.

Front 428

Psammoma body

Back 428

Microscopic zone of dystrophic tissue calcification, usually associated with a serous adenocarcinoma of the ovary, papillary carcinoma of the thyroid gland and meningiomas- classically, the calcium deposits in concentric rings and it may be detected radiographically.

Front 429

Salt & pepper

Back 429

Refers to an irregular pattern of chromatin condensations within the nucleus often associated with carcinoid tumors.

Front 430

Allele

Back 430

Alternate forms of a gene. These occur at specific sites on chromosomes and determine different characteristics for a specific trait

Front 431

Autosome

Back 431

Any one of the non-sex chromosomes. In humans there are 22 autosomes and 2 sex chromosomes.

Front 432

Centimorgan

Back 432

A unit of measure of genetic linkage, which is the percent crossing over between two traits. This is a measure of how close together specific traits are on a chromosome.

Front 433

Chromosome

Back 433

A rod like structure found in the nucleus of a cell that contains genetic material. Chromosomes are only visible during mitosis and during the remainder of the cell cycle the genetic material of the chromosomes are in a less packed form in the nucleus as chromatin.

Front 434

Codon

Back 434

A triplet of nucleotides in DNA or RNA that code for 1 of the 20 amino acids or a stop protein synthesis signal.

Front 435

Deletion

Back 435

A type of mutation where a segment of genetic information, DNA, is removed from the gene. Deletions can be as small as a single nucleotide or as large as entire chromosomes.

Front 436

Diploid

Back 436

Two copies of all the genetic information per cell. Written as 2N. Humans have 23 pairs of chromosomes, 22 autosomes and X and Y.

Front 437

DNA

Back 437

A large molecule containing genetic information stored in the form of nucleotide sequences.

Front 438

DNA probe

Back 438

A specific sequence of DNA isolated in the laboratory and labeled for detection. Used to find a complementary sequence on the target DNA.

Front 439

DNA restriction map

Back 439

A visual depiction of the locations of all sites in a segment of DNA which will be cleaved by specific restriction enzymes.

Front 440

Dominant trait

Back 440

A characteristic that is apparent even if inherited from only one parent and therefore only need to be present on one chromosome for the trait to be expressed.

Front 441

Downstream region

Back 441

Any region of DNA located on the 3'-side of the area of DNA under study. Exon- Coding sequences of genes which are retained and spliced together in a mature mRNA.

Front 442

Frame

Back 442

The phasing and position of the codons in a region of DNA or RNA. Also called the reading frame.

Front 443

Frameshift mutation

Back 443

A type of mutation, usually a deletion or an insertion, that causes the normal reading frame of a gene to shift. While only a small piece of the gene is altered, the protein coded by the gene with the frame shift mutation has no similarity with the native protein after the mutation.

Front 444

G-proteins

Back 444

Intracellular proteins involved in the signal transduction pathways from growth factor receptors to the genes in the nucleus. Mechanism of action of these proteins involves their phosphorylation and dephosphorylation.

Front 445

Gene

Back 445

A unit of heredity, a segment of DNA containing the code for a specific molecule. This gene can correlate with a physical trait.

Front 446

Gene amplification

Back 446

A type of mutation when a specific gene is aberrantly copied several times and reinserted into the chromosome.

Front 447

Gene expression

Back 447

The manifestation of the appropriate genetic material in a cell or tissue.

Front 448

Gene mapping

Back 448

The process of determining the specific position of genes on chromosomes.

Front 449

Gene rearrangement

Back 449

The movement of regions of DNA within a gene or between genes. Gene rearrangement occurs in normal processes such as immunoglobulin heavy chain class switching or can be abnormal and be a form of mutation.

Front 450

Genome

Back 450

The entire genetic material of a cell or organism. All the information to reproduce the cell or organism is contained within the genome.

Front 451

Growth factor

Back 451

A hormone-like substance that acts to signal cells to grow and divide.

Front 452

Growth factor receptor-

Back 452

The specific cellular receptor for a growth factor. Following growth factor binding the receptor starts the process of signal transduction to stimulate specific genes.

Front 453

Haploid-

Back 453

One copy of all the genetic information per cell. Written as N, human ova and sperm are haploid.

Front 454

Heterozygosity-

Back 454

The state of possessing different alleles at a given locus in regard to a specific gene or character.

Front 455

Homozygosity

Back 455

The state of possessing a pair of identical alleles at a given locus.

Front 456

Intron-

Back 456

A DNA sequence that interrupts the sequences coding for a gene product (the exons). The introns are spliced out and the exons are joined together to produce the mature mRNA.

Front 457

Linkage-

Back 457

The tendency of two or more genes to be co-inherited, measured by the degree of crossing over between the traits and expressed in centimorgans. This relationship can be between an identifiable trait and a genetic disorder.

Front 458

Locus-

Back 458

A specific site for the location of a gene and its alleles on a chromosome.

Front 459

LOH (Loss of heterozygosity)

Back 459

Condition in which a cell becomes homozygous for a mutant allele: In the case of tumor suppressor genes, if one of the 2 alleles is normal the tumor suppression action of the gene continues functioning. Should the remaining normal allele mutate, then the tumor suppression action is lost and cancer develops.

Front 460

Mutation-

Back 460

A change in the DNA sequence can be caused by nucleotide substitutions, deletions, insertions, or rearrangements.

Front 461

Non-dysjunction-

Back 461

The lack of separation of genes during meiosis.

Front 462

Northern blot-

Back 462

A technique for separating RNA fragments by electrophoresis, blotting the separated fragments onto nitrocellulose paper and identifying them by hybridization with labeled RNA of a specific type or DNA from a specific gene.

Front 463

Nucleotide-

Back 463

One of the five molecules that make up DNA or RNA. In DNA, which is usually double-stranded, adenine pairs with thymine and guanine pairs with cytidine. In RNA, which is usually single stranded, thymine is replaced by uracil.

Front 464

Oligonucleotide-

Back 464

A short piece or string of nucleotides, usually 15-50 nucleotide bases long.

Front 465

Oncogene

Back 465

The activated form of the normal proto-oncogene. This abnormal expression results in neoplasia.

Front 466

Abl-

Back 466

An oncogene producing a tyrosine kinase, activated by translocation to within the bcr gene. Morphologically this translocation produces the Philadelphia chromosome and is responsible for chronic myeloid leukemia.

Front 467

BCL-2-

Back 467

An oncogene of unknown function, activated by translocation. Associated with follicular lymphomas.

Front 468

Bcr (breakpoint cluster region)-

Back 468

A gene that when rearranged with c-Abl produces a hybrid protein that has unregulated tyrosine kinase activity. This is the molecular cause of chronic myeloid leukemia.

Front 469

Her-2-neu-

Back 469

An oncogene that resembles the epidermal growth factor receptor. Activated by gene amplification in highly malignant forms of breast cancer.

Front 470

Myc-

Back 470

A family of related nuclear oncogenes of undefined function. c-Myc is activated by translocation in Burkitt's lymphoma, N-Myc is activated by gene amplification and is associated with neuroblastoma, L-myc is also activated by amplification and may play a role in small cell lung carcinoma.

Front 471

Ras-

Back 471

A specific oncogene family which plays a role in the G-protein-mediated signal transduction pathways, activated by specific point mutations. Ras family members have been implicated in several forms of adenocarcinoma.

Front 472

Pedigree-

Back 472

A family map of a genetic disorder, illustrating affected and unaffected individuals.

Front 473

Penetrance-

Back 473

The likelihood that a genetic trait will be expressed in a person having the gene for that trait.

Front 474

Phosphodiester bond-

Back 474

The covalent bond holding adjacent nucleotides together.

Front 475

Ploidy-

Back 475

The general genetic content of a cell population. The total number of copies of the entire genome per cell.

Front 476

Point mutation-

Back 476

A type of mutation resulting from the substitution of one nucleotide for another.

Front 477

Polymerase chain reaction-

Back 477

A technique for the repetitive synthesis of a precise region of nucleic acid. The method is dependent on a thermostable DNA polymerase and a specific ÒprimerÓ DNA segment, so several million copies of the primer sequence can be made in a short period of time (if the genes contain the primer sequence).

Front 478

Primer-

Back 478

A short piece of DNA or RNA used as a starting point for a DNA polymerase. All DNA polymerases require primers.

Front 479

Proband-

Back 479

The first family member detected as having a genetic disorder.

Front 480

Proto-oncogene-

Back 480

The normal cellular form of a gene that when mutated or ÒactivatedÓ causes cancer. These proto-oncogenes play critical roles in normal growth and developmental processes.

Front 481

Recessive-

Back 481

A trait that will be apparent only if both copies of a chromosome have the requisite gene. Recessive traits imply that each parent caries at least one gene for that trait. Carriers, however, do not express the trait.

Front 482

Retinoblastoma gene-

Back 482

RB gene is a tumor suppressor gene. If both alleles are affected by mutation, activation of a single oncogene allows retinoblastoma (a rare eye tumor) to develop.

Front 483

RNA-

Back 483

A typically single-stranded nucleic acid, ribonucleic acid, which contains the sugar ribose instead of the deoxyribose found in DNA. There are several functional families of RNA in human cells: rRNA or ribosomal RNAs are the structural backbones of ribosomes, tRNAs which carry the amino acids to the ribosomes during protein synthesis and mRNAs that are read by the ribosomes during translation. There are additional RNA families responsible for splicing but these have not yet been named.

Front 484

Restriction enzyme-

Back 484

An enzyme that recognizes a specific 4,5,6 or 8 nucleotide sequence and then cuts the DNA containing the recognition site.

Front 485

Restriction fragment length polymorphism-

Back 485

The presence of variations within the positioning of restriction enzymes sites in a DNA segment, due to genetic variation or mutations. This information is useful in tracking the maternal or paternal origin of a DNA segment since RFLPÕs are inherited.

Front 486

Sex-linked-

Back 486

A trait that is inherited by means of the X chromosome.

Front 487

Southern blot-

Back 487

A technique for identifying DNA fragments by separating them with electrophoresis, blotting the fragments onto nitrocellulose paper and detecting specific gene fragments with a labeled gene probe.

Front 488

Splicing-

Back 488

The process of removing the introns during the production of mature mRNA. Tetraploid- Four copies of all the genetic information per cell. written as 4N.

Front 489

Transformation-

Back 489

A change from a functionally and morphologically normal cell appearance to a cell with altered function or morphology and malignant potential. Transformation may be caused by virus or chemical carcinogens.

Front 490

Translation-

Back 490

The process of protein synthesis. This occurs on ribosomes and involves the conversion of the code in the nucleic acid sequence to a polypeptide chain.

Front 491

Translocation-

Back 491

A form of mutation where large segments of chromosomes are moved from one chromosome to another.

Front 492

Transcription-

Back 492

The synthesis of RNA from the DNA template.

Front 493

Trisomy-

Back 493

The presence of three, instead of two, copies of a chromosome in a somatic cell.

Front 494

Tumor inducer-

Back 494

Substance that produces the first in a series of steps that lead to neoplasia.

Front 495

Tumor promoter-

Back 495

In chemical carcinogenesis, the substance which allows the effects of the inducer to become apparent and acts by stimulating cell division or replication.

Front 496

Tumor Suppressor Gene-

Back 496

Genes that act to block the action of oncogenes. These genes are often lost and deleted during carcinogenesis.

Front 497

Upstream region-

Back 497

The region of DNA or RNA on the 5'-side of the sequence in question.

Front 498

Western blot-

Back 498

A technique for identifying proteins by separating them according to molecular size with electrophoresis, blotting them onto nitrocellulose paper and reacting them with a labeled antibody. The technique can also be used to detect antibodies to antigens of an infectious agent by reacting serum with the blot and detecting labeled antibody to human immunoglobulin.

Front 499

Acute coronary syndrome

Back 499

Acute myocardial infarction, unstable angina, and sudden cardiac death. The acute coronary syndromes are frequently initiated by an unpredictable and abrupt conversion of a stable atherosclerotic plaque to an unstable and potentially life-threatening atherothrombotic lesion through superficial erosion, ulceration, fissuring, rupture, or deep hemorrhage, usually with superimposed thrombosis.

Front 500

Acute rheumatic carditis

Back 500

Occurs during the active phase of rheumatic fever and may progress to chronic rheumatic heart disease. An indication for ARC is the appearance of Aschoff bodies on histological examination.

Front 501

Angina pectoris

Back 501

a symptom complex of IHD characterized by paroxysmal and usually recurrent attacks of substernal or precordial chest discomfort (variously described as constricting, squeezing, choking, or knifelike) caused by transient (15 seconds to 15 minutes) myocardial ischemia that falls short of inducing the cellular necrosis that defines infarction

Front 502

Anitschkow cell

Back 502

Plump macrophages that are pathognomonic for Rheumatic fever. Abundant cytoplasm and central round-to-ovoid nuclei in which the chromatin is disposed in a central, slender, wavy ribbon (hence the designation "caterpillar cells").

Front 503

Aortic isthmus

Back 503

Structure that is related to coarctation of the aorta

Front 504

Arrhythmia

Back 504

Disorder of the heart’s regular rhythmic beating. Can occur in MI, mitral valve prolapse, and myocardial ischemia

Front 505

Aschoff body

Back 505

During acute RF, focal inflammatory lesions are found in various tissues, most commonly found in the heart

Front 506

Asymmetric septal hypertrophy

Back 506

Classic pattern is disproportionate thickening of the ventricular septum as compared with the free wall of the left ventricle (with a ratio greater than 1:3.

Front 507

Atrial fibrillation

Back 507

The most common abnormal rhythm of the heart; uncoordinated, chaotic contraction of the heart. Seen w/ left heart failure.

Front 508

Atrial septal defect (ASD)

Back 508

A defect in the wall b/t the right and left atria that results in the mixing of blood b/t the two; a left to right shunt that causes cyanosis w/in a few months to a few years after birth

Front 509

Beriberi heart disease

Back 509

A form of beriberi caused by a deficiency of thiamine characterized by cardiac failure and edema, but without extensive nervous system involvement. Caused by chronic alcoholism, thiamine deficiency, or malnutrition.

Front 510

Bicuspid aortic valve/unicuspid aortic valve

Back 510

When the aortic valve has only two or one leaflets, instead of the normal three. Predisposed to progressive degenerative calcification

Front 511

Calcific aortic stenosis

Back 511

Narrowing of the aorta due to calcification owing to progressive and advanced age-associated "wear and tear" of either previously anatomically normal aortic valves or congenitally bicuspid valves.

Front 512

Carcinoid heart disease

Back 512

Cardiac manifestation of the systemic syndrome caused by carcinoid tumors. Involves the endocardium and valves of the right heart. Cardiac lesions are present in one half of patients with the carcinoid syndrome which is characterized by episodic flushing of the skin, cramps, nausea, vomiting, and diarrhea.

Front 513

Cardiac amyloidosis

Back 513

Amyloid deposits in the heart that may occur along w/ systemic amyloidosis. Most frequently produces restrictive hemodynamics, but it can be asymptomatic or can be manifested by dilation, arrhythmias, or features mimicking those of ischemic or valvular disease owing to deposits in the interstitium, conduction system, vasculature, and valves, respectively

Front 514

Cardiac dilatation

Back 514

increase in the size of the cavities of the heart, which may be primary, with attenuation or thinning of its walls; or secondary, with thickening of its walls, hypertrophy, and dilatation.

Front 515

Cardiac rhabdomyoma

Back 515

hamartomas or malformations rather than true neoplasms; the most frequent primary tumor of the heart in infants and children

Front 516

Cardiac tamponade

Back 516

Compression of the heart caused by blood or fluid accumulation in the space between the myocardium (the muscle of the heart) and the pericardium (the outer covering sac of the heart). Often associated with pericarditis caused by bacterial or viral infections. Heart surgery, dissecting aortic aneurysm (thoracic), wounds to the heart, end-stage lung cancer, and acute MI can all lead to cardiac tamponade. Associated w/ anxiety, discomfort (sometimes relieved by sitting forward), difficulty breathing, rapid breathing, and chest pain

Front 517

Cardiogenic shock

Back 517

Results from myocardial pump failure. This may be caused by intrinsic myocardial damage (infarction), ventricular arrhythmias, extrinsic compression (cardiac tamponade), or outflow obstruction (e.g., pulmonary embolism).

Front 518

Cardiomyopathy

Back 518

Used to describe heart disease resulting from a primary abnormality in the myocardium.

Front 519

Chagas disease

Back 519

Caused by the protozoan, Trypanosoma cruzi, and is an important cause of myocarditis.

Front 520

Chordae tendinae

Back 520

Collagenous strands which extend from the apical margin of papillary muscles of the heart to various areas on the ventricular surface of the valve leaflets. Convey the contraction of the papillary muscles to the valve.

Front 521

Chronic ischemic heart disease

Back 521

Usually constitutes postinfarction cardiac decompensation owing to exhaustion of the compensatory hypertrophy of noninfarcted viable myocardium that is itself in jeopardy of ischemic injury.

Front 522

Chronic passive congestion of the liver

Back 522

Stasis of poorly oxygenated blood also causes chronic hypoxia, which can result in parenchymal cell degeneration or death, sometimes with microscopic scarring. Central regions of the hepatic lobules are grossly red-brown and slightly depressed (owing to a loss of cells) and are accentuated against the surrounding zones of uncongested tan liver (nutmeg liver).

Front 523

Chronic rheumatic heart disease

Back 523

Rheumatic cardiac valve destruction that is most commonly seen in the mitral valve (or mitral + aortic). Various cardiac murmurs, cardiac hypertrophy and dilation, and heart failure, arrhythmias (particularly atrial fibrillation in the setting of mitral stenosis), thromboembolic complications, and infective endocarditis are all associated w/ CRHD.

Front 524

Coarctation of the aorta

Back 524

A narrowing or constriction of the aorta that is a very common congenital abnormality. With a PDA (patent ductus arteriosus) leads to manifestations early in life. Survival beyond the neonatal period w/o intervention is rare. Without a PDA the patient may be asymptomatic until into adulthood

Front 525

Collateral circulation

Back 525

Process by which small (normally closed) arteries open up to connect two larger arteries, often b/c one has blockage, in order to maintain flow to the areas supplied by both large arteries. Important in the heart when one of the coronary arteries becomes blocked b/c it prevents (or at least delays) ischemic damage.

Front 526

Conduction system of the heart

Back 526

Impulse for contraction that originates at the SA node and is conducted through the myocardium to the atria and AV node and from there through His bundles to the ventricles.

Front 527

Compensated heart failure

Back 527

Physiological mechanisms maintain Cardiac output despite congestive heart failure; occurs through increased HR, ventricular contractility, or augmenting the preload. When the physiological mechanisms can no longer maintain CO, there is non-compensated heart failure.

Front 528

Congenital heart disease

Back 528

Caused by developmental abnormalities, most common cardiac abnormality in children. Examples are ASD, VSD, and a patent ductus arteriosus

Front 529

Congestion of the venous circulation

Back 529

A passive process resulting in impaired outflow from a tissue, may occur systemically, as in cardiac failure, or may be local, resulting from an isolated venous obstruction. Tissue has a cyanotic color.

Front 530

Congestive heart failure

Back 530

Heart is unable to pump blood at a rate commensurate with the requirements of the metabolizing tissues or can do so only at an elevated filling pressure. Usually occurs w/ slowly developing defects in myocardial contraction, but can also occur acutely when the heart is presented suddenly w/ a load that exceeds its capacity. The symptoms of pure left-sided heart failure are largely due to pulmonary congestion and edema. In contrast, in right-sided heart failure, respiratory symptoms may be absent or quite insignificant, and there is a systemic (and portal) venous congestive syndrome, with hepatic and splenic enlargement, peripheral edema, pleural effusion, and ascites. Right-sided heart failure often occurs secondarily to left-sided heart failure.

Front 531

Constrictive pericarditis

Back 531

Heart may be encased in a dense, fibrous or fibrocalcific scar that limits diastolic expansion and seriously restricts cardiac output, resembling restrictive cardiomyopathy.

Front 532

Contraction band necrosis

Back 532

An irreversible injury that occurs 12-24 hours after myocardial infarction; typically a reperfusion injury.

Front 533

Coronary vasospasm

Back 533

Typically occurs at the site of, or adjacent to, a fixed stenosis; can cause prinzmetal angina.

Front 534

Cor bovinum

Back 534

Massive cardiac hypertrophy (>1000 gm) that occurs with chronic left ventricular overload

Front 535

Coronary artery disease / Ischemic heart disease

Back 535

Generic designation for a group of closely related syndromes resulting from ischemia of the heart. Results in insufficiency of oxygen, reduced availability of nutrients and inadequate removal of metabolites. Caused by:
Reduced coronary blood flow; Increased myocardial demand; Angina pectoris; Myocordial infarction; Chronic ischemic heart disease; Sudden cardiac death

Front 536

Cor pulmonale/Pulmonary (right-sided) heart disease

Back 536

Right ventricle hypertrophy or dilation secondary to pulmonary hypertension caused by disorders affecting lung structure or function. EXCLUDES RV enlargement due to congenital heart disease or LV pathology. Acute cor pulmonale – RV dilation after massive pulmonary embolization. Chronic cor pulmonale – result of chronic RV pressure overload

Front 537

Coxsackieviruses A and B

Back 537

Viruses suspected as a cause of myocarditis

Front 538

Creatine kinase (CK)/CK-MB/CK-Index

Back 538

Creatine kinase - an enzyme that is highly concentrated in brain, myocardium, and skeletal muscle and is composed of two dimers, designated "M" and "B." The isoenzyme CK-MM is derived predominantly from skeletal muscle and heart; CK-BB from brain, lung, and many other tissues; and CK-MB principally from myocardium
CK-MB - leak out of fatally injured myocardial cells through damaged cell membranes; formerly the "gold standard," remains the best alternative to troponin measurement. Activity begins to rise within 2 to 4 hours of onset of MI, peaks at about 24 hours, and returns to normal within approximately 72 hours (persistence of elevated troponin levels for approximately 10 days). An absence of a change in the levels of CK and CK-MB during the first 2 days of chest pain and of troponin in the days following essentially excludes the diagnosis of MI. Other markers include myoglobin, cardiac troponins T and I (TnT, TnI), lactate dehydrogenase

Front 539

Cyanosis

Back 539

A bluish discoloration of the skin or mucous membranes caused by lack of oxygen in the blood. Caused by right-to-left shunts, appears late in left-to-right shunts (ASD, VSD, PDA)

Front 540

Dependent edema

Back 540

Edema influenced by gravity, eg., legs when standing, sacrum when recumbent. Typical of CHF

Front 541

Dextrocardia

Back 541

Heart is reversed and is in the right side of the chest rather than in its normal location on the left. Occurs in congenital Kartagener's syndrome

Front 542

Diaphoresis

Back 542

Excessive sweating commonly associated with MI, shock and other medical emergency conditions

Front 543

Diastole

Back 543

Part of the heart cycle during which the myocardium relaxes, expands and blood fills the heart chambers

Front 544

Dilated cardiomyopathy

Back 544

Gradual four-chamber hypertrophy and dilation. May occur at any age as slow, progressive CHF (only 25% survive past 5 years), with cause unkown
Genetic defect
Alcohol toxicity – direct effect on myocardium, indistinguishable from idiopathic
Peripartum cardiomyopathy – occurs before or after delivery
Not understood, but involves hypertension, volume overload
Postviral myocarditis
Morphology – cardiomegaly is present, but heart is flabby
Poor contractility and stasis  mural thrombi
Mild to moderate focal endocardial thickening sometimes in ventricles
Microscopically – nonspecific, diffuse myocyte hypertrophy and variable insterstitial myocardial fibrosis

Front 545

Arrythmogenic right ventricular cardiomyopathy

Back 545

Familial, right and sometimes left-sided heart failure with RV wall severely thinned, fatty infiltration, loss of myocytes, and interstitial fibrosis. Death from CHF, embolism, or arrhythmia unless transplanted

Front 546

Dressler syndrome

Back 546

Pericarditis developing about 28 weeks after acute MI or heart surgery

Front 547

Ductus arteriosus (Patent ductus arteriosus)

Back 547

In the fetus, the ductus arteriosus permits blood flow between the aorta (distal to the l. sublavian artery) and the PA
At term, high oxygen tension and decrease of local prostaglandin E synthesis lead to muscular contraction that closes the ductus within 1 to 2 days – persistent patency beyond this point is usually permanent. PDA occurs by itself 85-90% of time, with associated LV hypertrophy and PA dilation. Initially asymptomatic, except for “machinery-like” murmur. Long standing PDA induces pulmonary hypertension/RV hypertrophy/right-to-left shunt with late cyanosis. Early closure with surgery or prostaglandin inhibitors is advocated

Front 548

Dyspnea

Back 548

difficult or labored breathing

Front 549

Orthopnea

Back 549

inability to breathe easily unless one is sitting up straight or standing erect

Front 550

Exertional dyspnea

Back 550

excessive shortness of breath after exercise

Front 551

Paroxysmal nocturnal dyspnea (PND)

Back 551

awakened suddenly during the night feeling short of breath

Front 552

Ebstein anomaly/malformation

Back 552

Congenital downward displacement of the tricuspid valve with the septal and posterior leaflets being attached to the wall of the right ventricle. Subsequent atrialization of a portion of the morphologic right ventricle (which is then contiguous with the right atrium). Causes right atrium to be large and the anatomic right ventricle to be small. 50% of individuals with Ebstein's anomaly have an associated right-to-left atrium shunt, and either an ASD or patent foramen ovale. 50% of individuals with Ebstein's anomaly have evidence of Wolff-Parkinson-White syndrome, secondary to the atrialized right ventricular tissue.

Front 553

Endocardial cushion

Back 553

Discrete cushion-like swelling that forms in the developing heart and that gives rise to mature heart valves and to the membranous part of the ventricular septum. Area where defects in cell-cell and cell-ECM interactions might produce malformations, as evidenced by high frequency of endocardial cushion defects and atrioventricular septal defects in Down syndrome

Front 554

Endocardial fibroelastosis

Back 554

Focal-to-diffuse, cartilage-like fibroelastic thickening of the endocardium, LV>RV. Uncommon, may be endpoint of diverse disorders, most common <2 yo

Front 555

Endocarditis

Back 555

cardiac disorder marked by vegetations on the valves

Front 556

Infective endocarditis

Back 556

friable, infected vegetations and freqeuently valve injury

Front 557

Acute infective endocariditis

Back 557

Friable, infected vegetations and freqeuently valve injury
Acute infective endocariditis – necrotizing, ulcerative, and invasive infection that causes erosions or perforations of leaflets. Invades adjacent myocardium or aortic wall to produce abscess cavities. Caused by highly virulent organisms (Staphylococcus aureus). Fever, rigors, malaise, weakness. Larger vegetations cause embolism and splenomegaly, fast death in 50-60%

Front 558

Subacute infective endocarditis

Back 558

Smaller vegetations on abnormal or previously injured valve due to organism with moderate to low virulence. Insidious onset, malaise, low grade fever. Less frequent embolism.

Front 559

Nonbacterial thrombotic endocarditis

Back 559

Small, sterile, bland fibrin and platelet vegetations along lines of closure, without significan inflammation or valve damage. Related to systemic hypercoagulability. Typical in cancer or prolonged debilitating illness

Front 560

Erythema marginatum

Back 560

Macular skin lesions with erythematous rims and central clearing, typically in bathing suit distribution. One of Jones criteria for rheumatic fever

Front 561

Erythrosytosis / digital clubbing

Back 561

Increased red cell mass and accompanying increase in total blood volume. Leads to abnormal blood flow, vascular distention, and vascular stasis>> ruddy red appearance, cyanosis, hypertension and digital clubbing (a deformity of the fingers and fingernails)

Front 562

External rupture of infarct

Back 562

Rupture of the ventricular free wall (most commonly), with hemopericardium and cardiac tamponade, usually fatal. Result from the mechanical weakening that occurs in necrotic and subsequently inflamed myocardium. Most frequent time is 3 to 7 days after onset. Risk factors - age older than 60, female, pre-existing hypertension, and lack of LV hypertrophy

Front 563

Fibrinous pericarditis

Back 563

An acute pericarditis where surface is dry, with a fine granular roughening, most often of viral origin. Most common form, seen with MI, associated with loud pericardial friction rub. As with all pericarditis, occurs secondary to disorders involving heart or adjacent mediastinal structures (MI, surgery, trauma, radiation, tumors, infections). Most common finding in rheumatoid heart disease

Front 564

Fish-mouth deformity

Back 564

A bridging fibrosis across commissures (commissural fusion) of chronic (or healed) valves of rheumatic heart disease

Front 565

Foramen ovale

Back 565

Oval opening between the two atria that is a normal feature of the fetal and neonatal circulation. Normally closes on its own by 3 months of age.

Front 566

alpha-hemolytic (viridans) streptococci

Back 566

Moderate to low virulence organism that seeds an abnormal or previously injured valve to cause subacute infective endocarditis

Front 567

Giant cell myocarditis

Back 567

Myocarditis (inflammation of the myocardium) where there is focal myocyte necrosis associated with granulomatous inflammation, including multinucleated giant cells – has poor prognosis

Front 568

HACEK group

Back 568

Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella. Commensals in the oral cavity that cause infective endocarditits

Front 569

Heart failure (often called congestive heart failure (CHF))

Back 569

Pathophysiological state resulting from impaired cardiac function that renders the heart unable to maintain an output sufficient for the metabolic requirements of the tissues and organs of the body. Usually caused by a slowly developing intrinsic deficit in myocardial contraction. Similar clinical syndrome is present in some patients with heart failure caused by conditions in which the normal heart is suddenly presented with a load that exceeds its capacity (e.g., fluid overload, acute myocardial infarction, acute valvular dysfunction) or in which ventricular filling is impaired

Front 570

Heart failure cells

Back 570

Hemosiderin-laden macrophages seen in lungs typically involved in left ventricular failure. Usually seen with engorged capillaries and septal edema in acute congestion of lungs

Front 571

Hemopericardium

Back 571

Accumulation of pure, often clotted blood in the pericardium without an inflammatory component. Due to traumatic perforation myocardial rupture after a transmural MI, or hemorrhage from an abscess. Escaping blood fills pericardial sac quickly, and as little as 200-300 mil may cause tamponade

Front 572

High output failure

Back 572

Pumping action of the heart may be intact, other factors due to abnormal demands by the body's tissues may make it difficult for the heart to supply an adequate blood flow

Front 573

Hypertension

Back 573

Elevated blood pressure, defined clinically as diastolic BP of 90 mmHG and/or systolic pressure over 140 mmHG. Can lead to CHF, renal failure, and aortic dissection

Front 574

Hypertensive heart disease (left-sided HD)

Back 574

LV hypertrophy with history of hypertension and an absence of other lesions that may induce cardiac hypertrophy

Front 575

Hypertrophic cardiomyopathy (idiopathic hypertrophic subaortic stenosis, hypertrophic obstructive cardiomyopathy)

Back 575

Heavy, muscular, hypercontractile, poorly compliant heart with poor diastolic relaxation. 50% are autosomal dominant. Symptoms – young adults with dyspnea, angina, near-syncope, CHF

Front 576

Hypertrophy of the myocardium

Back 576

An increase in the number of organelles and size of cells in the myocardium due to mechanical forces (stretch) and trophic forces (growth factors and vasoactive agents). Leads to slowing of velocity of contraction
Eventually reaches a limit, at which time degenerative changes occur – ie, cardiac failure

Front 577

Acute infective endocariditis

Back 577

Necrotizing, ulcerative, and invasive infection that causes erosions or perforations of leaflets. Invades adjacent myocardium or aortic wall to produce abscess cavities. Caused by highly virulent organisms (Staphylococcus aureus). Fever, rigors, malaise, weakness. Larger vegetations cause embolism and splenomegaly, fast death in 50-60%

Front 578

Subacute infective endocarditis

Back 578

Smaller vegetations on abnormal or previously injured valve due to organism with moderate to low virulence. Insidious onset, malaise, low grade fever. Less frequent embolism

Front 579

Intraventricular septal rupture

Back 579

Rupture of the septum producing left-to-right shunt with right-sided heart volume overload. A possible complication of MI

Front 580

Left-to-right shunt

Back 580

ASD, VSD, and PDA increase pulmonary blood flow and are not initially associated with cyanosis (late cyanosis). ASD - increased pulmonary blood flow. VSD, PDA - increased pulmonary blood flow and pressure. Eventually pulmonary vascular resistance increases toward systemic levels, thereby reversing the shunt to right-to-left with unoxygenated blood in the systemic circulation

Front 581

Left ventricular hypertrophy/Concentric hypertrophy

Back 581

Myocytes increase in size due to increased pressure in the aorta. Can be caused by hypertension, tertiatry syphilis, aortic valve stenosis or insufficiency or primary hypertrophic cardiomyopathy. Can be linked to sudden cardiac death in young athletes. Concentric hypertrophy consists of symmetric, circumferential pattern

Front 582

Libman - Sacks endocarditis

Back 582

Sterile vegetations that may develop on the cardiac valves of patients with SLE

Front 583

Ligamentum arteriosum

Back 583

The patent ductus arteriosus (pulm a. to aorta) closes completely within the first few months of life and forms the ligamentum arteriosum

Front 584

Loeffler syndrome

Back 584

A fibrosis syndrome of restrictive cardiomyopathy in which the atria become dilated

Front 585

Lipoma

Back 585

Not true neoplasms; usually arise in the IV septum and cause lipomatous hypertrophy; Normally benign but can cause sudden cardiac death

Front 586

Machinery murmur

Back 586

The murmur heard from a patent ductus arteriosis
marantic endocarditis - This is a type of nonbacterial thrombotic endocarditis that is usually restricted to diseases associated with wasting and debility (cachexia)

Front 587

Marfan syndrome

Back 587

A disease of extracellular fibrillin synthesis that can predispose patients to aortic dissection

Front 588

mid-systolic click

Back 588

Heard on physical exam and is diagnostic for mitral valve prolapse

Front 589

Migratory polyarthritis

Back 589

The predominant clinical manifestation of rheumatic heart disease, in which a fever accompanies pain in the large joints

Front 590

Mitral valve prolapse

Back 590

An accumulation of loose ground substance within the mitral valve leaflets that causes the valve to become “floppy” and incompetent during systole, causing regurgitation. The valve leaflets balloon into the L atrium during systole. May be caused by Marfan syndrome

Front 591

Mural thrombus

Back 591

Develop on the endocardial surface overlying an infarct and can cause systemic emboli and are common in patients with a ventricular aneurysm

Front 592

Myocardial infarction

Back 592

Development of an area of myocardial necrosis caused by local ischemia, usually because of coronary artery thrombosis secondary to atherosclerotic plaque formation in the coronary arteries

Front 593

Mycotic aneurysm

Back 593

An abdominal aortic aneurysm that has become infected by bacteria (usually Salmonella), causing rapid dilation and rupture of the AAA

Front 594

Myocarditis

Back 594

A disease that occurs because of inflammatory processes causing damage to the myocardium, usually as a result of viral, bacterial infection, rheumatic fever, SLE, transplant rejection or sarcoidosis. Can be caused by Trypanosoma cruzi parasite (Chagas Disease). Giant cell myocarditis has large multinucleated cells

Front 595

Myocytolysis

Back 595

Dissolution of muscle fiber
A sublethal ischemic change seen in the margins of infarcts. Leads to vacuolar degeneration involving large vacuolar spaces within cells that contain water

Front 596

Myxoma

Back 596

The most common primary tumor of the heart

Front 597

nonbacterial thrombotic endocarditis (NBTE)/marantic endocarditis

Back 597

Sterile, small depositions of fibrin, platelets, and other blood components on the leaflets of the cardiac valves. Usually found on previously normal valves. Malignancy and hypercoagulability are also common in patients with NBTE

Front 598

Ostium primum

Back 598

A gap that normally separates the developing septum primum from the endocardial cushions

Front 599

Ostium secundum

Back 599

The gap that forms during fetal heart development after the ostium primum has been obliterated. Allows continued flow of oxygenated blood from the RA to the LA. Essential for fetal life

Front 600

Pancarditis

Back 600

A symptom of acute rheumatic heart disease, affecting all three layers of the heart (pericardium, myocardium, endocardium). Demonstrates diffuse inflammation and Aschoff bodies

Front 601

papillary muscle

Back 601

dysfunction of these muscles occurs in MI because of ischemia that causes the muscle to rupture, leading to detachment of the chordae tendinae and severe mitral insufficiency

Front 602

Patent ductus arteriosus

Back 602

An open arterial channel between the pulmonary artery and the aorta. During fetal life, the DA permits blood to flow freely from the PA to the aorta, bypassing the unoxygenated lungs. The obliterated DA is called the ligamentum arteriosum.

Front 603

Pericardial effusion/ serous/serosanguineous/chylous

Back 603

Accumulation of fluid in the pericardial space following right heart failure

Front 604

Pericarditis

Back 604

Inflammation of the pericardium, usually due to cardiac disease, thoracic disorders, metastases, viral or bacterial infections, or fungal infections

Front 605

Peripartum cardiomyopathy

Back 605

Cardiomyopathy associated with pregnancy and caused by htn, volume overload, nutritional deficiency, or immunologic reaction

Front 606

Pleural effusion

Back 606

Associated with right heart failure and can cause partial atelectasis of the right lung

Front 607

Prinzmetal angina

Back 607

Angina that occurs at rest and is unrelated to physical activity, heart rate or blood pressure

Front 608

Pulmonary edema

Back 608

Hemodynamic disturbances or changes in microvascular permeability cause pulmonary edema. In addition to impairing normal respiratory function, chronic edema predisposes to infection

Front 609

reperfusion injury

Back 609

Ischemia causes progressive compromise of multiple biochemical pathways and structural component integrity. Up to a certain point, such injury may be compensated for, and the affected cells can recover if blood flow (and especially oxygen) is restored (reversible injury). Beyond a point of no return, the cells’ energy-generating machinery becomes irreparably damaged (irreversible injury). In that setting restoration of blood flow can actually exacerbate injury, so called reperfusion injury; this is clinically important in contributing to the tissue damage following myocardial infarction and stroke.

Front 610

Restrictive cardiomyopathy

Back 610

Relatively rare and with multiple etiologies, this entity is marked by a restriction of ventricular filling leading to reduced cardiac output. Interstitial myocardial fibrosis is usually present. Specific entities include Endomyocardial fibrosis, Loeffler endocarditis, and Endocardial fibroelastosis

Front 611

rhabdomyoma

Back 611

less common than myxomas, but are the most common primary heart tumor in children. Rhabdomyomas may cause valvular or outflow tract obstruction; they are probably hamartomas and may be associated with tuberous sclerosis.

Front 612

Rheumatic fever

Back 612

an acute inflammatory disease classically occurring in children (5-15 y/o) within 5 weeks following group A streptococcal infection (usually pharyngitis). It is attributed to host antistreptococcal antibodies that cross-react with cardiac antigens. Diagnosis is based on clinical history, and, two of five major (Jones) criteria (minor criteria include fever, arthralgia, and leukocytosis):
Erythema marginatum
Sydenham chorea
Carditis
Subcutaneous nodules
Migratory large joint polyarthritis

Front 613

rheumatoid heart disease

Back 613

Involves the heart in 20-40% of severe chronic cases. The typical finding is pericarditis, with a mixture of fibrin and necrotic debris derived from pericardial rheumatoid granulomas that can progress to form dense, fibrous, and potentially restrictive adhesions. Less frequently, granulomatous rheumatoid nodules occur in the myocardium, endocardium, aortic root, or valves, where they are particularly damaging. Rheumatoid valvulities can produce changes similar to those seen in rheumatic heart disease but classically without commissural fusion

Front 614

Right-to-left shunt (cyanotic congenital heart disease)

Back 614

Cause cyanosis from the outset by allowing poorly oxygenated blood to flow directly into the systemic circulation (they also permit paradoxical embolism). Secondary findings in long-standing cyanotic heart disease include: Fingers and toe clubbing, Hypertrophic osteoarthropathy, and Polycythemia. The Major congenital right-to-left shunts are: Tetralogy of Fallot, Transposition of the great arteries (TGA), and Truncus Arteriosus

Front 615

Ring abscess

Back 615

Caused by vegetations that erode into the underlying myocardium

Front 616

Secondary hyperaldosteronism

Back 616

Syndrome characterized by chronic excess of aldosterone, arising from a non-adrenal source

Front 617

Streptococcal epidermidis

Back 617

Staphylococci infection of patients with prosthetic heart valves, or intravenous drug abusers.

Front 618

Septum primum

Back 618

A crescentic septum in the embryonic heart that develops on the dorsocephalic wall of the originally single atrium and initiates its partitioning into right and left chambers; the tips of the septum grow toward and fuse with the atrioventricular canal cushions.

Front 619

Septum secundum

Back 619

the second of two major septal structures involved in the partitioning of the atrium, developing later that the s. primum and located to the right of it; like the s. primum, it is crescentic, but its tips are directed toward the sinus venosus, and it is more heavily muscular; it remains an incomplete partition until after birth, with its unclosed area constituting the foramen ovale.

Front 620

Sinus of Valsalva

Back 620

This is where the aortic cusps protrude in calcific aortic stenosis

Front 621

Staphylococcus aureus

Back 621

Causes skin infections, osteomyelitis, pneumonia, endocarditis, food poisoning, and toxic shock syndrome

Front 622

stenosis

Back 622

a stricture of any canal or orifice

Front 623

Streptolysin O/DNAse B/Streptozyme test

Back 623

Strep proteins that are indicative of rheumatic heart disease-causing bacteria

Front 624

Subendocardial infarction

Back 624

Typically limited to the inner one third of the ventricular wall; it is caused by increased cardiac demand in the setting of limiting supply due to fixed atherosclerotic disease; alternatively, subendothelial infarction can occur in an evolving transmural infarct when the coronary obstruction is relieved in sufficient time to prevent transmural necrosis.

Front 625

Sudden cardiac death

Back 625

unexpected cardiac death within 1 hour of symptom onset

Front 626

Syncope

Back 626

loss of consciousness and postural tone caused by diminished cerebral blood flow.

Front 627

systole

Back 627

contraction of the heart, especially of the ventricles, by which the blood is driven through the aorta and pulmonary artery to traverse the systemic and pulmonary circulations, respectively; its occurrence is indicated physically by the first sound of the heart heard on auscultation, by the palpable apex beat, and by the arterial pulse.

Front 628

Tachycardia

Back 628

rapid beating of the heart, conventionally applied to rates over 90 bpm, but some sources indicate >100 bpm

Front 629

Tardive cyanosis

Back 629

late cyanosis (tardive – late; tardy)

Front 630

tetralogy of Fallot

Back 630

has four clinical features:
VSD
obstruction to the right ventricular outflow tract (subpulmonary stenosis)
an aorta that overrides the VSD
right ventricular hypertrophy

Front 631

Transposition of the great arteries

Back 631

systemic and pulmonary venous return – to the right and left atria, respectively – are normal; however, the aorta arises from the right ventricle and the pulmonary artery from the left, so that the pulmonary and systemic circulations are functionally separated. TGA is particularly common in children of diabetic mothers

Front 632

truncus arteriosus

Back 632

Associated with numerous concomitant cardiac defects, truncus arteriosus is basically a failure of the aorta and pulmonary artery to separate. It results in an infundibular VSD with a single vessel receiving blood from both right and left ventricles. Right-to-left shunting causes early cyanosis. Eventually the flow reverses, and patients develop right ventricle hypertrophy and pulmonary hypertension. The anomaly carries a poor prognosis.

Front 633

Transmural infarction

Back 633

An MI involving the full thickness of the ventricular wall; it is usually caused by severe coronary atherosclerosis, with acute plaque rupture and superimposed occlusive thrombosis.

Front 634

Troponin

Back 634

A globular protein of muscle that binds to tropomyosin and has considerable affinity for calcium ions; a central regulatory protein of muscle contraction

Front 635

unstable angina

Back 635

Unstable or crescendo angina refers to a pattern of pain that occurs with progressively increasing frequency, is precipitated with progressively less effort, often occurs at rest, and tends to be of more prolonged duration. In most patients, unstable angina is induced by disruption of an atherosclerotic plaque with superimposed partial (mural) thrombosis and possibly embolization or vasospasm (or both).

Front 636

valvular insufficiency

Back 636

Valvular heart disease in adults is typically caused by degeneration (e.g., calcific aortic stenosis, mitral annular calcification, mitral valve prolapse), immunologic inflammatory processes (e.g., rheumatic heart disease), or infection (e.g., infective endocarditis).

Front 637

valvular regurgitatioin

Back 637

can occur from inadequate systolic contraction of the mitral valve ring.

Front 638

Valvular stenosis

Back 638

can occur because leaflets are unable to open over bulky deposits.

Front 639

Vegetation

Back 639

large, thrombotic masses

Front 640

Ventricular aneurysm

Back 640

thinning, stretching, and bulging of a weakened ventricular wall, usually as a result of myocardial infarction; rarely postinflammatory or congenital

Front 641

Ventricular septal defect (VSD)

Back 641

abnormal openings in the ventricular septum allowing shunting of blood, VSDs are the most common congenital cardiac anomaly overall. VSDs are frequently associated with other anomalies, particularly tetrology of fallot, but 30% are isolated: 90% involve the membranous septum (membranous VSD) near the aortic valve, while the remainder are muscular.
With small to moderate-sized VSDs, patients are at increased risk of infective endocarditis.

Front 642

Wavy fiber change

Back 642

Histological change of infracted heart tissue that is the result of forceful systolic tugs by the viable fibers immediately adjacent to the noncontractile dead fibers. Usually seen in the first 4 – 12 hours after the infarction.

Front 643

Abdominal aortic aneurysm (AAA)

Back 643

Localized abnormal dilation of the abdominal aorta, the most common aneurysm caused by atherosclerosis. Usually below the renal arteries and above the bifurcation of the aorta; or in common iliac artieries. Atherosclerotic aortic vascular disease usually accompanied by severe CA atherosclerosis – high incidence of ischemic heart disease

Inflammatory AAA
Caused by inflammatory process that weakens wall of aorta
Involves dense periaortic fibrosis containing abundant inflammatory cell infiltrate
Mycotic AAA
Caused by infection that weakens wall of aorta
Infective endocarditis releases septic emboli, adjacent suppurative processes spread or circulating organism directly infect arterial wall

Front 644

Allergic granulomatis angiitis (Churg-Strauss Syndrome)

Back 644

Variant of microscopic polyangiitis, a systemic vasculitis disease with necrotizing inflammation throughout the walls of smaller vessels (arterioles, capillaries, and venules)
Characterized by eosinophilia and bronchial asthma, with pulmonary and splenic vessel involvement and intravascular and extravascular granulomas
P-ANCA (perinuclear antineutrophilic cytoplasmic autoantibodies) may be present (50%)

Front 645

Angiitis

Back 645

Another term for vasculitis, an inflammation of the blood vessels

Front 646

Antineutrophili cytoplasmic antibody (ANCA)/p-ANCA, c-ANCA

Back 646

In many patients with vasculitis, serum ANCA reacts with cytoplasmic antigens in neutrophils
Precise mechanism by which ANCA induces vascular injury is not known
P-ANCA (perinuclear)
Major antigen is myeloperoxidase
Found in most cases of microscopic polyangiitis and Churg-Strauss syndrome
C-ANCA (cytoplasmic)
Major leukocyte antigen is proteinase 3
Characteristic of Wegener granulomatosis

Front 647

Aneursym

Back 647

Localized abnormal dilations of vessels
Morbidity and mortality secondary to:
Rupture
Impingement on adjacent structures
Occlusion of proximate vessels
Embolism from mural thrombosis
Causes include atherosclerosis and cystic medial degeneration (Marfan syndrome), syphilis, trauma, PAN, congenital defects, and infections (mycotic)
True aneurysm – bounded bv generally complete but often attenuated arterial wall components
False anerysm – extravascular hematoma that communicates with intravascular space (part of wall gone)

Front 648

Aortic dissection (dissecting hematoma)

Back 648

Dissection of blood along the laminar planes of the aortic media, with formation of an intramural blood-filled channel
Often ruptures, causing massive hemorrhage and sudden death
NOT usually associated preexisting marked dilation of the aorta
Usually affects hypertensive men (age 40-60) or younger individuals with connective tissue abnormalities (Marfan Syndrome)
Can be a complication of therapeutic or diagnostic arterial cannulation or other trauma
Symptoms include sudden onset of excruciating chest pain, starting anterior, moving back, then down
Proximal lesion – Type I/A - involves ascending and descending aorta
Type II/A – involves ascending aorta ending before the aortic arch vessels
Distal lesion – Type III/B – does NOT involve ascending aorta and begins distal to subclavian artery

Front 649

Arterioles

Back 649

Smallest vessels, found within tissues, characterized by media on 1-2 smooth muscle cells thick. Regulate blood flow to capillary beds acting as principle points of physiological resistance to blood flow

Front 650

Arteriosclerosis

Back 650

Generic term for thickening and loss of elasticity of the arterial wall. Three main patterns: atherosclerosis, Monckenberg medial calficic sclerosis, and arteriolosclerosis

Front 651

ArterioLOsclerosis (pattern of arteriosclerosis)

Back 651

Diffuse arteriolar (small arteries/arterioles) wall thickening, luminal narrowing, and resultant ischemia of distal tissue
Hyaline arteriolosclerosis
Typical in elderly with mild hypertension and mild diabetes
Reflects endothelial injury, leakage of plasma components into arteriolar walls, synthesis of ECM by smooth muscle cells
Microscopically – diffuse, pink, hyaline thickening of arteriolar walls
Major microscopic feature of benign nephrosclerosis
Hyperplastic arteriosclerosis
Characteristic of malignant hypertension
Microscopically – laminated (onionskin) arteriolar thickening, reduplicated basement membrane, smooth muscle proliferation, fibrin deposit, and necrotizing arteriolitis

Front 652

Arteriovenous fistula/Arteriovenous malformation

Back 652

Small, abnormal communication between arteries and veins
Arise from developmental defects, vascular injuries, or can be made intentionally (chronic hemodialysis)
May cause left-to-right vascular shunts, increasing venous return and predisposing to heart failure

Front 653

Arteritis

Back 653

Inflammation of the arteries
Most common forms include giant cell (temporal) arteritis and Takayasu arteritis

Front 654

Ascites

Back 654

an abnormal accumulation of fluid in the abdomen

Front 655

Chylothorax

Back 655

an accumulation of chyle (lymphatic fluid) in the pleural cavity

Front 656

Chylopericardium

Back 656

an accumulation of chyle (lymphatic fluid) in the pericardial sac

Front 657

Atheroma (atheromatous plaques)

Back 657

Intimal fibrofatty plaques which protrude into and obstruct vascular lumens and weaken underlying media
Histologically
Fibrous cap - smooth muscle cells, leukocytes, and dense connective tissue ECM
Necrotic core - dead cells, lipid, cholesterol clefts, lipid-laden foam cells, plasma proteins
Two common variants – Fatty streak and Complicated plaques

Front 658

Atherosclerosis

Back 658

Slowly progressive disease of arteries, marked by elevated fibrofatty intimal plaques (atheromas)
Large to medium sized muscular and elastic arteries involved
Abdominal aorta, coronary arteries, popliteal arteries, descending thoracic aorta, internal carotid arteries, and circle of Willis.
50% of all deaths in the US attributed to atherosclerosis, half from myocardial infarct or ischemic HD
Major risk factors – hypertension, cigarette smoking, hypercholesterolemia, and diabetes
Cause unknown, but suspect damage to the endothelium or underlying media from risk factors/infection
Consequences of damage are: increased endothelial permeability, adhesion of white cells and platelets, and coagulation activation, followed by release of mediators that cause migration and proliferation of smooth muscle cells in the intima to produce the atheroma
Starts as fatty streak>>fibrofatty plaque>> advanced/vulnerable plaque>> aneurysm/occlusion/stenosis
Asymoptomatic for decades, then:
Narrowing of vascular lumens
Plaque rupture (superimposed thrombus or atheroembolism)
Weakening of wall of a vessel (aneurysm)

Front 659

Benign nephrosclerosis

Back 659

Changes due to narrowing of lumens of renal arterioles and small arteries associated with hyaline arteriolosclerosis
Cause diffuse ischemic atrophy of nephrons>> small kidneys and diffuse granular surfaces
More severe with hypertension, diabetes mellitus
Rarely causes renal failure, but mild proteinuria may occur

Front 660

Capillaries

Back 660

Smallest vessels with an endothelial lining only one cell thick and no media
Provide the largest total cross sectional area in the vasculature and are sites of nutrient exchange in tissues

Front 661

Chylous

Back 661

Effusion from lymphatics (chyle), usually occurs secondary to rupture of obstructed, dilated lymphatics

Front 662

Claudication

Back 662

Symptom caused by lack of blood flow (thus, a poor supply of oxygen ) to the muscles caused by narrowing of the arteries
Usually occurs in the calf or in an arm, and is an aching pain that resolves with rest
Instep Claudation – symptom of Buerger disease, characterized by pain in instep of foot with exercise

Front 663

Complicated plaques

Back 663

Calcified, hemorrhagic, fissured, or ulcerated atheromas, predisposing to local thrombosis, medial thinning, cholesterol microemboli, and aneruysmal dilation

Front 664

Cystic medial degeneration

Back 664

An aortic dissection due to focal separation of the elastic and fibromuscular elements by small, cleftlike or cystic spaces filled with material resembling amorphous ECM of connective tissue without inflammation
Frequently accompanies Marfan Syndrome (a connective tissue disorder)
due to genetic decrease or loss of microfibrillary protein of elastic tissue

Front 665

Deep vein thrombosis

Back 665

A thrombosis in larger leg veins typically above the knee that readily embolize

Front 666

High Density Lipoprotein

Back 666

Help clear cholesterol from vessel wall lesions, resulting in decreased risk of atherosclerosis

Front 667

Elastic arteries

Back 667

Elastic – Large vessels (aorta, its larger branches, and iliac) which receive blood from the heart have thick, strong walls to cope with the sudden high pressure produced during diastole – TYPICALLY WHERE ATHEROSCLEROSIS OCCURS
Contain abundant elastin in the thick media to allow stretch so that the vessel lumen may accommodate the change of volume
Have thick, outer coat of collagenous connective tissue whose tensile strength prevents over-distension of the elastic tissue
Elastic recoil of these elastic arteries is responsible for maintaining a continuous, though decreased, flow of blood to smaller vessels during systole

Front 668

Muscular arteries

Back 668

Medium vessels (coronary, renal) whose elastic components gradually diminish with most of the muscle arranged circularly in the middle layer of the vessel wall (the thick tunica media) and contribute to the regulation of the amount of blood flowing into a region – TYPICALLY WHERE ATHEROSCLEROSIS OCCURS

Front 669

Endothelium

Back 669

Endothelial cells (EC) form a semipermeable, monolayer that lines the entire vascular sytem
Acts to control transfer of molecules into the vascular wall
Plays a role in blood clotting and contains Weibel-Palade bodies – storage organells for von Willebrand f.

Front 670

Essential hypertension

Back 670

Accounts for 95 % of hypertension and is due to idiopathic (unknown) causes
Controllable and generally asymptomatic unless a complication intervenes

Front 671

False anerysm

Back 671

Extravascular hematoma that communicates with intravascular space (part of wall gone)

Front 672

Fatty streak

Back 672

Intimal collections of lipid-laden macrophages and smooth muscle cells
Occurs in patients as young as 1 yo
Suspected casual relationship of fatty streaks to subsequent atheromatous plaques

Front 673

Fibrofatty plaque

Back 673

Formed by lipid deposition, smooth muscle cell proliferation, and synthesis of ECM in the intima of arteries
Marks atherosclerosis

Front 674

Fibromuscular displasia

Back 674

Heterogenous group of lesions characterized by fibrous or fibromuscular thickening and may involve the intima, media, or adventitia of the artery (media being most common)
Leads to stenosis of the artery (typically renal)

Front 675

Fibrous cap

Back 675

Smooth muscle cells, leukocytes, and dense connective tissue ECM that makes up outer portion of Atheroma (atheromatous plaques)

Front 676

Fusiform aneurysm

Back 676

An aneurysm involving a long segment
Vary in diameter (up to 20 cm) and in length
May involve entire ascending and transverse portions of the aortic arch/abdominal aorta/iliacs

Front 677

Gangrene

Back 677

Death and decay of tissue in a part of the body--usually a limb-- due to injury, disease, or failure of blood supply
May be caused by certain bacteria which spread rapidly through tissues

Front 678

Giant cell (temporal) arteritis

Back 678

Most common form of arteritis, characterized by focal granulomatous inflammation of medium and small arteries, chiefly cranial vesses (most commonly temporal in elderly) and may rarely involve the aortic arch (giant cell)
Cause is unknown, responds well to steroids
Symptoms include headache, facial pain, systemic symptoms (including polymyalgia rheumatica)
Morphologically, there may be one of three general appearance
Granulomatous vasculitis with fragmented internal elastic lamina and a giant cell reaction (2/3)
Nonspecific leukocytic infiltration by neutrophils, eosinophils, lymphocytes of vessel wall
Intimal fibrosis with thickening of the walls and narrowing of the lumens

Front 679

Glomus tumor (glomangioma)

Back 679

Benign, extremely painful tumor of modified smooth muscle cells arising from the glomus body – a temperature sensitive neuromyoarterial receptor that regulates arteriolar flow
Most commonly found in distal phalanges, especially beneath nail beds
Grossly – less than 1 cm, may be pinpoint
Histologically – branching vascular channels separated by a stroma of aggregates, nests, masses of specialized glomus cells (look like smooth muscle on EM)

Front 680

Hemangioma

Back 680

Common benign lesion, usually superficial, often of the head or neck, most are present at birth and expand with child

Front 681

Capillary hemangioma

Back 681

Skin or mucous membranes (occasional viscera) tumor from 1-2 mm to several cm in diameter
Well-defined, unencapsulated lesions of aggregates of capillary sized, thin-walled vessels

Front 682

Juvenile capillary (strawberry) hemangioma

Back 682

Present at birth, grow rapidly for a few months, begin regressing at 1-3 yo (80% gone be age 7)

Front 683

Cavernous hemangioma

Back 683

Distiniguished by formation of large, cavernous vascular channels, unencapsulated but discrete lesions 1-2 cm in diameter
Common in liver, may involve CNS or other viscera

Front 684

Pyongenic granulomas (lobular capillary hemangiomas)

Back 684

Ulcerated polypoid variant of capillary hemangiomas on skin or oral mucosa, 2ndary to trauma
Consist of proliferating capillaries with significant interspersed edema and inflammatory infiltrates (resembles exuberant granulation tissue)

Front 685

Hemorrhoid

Back 685

Variceal dilation of anal and perianal submucosal venous plexuses, affecting 5% of adult population
Associated with constipation, venous stasis of pregnancy, and cirrhosis (portal hypertension)

Front 686

Homan sign

Back 686

Indicator of deep venous thrombosis - present where pain in the calf is produced by passive dorsiflexion of the foot
Has fallen into disfavour because of the risk of precipitating a pulmonary embolism

Front 687

Hyperhomocysteinemia

Back 687

Elevated levels of homocysteine contribute to arterial and venous thrombosis and atherosclerosis
Can be caused by low folate and vitamin B uptake/inherited/acquired
Effect is most likely due to inhibition of antithrombin III and endothelial thrombomodulin

Front 688

Malignant Hypertension

Back 688

Characterized by rapidly increasing BP (>200 mmHG) leading to death within 2 years if not treated
Small arteries become thickened and occluded, causing distal tissue ischemia, renal failure, retinal hemorrhages, and sometimes papilledema

Front 689

Inferior vena cava syndrome

Back 689

Caused by neoplasms (hepatocellular and renal cell carcinomas) that compress or invade the IVC, or by thrombi from femoral or iliac veins
Causes edema in the legs, distention of superficial veins of lower abdomen
If renal veins involved, massive proteinuria occurs

Front 690

Internal elastic lamina

Back 690

Dense elastic membrane separating the tunica intima and media

Front 691

External elastic lamina

Back 691

Outer limit of the tunica media, separating it from adventitia

Front 692

Intima

Back 692

Innermost concentric layer of vessel walls composed of a single layer of endothelial cells
Thickens (smooth muscle cells migrate into it and multiply) in response to vascular injury

Front 693

Media

Back 693

Middle layer of vessel walls composed of smooth muscle cells
Supplied with oxygen and nutrients by diffusion from lumen and by vaso vasorum

Front 694

Adventitia

Back 694

Outer layer of vessels, consisting of connective tissue and vaso vasorum

Front 695

Kawasaki disease (mucocutaneous lymph node disease)

Back 695

Acute illness of infants and children characterized by fever, lymphadenophathy, skin rash, oral/conjuctival erthema
20% of cases involve coronary arteritis (often with aneurysms)
Endemic in Japan, cause unknown
Has immunoregulatory disturbances (T-cell activation, autoantibodies to endothelium, immune complexes)
Morphologically – resembles PAN (necrotizing inflammation throughout wall of small/medium arterial beds)

Front 696

Leukocytoclastic vasculitis

Back 696

Fragmented neutrophilic nuclei occurring perivascularly
Occurs with microscopic polyangiitis, a systemic vasculitis disease with necrotizing inflammation throughout the walls of smaller vessels (arterioles, capillaries, and venules)

Front 697

Lymphangioma

Back 697

Benign tumor of lymph nodes
Typically in head, neck, and axillary subcutaneous tissue
Grossly – 1-2 cm cutaneous or pedunculated lesions or well-demarcated, compressible gray pink masses
Microscopically – made up of network of endothelium-lined spaces, WITHOUT blood cells

Front 698

Lymphangitis

Back 698

Infection involving lymphatics draining a locus of inflammation, frequently from B-hemolytic streptococci
Presents as a cluster of painful subcutaneous red streaks along lymph channels, with lymphadenopathy

Front 699

Lymphatics

Back 699

Thin-walled, endothelium-lined channels that drain interstitial fluid and lymphocytes from tissue, returning it to blood

Front 700

Lymphedema

Back 700

Lymphatic obstruction with lymphatic dilation and abnormal accumulation of interstitial fluid in affected drainage site
When prolonged, causes interstitial fibrosis; in skin/subcutaneous gives peau d’orange appearance
Most causes of obstruction are malignancy, surgical resection, post-radiation fibrosis, filiariasis

Front 701

Kaposi sarcoma

Back 701

A hemangioendothelioma (intermediate grade neoplasm) that lies in the interface between benign and malignant
Microscopically - Plump, spindle-shaped cells creating slitlike vascular spaces filled with red blood cells, with scattered microhemorrhages and hemosiderin deposits
Four forms are recognized:
Chronic/classic/European
Multiple red-to-purple cutaneous plaques/nodules on lower extremities
Erratic course of relapses and remissions, rarely causes death, common in elderly
Lymphadenopathic/African
Like Classic, but restricted to lymph nodes
Is aggressive, occurs in younger men, 10% of all tumors in equatorial Africa
Transplant Associated
During immunosuppressive therapy, both cutaneous and visceral systemic involvement
AIDS-Associated (epidemic)
Anywhere in skin and mucous membranes, lymph nodes, GI, viscera
More common in homosexuals than other risk groups, responds to cytotoxic chemotherapy

Front 702

Marfan Syndrome

Back 702

Disorder of connective tissues affecting skeletal, ocular, CV systems

Front 703

Microscopic polyangitis

Back 703

Systemic necrotizing inflammation of smaller vessels (arterioles, capillaries, and venules)
Lesions all typically synchronized to same stage, suggesting acute inciting agent forming immune complexes (disease goes away with removal of offending agent)
May be confined to skin or may involve lung, brain, heart, and kidneys
Fibroid necrosis may occur, with fragmented neutrophilic nuclei in vessel walls and perivascularly

Front 704

Migratory thrombophlebitis (Trousseau syndrome)

Back 704

Multiple venous thrombi appearing in one place then disappearing to crop up elsewhere
Attributed to hypercoagulability associated with cancer or nonbacterial thrombotic endocarditis

Front 705

Monckenberg medial calcific sclerosis

Back 705

Arteriosclerosis characterized by calcific deposits in the media of small/medium muscular arteries that do NOT encroach on lumen without inflammation
Affects people over 50, in femoral, tibial, radial, and ulnar arteries, seen on x-ray and palpable
Unrelated to atherosclerosis

Front 706

Mycotic Aneurysm

Back 706

Localized abnormal dilations of vessels due to infection

Front 707

Neovascularization

Back 707

Proliferation of new blood vessels, occurs around the periphery of atherosclerotic lesions and plaques

Front 708

Obliterative endarteritis

Back 708

Syphilis causes endarteritis of the vaso vasorum leading to syphilitic aneurysm formation (chiefly of ascending aorta)

Front 709

Osler-Weber-Rendu (Hereditary hemorrhagic telangiectasa)

Back 709

Rare, Mendelian dominant disorder characterized by multiple small (<5 mm) aneurismal lesions or telangiectasia dilated capillaries and veins of skin and mucous membranes
Typically presents with epstaxis, hemoptysis, or GI/GU bleeding, more serious with age

Front 710

Phlebosclerosis

Back 710

Elastic tissue degeneration and spotty calcifications within the media of veins with varicosities

Front 711

Phlebothrombosis

Back 711

Thrombosis within a vein that typically incites thrombophlebitis

Front 712

Phlegmasia alba dolens (“painful white legs”)

Back 712

Variant of primary phlebothrombosis where an iliofemoral venous thrombosis occurs in pregnant women prior to or after delivery

Front 713

Polyarteritis nodosa (PAN)

Back 713

Systemic disease characterized by necrotizing inflammation throughout wall of various small/medium arterial beds
Lesions are sharply demarcated, often inducing thrombosis
Typically affecting renal and visceral muscular arteries (NOT arterioles, capillaries, veins)
Microscopically
Acute lesions – segmental, with fibrinoid necrosis of arterial wall, and pan-vascular neutrophilic inifiltrate that may go into adventitia
Healing lesions – show fibroblast proliferation on top of fibrinoid necrosis
Healed lesions – only marked fibrotic thickening of the arterial wall, elastic lamina fragmentation
Clinically
Young adults, nonspecific clinical signs/symptoms related to whatever tissue is involved
Fever, malaise, weight loss, may be associated with Hepatitis B antigen

Front 714

Portal hypertension

Back 714

Increased resistance to portal blood flow
May be due to obstructive thrombosis/narrowing of the portal vein, massive splenomegaly, right-sided heart failure, constrictive pericarditis, hepatic vein outflow obstruction, or cirrhosis
Major consequence include: ascites, formation of portosystemic venous shunts, congestive splenomegaly, hepatic encephalopathy

Front 715

Pseudoaneurysm

Back 715

extravascular hematoma that communicates with intravascular space (part of wall gone)

Front 716

Raynaud DISEASE

Back 716

paroxysmal pallor or cyanosis of digits of hands or feet and infrequently the tips of nose/ears
Caused by intense vasospasm of local small arteries or arterioles (an exaggeration of normal central and local vasomotor response to cold or emotion, principally of young people)

Front 717

Raynaud PHENOMENON

Back 717

arterial insufficiency of the extremities secondary to arterial narrowing induced by various condition, including atherosclerosis, SLE, scleroderma, and Buerger disease

Front 718

Saccular aneurysm

Back 718

Spherical aneurysm involving only a portion of the vessel wall
Vary in size (5-20 cm) and often partially or completely filled by thrombus

Front 719

Stasis ulcers

Back 719

Ulcer that develops in an area in which the circulation is sluggish and the venous return is poor
common location is on the ankle

Front 720

Superior vena cava syndrome

Back 720

Caused by neoplasms that compress or invade the SVC, most commonly a primary bronchogenic carcinoma or mediastinal lymphoma
Manifests as dusky cyanosis and marked dilation of the veins of head, neck, arms

Front 721

Syphillitic aneurysm

Back 721

Aneurysm caused by tertiary-stage syphilis
Inflammation begins with vaso vasorum of aorta causing narrowing of lumina leading to ischemic injury of aortic media>> aorta loses elastic recoil and begins to dilate (sphyilitic aneurysm)

Front 722

Takayasu arteritis

Back 722

Granulomatous vasculitis of medium to large arteries, with fibrous thickening of the aortic arch with obliteration of the mouths of the great vessels
Cause is unknown, most common in Asia in women 15-45
Results in ocular disturbance, neurological defects, and diminished upper extremity pulses
Cases may involve aortic valvular insufficiency; hypertension may occur with renal artery involvement
Grossly – Irregular thickening of the aortic wall with intimal wrinkling
Microscopically – may be indistinguishable from giant cell (temporal) arteritis
Early – adventitial perivascular (vasa vasorum) mononuclear cell infiltrate
Later – medial fibrosis, occasional granulomas an acellular intimal thickening

Front 723

Telangiectasis (spider telangiectasis)

Back 723

Minute focal or subcutaneous arteries or arterioles, often pulsatile, arranged, arranged in radial fashion around a central core
Subgroup of ectasias – an aggregation of abnormally prominent capillaries, venules, and arterioles in skin or mucous membranes, which are acquired exaggerations of existing vessels
Typically occur above the waist, associated with hyperestrogenic states, such as pregnancy or cirrhosis

Front 724

Thromboangiitis obliterans (Buerger disease)

Back 724

Segmental, thrombosing, acute, and chronic inflammation of intermediate and small arteries and veins in extremities
Acute lesions – neutrophilic infiltration of arterial wall, thrombi with microabscesses, giant cell formation
Late lesions – show organization and recanalization
Cause is unknown, but typically with heavy smokers, before 35, excruciating pain, gangrene
Instep Claudation – symptom of Buerger disease, characterized by pain in instep of foot with exercise

Front 725

Thrombophlebitis

Back 725

Inflammation within the vein wall that is incited by thrombosis within a vein (phlebothrombosis)
Predisposing factors include CHF, neoplasia, pregnancy, post-op, immobilization, local infection

Front 726

Varicose veins

Back 726

Abnormally dilated, tortuous veins (typically from superficial veins of the lower extremities) resulting from chronic increased intraluminal pressure

Front 727

Vasculitis

Back 727

Vascular inflammatory injury, often with necrosis
Caused by
Direct invasion of vascular walls by infectious pathogens
Immune mediated mechanisms
Non-infectious, systemic immune-mediated (hypersensitivity or cross-reactivity)
Physical or chemical injury
May be localized (direct injury) or systemic (necrotizing vasculitis and thrombosis)
Systemic are thought to have immune origin
In many patients, involves serum reacting with cytoplasmic agents in neutrophils (P/C-ANCA)

Front 728

Wegener granulomatous

Back 728

Consists of the following triad:
Focal necrotizing vasculitis of the lung and upper airway
Necrotizing granulomas of the upper and lower respiratory tract
Necrotizing glomerulitis
Vascular lesions resemble those of acute polyarteritis nodosa (PAN) with necrotizing inflammation throughout the wall of various small to medium sized arterial beds
Frequently accompanied by granuloma formation
No causative agent, but C-ANCA is a good marker
80% die within a year without treatment

Front 729

Weibel-Palade bodies

Back 729

Storage organelles for von Willebrand factor in endothelium