Study your flashcards anywhere!

Download the official Cram app for free >

  • Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off

How to study your flashcards.

Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key

Up/Down arrow keys: Flip the card between the front and back.down keyup key

H key: Show hint (3rd side).h key

A key: Read text to speech.a key


Play button


Play button




Click to flip

729 Cards in this Set

  • Front
  • Back
Aging (senile atrophy).
The aging process is associated with cell loss, typically seen in tissues containing permanent cells, particularly the brain and heart.
<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.
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
refers also to the absence of an organ but one owing to failure of development of the primordium.
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.
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.
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
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.
BAX binds to and antagonizes the apoptosis-inhibiting protein BCL-2; thus, BAX promotes cell death.
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
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
Caseous necrosis
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.
present in peroxisomes, which decomposes H2 O2 (2 H2 O2 → O2 + 2 H2 O).
Coagulative necrosis
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.
dystrophic calcification
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.
<embryology> Abnormality of development, in pathology, alteration in size, shape and organisation of adult cells
Fat necrosis
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
gangrenous necrosis
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).
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
heat-shock proteins
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.
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.
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.
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.
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.
an increase in the number of cells
an increase in the sizes of individual cells
<embryology> The incomplete development or underdevelopment of an organ or tissue.
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
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
Ischemia-Reperfusion injury
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.
The basophilia of the chromatin may fade (karyolysis), a change that presumably reflects DNase activity
characterized by nuclear shrinkage and increased basophilia. Here the DNA apparently condenses into a solid, shrunken basophilic mass
the pyknotic or partially pyknotic nucleus undergoes fragmentation
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
Liquefactive necrosis
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.
Primary lysosomes are membrane-bound intracellular organelles that contain a variety of hydrolytic enzymes, including acid phosphatase, glucuronidase, sulfatase, ribonu-clease, and collagenase
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.
metastatic calcification
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.
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.
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.
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.
Steatosis (Fatty Change)
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.
Superoxide dismutase
found in many cell types and convert superoxide to H2 O2 (2 O2 - + 2 H → H2 O2 + O2 )
Complete absence of an organ or its anlage
Accumulation of fat and connective tissue within the wall of arteries, often causing progressive narrowing of the lumen and decreased blood flow to tissues.
Liver disease characterized pathologically by loss of normal microscopic lobular architecture with fibrosis and nodular regeneration
Cushing's syndrome
A constellation of clinical findings caused by excessive blood levels of glucocorticosteroid hormones
Disruption of normal neural supply, due to traumatic or degenerative damage to the peripheral nerve or central nervous system motor neurons.
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.
Areas of a cell or tissue that stain with eosin, a rose-colored dye. This dye usually stains the cytoplasm of a cell.
An iron-protein (apoferritin) complex. Chief form of intracellular iron storage present in many types of cells.
Fibrinoid necrosis
Conversion of necrotic tissue to an amorphous, fibrillar eosinophilic mass that resembles fibrin.
"Dry" gangrene
Tissue appears black grossly; not accompanied by bacterial infection.
"Wet" gangrene
Necrotic tissue secondarily invaded by bacteria, resulting in liquefactive necrosis.
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
Regrowth of normal tissue. Only labile cells and stable cells regenerate; regeneration does not occur in permanent cells.
A mobile organ twists obstructing its blood supply and/or drainage.
A serum glycoprotein that binds and transports iron (Fe).
a localized collection of neutrophils and necrotic debris (pus) in a cavity
Acute inflammation
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.
Acute phase protein
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.
a crowded mass of independent but similar units; a cluster.
cells that respond to signaling substances produced by themselves
Polypeptide produced by action of Hageman factor and kallikrein; increases vascular permeability; also causes pain.
a complement cleavage product (“byproduct” of cell attack sequence); increases vascular permeability. Also called “anaphylatoxin” because C3a stimulate histamine release from mast cells.
remains attached to cells, activates the cell attack sequence of complement which leads to cell lysis; also the most important opsonin.
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.
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.
deep-seated pyogenic infection of the skin and subcutaneous tissues, usually arising in several contiguous hair follicles, with formation of connecting sinuses
inflammation of subcutaneous, loose connective tissue (formerly called cellular tissue)
Chediak-Higashi syndrome
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.
the migration of a cell in response to a chemical compound; a compound causing chemotaxis is called a chemoattractant
Granulomatous inflammation
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.
Chronic inflammation
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.
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.
Chronic Granulomatous disease
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.
a hormone-like mediator produced by inflammatory cells
Excess fluid in the interstitial tissue or body cavities; may be either an exudates or a transudate
an exudate or transudate that has passed into a part or tissue
passage of white blood cells through the endothelium and wall of small blood vessels.
secreting internally, most commonly into the systemic circulation; of or pertaining to such secretion.
focal, complete loss of epidermis
Erythema – redness due to capillary dilation
An inflammatory extravascular fluid that has a high protein concentration and cellular debris; sg above 1.020
containing amount of fibrin
Fibrinous inflammation
characterized with exudate rich in fibrin; usually found upon inflammation of serosal or mucosal surfaces
granulation tissue
so called because grossly, under the scab, it has a granular appearance; characterized by ingrowth of new blood vessels (angiogenesis) and scar tissue (myofibroblasts)
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
Hageman factor
factor XII in clotting cascade
preformed inflammatory mediator; stored in mast cell and platelet granules, causes increased vascular permeability
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
the response of vascularized living tissue to injury
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
Interleukin 1 (IL-1)
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).
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.
an exaggerated form of scar that protrudes upward from the skin. Characterized by the presence of dense connective tissue
Leukocyte adhesion
results from interaction between endothelial adhesion molecules and leukocyte receptors
Leukocyte adhesion deficiency
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
Leukocyte rolling
during inflammation there is increased permeability, which results in blood flow stasis allowing leukocytes to fall out of laminar flow and roll along endothelium
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
An enzyme that plays a pivotal role in the synthesis of inflammatory mediators known as leukotrienes
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
accumulation of blood cells (neutrophils) along the endothelium
Nitric oxide (a.k.a. endothelium-derived relaxing factor)
produced by endothelial cells; stimulates relaxation of smooth muscle, thus playing a role in controlling vascular tone; inhibits platelet aggregation, contributing to endothelial thromboresistance
oncotic pressure
pressure resulting from or caused by edema or any swelling (oncosis)
a compound that attaches to a foreign cell, such as a bacterium, and makes it more susceptible to a phagocytic cell
Oxidative burst
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)
relating to a kind of hormone function in which the effects of the hormone are restricted to the local environment
In time, the endothelium can be virtually lined by white cells, an appearance called pavementing
PECAM-1 (platelet endothelial cell adhesion molecule 1)
also known as CD31, major role involves leukocyte transmigration through endothelium
a body formed by union of a phagosome or ingested particle with a lysosome having hydrolytic enzymes
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
phagosome (secondary lysosome)
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.
-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
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
Platelet activating factor (PAF)
a phospholipid released from inflammatory cells of various types; activates release of enzymes from polymorphonuclear cell. Also causes platelet aggregation
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
proud flesh
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
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)
A purulent inflammatory exudate rich in neutrophils and cell debris
producing pus
Residual Body (myelin figure)
-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
. 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
cell surface adhesion molecules playing important role in acute inflammation
induced by the cytokines interleukin-1 (IL-1) and tumor necrosis factor (TNF)
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
denoting an exudate or a discharge composed of or containing serum and also blood
of exudate: virtually devoid of inflammatory cells or fibrin; resembles the appearance of serum
inflamed due to the formation of pus
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
Serous inflammation
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)
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
Substance P
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
Suppurative inflammation
(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)
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
Toll-like receptor (TLR)
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
Transforming growth factor-beta (TGF-B)
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
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
Tumor necrosis factor-alpha (TNF-a)
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
a local tissue defect, or excavation involving the epithelial surface of an organ or tissue
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
Vasoactive amine
mediators in inflammation; they cause vasodilation and increased vascular permeability; histamine and serotonin are most notable
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
the physiological process involving the growth of new blood vessels from pre-existing vessels
Autocrine signaling
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
Basement membrane
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
Cell Adhesion Proteins
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
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
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
The formation of new tissue in the process of wound healing
Contact inhibition
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").
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
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
Endocrine signaling
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
Epidermal Growth Factor (EGF)
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
Transforming Growth Factor-α (TGF-α)
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
Extracellular matrix
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
Fibroblast Growth Factor (FGF)
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
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
G0, G1, S, G2 stages of the cell cycle
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.
Granulation tissue
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
Healing by first intention
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
Healing by second intention
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
Hepatocyte Growth Factor (HGF)
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
Hyaluronic Acid
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
Insulin-like growth factors
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
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
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
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
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
Labile cells
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
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
Paracrine signaling
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).
Permanent cells
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
Platelet derived growth factor (PDGF)
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
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
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
RGD motif
Several integrins bind to Arg-Gly-Asp (RGD) sequences in the fibronectin and vitronectin molecules
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
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
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
Stable Cells
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
A narrowing, especially of a tube or canal, due to scar tissue or tumour
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
Tumor Necrosis Factor (TNF)
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.
Vascular Endothelial Growth Factor (VEGF)
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
Accumulation of fat and connective tissue within the intima of arteries, often causing progressive narrowing of the lumen and decreased blood flow to tissues
Accumulation of blood within an organ due to venous stasis.
Deep vein thrombosis
Typically occurs in the deep veins. These thrombi are usually loosely attached and thus easily dislodged
The accumulation of excess fluid in the intercellular (interstitial) tissue spaces or body cavities
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).
Heart failure
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
Heart failure cells
Hemosiderin-containing macrophages within alveolar spaces caused by microscopic or macroscopic hemorrhage
Accumulation of blood within dilated arteries
Infarct or infarction
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
Lines of Zahn
Laminations of platelets and fibrin in a thrombus. Easier to visualize in arterial thrombus than in venous thrombus
Mural thrombus
A non-occlusive thrombus, usually occurring in the heart or a large artery
the process of repair and granulation tissue formation within a thrombus
Propagation of thrombus
increase in size of an already formed thrombus.
Reestablishment of a lumen, through organization, in a vessel previously obstructed by a thrombus
the lay term used to describe the sudden onset of signs and symptoms in a patient with a cerebral infarct
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
An ultrafiltrate of blood plasma that has passed from within blood vessels into tissues due to a change in hydrostatic pressure (low protein concentration)
A twisting of the intestine about the axis of its mesentery or around an abnormal fibrous band (often a postsurgical adhesion).
Adenosine diphosphate
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
Air embolism
Embolism due to air bubbles entering the blood vessels after trauma, surgical procedures, or changes in atmospheric pressure
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.
Anasarca is a severe and generalized edema with profound subcutaneous tissue swelling
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
Abnormal accumulation of serous fluid in the spaces between tissues and organs in the cavity of the abdomen. Also called hydroperitoneum
Cardiac cirrhosis
In severe, long-standing hepatic congestion (most commonly associated with heart failure), there may even be grossly evident hepatic fibrosis (cardiac cirrhosis
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
Coagulation cascade
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).
Intrinsic pathway
Coagulation cascade initiated by the activation of Hageman factor (XII)
Extrinsic pathway
Coagulation cascade activated by tissue factor, a cellular lipoprotein exposed at sites of tissue injury
an excessive accumulation especially of blood or mucus
Congestive heart failure
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
Decompression sickness
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
Dense bodies
Gamma granules in platelets. They contain ADP, ionized calcium, histamine, serotonin, and epinephrine
Disseminated intravascular coagulation (DIC)
the sudden or insidious onset of widespread fibrin thrombi in the microcirculation – screws up kidneys, heart, brain, lungs
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
Inflammatory edema
Because of increased vascular permeability, inflammatory edema is a protein-rich exudate, with a specific gravity usually over 1.02
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
Noninflammatory edema
Caused by increased hydrostatic pressure, reduced plasma osmotic pressure, lymphatic obstruction, and sodium retention
the escape of a fluid from anatomical vessels by rupture or exudation
the sudden obstruction of a blood vessel by an embolus
an abnormal particle (like a thrombus) circulating in the blood
Endothelial prostacyclin (PGI2)
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
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
Endotoxin / lipopolysaccharide
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
Fat embolism
Fat from long bone marrow after a break, or occasionally tissue trauma becomes an embolus
a white insoluble fibrous protein formed from fibrinogen by the action of thrombin especially in the clotting of blood
Fibrin split products
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)
a plasma protein that is produced in the liver and is converted into fibrin during blood clot formation
Glycoprotein Ib (GpIb)
Platelet surface receptor – binds to vWF which in turn binds to exposed collagen at injury site. Deficiency causes Bernard-Soulier syndrome
Heart failure cells
macrophages in the lung during left heart failure that often carry large amounts of haemosiderin.
a mass of usually clotted blood that forms in a tissue, organ, or body space as a result of a broken blood vessel
a copious discharge of blood from the blood vessels
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
1 : stoppage or sluggishness of blood flow
2 : the arrest of bleeding (as by a hemostatic agent)
Active process – excess of blood in a body part (as from an increased flow of blood due to vasodilation) erythema results
passive process caused by decreased outflow of blood from area – hypoxia results
an area of necrosis in a tissue or organ resulting from obstruction of the local circulation by a thrombus or embolus
Pale infarct
anemic – in harder organs (spleen, kidney, heart) blood can’t flow outside of infarct area – turns pale
Red infarct
hemmorhagic – softer tissue (gut, ovaries, lungs) blood is able to hemmorhage outside of infarct area
Lines of Zahn
Laminations in a thrombus usually found in heart or aorta – not as likely in deep leg vein thrombosis
edema due to faulty lymphatic drainage
Refers to ingrowth of endothelial cells, smooth muscle cells, & fibroblasts into the fibrin-rich thrombus to re-establish circulation – eventually to recanalize
Nitric oxide
Similar to PGI2 – acts as vasodilator & inhibitor of platelet aggregation
Paradoxical embolism
Rarely an embolism may pass through an interatrial or interventricular defect and get into systemic circulation
a minute reddish or purplish spot containing blood that appears in skin or mucous membrane as a result of localized hemorrhage – 1-2mm diameter
venous thrombosis accompanied by little or no inflammation
a proteolytic enzyme that dissolves the fibrin of blood clots
Plasminogen activator inhibitors
Endothelial cells produce PAIs to block fibrinolysis by decreasing t-PA binding to fibrin – a procoagulant
Protein c
Inhibits clotting by proteolytic cleavage factors Va and VIIIa, requires protein s, activated by thrombomodulin
Protein s
Synthesized by endothelial cells – cofactor to protein c to inhibit clotting
Pulmonary embolism
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
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
the process of restoring flow to or reuniting an interrupted channel of a bodily tube (as an artery or the vas deferens)
Secondary aldosteronism
Decreased CO triggers decreased renal perfusion, which spurs the renin – angiotensin – aldosterone axis which increases Na+ and H2O by the kidneys
systemic hypoperfusion caused by low CO or low effective blood volume
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
persistent decrease in the number of blood platelets that is often associated with hemorrhagic conditions
increase and especially abnormal increase in the number of blood platelets
inflammation of a vein with formation of a thrombus
the formation or presence of a blood clot within a blood vessel
Thromboxane A2 (TXA2)
(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
a clot of blood formed within a blood vessel and remaining attached to its place of origin
Tissue factor
membrane bound pro-coagulant factor synthesized by endothelium – acts in conjunction with secreted platelet factors to activate coagulation cascade, which activates thrombin
Tissue plasminogen activator (t-PA)
Counter regulatory mechanism to limit the hemostatic process to the injury site – promotes fibrinolytic activity to clear fibrin deposits from endothelial surfaces
Trousseau syndrome
Increased thrombosis, migratory thrombophlebitis
Virchow triad
3 influences that predispose to thrombus formation 1. endothelial injury 2. stasis or turbulence of blood flow 3. blood hypercoagulability
Von willebrand factor (vWF)
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
ABL gene/BCR-ABL hybrid gene
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
a carcinoma with a glandular growth pattern – it is common to specify the organ of origin, eg renal cell
a benign neoplasia made up of cells forming glands
Adenomatous polyposis coli (APC) gene
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
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.
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
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
Balanced translocation
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
Basic fibroblast growth factor (bFGF)
bFGF, a member of the fibroblast growth factor family, is expressed in human melanomas but not in normal melanocytes
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.
not cancerous
Dietary carcinogen and mutagen
Bloom syndrome/ataxia-telangectasia/Fanconi anemia
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.
borderline malignancy
Borderline malignant neoplasms have some, but not all, of the features of a fully malignant neoplasm
BRCA1 gene/BRCA2 gene
• 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
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.
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
Carcinoembryonic antigen (CEA)
, 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.
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.
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
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
A malignant neoplasm that contains elements of carcinoma and sarcoma so extensively intermixed as to indicate neoplasia of epithelial and mesenchymal tissue.
• 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
CD95 (Fas)
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
CDKN2A/cyclin D/CDK4/RB
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
Benign tumor of the connective tissue (cartilage)
Malignant tumor of the connective tissue (cartilage)
• 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.
Chromosome deletion
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
contact inhibition
inhibition of cell proliferation that occurs when cultured normal cells contact each other
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
A malignant epithelial neoplasm that forms in large cystic spaces
A benign epithelial neoplasm that forms in large cystic spaces
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
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
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.
DNA repair gene
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
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.
Referring to an infiltrative, invasive tumour
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
Epstein-Barr virus (EBV)
Member of herpesvirus family; Associated with: Burkitt lymphoma, nasopharyngeal cancer, B-cell lymphoma in immunosuppressed pts.; and some forms of Hodgkin’s disease
Denoting a neoplasm or lesion that grows outward from an epithelial surface
Familial cancer
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
Benign neoplasm that differentiates toward collagenous connective tissue
Malignant neoplasm that differentiates toward collagenous connective tissue
Flow cytometry
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.
Frozen section/fine needle aspiration (FNA)/cytologic smears
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.
Gene amplification
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
Giant cells
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.
Grade vs. Stage
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
Growth factors
PDGF-B>>sis (protooncogen) overexpression  astrocytoma, osteosarcoma
Fibroblast GF>> hist-1 overexpression>>stomach cancer
Fibroblast GF >>int-2 amplificaiton>> bladder, breast cancer, melanoma
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
Helicobacter pylori
Linked to peptic ulcer, gastric lymphoma, and carcinoma. Induces reactive T cells that cause proliferation of polyclonal B-cell populations via cytokine secretion.
Hematogenous spread
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.
Hepatitis B Virus/HCV
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
HER2 protein
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
Hereditary nonpolyposis colon carcinoma
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
Microscopically normal cells or tissues that are present in abnormal locations. Usually of little significance but may be clinically confused with true neoplasms
Heterotopic rest
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.
Human papillomavirus (HPV)
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.
Human T-cell leukemia virus type 1 (HTLV-1)
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)
Darkly stained nuclei that frequently contain prominent nucleoli. Charactierized as anaplastic, or poorly differentiated tumors
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
in situ
In the natural or normal place, confined to the site of origin without invasion of neighbouring tissues
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.
Within the layer of cells that forms the surface or lining of an organ.
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.
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
Latent membrane protein 1 (LMP-1)
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.
Benign mesenchymal tumor with smooth muscle differentiation
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).
Li-Fraumeni syndrome
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
Selected Tumor Suppressor Genes Involved in Human Neoplasms
TGF-β receptor; E-cadherin; APC/β-catenin; RB; p53; WT-1; BRCA-1 and BRCA-2
Loss of heterozygosity
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
Lymphatic spread
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
Tending to become progressively worse and to result in death. Having the properties of anaplasia, invasion and metastasis, said of tumours.
Secreted by tumors to degrade the matrix components and create passageways for migration
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.
Invasion of tissue immediately adjacent to a carcinoma in situ, the earliest stage of malignant neoplastic invasion.
mixed tumor
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)
 A tumor is formed by the clonal expansion of a single precursor cell that has incurred the genetic damage
 High molecular weight glycoproteins which are altered in tumors and used for diagnostic markers and targets for therapy
MYC gene
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
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.
Can be synthesized in the GI tract from ingested nitrites or derived from digested proteins. Carcinogen that may contribute to gastric cancer
occult malignancy
Obscure, concealed from observation, difficult to understand.
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.
The study of diseases that cause cancer.
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
Benign epithelial neoplasia producing micro- or macroscopic finger like projections
paraneoplastic syndrome
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
Paraneoplastic Syndromes
Endocrinopathies (Cushing syndrome, hypercalcemia); Nerve and muscle syndromes (Myasthenia); Dermatologic disorders (Dermatomyositis)
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
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
point mutation
Mutation that causes the replacement of a single base pair with another pair.
A tumor projecting from the mucosa into the lumen of a hollow viscus (eg, stomach or colon)
Poorly differentiated carcinoma
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
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.
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.
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.
RAS gene
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
Retinoblastoma gene
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
Two-hit hypothesis
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
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.
Literally, scar-like. Describes tumors with a hard consistency due to the desmoplasia associated with malignant cells. Seen especially in breast cancers
The process by which the distant spread of tumors moves into peritoneal, pericardial, and subarachnoid spaces
Squamous cell carcinoma
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)
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
Totipotential cells
An undifferentiated cell capable of developing into any type of body cell.
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.
Tumor associated antigen
Present on tumor cells and also on some normal cells
Tumor progression
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.
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
Tumor specific antigen
Present only on tumor cells and not on any normal cells
tumor suppressor gene
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
Vascular endothelial growth factor (VEGF)
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
Xeroderma pigmentosum (XP)
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
α-fetoprotein (AFP)
Normally produced by fetal yolk sac and liver. Markedly elevated noted in cancers of the liver and testicular germ cells
An aniline dye used in the rubber industries, was in the past responsible for bladder cancers
Atypia (Atypical)
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.
Refers to lack of harm: a neoplasia lacking the ability to do damage by local invasion or metastasis.
Borderline (worrisome) lesion
Pathologists' term for a lesion that shows atypical cells or growth pattern suspicious of a dysplastic or neoplastic process
Currently used as a lay and medical synonym for any malignant neoplasm. Previously used as a more specific medical synonym for carcinoma
A neoplasm with neuroendocrine characteristics, usually arising from epithelium in the lung or GI tract, but can be found in other locations
Carcinoma in situ
A non-invasive proliferation of malignant epithelial cells which is within the confines of mucosa (i.e. has not penetrated the basement membrane).
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).
A benign epithelial neoplasm that forms large cystic spaces
Proliferation of normal fibrous tissue in response to growth factors produced by neoplastic cells.
The extent to which neoplastic stem cells form mature progeny that resemble their normal counterparts morphologically and/or functionally
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.
Ectopic hormone production
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.
CIN (cervical intraepithelial neoplasia)
in cervical carcinoma, dysplasia is often classified as cervical intraepithelial neoplasia types I-Ill or mild, moderate, severe
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.
- 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
A malignant proliferation of cells with hepatocytic or choledochal differentiation
A benign mesenchymal tumor with smooth muscle differentiation
A malignant tumor with differentiation toward smooth muscle cells
- A neoplasia derived from hematopoietic stem cells, in which the bulk of malignant cells are found circulating in the blood.
A benign mesenchymal tumor with adipose differentiation
A malignant mesenchymal tumor with differentiation toward fat cells.
A neoplasia derived from hematopoietic stem cells with differentiation toward lymphocytes.
A secondary neoplastic growth in a tissue location disconnected from the primary.
Neoplastic growth
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.
A benign epithelial neoplasia producing micro- or macroscopic finger-like projections.
Paraneoplastic syndrome
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.
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
A malignant neoplasia of germ cell origin found in the testicle
Scirrhous- Literally, scar-like. Describes tumors with a hard consistency due to the desmoplasia associated with malignant cells. Seen especially in breast cancers.
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.
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.
Refers to cell cytologic features or a growth pattern which does not differ significantly from the normal background
Refers to abnormal crowding of cells
interweaving back to back pattern of neoplastic glands that lack stromal boundaries- indicative of malignancy
Increased staining of nucleus related to increased DNA content
Cytopathologists' term for a change in configuration of neoplastic cell nuclei due to loss of membrane rigidity and compression by adjacent cells.
Myxoid (stroma)
Connective tissue product resembling mucus and associated with some soft tissue tumors.
Psammoma body
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.
Salt & pepper
Refers to an irregular pattern of chromatin condensations within the nucleus often associated with carcinoid tumors.
Alternate forms of a gene. These occur at specific sites on chromosomes and determine different characteristics for a specific trait
Any one of the non-sex chromosomes. In humans there are 22 autosomes and 2 sex chromosomes.
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.
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.
A triplet of nucleotides in DNA or RNA that code for 1 of the 20 amino acids or a stop protein synthesis signal.
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.
Two copies of all the genetic information per cell. Written as 2N. Humans have 23 pairs of chromosomes, 22 autosomes and X and Y.
A large molecule containing genetic information stored in the form of nucleotide sequences.
DNA probe
A specific sequence of DNA isolated in the laboratory and labeled for detection. Used to find a complementary sequence on the target DNA.
DNA restriction map
A visual depiction of the locations of all sites in a segment of DNA which will be cleaved by specific restriction enzymes.
Dominant trait
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.
Downstream region
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.
The phasing and position of the codons in a region of DNA or RNA. Also called the reading frame.
Frameshift mutation
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.
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.
A unit of heredity, a segment of DNA containing the code for a specific molecule. This gene can correlate with a physical trait.
Gene amplification
A type of mutation when a specific gene is aberrantly copied several times and reinserted into the chromosome.
Gene expression
The manifestation of the appropriate genetic material in a cell or tissue.
Gene mapping
The process of determining the specific position of genes on chromosomes.
Gene rearrangement
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.
The entire genetic material of a cell or organism. All the information to reproduce the cell or organism is contained within the genome.
Growth factor
A hormone-like substance that acts to signal cells to grow and divide.
Growth factor receptor-
The specific cellular receptor for a growth factor. Following growth factor binding the receptor starts the process of signal transduction to stimulate specific genes.
One copy of all the genetic information per cell. Written as N, human ova and sperm are haploid.
The state of possessing different alleles at a given locus in regard to a specific gene or character.
The state of possessing a pair of identical alleles at a given locus.
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.
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.
A specific site for the location of a gene and its alleles on a chromosome.
LOH (Loss of heterozygosity)
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.
A change in the DNA sequence can be caused by nucleotide substitutions, deletions, insertions, or rearrangements.
The lack of separation of genes during meiosis.
Northern blot-
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.
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.
A short piece or string of nucleotides, usually 15-50 nucleotide bases long.
The activated form of the normal proto-oncogene. This abnormal expression results in neoplasia.
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.
An oncogene of unknown function, activated by translocation. Associated with follicular lymphomas.
Bcr (breakpoint cluster region)-
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.
An oncogene that resembles the epidermal growth factor receptor. Activated by gene amplification in highly malignant forms of breast cancer.
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.
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.
A family map of a genetic disorder, illustrating affected and unaffected individuals.
The likelihood that a genetic trait will be expressed in a person having the gene for that trait.
Phosphodiester bond-
The covalent bond holding adjacent nucleotides together.
The general genetic content of a cell population. The total number of copies of the entire genome per cell.
Point mutation-
A type of mutation resulting from the substitution of one nucleotide for another.
Polymerase chain reaction-
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).
A short piece of DNA or RNA used as a starting point for a DNA polymerase. All DNA polymerases require primers.
The first family member detected as having a genetic disorder.
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.
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.
Retinoblastoma gene-
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.
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.
Restriction enzyme-
An enzyme that recognizes a specific 4,5,6 or 8 nucleotide sequence and then cuts the DNA containing the recognition site.
Restriction fragment length polymorphism-
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.
A trait that is inherited by means of the X chromosome.
Southern blot-
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.
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.
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.
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.
A form of mutation where large segments of chromosomes are moved from one chromosome to another.
The synthesis of RNA from the DNA template.
The presence of three, instead of two, copies of a chromosome in a somatic cell.
Tumor inducer-
Substance that produces the first in a series of steps that lead to neoplasia.
Tumor promoter-
In chemical carcinogenesis, the substance which allows the effects of the inducer to become apparent and acts by stimulating cell division or replication.
Tumor Suppressor Gene-
Genes that act to block the action of oncogenes. These genes are often lost and deleted during carcinogenesis.
Upstream region-
The region of DNA or RNA on the 5'-side of the sequence in question.
Western blot-
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.
Acute coronary syndrome
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.
Acute rheumatic carditis
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.
Angina pectoris
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
Anitschkow cell
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").
Aortic isthmus
Structure that is related to coarctation of the aorta
Disorder of the heart’s regular rhythmic beating. Can occur in MI, mitral valve prolapse, and myocardial ischemia
Aschoff body
During acute RF, focal inflammatory lesions are found in various tissues, most commonly found in the heart
Asymmetric septal hypertrophy
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.
Atrial fibrillation
The most common abnormal rhythm of the heart; uncoordinated, chaotic contraction of the heart. Seen w/ left heart failure.
Atrial septal defect (ASD)
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
Beriberi heart disease
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.
Bicuspid aortic valve/unicuspid aortic valve
When the aortic valve has only two or one leaflets, instead of the normal three. Predisposed to progressive degenerative calcification
Calcific aortic stenosis
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.
Carcinoid heart disease
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.
Cardiac amyloidosis
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
Cardiac dilatation
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.
Cardiac rhabdomyoma
hamartomas or malformations rather than true neoplasms; the most frequent primary tumor of the heart in infants and children
Cardiac tamponade
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
Cardiogenic shock
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).
Used to describe heart disease resulting from a primary abnormality in the myocardium.
Chagas disease
Caused by the protozoan, Trypanosoma cruzi, and is an important cause of myocarditis.
Chordae tendinae
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.
Chronic ischemic heart disease
Usually constitutes postinfarction cardiac decompensation owing to exhaustion of the compensatory hypertrophy of noninfarcted viable myocardium that is itself in jeopardy of ischemic injury.
Chronic passive congestion of the liver
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).
Chronic rheumatic heart disease
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.
Coarctation of the aorta
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
Collateral circulation
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.
Conduction system of the heart
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.
Compensated heart failure
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.
Congenital heart disease
Caused by developmental abnormalities, most common cardiac abnormality in children. Examples are ASD, VSD, and a patent ductus arteriosus
Congestion of the venous circulation
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.
Congestive heart failure
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.
Constrictive pericarditis
Heart may be encased in a dense, fibrous or fibrocalcific scar that limits diastolic expansion and seriously restricts cardiac output, resembling restrictive cardiomyopathy.
Contraction band necrosis
An irreversible injury that occurs 12-24 hours after myocardial infarction; typically a reperfusion injury.
Coronary vasospasm
Typically occurs at the site of, or adjacent to, a fixed stenosis; can cause prinzmetal angina.
Cor bovinum
Massive cardiac hypertrophy (>1000 gm) that occurs with chronic left ventricular overload
Coronary artery disease / Ischemic heart disease
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
Cor pulmonale/Pulmonary (right-sided) heart disease
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
Coxsackieviruses A and B
Viruses suspected as a cause of myocarditis
Creatine kinase (CK)/CK-MB/CK-Index
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
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)
Dependent edema
Edema influenced by gravity, eg., legs when standing, sacrum when recumbent. Typical of CHF
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
Excessive sweating commonly associated with MI, shock and other medical emergency conditions
Part of the heart cycle during which the myocardium relaxes, expands and blood fills the heart chambers
Dilated cardiomyopathy
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
Arrythmogenic right ventricular cardiomyopathy
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
Dressler syndrome
Pericarditis developing about 28 weeks after acute MI or heart surgery
Ductus arteriosus (Patent ductus arteriosus)
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
difficult or labored breathing
inability to breathe easily unless one is sitting up straight or standing erect
Exertional dyspnea
excessive shortness of breath after exercise
Paroxysmal nocturnal dyspnea (PND)
awakened suddenly during the night feeling short of breath
Ebstein anomaly/malformation
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.
Endocardial cushion
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
Endocardial fibroelastosis
Focal-to-diffuse, cartilage-like fibroelastic thickening of the endocardium, LV>RV. Uncommon, may be endpoint of diverse disorders, most common <2 yo
cardiac disorder marked by vegetations on the valves
Infective endocarditis
friable, infected vegetations and freqeuently valve injury
Acute infective endocariditis
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%
Subacute infective endocarditis
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.
Nonbacterial thrombotic endocarditis
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
Erythema marginatum
Macular skin lesions with erythematous rims and central clearing, typically in bathing suit distribution. One of Jones criteria for rheumatic fever
Erythrosytosis / digital clubbing
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)
External rupture of infarct
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
Fibrinous pericarditis
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
Fish-mouth deformity
A bridging fibrosis across commissures (commissural fusion) of chronic (or healed) valves of rheumatic heart disease
Foramen ovale
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.
alpha-hemolytic (viridans) streptococci
Moderate to low virulence organism that seeds an abnormal or previously injured valve to cause subacute infective endocarditis
Giant cell myocarditis
Myocarditis (inflammation of the myocardium) where there is focal myocyte necrosis associated with granulomatous inflammation, including multinucleated giant cells – has poor prognosis
HACEK group
Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella. Commensals in the oral cavity that cause infective endocarditits
Heart failure (often called congestive heart failure (CHF))
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
Heart failure cells
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
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
High output failure
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
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
Hypertensive heart disease (left-sided HD)
LV hypertrophy with history of hypertension and an absence of other lesions that may induce cardiac hypertrophy
Hypertrophic cardiomyopathy (idiopathic hypertrophic subaortic stenosis, hypertrophic obstructive cardiomyopathy)
Heavy, muscular, hypercontractile, poorly compliant heart with poor diastolic relaxation. 50% are autosomal dominant. Symptoms – young adults with dyspnea, angina, near-syncope, CHF
Hypertrophy of the myocardium
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
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%
Subacute infective endocarditis
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
Intraventricular septal rupture
Rupture of the septum producing left-to-right shunt with right-sided heart volume overload. A possible complication of MI
Left-to-right shunt
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
Left ventricular hypertrophy/Concentric hypertrophy
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
Libman - Sacks endocarditis
Sterile vegetations that may develop on the cardiac valves of patients with SLE
Ligamentum arteriosum
The patent ductus arteriosus (pulm a. to aorta) closes completely within the first few months of life and forms the ligamentum arteriosum
Loeffler syndrome
A fibrosis syndrome of restrictive cardiomyopathy in which the atria become dilated
Not true neoplasms; usually arise in the IV septum and cause lipomatous hypertrophy; Normally benign but can cause sudden cardiac death
Machinery murmur
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)
Marfan syndrome
A disease of extracellular fibrillin synthesis that can predispose patients to aortic dissection
mid-systolic click
Heard on physical exam and is diagnostic for mitral valve prolapse
Migratory polyarthritis
The predominant clinical manifestation of rheumatic heart disease, in which a fever accompanies pain in the large joints
Mitral valve prolapse
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
Mural thrombus
Develop on the endocardial surface overlying an infarct and can cause systemic emboli and are common in patients with a ventricular aneurysm
Myocardial infarction
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
Mycotic aneurysm
An abdominal aortic aneurysm that has become infected by bacteria (usually Salmonella), causing rapid dilation and rupture of the AAA
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
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
The most common primary tumor of the heart
nonbacterial thrombotic endocarditis (NBTE)/marantic endocarditis
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
Ostium primum
A gap that normally separates the developing septum primum from the endocardial cushions
Ostium secundum
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
A symptom of acute rheumatic heart disease, affecting all three layers of the heart (pericardium, myocardium, endocardium). Demonstrates diffuse inflammation and Aschoff bodies
papillary muscle
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
Patent ductus arteriosus
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.
Pericardial effusion/ serous/serosanguineous/chylous
Accumulation of fluid in the pericardial space following right heart failure
Inflammation of the pericardium, usually due to cardiac disease, thoracic disorders, metastases, viral or bacterial infections, or fungal infections
Peripartum cardiomyopathy
Cardiomyopathy associated with pregnancy and caused by htn, volume overload, nutritional deficiency, or immunologic reaction
Pleural effusion
Associated with right heart failure and can cause partial atelectasis of the right lung
Prinzmetal angina
Angina that occurs at rest and is unrelated to physical activity, heart rate or blood pressure
Pulmonary edema
Hemodynamic disturbances or changes in microvascular permeability cause pulmonary edema. In addition to impairing normal respiratory function, chronic edema predisposes to infection
reperfusion injury
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.
Restrictive cardiomyopathy
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
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.
Rheumatic fever
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
Subcutaneous nodules
Migratory large joint polyarthritis
rheumatoid heart disease
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
Right-to-left shunt (cyanotic congenital heart disease)
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
Ring abscess
Caused by vegetations that erode into the underlying myocardium
Secondary hyperaldosteronism
Syndrome characterized by chronic excess of aldosterone, arising from a non-adrenal source
Streptococcal epidermidis
Staphylococci infection of patients with prosthetic heart valves, or intravenous drug abusers.
Septum primum
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.
Septum secundum
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.
Sinus of Valsalva
This is where the aortic cusps protrude in calcific aortic stenosis
Staphylococcus aureus
Causes skin infections, osteomyelitis, pneumonia, endocarditis, food poisoning, and toxic shock syndrome
a stricture of any canal or orifice
Streptolysin O/DNAse B/Streptozyme test
Strep proteins that are indicative of rheumatic heart disease-causing bacteria
Subendocardial infarction
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.
Sudden cardiac death
unexpected cardiac death within 1 hour of symptom onset
loss of consciousness and postural tone caused by diminished cerebral blood flow.
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.
rapid beating of the heart, conventionally applied to rates over 90 bpm, but some sources indicate >100 bpm
Tardive cyanosis
late cyanosis (tardive – late; tardy)
tetralogy of Fallot
has four clinical features:
obstruction to the right ventricular outflow tract (subpulmonary stenosis)
an aorta that overrides the VSD
right ventricular hypertrophy
Transposition of the great arteries
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
truncus arteriosus
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.
Transmural infarction
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.
A globular protein of muscle that binds to tropomyosin and has considerable affinity for calcium ions; a central regulatory protein of muscle contraction
unstable angina
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).
valvular insufficiency
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).
valvular regurgitatioin
can occur from inadequate systolic contraction of the mitral valve ring.
Valvular stenosis
can occur because leaflets are unable to open over bulky deposits.
large, thrombotic masses
Ventricular aneurysm
thinning, stretching, and bulging of a weakened ventricular wall, usually as a result of myocardial infarction; rarely postinflammatory or congenital
Ventricular septal defect (VSD)
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.
Wavy fiber change
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.
Abdominal aortic aneurysm (AAA)
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
Allergic granulomatis angiitis (Churg-Strauss Syndrome)
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%)
Another term for vasculitis, an inflammation of the blood vessels
Antineutrophili cytoplasmic antibody (ANCA)/p-ANCA, c-ANCA
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
Localized abnormal dilations of vessels
Morbidity and mortality secondary to:
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)
Aortic dissection (dissecting hematoma)
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
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
Generic term for thickening and loss of elasticity of the arterial wall. Three main patterns: atherosclerosis, Monckenberg medial calficic sclerosis, and arteriolosclerosis
ArterioLOsclerosis (pattern of arteriosclerosis)
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
Arteriovenous fistula/Arteriovenous malformation
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
Inflammation of the arteries
Most common forms include giant cell (temporal) arteritis and Takayasu arteritis
an abnormal accumulation of fluid in the abdomen
an accumulation of chyle (lymphatic fluid) in the pleural cavity
an accumulation of chyle (lymphatic fluid) in the pericardial sac
Atheroma (atheromatous plaques)
Intimal fibrofatty plaques which protrude into and obstruct vascular lumens and weaken underlying media
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
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)
Benign nephrosclerosis
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
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
Effusion from lymphatics (chyle), usually occurs secondary to rupture of obstructed, dilated lymphatics
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
Complicated plaques
Calcified, hemorrhagic, fissured, or ulcerated atheromas, predisposing to local thrombosis, medial thinning, cholesterol microemboli, and aneruysmal dilation
Cystic medial degeneration
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
Deep vein thrombosis
A thrombosis in larger leg veins typically above the knee that readily embolize
High Density Lipoprotein
Help clear cholesterol from vessel wall lesions, resulting in decreased risk of atherosclerosis
Elastic arteries
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
Muscular arteries
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
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.
Essential hypertension
Accounts for 95 % of hypertension and is due to idiopathic (unknown) causes
Controllable and generally asymptomatic unless a complication intervenes
False anerysm
Extravascular hematoma that communicates with intravascular space (part of wall gone)
Fatty streak
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
Fibrofatty plaque
Formed by lipid deposition, smooth muscle cell proliferation, and synthesis of ECM in the intima of arteries
Marks atherosclerosis
Fibromuscular displasia
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)
Fibrous cap
Smooth muscle cells, leukocytes, and dense connective tissue ECM that makes up outer portion of Atheroma (atheromatous plaques)
Fusiform aneurysm
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
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
Giant cell (temporal) arteritis
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
Glomus tumor (glomangioma)
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)
Common benign lesion, usually superficial, often of the head or neck, most are present at birth and expand with child
Capillary hemangioma
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
Juvenile capillary (strawberry) hemangioma
Present at birth, grow rapidly for a few months, begin regressing at 1-3 yo (80% gone be age 7)
Cavernous hemangioma
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
Pyongenic granulomas (lobular capillary hemangiomas)
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)
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)
Homan sign
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
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
Malignant Hypertension
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
Inferior vena cava syndrome
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
Internal elastic lamina
Dense elastic membrane separating the tunica intima and media
External elastic lamina
Outer limit of the tunica media, separating it from adventitia
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
Middle layer of vessel walls composed of smooth muscle cells
Supplied with oxygen and nutrients by diffusion from lumen and by vaso vasorum
Outer layer of vessels, consisting of connective tissue and vaso vasorum
Kawasaki disease (mucocutaneous lymph node disease)
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)
Leukocytoclastic vasculitis
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)
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
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
Thin-walled, endothelium-lined channels that drain interstitial fluid and lymphocytes from tissue, returning it to blood
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
Kaposi sarcoma
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:
Multiple red-to-purple cutaneous plaques/nodules on lower extremities
Erratic course of relapses and remissions, rarely causes death, common in elderly
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
Marfan Syndrome
Disorder of connective tissues affecting skeletal, ocular, CV systems
Microscopic polyangitis
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
Migratory thrombophlebitis (Trousseau syndrome)
Multiple venous thrombi appearing in one place then disappearing to crop up elsewhere
Attributed to hypercoagulability associated with cancer or nonbacterial thrombotic endocarditis
Monckenberg medial calcific sclerosis
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
Mycotic Aneurysm
Localized abnormal dilations of vessels due to infection
Proliferation of new blood vessels, occurs around the periphery of atherosclerotic lesions and plaques
Obliterative endarteritis
Syphilis causes endarteritis of the vaso vasorum leading to syphilitic aneurysm formation (chiefly of ascending aorta)
Osler-Weber-Rendu (Hereditary hemorrhagic telangiectasa)
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
Elastic tissue degeneration and spotty calcifications within the media of veins with varicosities
Thrombosis within a vein that typically incites thrombophlebitis
Phlegmasia alba dolens (“painful white legs”)
Variant of primary phlebothrombosis where an iliofemoral venous thrombosis occurs in pregnant women prior to or after delivery
Polyarteritis nodosa (PAN)
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)
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
Young adults, nonspecific clinical signs/symptoms related to whatever tissue is involved
Fever, malaise, weight loss, may be associated with Hepatitis B antigen
Portal hypertension
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
extravascular hematoma that communicates with intravascular space (part of wall gone)
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)
arterial insufficiency of the extremities secondary to arterial narrowing induced by various condition, including atherosclerosis, SLE, scleroderma, and Buerger disease
Saccular aneurysm
Spherical aneurysm involving only a portion of the vessel wall
Vary in size (5-20 cm) and often partially or completely filled by thrombus
Stasis ulcers
Ulcer that develops in an area in which the circulation is sluggish and the venous return is poor
common location is on the ankle
Superior vena cava syndrome
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
Syphillitic aneurysm
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)
Takayasu arteritis
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
Telangiectasis (spider telangiectasis)
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
Thromboangiitis obliterans (Buerger disease)
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
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
Varicose veins
Abnormally dilated, tortuous veins (typically from superficial veins of the lower extremities) resulting from chronic increased intraluminal pressure
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)
Wegener granulomatous
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
Weibel-Palade bodies
Storage organelles for von Willebrand factor in endothelium