Pathology Test 2

Front 1

Neoplasia

Back 1

A "new growth" of abnormal tissue (usually derived from a single cell precursor) that serves no physiologic function, and for the most part, is independent of normal restraints on orderly growth.

Front 2

Normal cell do not replicate unless they are stimulated by:

Back 2

endogenous or exogenous growth factors released in response to physiologic, pathologic, or reparative demands.

Front 3

Neoplastic cells can replicate differently than other cells

Back 3

they have the ability to replicate in the absence of physiologic, pathologic, or reparative factors or may replicate excessively in response to normal stimuli.

Front 4

Factors that play a role in neoplasm development

Back 4

1) inherited genetic influences
2) environmental factors (75-90%)
3) somatic mutations of cellular DNA

Front 5

The essence of neoplasia

Back 5

a "genetic" disease in that the fundamental cellular changes occur at the level of DNA but that these changes are induced by environmental factors.

Front 6

tissue that tend to show higher rates of neoplastic transformation

Back 6

tissues most directly exposed to the environment (skin, respiratory tract, gastrointestinal tract)

Front 7

"-oma"

Back 7

tumors are denoted by this suffix. And this usually indicates a neoplastic process but occassionally may be applied to a non-neoplastic mass

Front 8

an unmodified "oma" suffix generally denotes:

Back 8

a benign neoplasm

Front 9

carcinoma

Back 9

referring to epithelial malignancies

Front 10

sarcoma

Back 10

referring to mesenchymal/connective tissue malignancies

Front 11

melanoma

Back 11

malignant neoplasm of melanocytes

Front 12

lymphoma

Back 12

malignant neoplasm of lymphoid tissue

Front 13

glioma

Back 13

malignant neoplasms of supporting tissue of the CNS

Front 14

blastoma

Back 14

malignant tumors arising from early, partially differentiated embryonal tissue

Front 15

teratoma

Back 15

a neoplasm which contains cells from more than one embryonic germ cell layer and may be benign or malignant

Front 16

hamartoma

Back 16

a non-neoplastic "tumor" that represents abnormal overgrowth or differentiation of cells native to the tissue of origin

Front 17

choristoma

Back 17

the presence of normal tissue in an abnormal location (also termed ectopic or heterotopic tissue)

Front 18

Most neoplasms have a different features than surrounding normal tissue

Back 18

-color
-texture
-consistency

Front 19

squamos-

Back 19

squamos epithelium

Front 20

adeno-

Back 20

grandular epithelium

Front 21

transitional-

Back 21

transitional epithelium

Front 22

fibro-

Back 22

fibrous connective tissue

Front 23

leiomyo-

Back 23

smooth muscle

Front 24

rhabdomyo-

Back 24

skeletal muscle

Front 25

lipo-

Back 25

adipose tissue

Front 26

chondro-

Back 26

cartilage

Front 27

osteo-

Back 27

bone

Front 28

hemangio-

Back 28

blood vessel

Front 29

lymphangio-

Back 29

lymphatic vessel

Front 30

scirrhous-

Back 30

hard due to excessive production of tumor stroma

Front 31

medullary-

Back 31

soft, resembling marrow, due to scant production of tumor stroma

Front 32

colloid-

Back 32

gelatinous, mucinous

Front 33

cystic-

Back 33

fluid or gas filled spaces

Front 34

follicular-

Back 34

forming follicles

Front 35

cyst-

Back 35

forming small cystic spaces

Front 36

papillary-

Back 36

forming "nipple-like" projections

Front 37

villous-

Back 37

forming shaggy, "finger-like" projections

Front 38

tubular-

Back 38

forming cylindrical tubules

Front 39

cribriform-

Back 39

pierced by small holes

Front 40

Benign neoplastic cells resemble:

Back 40

the normal morphology of the cell of origin.

Front 41

Malignant neoplastic cells are charcterized by:

Back 41

cellular and nuclear pleomorphism (due to alterations in the cell cytoskeleton); increased nuclear/cytoplasmic ratio; increased nuclear chromatin which is frequently "clumped" along an irregular nuclear membrane; large nucleoli; bizarre mitoses; loss of cellular orientation; and to some degree, loss of normal functional capacity.

Front 42

Benign neoplasms

Back 42

-well differentiated
-have a normal number of chromosomes
-retain functional capabilities
-generally show slow growth or may spontaneously regress
-grow by expansion and tend to compress the surrounding tissue into a "capsule" that separates the tumor from normal tissue
-do not metastasize

Front 43

Malignant cells

Back 43

-often show abnormalities in the number or structure of chromosomes
-may vary from complete lack of differentiation (anaplasia) to well differentiated
-grow by infiltration and invasion of the surrounding tissue and are not confined by capsule
-have metastatic potential

Front 44

lymphatic dissemination

Back 44

this is the most common route of metastasis, especially of epithelium neoplasms (carcinomas) and follows the natural lymphatic drainage of the site of malignancy. Regional lymph notes may be enlarged due to metastatic tumor or to immune reaction to the presence of tumor products.

Front 45

hematogenous dissemination

Back 45

This is characteristic of connective tissue neoplasms (sarcomas). Carcinomas, however, are also spread by a hematogenous route since there are vascular-lymphatic anastomoses. Invasion and metastases are more likely to occur via the venous system due to its thin walled structure.

Front 46

transcoelomic seeding

Back 46

this may occur with malignancies that involve coelomic (peritoneal, pleural) surfaces.

Front 47

traumatic seeding

Back 47

excessive manipulation or cutting into malignant tumors may detach and carry small portions of the tumor to other sites.

Front 48

Both benign and malignant neoplasms:

Back 48

-may cause significant morbidity or kill patients by virtue of their anatomic position (even small tumors may cause sudden death by interfering with vital functions)
-may cause compression of surrounding structures
-may produce hormones or hormone-like substances that can have systemic effects known as paraneoplastic syndromes

Front 49

Malignant neoplasms are more prone to:

Back 49

infarction, necrosis, hemorrhage, ulceration, and infection. They may also stimulate excessive production of connective tissue (desmoplasia).

Front 50

Carcinogenicity of various chemicals:

Back 50

appears to be dose dependent so that multiple fractional doses over time have the same transforming potential as a comparable one-time dose. In addition, a single chemical may not be sufficient to induce cellular change, but 2 or more different chemicals may act synergistically to induce cell transformation (co-carcinogenesis)

Front 51

Most known carcinogens are metabolized by:

Back 51

cytochrome P-450-dependent mono-oxygenases in the liver

Front 52

The carcinogenic metabolism is affected by

Back 52

-age
-sex
-nutritional status

Front 53

Initiation (First stage in transforming a normal cell to a neoplastic cell)

Back 53

Cell contact with chemical initiators can produce permanent changes in the genetic make-up of a cell.

Front 54

Initiators

Back 54

-They react with DNA to cause strand breaks, to alter methylation, or to hinder DNA repair.
-Do not stimulate division

Front 55

Initiated cells

Back 55

-do not have growth autonomy
-do not have unique, readily identifable genotype or phenotype markers

Front 56

Promotion (Second stage in transformation of a normal cell to a neoplastic cell)

Back 56

Chemical promoters can induce neoplastic transformation in a previously initiated cell but cannot cause neoplastic transformation in and of themselves in a non-initiated cell. Instead of altering the DNA, their action seems to induce clonal proliferation of initaited cells by altering the regulation of mitosis and the differentiation and maturation pathways.

Front 57

Conversion (Third stage in transformation of a normal cell to a neoplastic cell)

Back 57

Ultimately the cells become converted and are no longer dependent on the promoters for proliferation.

Front 58

Progression (Fourth stage in transformation of a normal cell to a neoplastic cell)

Back 58

Once the neoplastic cells become autonomous, continued genetic mutation confers new attributes to subclones of the neoplastic cells (see clonal evolution and heterogeneity).

Front 59

Radiation

Back 59

Ionizing radiation may directly ionize critical cellular macromolecules or interact with cellular water to produce free radicals that mediate cellular damage by breaking or altering chemical bonds.
It can:
-inactivate enzymes
-alter proteins
-cause chromosomal breakage
-cause translocation
-cause point mutations
-inhibit cell-mediated immunity and therefore tumor surveillance

Front 60

Viruses

Back 60

Both DNA and RNA viruses have been found associated with human neoplasia (carcinoma of the uterine cervix, hepatocellular carcinoma, Burkitt's lymphoma). Through the process of transduction and insertional mutagenesis, viruses may directly rearrange the structure or alter the expression of the host cell genome. In order to be transformed, the host cell must survive the viral infection and be able to reproduce.

Front 61

Malignant transformation

Back 61

Requires that cells acquire an extensive variety of traits that are not present in their normal state.

Front 62

Malignant cells

Back 62

They lose, to a variable extent, the functional capacity of their normal state and may revert to a more primitive or embryologic function.

Front 63

In tissue culture, neoplastic cells appear to be:

Back 63

-freed from normal regulatory controls
-have an increased rate of stem cell renewal
-loss of contact inhibition
-anchorage independent growth
-less cohesive
-require fewer exogenous growth factors
-immortal
-can develop invasive properties
-metastatic potential

Front 64

regulators

Back 64

These direct multiple parameters of cell function (pleiotropy).

Front 65

Viral Oncogenes (v-onc)

Back 65

Specific genetic sequences that were capable of transforming normal cells into neoplastic cells. They were first identified in small DNA viruses and RNA tumor viruses (retroviruses) that were known to produce malignancies in animals.

Front 66

Proto-oncogenes

Back 66

Genetic information within a normal cell that could potentially transform that cell into a neoplastic cell under appropriate conditions. (naturally occurring cellular genetic segments found in almost all life forms and coded for almost identical protein products indicating that they must play a fundamental role in normal cell physiology)

Front 67

Biochemical pathway for cell division

Back 67

-interaction of a messenger with cell membrane receptors
-transduction of that signal through the membrane to a second messenger in the cytoplasm
-transmission by the second messenger to the nucleus
-initiation of DNA transcription and replication

Front 68

Biochemical pathway of cell division is mediated in part by:

Back 68

the protein products encoded by cellular proto-oncogenes.

Front 69

Cellular oncogenes (c-onc)

Back 69

genetic sequences capable of transforming a normal cell into a neoplastic cell. They are similar to normal proto-oncogene sequences and may have arisen through simple somatic mutation of the proto-oncogenes.

Front 70

Proto-oncogenes potential:

Back 70

They have the potential of being converted (through mutation, retroviral transduction, increased expression) to oncogenes that can promote excessive or inappropriate cell proliferation.

Front 71

Structural changes of a proto-oncogene

Back 71

Structural mutations can lead to synthesis of a protein that has aberrant structure and function. This can occur through point mutations, insertions/deletions, or translocations.

Front 72

Regulatory changes of a proto-oncogene

Back 72

With regulatory changes, mutations affect the amount of protein product rather than the structure. This can occur through translocation or gene amplification.

Front 73

Effects of oncogene activation:

Back 73

-may code for large amounts of growth factors to which the cell can respond (autocrine stimulation)
-may impart growth autonomy by deregulating genes that encode growth factors
-may encode for defective receptors that transmit stimulatory signals in the absence of a growth factor
-may render tumor cells excessively sensitive to low levels of growth factors that are below the threshold for stimulating normal cells

Front 74

Tumor suppressor genes

Back 74

Serve to protect the cell from the events leading to neoplastic transformation. The protein product of these genes modulate the activity of proto-oncogenes, oncogenes, or their protein products.

Front 75

p53 tumor suppressor gene

Back 75

-on the short arm of chromosome 17
-becomes much more active after DNA damage
-it codes for a protein that binds to damaged DNA and inhibits cell mitosis until the damaged DNA can be repaired by the DNA repair genes. (if the damage is too severe to be repaired, the cell will undergo apoptosis)

Front 76

In the absence of functional p53 protein:

Back 76

the cell may continue to reproduce incorporating the DNA mutation into the genome of the cell line. Mutations and inactivation of the p53 gene are seen in neumerous human malignancies

Front 77

Defects in the DNA repair genes:

Back 77

may also predispose to malignant transformation and have been associated with various cancer syndromes such as xeroderma pigmentosum.

Front 78

Heterozygous mutations

Back 78

Activate an oncogene allele or inactivate a tumor suppressor gene allele may be inherited and could be a predisposing risk factor for the development of neoplasia since that individual has inherited only on, rather than two, normal copies of the gene allele.

Front 79

Oncogene activation

Back 79

May result in overt neoplastic development by somatic mutation.

Front 80

Inherited mutated allele

Back 80

-present in all cells
-a greater tendency to to develop multiple tumors
-many of the autosomal dominant neoplasia syndromes appear to be the result of inheriting at least one mutated gene allele
-somatic mutation and activation of an oncogene allele may also occur, but the chances of altering both alleles in a single cell are much less than the chance of altering one allele.

Front 81

DNA transfection experiments have shown that:

Back 81

No single oncogene will transform normal cells into neoplastic cells. It appears that more than one oncogene may be involved, with each oncogene supplying some functions required to convert a normal cell into a neoplastic one.

Front 82

Sequential activation of oncogenes (or suppression of tumor suppressor genes)

Back 82

May be reflected in the gradual transition of normal cells to neoplastic cells through stages of dysplasia or pre-neoplasia. And, since cell replication is central to neoplastic transformation, it is also not surprising that preexisting regenerative and/or hyperplastic conditions are occassionally associated with subsequent neoplasia.

Front 83

Propensity of tumor cells to reproduce

Back 83

-a distinguishing feature of neoplasia
-may be the result of genetic alterations (oncogene activation, tumor suppressor inactivation) that direct the cell to replicate rather than to continue to differentiate.

Front 84

Most tumors are of monoclonal origin

Back 84

A single cell from normal or pre-neoplastic tissue becomes neoplastic at a specific level of differentiation and the clonal derivative of that cell produces the neoplasm.

Front 85

Growth Fraction

Back 85

Refers to the proportion of cells within a tumor population that are in the proliferating pool. Most tumors have low growth fraction and proliferation only slightly exceeds cell loss. The growth fraction of a tumor has a profound effect on its susceptibility to chemotherapy. Most cancer drugs act primarily on dividing cells, therefore those tumors which have a high growth fraction are most vulnerable. Slow growing tumors which have a high proportion of cells outside the cell cycle respond less favorably and harbor cells which can potentionally reenter the cycle at a later time.

Front 86

The rate of tumor growth depends on:

Back 86

-growth fraction
-the degree of imbalance between cell production and cell loss.

Front 87

Tumor growth is dependent upon:

Back 87

-vascularization; without it, neoplastic growth will stop at approximately one millimeter diameter due to the limited diffusion capacity of oxygen and solutes.

Front 88

Angiogenic factors

Back 88

Include fibrinogen and various substances produced by the tumor cells. They promote and control the neovascularization of the expanding cell mass.

Front 89

Tumor neovasculature

Back 89

Tends to be abnormal due to loose endothelial junctions.

Front 90

Hemorrhage into tumors

Back 90

Not uncommon and, in the case of malignant tumors, this may even help assist the tumor cells to spread to other sites.

Front 91

Hypoxia in the tumor environment

Back 91

Significantly impairs the biologic effect of radiation therapy and some forms of chemotherapy which is oxygen dependent.

Front 92

Circulating hormones in the tumor

Back 92

Can influence the growth rate of hormonally responsive tissues.

Front 93

The degree of tumor-associated angiogenesis can be quantified by:

Back 93

-microvessel density
A greater degree of angiogenesis within a tumor is correlated with a more aggressive behavior and poorer prognosis.

Front 94

As tumor size increase:

Back 94

The time it takes for a tumor to double in volume also increases. This is due to diminished blood supply, competition for metabolites, and other factors that lead to a decrease in the growth fraction and an increase in cell loss.

Front 95

As tumors enlarge:

Back 95

An increasing proportion of tumor cell drops out of the mitotic cycle either because of necrosis or by entering into prolonged G1 periods or the G0 phase of the cell cycle.

Front 96

The earlier a tumor is identified, the greater the chance of successful radiation and/or chemotherapy

Back 96

Even though the doubling time slows down as tumors enlarge, by the time a solid tumor is clinically detected it has already completed a major portion of its life cycle.

Front 97

By the time cells have reached clinical detection:

Back 97

The cell population is heterogenous in respect to morphologic appearance, karyotype, degree of differentiation, invasiveness, metaplastic capabilities, etc implying that tumors can undergo clonal evolution as they develop, probably related to DNA instability and the high rate of random mutation in neoplastic cells.

Front 98

Dedifferentiated cells

Back 98

Are more likely to have characteristics that enable them to spread (increased motility, decreased adhesiveness, decreased anchorage dependence).

Front 99

Clonal evolution

Back 99

Like the progression of pre-neoplasia to neoplasia, appears to involve a sequence of oncogene activations that, over time, leads to more highly malignant cells i.e. those that have survival a survival advantage due to their growth rate, invasiveness, drug resistance, etc.

Front 100

By the time most malignant neoplasms have become clinically detectable, it is likely that they have evolved several subclones with metastatic potential.

Back 100

This implies that the earlier a cancer can be identified, the less likely it is that more aggressive subclones have developed.

Front 101

Malignant cells

Back 101

An important feature of malignant cells is their ability to invade surrounding tissue and ultimately to spread to distant sites. Only certain cells within a tumor develop a high invasice and/or metastatic potential, and these tend to be cell clones with a high mutation rate. There is evidence that oncogene activation is involved in conferring metastatic potential on tumor cells by enabling the cell to attach to, degrade, and penetrate basement membranes and interstitial connective tissue.

Front 102

Tumor specific antigens

Back 102

Antigens that are found on neoplastic cells and not on normal cells. In animals, each individual tumor induced by a given chemical carcinogen frequently carries its own unique tumor antigen while all tumors produced by a given virus share a common antigen. These tumor-specific antigens can activate host immunologic destruction of cancer cells in animals but whether this occurs in humans to any significant extent is not known.

Front 103

Tumor associated antigens

Back 103

Antigens found in normal cells but which are present in higher concentration in tumor cells. Examples include differentiation antigens (beta HCG) which are expressed at certain stages of a cell's maturation and oncofetal antigens (CEA, AFP) which are expressed during embryonic development but normally repressed during adult life.

Front 104

Grading

Back 104

This refers to a microscopic pathologic determination of tumor aggressiveness based on the degree of differentiation of the neoplastic cells and the number of mitosis as an estimate of the rate of growth. Most tumors are graded from I (low grade, well differentiated) through IV (high grade, undifferentiated). Many malignant neoplasms progress to a higher grade over time as less differentiated clones of cells become dominant. In general, the lower the grade the better the prognosis.

Front 105

Staging

Back 105

This refers to a clinical and pathologic determination of tumor aggressiveness based on the size of the neoplasm, the presence or absence of regional lymph node involvement, and the presence or absence of distant metastases. This is the basis of the TNM (tumor size, node involvement, and metastasis) staging system. Alternatively, some tumors are staged numerically from 0 (localized tumor) through IV (distant metastases), and some are staged alphabetically from A (localized tumor) to D (metastatic tumor). In general, the smaller the tumor and the more localized it is, the better the prognosis.

Front 106

The cardiovascular system is madatory in early gestation in order to:

Back 106

-supply oxygen
-supply essential nutrients
-remove waste products from the rapidly developing tissues

Front 107

Right-sided pulmonary circulation

Back 107

Deoxygenated venous system blood returns to the right side of the heart where it is pumped through the pulmonary circuit to become oxygenated.

Front 108

Left-sided systemic circulation

Back 108

The oxygenated blood from the right-sided pulmonary circulation returns to the left side of the heart where it is pumped through the systemic circulation to the tissues of the body.

Front 109

Oxgenated blood in the fetus is supplied by:

Back 109

The mother via the placenta. This is because the lungs are not functional yet.

Front 110

Right-to-left shunts

Back 110

Divert non-oxygenated blood away from the pulmonary circuit and into the systemic circulation, reducing the oxygen saturation of the arterial blood. This results in cyanosis at or soon after birth. This shunt must always be present during the development of the heart and fetus in order to direct the maternally derived oxygenated blood into the let-sided systemic circulation. At birth, these shunts need to be closed in order to establish the normal adult circulatory blood flow.

Front 111

Cyanosis

Back 111

A bluish discoloration of the skin due to accumulation of reduced hemoglobin in capillary beds and seen most readily around the lips and nail beds.

Front 112

Right-to-left shunt examples

Back 112

-truncus arteriosus
-transoposition of the great vessels
-tetralogy of Fallot
-tricupsid atresia

Front 113

Left-to-right shunts

Back 113

Divert oxygenated blood from th systemic circulation (including the myocardial circulation) and into the pulmonary circulation, depriving the systemic tissues of oxygen. Additionally, the excess blood flowing through the pulmonary circulation produces a pulmonary hypertension.

Front 114

Left-to-right shunts examples

Back 114

-atrial septal defect
-ventricular septal defect
-patent ductus arteriosus

Front 115

Obstructive disorders

Back 115

These are physical barriers to blood flow and generally do not cause cyanosis. They do, however, lead to hemodynamic disturbances.

Front 116

Obstructive disorder examples

Back 116

-coarctation of the aorta
-valvular stenosis

Front 117

Arteriosclerosis

Back 117

A group of vascular disorders which are characterized by thickening and loss of elasticity of arterial walls.

Front 118

the most common type of arteriosclerosis

Back 118

atherosclerosis. These 2 terms are often used interchangeably.

Front 119

Atherosclerosis

Back 119

a slow progressive disease of the large elastic and large and medium sized muscular arteries characterized by the formation of atherosclerotic plaques.

Front 120

50% of all deaths in the U.S. are related to:

Back 120

Cardiovascular disease, most of which are related to atherosclerosis.

Front 121

Major risk factors of arteriosclerosis:

Back 121

-hyperlipidemia
-hypertension
-cigarette smoking
-diabetes mellitus

Front 122

Minor risk factors of arteriosclerosis

Back 122

-physical inactivity
-stress and behavior patterns
-obesity
-long termoral contraceptive use

Front 123

Role of plasma lipids

Back 123

Among other metabloic functions, cholesterol is vital for the synthesis of cellular membranes, steroid hormones, and bile acids. 93% of the body cholesterol is therefore located intracellularly to provide substrate for these metabolic functions while 7% is circulating as plasma cholesterol.

Front 124

Plasma lipids are primarily derived from:

Back 124

-exogenous dietary cholesterol and triglycerides that are abdorbed across the intestinal mucosa
-endogenous cholesterol and triglycerides that are synthesized in the liver
-free fatty acids derived from adipose tissue

Front 125

Cholesterol and triglycerides

Back 125

Insoluble in blood and are, therefore, complexed with a variety of specific proteins to form soluble lipoproteins.

Front 126

Chylomicrons

Back 126

A lipoprotein which primarily transport dietary triglycerides and, to a lesser extent, dietary cholestorol.

Front 127

Beta lipoproteins

Back 127

("low density lipoprotein", LDL) which primarily transport endogenous cholesterol and are the major plasma cholesterol carriers

Front 128

Pre-beta lipoproteins

Back 128

"very low density lipoproteins", VLDL) which primarily transport endogenously produced hepatic triglycerides to adipose and muscle tissue

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Alpha lipoproteins

Back 129

"high density lipoprotein", HDL) which primarily transport endogenous cholesterol acquired from extrahepatic tissues and returns it to the liver.

Front 130

Receptor pathway (major clearance mechanism)

Back 130

-Liver cells have specific cell surface receptors that bind LDL. The mjority of cholesterol-rich LDL is cleared from the plasma by incorporation into the liver cell where it can then be excreted into bile.
-In cells outside the liver, excess free cholesterol is stored in the cytoplasm but there is only a limited storage capacity. HDL can extract cholesterol from the cell and transfer it to the liver where it can then be excreted.

Front 131

Elevated levels of plasma HDL

Back 131

Directly related to the development of clinically significant atherosclerosis

Front 132

Elevated levels of HDL

Back 132

seem to have a protective effect

Front 133

Phagocytic (receptor-independent) pathway

Back 133

Cells of the monocyte/macrophage phagocytic system have receptors for "modified" LDL and normally clears approximately one third of the plasma LDL. However, they cannot regulate the amount of cholesterol taken into the cell and in conditions of high levels of plasma LDL the cells become overstuffed and lead to the development of xanthomas.

Front 134

Familial hyperlipidemias

Back 134

Occur as a result of inherited genetic defects and are among the most frequently encountered inherited disorders.

Front 135

Hypercholesterolemia

Back 135

Due to dietary excess or a combination of dietary and genetic factors.

Front 136

Major contributors to hypercholesterolemia:

Back 136

-excessive caloric intake
-excessive dietary cholesterol
-saturated fatty acids

Front 137

Total cholesterol (TC)

Back 137

Initial screening for atherosclerotic risk involves measurement of total serum cholesterol. In middle aged adults, (>40), a value between 200 mg/dl and 240 mg/dl is considered borderline and overt hypercholesterolemia is considered to be a plasma cholesterol >240 mg/dl.

Front 138

TC/HDL-C ratio

Back 138

If the total cholesterol levels are high, the cholesterol associated with HDL (HDL-C) can be measured in the laboratory. Since HDL-C has a protective effect, the lower the ratio the less risk for developing coronary artery disease. A "good" ratio would be 4:1 or less.

Front 139

LDL-C/HDL-C ratio

Back 139

This can also be a useful ratio and gives us much the same information as TC/HDL-C ratio

Front 140

Plasma total homocysteine level

Back 140

Studies have shown that an increased plasma total homocysteine level is an independent risk factor for atherosclerotic disease whether or not serum cholesterol is elevated. A metabolite of methionine homocysteine impairs endothelial function. Since normal homocysteine metabolism requires vitamin B12, vitamin B6, and folic acid, deficiencies of these vitamins lead to elevated homocysteine levles.

Front 141

Chlamydia pneumonia and cytomegalovirus infections

Back 141

These microbiologic agents have been shown to confer an increased risk of developing clinically significant atherosclerosis. Since these are common infections (approximately 50% of middle-aged adults), there must also be other genetic or environmental factors at play that place these individuals at increased risk.

Front 142

Vascular endothelial damage

Back 142

Injury to the endothelium results in an increased permeability of the vessel to plasma constituents at the site of injury and LDL and VLDL are able to penetrate under the endothelium. Some are precipitated as exracellular lipid while others are incorporated as intracellular lipids.

Front 143

Uncontrolled intracytoplasmic accumulation

Back 143

Eventually causes cell death and rupture leading to the formation of non-reversible atherosclerotic plaques.

Front 144

Fatty streaks

Back 144

these are probably reversible lesions and may or may not represent precursor lesions of adult plaques. These appear as multiple, essentially flat yellow streaks on the inner surface of vessels.

Front 145

Atherosclerotic plaques

Back 145

These appear as multifocal asymmetric elevations of the vessel lining. The firmess of the plaque varies from hard to soft but most have a firm fibrous cap overlying a softer core of atheromatous and necrotic debris. they tend to be most severe in the abdominal aorta, particularly in areas of vascular branching.

Front 146

Hard plaque

Back 146

fibrous plaques which contain a large amount of collagen

Front 147

soft plaque

Back 147

atheromatous plaques which contain abundant lipid material

Front 148

"routine" plaques may evolve into clinically significant "complicated" plaques when there is:

Back 148

-associated thrombus formation
-ulceration of the fibrous cap
-hemorrhage into the plaque
-dystrophic calcification
-weakening of the vessel wall

Front 149

Arteriosclerosis is related to:

Back 149

-physical obstruction to blood flow
-the risk of thrombosis
-alteration of normal activity of endothelial cells

Front 150

Clinical symptoms of arteriosclerosis are generally related to the hemodynamic effects on:

Back 150

-brain
-kidney
-small bowel
-lower extremeties

Front 151

Ischemic heart disease (IHD)

Back 151

results from an imbalance between the availablity of oxygen and the metabollic demand of the heart.

Front 152

Ischemic heart disease (IHD) is responsible for:

Back 152

-30% of the total mortality in the U.S.
-75% of the deaths due to heart disease

Front 153

Availability of oxygen is affected by:

Back 153

-reduced coronary flow
-increased metabolic demand
-decreased saturated hemoglobin

Front 154

Acute Ischemic heart disease

Back 154

Clinically, acute IHD is manifested as angina pectoris, the most sever myocardial infarct, or occassionally sudden cardiac death

Front 155

Angina pectoris

Back 155

A symptom complex manifested by paroxysmal attacks of substernal or precordial chest discomfort often described as a pressure, constriction, or heaviness which may extend to the neck, left jaw, left shoulder, and left arm. The discomfort arises from a temporary inability to supply sufficient oxygen to the heart muscles, i.e. myocardial ischemia and hypoxia. In 99% of the cases, angina is the result of atherosclerotic stenosis (narrowing) of the coronary arteries.

Front 156

Angina pectoris is induced or aggrevated by:

Back 156

-cold weather
-exercise
-heavy meals
-cigarette smoking
-emotional stress

Front 157

Nitroglycerin

Back 157

Helps angina pectoris by causing peripheral venous dilation, thereby reducing blood return and therefore the workload on the heart.

Front 158

Acute myocardial infarction

Back 158

Due to irreversible myocardial damage resulting from inadequate oxygenation of myocardial fibers. Due to either occluded or markedly reduced blood flow rather than increased metabolic demand. The reduced blood flow is usually due to an occlusive thrombus developing on the surface of an atherosclerotic plaque. The risk of acute thrombosis depends more on the biology of the plaque than it does on the size. Clinical symptoms are often dependant on the site of the infarct and its severity, typical presentation is a crushing, substernal chest pain, unrelieved by rest or nitroglycerin.

Front 159

Acute myocardial infarction causes

Back 159

-60% of the deaths related to ischemic heart disease

Front 160

Acute myocardial infarction is accompanied by

Back 160

-nausea
-vomitting
-diaphoresis
-arrhythmias
-hypotension
-shock

Front 161

Most infarcts occur in the distribution of

Back 161

the left anterior descending coronary artery (i.e. the anterior interventricular septum and the anterior and lateral left ventricular wall)

Front 162

Changes due to an infarct:

Back 162

-one day after the infarct, the affected area becomes pale
-there is a typical acute inflammatory response to the damaged myocardial cells followed by the appearance of granulation tissue and eventual scar formation

Front 163

When myocardial cells die they release cytoplasmic enzymes into circulatin

Back 163

First, there is elevation of serum CPK during the first 24 hours but this will return to normal in 3-5 days. There is a slower rise in serum LDH which persists 7-12 days.

Front 164

Troponins

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Part of the contractile proteins of skeletal and myocardial muscle that are released into the serum when muscle necrosis occurs.

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cardiac Troponin-1 (cTn-1)

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Is the most cardiac specific troponin. It does not rise in response to skeletal muscle injury. However, it does begin to rise within 2 hours of myocardial cell injury and remains elevated for up to 2 weeks. It may become the preferred diagnostic marker of the future replacing both CK and LDH determinations.

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Complications of acute myocardial infarction

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-cardiac arrhythmias (90%)
-left ventricular dysfunction
-mural thrombosis and embolization
-rupture of left ventricular wall
-ventricular aneurysms

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Modes of intervention for acute myocardial infarction

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-thrombolytic therapy
-angioplasty
-coronary bypass

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Sudden cardia death

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Occurs less than one house after onset of symptoms. This is usually associated with fatal arrhythmias precipitated by an acute ischemic event. 90% of patients have severe coronary disease and 50% have evidence of old infarcts but only rarely acute infarcts. Sudden cardiac death can occur without clinical or morphologic evidence of coronary disease.

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Chronic Ischemic heart disease

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Asymptomatic, slow, progressive atherosclerotic coronary disease may become manifested by the insidious onset of congestive heart failure as the cardiac reserve is slowly depleted. Accounts for 40% of deaths from Ischemic heart disease. Most patients have a past history of angina or myocardial infarction, and the heart failure may allow a precipitating illness such as pneumonia.

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Chronic ischemic heart disease is characterized by:

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-diffuse myocardial atrophy
-spotty loss of myocardial cells (myocyolysis)
-diffuse fibrosis
-possible scarring from previous infarcts

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Valvular stenosis

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Implies failure of a valve to open properly thereby creating obstruction to the forward flow of blood.

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Acquired stenosis

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Almost always due to a primary abnormality of the cusps or leaflets.

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Valvular Insufficiency

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Implies an inability of a valve to close properly and thereby allows for the backward flow of blood. It can be due to intrinsic valve disease or damage to the valve's supporting structures.

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Rheumatic heart disease

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A consequence of cardiac involvement in a systemic inflammatory disease, rheumatic fever.

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Rheumatic fever

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May follow an infection by B-hemolytic streptococci (usually strep throat). It is much more common in children than in adults (90% of first attacks occur between 5 and 15) and at that age is more likely to involve the heart. It induces an inflammatory reaction in all layers of the heart (pancarditis). As the frequency of rheumatic fever decreases with age, the signs and symptoms are more likely to be milder and related primarily to arthritis.

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Rheumatic fever is characterized by one or more of the following:

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-migratory polyarthritis
-carditis
-erythema marginatum
-subcutaneous nodules
-Sydenham chorea

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Rheumatic fever symptoms are due to:

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Immunologic cross reactivity between streptococcal antigens and host tissue antigens.

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Pericarditis

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Acute fibrinous inflammation of the pericardium may cause a friction rub on auscultation. Aspect of rheumatic fever.

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Myocarditis

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Focal necrosis and inflammation of the myocardium may lead to cardiac arrhythmias. Aspect of rheumatic fever.

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Endocarditis

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This is the most crippling and destructive aspect of rheumatic heart disease. Healing of inflammation that occurs in the heart valves results in fibrous, thickened, rigid valves whose leaflets or cusps become fused and calcified. This leads to valvular stenosis and insufficiency (primarily involving the mitral valve and, in some cases, the aortic valve).

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Calcific aortic stenosis

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Calcified nodules develop and obstruct the flow of blood through the valve. This is most often seen in elderly patients and may be the result of chronic "wear and tear" valvular damage. Unlike rheumatic valves, however, there is little or no fusion of the valve cusps or leaflets. Symptoms (dyspnea, angina, syncope) generally are referable to the left heart failure or inadequate cardiac output and once they appear, median survival is only 2-3 years unless the valve is replaced.

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Mitral valve prolapse

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This is a common condition (5-7% of general population, more frequent in young women) which may in some cases be congenital in orgin. It may be related to a metabolic defect in connective tissue metabolism. The majority of patients are asymptomatic but death can result from complications of infective endocarditis, from chronic congestive failure, from chordal rupture or from arrhythmia.

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Mitral valce prolapse is characterized by:

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-enlarged mitral leaflets
-elongated chordae
-Eventually, the leaflets thicken as do the chordae (which may also fuse)

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Infective endocarditis

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This involves the development of friable septic vegetations (thrombi with embedded bacteria) on heart valves or endocardial surfaces. Fragments of these vegetations may break off and spread infection throughout the body via septic emboli.

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Acute Endocarditis (ABE)

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In this form of infective endocarditis, virulent organisms such as staphylococcus aureus can directly damage the heart valves and promote thrombus formation. The bacterial damage of the endocardial surface which promotes thrombus formation and the bacterial colonies get entrapped within the developing thrombus. As many as 70% of these patients may die as a result of heart failure, emboli, arrhythmias, or uncontrolled sepsis.

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Acute endocarditis can be seen in:

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-IV drug users
-chronic alcoholics whose hearts usually do not have underlying abnormality
-patients on whom previous cardiac surgery has been performed
-patients who have had "foreign bodies" introduced into the cardiovascular system

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Acute endocarditis causes an abrupt onset of:

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-high fever
-shaking chills
-profound weakness

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I.V. drug users

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They inject microorganisms directly into veins, hence the endocarditis tends to predominantly affect right-sided valves.

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Subacute endocarditis (SBE)

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In this form of infective endocarditis, hearts characteristically have some underlying disease with either valvular or congenital abnormalities that predisposes to thrombus formation on the endocardial surfaces. These may then become seeded by organisms of relatively low virulence. Streptococcus viridians is the predominant organism and the mitral and/or aortic valves are the most commonly affected valves. Mortality ranges up to 15%.

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Subacute endocarditis onsets:

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-insidious with progressive weakness
-weight loss
-anemia
-fever
-occassional night sweats

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After ischemic heart disease, what is the most common cause of cardiac failure and death?

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Hypertensive heart disease

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What causes hypertension?

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-chronic renal disease
-certain hormone-producing tumors

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Hypertensive heart disease

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(blood pressure > 140/90)
Widespread arteriolar vasoconstriction increases resistance to left ventricular outflow and creates a pressure overload on the left ventricle. The heart responds to a pressure overload by concentric hypertrophy of the ventricle which thickens the wall, increases heart weight (without significant increase in size), and decreases ventricular volume. In the absence of any other abnormality that might produce left ventricular hypertrophy (i.e. valve disease), this is the identifying hallmark of hypertension. With an increased diastolic pressure, the heart must work harder to pump the same amount of blood. When it is no longer able to adapt to the change in work load, the heart begins to decompensate and the ventricle dilates (increasing heart size) and obscures the hypertrophic changes. Hypertension is generally asymptomatic until cardiac decompensation intervenes and there is an insidious onset of symptoms of left heart failure.

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Blood pressure is principally governed by:

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-cardiac volume output
-the peripheral arteriolar resistance

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Untreated hypertension will result in death due to:

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-heart failure
-stroke
-renovascular disease
-vascular complications

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Myocarditis

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This refers to any inflammatory condition that involves the myocardium. It ranges from a fulminant disease with abrupt onset and acute cardiac failure to asymptomatic disease. Over half of the cases are caused by viruses and are most frequently seen in infants, pregnant women, and immnuosuppressed patients. the viral infections tend to make the hard soft and flabby. The inflammation usually resolves in 6-8 weeks but may progress to chronic disease requiring heart transplantation.

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Symptoms of myocarditis:

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-tachycardia
-arrhythmias
-low grade fever
-dyspnea
-malaise

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Cardiomyopathy

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Refers to non-inflammatory diorders of the myocardium.

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Dilated (congestive) cardiomyopathy

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Characterized by dilation and hypertrophy of all chambers of the heart with impairment of ventricular contraction and congestive heart failure. There is always ventricular heart weight due to ventricular hypertrophy. The myocardium shows diffuse interstitial fibrosis without evidence of inflammation or severe coronary atherosclerosis. Due to poor contractility, mural thrombi are prone to develop (most frequently in the lefft ventricle).

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Causes of dilated (congestive) cardiomyopathy

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-alcoholic
-familial
-peripartum
-nutritional
-post-infectious cardiomyopathies

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Hypertrophic (obstructive) cardiomyopathies is also known as

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Also known as asymmetric septal hypertrophy (ASH) and idiopathic hypertrophic subaortic stenosis (IHSS).

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Hypertrohpic (obstructive) cardiomyopathy is characterized by:

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-disproportional hypertrophy of the interventricular septum with myofiber disarray
-dilated atria
-decreased ventricular volume
-mitral valve thickening
-endocardial thickening of left ventricular outflow tract
-thickening of the intramural arterioles

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Hypertrophic (obstructive) cardiomyopathy

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The asymmetrically hypertrophied septum of the left ventricle may or may not result in signs and symptoms of obstruction of the left ventricular outflow. If the septal hypertrophy is more prominent in the lower portion of the IVs, obstructive symptoms are less likely to occur than if the hypertrophy is higher in the septal wall. In those cases where the aortic outflow tract is compromised, as the heart begins to fail and dilate, the obstruction is relieved and the symptoms paradoxically improve. Some people develop sudden fatal arrhythmias or progressive heart failure complicated by embolization from atrial thrombi or infective endocarditis.

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Restrictive/Infiltrative cardiomyopathies

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These are rare conditions characterized by restriction of ventricular filling. Although the pathologic process is different, the clinical signs and symptoms are essentially the same as dilated cardiomyopathy. Amyloidosis, sarcoidosis, hemochromatosis, Pompe diesease all result in diffuse infiltration of the myocardium by abnormal substances thereby restricting normal myocardial compliance and elevating the ventricular filling pressures.

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Acute pericarditis

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This is generally due to infectious organisms or irritation of the pericardium and can lead to the accumulation of either fibrinous, serous, purulent, or hemorrhagic fluid. In general, rapid fluid buildup (effusions, exudates, blood, etc) will compress the heart, prevent venous blood from entering, and therefore decrease cardiac output (cardiac tamponade).

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Chronic pericarditis

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This may lead to obliteration of the pericardial sac which can interfere with the ability of the heart to contract normally and thereby interfere with cardiac output.

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Abdominal aortic aneurysm

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These are the most commonly encountered aortic aneurysms and almost all are the result of the atherosclerotic weakening of the aortic wall. They generally occur in middle-aged to elderly males, half of whom are hypertensive. they develop slowly over time and do not produce clinical symptoms until they become large or until they rupture.

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The majority of abdominal aortic aneurysms occur in:

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The distal abdominal aorta where atherosclerosis tends to be most severe

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Thoracic aortic aneurysms

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Clinical symptoms are more common because of the location. Compression of lungs, trachea or bronchi may lead to respiratory problems; compression of the esophagus may lead to dysphagia; compression of the recurrent laryngeal nerver may lead to hoarseness; and erosion of bony structures may lead to pain.

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Cystic Medial necrosis

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This disorder is responsible for the majority of thoracic aortic aneurysms. It is a chronic degenerative process of unknown etiology that results in focal destruction of the media of the thoracic aorta. It is most likely due to a metabolic defect in the synthesis of collagen and elastin and is frequently associated with Marfan syndrome (a metabolic connective tissue disorder). However, it is also seen in other conditions (hypertension) as well as normal aging.

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Syphilis (luetic)

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A consequence of tertiary syphilis, these aneurysms are generally limited to the ascending aorta and aortic arch. Inflammation caused by the organism produces weakening of the aortic wall thereby allowing aneurysm formation. Most patients will die of heart failure, but the aneurysm may rupture.

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Aortic dissection (dissecting aneurysm)

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This is more common than rupture of atherosclerotic aneurysms and involves tearing of the inner linging of the aorta with dissection of blood into and along the wall. Hypertension is frequently an associated condition. These present as a "tearing" pain in anterior chest radiating into and down the back. May be very similar to myocardial infarction or perforated peptic ulcer.

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When aortic dissections occur in the proximal aorta, a major cause of death is:

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-retrograde dissection
-rupture into the pericardial cavity
-cardiac temponade

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Peripheral vascular disease

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This occurs as a result of gradual buildup of atheroscleotic plaques (often as a complication of diabetes) in peripheral arteries, most frequently the arteries to the legs. As the arteries are narrowed by atherosclerosis, there will be eventual ulceration and gangrenous necrosis of the skin and underlying tissues.

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Varicose veins

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Most commonly seen in the superficial leg veins and becomes more clinically apparent with increasing age, especially in females. Increased hydrostatic pressure may simply be the result of gravitational effects or it may be due to venous obstruction or compression. As the vessels dilate, they become elongated and tortuous. The overall effect is to create chronic soft tissue edema, venous stasis, and thrombosis. The skin may develop stasis dermatitis and chronic ulcerations.

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Varix

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refers to any venous dilation that results from chronic elevations of intravascular hydrostatic pressure.