BIOCHEMICAL COMPONENTS

Estrogen

Hormone that stimulates multicentric subcoelomic mesenchymal cells in the uterus to differentiate into smooth muscle cells

Osteoid

Protein (organic), non-mineralized component of bone matrix produced by an osteosarcoma

KRAS

Oncogene primarily involved in cell division regulation via the RAS/MAPK signaling pathway

Beta-catenin

Protein regulated by CDK8 and involved in the Wnt signaling pathway

APC (adenomatous polyposis coli)

Tumor suppressor protein responsible for degrading beta-catenin when it is no longer needed

p53

Tumor suppressor protein that repairs DNA damage and elicits apoptosis in cells with irreparable DNA damage

STK11 (serine/threonine kinase 11)

Tumor suppressor protein that regulates cell division, assists cells with polarization, and promotes apoptosis

PTEN (phosphatase and tensin homolog)

Protein that signals cells to stop dividing

BMPR1A (bone morphogenetic protein receptor 1A)

Receptor that activates Smad proteins upon binding to a ligand

Smad proteins

Effectors of the TGF-beta signaling pathway that normally inhibit cell growth/division

TGF-beta (transforming growth factor-beta)

Signaling pathway whose effector is the Smad protein, involved in regulating cell growth/division

Carcinoembryonic antigen (CEA)

A tumor marker associated with colon adenocarcinoma

CA 19-9

A tumor marker associated with colon adenocarcinoma

HER2/neu (c-erbB)

A molecule/marker whose overexpression in breast cancer connotes poor prognosis

BRCA1 and BRCA2

Tumor suppressors that regulate transcription and repair double stranded DNA breaks

CHEK2 (Checkpoint Kinase 2)

Cell-cycle checkpoint kinase that phosphorylates p53 and BRCA1 in response to DNA damage

Melanin

Pigment produced by melanoma cells, present in the cytoplasm as fine, brown granules

BRAF

Proto-oncogene that activates the MAPK pathway in melanomas

NRAS

Proto-oncogene that activates the MAPK and PI3K/AKT pathways in melanomas

KIT

Proto-oncogene that activates the PI3K/AKT pathway in melanomas

TERT

Gene whose mutations activate telomerase in melanomas

CDKN2A (INK4a)

Tumor suppressor gene encoding p16 and p14

p16

Tumor suppressor protein whose loss leads to unregulated CDK4 and CDK6 in melanomas

MDM2 and CDK4

Oncogenes that inhibit p53 and RB function and are overexpressed in osteosarcomas

VHL gene

Gene on chromosome 3 responsible for hereditary and sporadic clear cell renal cell carcinomas

PBRM-1, SETD2, BAP-1, KDM5C, and MTOR

Genes that contribute to the pathogenesis of clear cell renal cell carcinoma

MET oncogene

Oncogene associated with increased expression and activating mutations in papillary renal cell carcinoma

Parathyroid hormone (PTH)

Hormone produced by Renal Cell Carcinoma specimens that causes hypercalcemia

Parathyroid hormone-related peptide (PTHrP)

Hormone produced by Renal Cell Carcinoma specimens that causes hypercalcemia

Erythropoietin (EPO)

Hormone produced by Renal Cell Carcinoma tumor cells causing ectopic EPO production and polycythemia

UVB light

Chemical cause of DNA damage in skin cells that causes pyrimidine dimers to form in DNA, leading to melanoma

M protein

Streptococcal capsular protein involved in molecular mimicry and immunologic cross-reaction causing Rheumatic Heart Disease

NOTCH1

Gene with gain-of-function mutations associated with T-ALL, essential for T-cell development

PAX 5, E2A, and EBF

Genes with loss-of-function mutations required for B-cell development, associated with B-ALL

MLL gene

Gene whose translocations are strongly associated with poor prognosis T-ALL in individuals under 2 years old

BCL-2

Protein/gene whose overexpression causes lymph follicles to be almost non-distinguishable in Non-Hodgkin Lymphoma

BCL6

Protein/gene whose dysregulation results in the repression of signals that promote germinal center B-cell differentiation in Diffuse Large Cell B-cell Lymphoma

MYC proto-oncogene

Gene involved in translocations strongly associated with Burkitt Lymphoma

Collagen (Subendothelial)

Component of the atherosclerotic plaque exposed upon erosion that triggers platelet adherence and aggregation

Thromboxane A2

Molecule released by activated platelets, causing further platelet aggregation and vasospasm

ADP

Molecule released by activated platelets, causing further platelet aggregation and vasospasm

Serotonin

Molecule released by activated platelets, causing further platelet aggregation and vasospasm

Tissue factor

Molecule that activates coagulation and other mechanisms, adding to the growing thrombus in MI pathogenesis

Lactic acid

Potentially noxious metabolite that accumulates rapidly after cessation of aerobic metabolism in myocardial ischemia

ATP (adenosine triphosphate)

High-energy phosphate that shows inadequate production seconds after aerobic metabolism ceases in myocardial ischemia

Creatine phosphate

High-energy phosphate that shows inadequate production after aerobic metabolism ceases in myocardial ischemia

Sarcolemmal membrane

Structure whose disruption is the earliest detectable feature of myocyte necrosis, allowing intracellular macromolecules to leak out

Myocardial proteins (Intracellular)

Macromolecules that leak out of necrotic cells after sarcolemmal membrane disruption, forming the basis for MI blood tests

Reactive oxygen species (ROS)

Myocardial-derived chemical/molecule that drives the wavefront of cell death during prolonged ischemia

Superoxide anion (O2)

A free radical produced within minutes of reperfusion injury

Hydrogen peroxide (H2O2)

A free radical produced within minutes of reperfusion injury

Hypochlorous acid (HOCl)

A free radical produced within minutes of reperfusion injury

Nitric oxide-derived peroxynitrite

A free radical produced within minutes of reperfusion injury

Hydroxyl radicals (OH)

A free radical produced within minutes of reperfusion injury

Calcium ion

Ion whose influx across plasma membranes heightens actin-myosin interaction during reperfusion injury, causing contraction band necrosis

Actin

Thin myofilament whose interaction with myosin is regulated by calcium, contributing to contraction band necrosis

Myosin

Thick myofilament whose interaction with actin is regulated by calcium, contributing to contraction band necrosis

Tissue plasminogen activator (TPA)

Agent used in thrombolysis to dissolve thrombi and restore blood flow to ischemic myocardium

Cardiac-specific troponins T and I (cTnT and cTnI)

Most sensitive and specific biomarkers of myocardial damage that regulate calcium-mediated contraction

Creatine kinase (CK)

Enzyme expressed in the brain, myocardium, and skeletal muscle

MB fraction of creatine kinase (CK-MB)

MB heterodimer principally localized to cardiac muscle, used as a biomarker for MI

Myoglobin

Cardiac biomarker that elevates acutely following myocardial infarction

Aspirin

Antiplatelet agent used in therapeutic interventions for MI

ADP receptor inhibitors and GPIIb/IIIa inhibitors

Antiplatelet agents used in therapeutic interventions for MI

Unfractionated heparin, low-molecular weight heparin, direct thrombin inhibitors, and factor Xa inhibitors

Anticoagulant therapy used to prevent coronary artery thrombus propagation

Morphine

Chemical used to relieve pain and improve dyspneic symptoms in MI

Angiotensin-converting enzyme (ACE) inhibitors

Medications used to limit ventricular dilation post-MI

Actin and Myosin

The thick and thin filaments that form the cross-bridges in the sarcomere

Norepinephrine

Hormone released by adrenergic cardiac nerves, increasing heart rate, myocardial contractility, and vascular resistance

Aldosterone

Mineralocorticoid hormone that retains sodium and water, augmenting circulatory volume and increasing blood pressure

ANP (Atrial Natriuretic Peptide)

Hormone released to counterbalance the Renin-Angiotensin-Aldosterone System through diuresis and vascular smooth muscle relaxation

Amyloid

Protein that deposits in the heart and kidneys in infiltrative disorders; stains apple green with Congo red stain

Trophic signals

Signals mediated through activation of beta-adrenergic receptors that stimulate cardiac hypertrophy

Hemosiderin

Iron storage form seen in hemosiderin-laden macrophages ("heart failure cells") in the lungs due to previous pulmonary edema

Calcium salts/deposits

Substance that causes calcific aortic stenosis by affecting normal or bicuspid aortic valves

Osteoblasts

Cells resembling this type synthesize bone matrix proteins and promote calcium salt deposition in abnormal valves causing calcific aortic stenosis

Fibrillin-1 (FBN-1)

Gene mutated in Marfan syndrome, which alters cell-matrix interactions and dysregulates TGF-beta signaling

TGF-beta

Signaling molecule whose dysregulation leads to structural laxity and myxomatous change in mitral valve prolapse

Proteoglycans

Mucoid/myxomatous material deposited in the spongiosa layer of the valve in mitral valve prolapse

Histamine

Chemical released by sensitized mast cells that causes immediate vasodilation and increased vascular permeability in a wheal-and-flare reaction

Antibodies (against M proteins)

Autoantibodies that cross-react with self-antigens in the heart, driving the pathogenesis of Rheumatic Fever

Streptolysin O and DNase B

Streptococcal enzymes against which antibodies are seen in the serum of patients with Rheumatic Fever, indicating a previous infection

Cytokines

Molecules produced by CD4+ T-cells reacting with streptococcal peptides, activating macrophages (Anitschkow cells) in Rheumatic Fever

Fibrin

Protein that forms the thrombotic debris component of vegetations/verrucae in infective endocarditis

Tissue factor

Procoagulant molecule that may be tumor-derived, associated with the hypercoagulable state seen in NBTE associated with mucinous adenocarcinomas

Anti-nuclear antigen bodies

Antibodies that damage nuclei, forming homogenous remnants (hematoxylin bodies) seen in Libman-Sacks Endocarditis

Calretinin

Immunohistochemical stain that stains mesothelioma cells but not adenocarcinoma cells, aiding differentiation

CD34

Endothelial cell marker that solitary fibrous tumor cells stain positive for

Collagen, Elastin, and Proteoglycans

Extracellular matrix components synthesized by Vascular Smooth Muscle Cells

C-reactive protein (CRP)

Circulating marker of inflammation secreted from cells within atherosclerotic intima that activates endothelial cells and induces a prothrombotic state

Homocysteine

Serum molecule whose elevated levels are a risk factor for atherosclerosis

Vitamin B9 (folate) and Vitamin B12 (cobalamin)

Vitamins whose low intake can cause elevated homocysteine levels

LDL (low-density lipoprotein)

The "bad cholesterol" that brings cholesterol to peripheral tissues

HDL (high-density lipoprotein)

The "healthy cholesterol" that removes cholesterol from peripheral tissue to the liver for excretion

Lipoprotein (a)

Altered form of LDL associated with increased coronary and cerebrovascular disease risk

Thrombin and Platelet-derived factors

Molecules that affect hemostasis and are associated with atherosclerosis

VCAM-1 (vascular cell adhesion molecule-1)

Adhesion molecule that binds monocytes and T lymphocytes in early atherogenesis

ICAM-1 (intercellular adhesion molecule-1)

Adhesion molecule induced by TNF and IL-1 that facilitates leukocyte adhesion

Chemokines

Inflammatory mediators that influence monocytes to migrate between endothelial cells

Integrins

Molecules found in WBCs that mediate firm adhesion to endothelial ligands like VCAM-1 and ICAM-1