Histopathologic and Cytologic Techniques PDF

Histopathologic and Cytologic Techniques LECTURE TOPICS 1 AND 2 Christian James R. Romawak, RMT Introduction to Pathology Pathology Logos – study Pathos – suffering - involves the investigation of the causes of disease and the associated changes at the levels of cells...

Histopathologic and Cytologic Techniques LECTURE TOPICS 1 AND 2 Christian James R. Romawak, RMT Introduction to Pathology Pathology Logos – study Pathos – suffering - involves the investigation of the causes of disease and the associated changes at the levels of cells, tissues, and organs, which in turn give rise to the presenting signs and symptoms of the patient Signs - Objective evidence - Measurable - Physical Observation Symptoms - Subjective evidence - Perceived by the patient Etiology - origin of a disease, including the underlying causes and modifying factors - “Why a disease arises?” (Genetic or Acquired) Pathogenesis - refers to the steps/ sequence in the development of disease - “How a disease develops?” Divisions of Pathology (Traditional) General Pathology - focuses on the cellular and tissue alterations caused by pathologic stimuli in most tissues Systemic Pathology - examines the reactions and abnormalities of different specialized organs Laboratory Classification by Function (Administrative Order No. 2007-0027) Clinical Pathology - Clinical Chemistry, Hematology, Immunohematology, Microbiology, Immunology, Clinical Microscopy, Endocrinology, Molecular Biology, Cytogenetics, Toxicology and Therapeutic Drug Monitoring, and other similar disciplines Laboratory Classification by Function (Administrative Order No. 2007-0027) Anatomic Pathology - Surgical Pathology, Immunohistopathology, Cytology, Autopsy, Forensic Pathology and Molecular Pathology  Cellular Response to Stress and Toxic Insult Cellular Adaptation 1. Retrogressive Changes - Becoming smaller than normal 2. Progressive Changes - Becoming larger than normal 3. Degenerative Changes - Due to aberrations in cell growth Retrogressive Changes 1. DEVELOPMENTAL CHANGES a. APLASIA - Incomplete or defective development of tissue/ organ bearing no resemblance to the adult structure - Organ or tissue is just a mass of fatty or fibrous tissue a. AGENESIA - Complete non-appearance of the organ Retrogressive Changes 1. DEVELOPMENTAL CHANGES c. HYPOPLASIA - Failure of organ to reach its adult size due to incomplete development d. ATRESIA - Failure of an organ to form an opening Retrogressive Changes 2. ATROPHY - Acquired decrease in size of normal mature tissue/organ - TYPES: a. PHYSIOLOGIC ATROPHY - natural, due to aging b. PATHOLOGIC ATROPHY - due to disease Progressive Changes 1. HYPERTROPHY - Increase in size of tissues/organs due to increase in size of individual cells - TYPES: a. TRUE HYPERTROPHY - Due to increase workload and endocrine stimulation b. FALSE HYPERTROPHY - Due to edema fluid and connective tissue proliferation Progressive Changes 1. HYPERTROPHY - TYPES: c. COMPENSATORY HYPERTROPHY - Occurs when one of the paired organs has been removed or functional insufficiency Progressive Changes 2. HYPERPLASIA - Increase in size due to increase in number of cells - TYPES: a. PHYSIOLOGIC HYPERPLASIA - Natural b. PATHOLOGIC HYPERPLASIA - Due to disease Degenerative Changes 1. METAPLASIA - Replacement of one type of cell to another - Adaptation to chronic injury/ irritation - Reversible, prone to malignancy 2. DYSPLASIA - “disordered growth” - Variation in size, shape and orientation associated with chronic inflammation and protracted irritation Degenerative Changes 3. ANAPLASIA - Regressive change in adult’s cells towards a more primitive or embryonic cell type - Utilized as criterion towards malignancy 4. NEOPLASIA - Continuous abnormal proliferation of cells w/o control Cell Injury - results when cells are stressed so severely, exposed to inherently damaging agents, or suffer from intrinsic abnormalities that they are no longer able to adapt - CAUSES: 1. Oxygen Deprivation 5. Genetic Factors 2. Chemical Agents 6. Nutritional Imbalances 3. Infectious Agents 7. Physical Agents 4. Immunologic 8. Aging Reactions Cell Death - With continuing damage, the injury becomes irreversible, at which time the cell cannot recover and dies - TWO TYPES: 1. Necrosis - Pathologic - Severe damage to membranes  enzymes leak out of lysosomes, enter the cytoplasm, digest the cell 2. Apoptosis - Normal cell death - Cell is deprived of growth factors or cell proteins are damaged beyond repair  cell kills itself Cell Death Cell Death Necrosis CYTOPLASMIC CHANGES increased eosinophilia - due to increase binding of eosin to denatured cytoplasmic proteins - loss of the basophilia that is normally imparted by the ribonucleic acid RNA in the cytoplasm more glassy homogeneous appearance mostly because of the loss glycogen particles may appear large and granular (cloudy swelling) Cell boundary lost Necrosis NUCLEAR CHANGES 1. KARYOLYSIS - Basophilia of the chromatin fades - Dissolution of nucleus 2. PYKNOSIS - Nuclear shrinkage, increased basophilia - DNA condenses into a solid shrunken mass 3. KARYORRHEXIS - Pyknotic nucleus undergoes fragmentation Necrosis PATTERNS OF TISSUE NECROSIS 1. COAGULATIVE NECROSIS - Tissues take on a firm texture - Rapid coagulation of cytoplasm due to intracellular enzymes set free - Microscopically, normal cells turn into ‘TOMBSTONES’ Necrosis PATTERNS OF TISSUE NECROSIS 2. LIQUEFACTIVE NECROSIS - Rapid total enzymatic dissolution of cells with complete destruction of entire cell - seen in bacterial or occasionally in fungal infections - e.g. pus in acute inflammation due to bacteria Necrosis PATTERNS OF TISSUE NECROSIS 3. GANGRENOUS NECROSIS - Massive necrosis due to loss of blood supply and superimposed bacterial infection 4. CASEOUS NECROSIS - Often due to tuberculous infection - Cheese-like, friable yellow-white appearance - Destroyed cells converted into granular, friable mass made of coagulated protein and fat mixture Necrosis PATTERNS OF TISSUE NECROSIS 5. FAT NECROSIS - Due to release of activated pancreatic lipase into the tissues - Destruction of adipose tissue - FAT SAPONIFICATION - fatty acids plus calcium - Grossly visible chalky white areas Necrosis PATTERNS OF TISSUE NECROSIS 6. FIBRINOID NECROSIS - Immunologically mediated - FIBRINOID = Antigen-Antibody Complexes deposited in arterial walls plus Fibrin that has leaked out of the vessels Acute and Chronic Inflammation Inflammation - Brings leukocytes and plasma proteins to the site of infection and tissue damage to eliminate microbes and dead tissues - CARDINAL SIGNS 1. Calor (Heat) – due to increased rate of blood flow to site 2. Rubor (Redness) – transfer of heat to surface due to increased blood content Inflammation - CARDINAL SIGNS 3. Tumor (Swelling) – increased capillary permeability, allowing extravasation of blood fluid causing localized edema 4. Dolor (Pain) – damage on nerve ending or direct pressure on sensory nerve 5. Functio Laesa (Loss of Function) – due to pain interference with nerve supply and destruction of functioning units of tissue or limited movement due to swelling Inflammation Inflammation EXUDATES – high protein fluid or even blood cells escaping into the extravascular tissue due to increased permeability CLASSIFICATION ACCDG TO CHARACTER OF EXUDATE 1. SEROUS INFLAMMATION - Outpouring of watery, low-protein fluid 2. FIBRINOUS INFLAMMATION - Exudation of large amounts of fibrinogen and precipitation of fibrin masses Inflammation CLASSIFICATION ACCDG TO CHARACTER OF EXUDATE 3. HEMORRHAGIC INFLAMMATION - Exudate plus blood 4. PURULENT OR SUPPURATIVE INFLAMMATION - Pus or purulent exudates 5. CATARRHAL INFLAMMATION - Affects mucus surfaces - Hypersecretion of mucosa with degenerative changes in eputhelium - Mucus main component Inflammation GRANULOMATOUS INFLAMMATION - Chronic inflammation characterized by activated macrophages - Cellular attempt to contain an offending agent difficult to eradicate Mechanism of Tissue Renewal, Repair and Regeneration Repair/ Healing - Restoration of tissue architecture and function after an injury - TWO TYPES 1. REGENERATION - Proliferation of residual/ uninjured cells that retain the capacity to divide - Skin, intestines, liver Repair/ Healing - TWO TYPES 2. SCAR FORMATION - Laying down of connective tissue resulting to scar formation - Due to inability to regenerate, or supporting structure is severely damaged FIBROSIS – extensive deposition of collagen due to chronic inflammation Cell Proliferation INTERPHASE – period between mitosis CELL CYCLE G0 – Quiescent Phase CHECKPOINT G1 – Pre-synthetic Phase CHECKPOINT S – DNA Synthesis G2 – Pre-mitotic Phase M – Mitotic Phase Cell Proliferation G1 (Pre-mitotic gap) Phase - stage when messenger RNAs for the proteins and the proteins themselves required for DNA synthesis (e.g. DNA polymerase) are synthesized. S phase - replication of nuclear DNA. Cell Proliferation G2 (Pre-mitotic gap) Phase - short gap phase in which correctness of DNA synthesized is assessed. Mitotic Phase - Prophase, Metaphase, Anaphase, Telophase Stem Cells - Differentiate to become adult cells - TWO PROPERTIES: 1. Self-renewal 2. Asymmetric replication Stem Cells - TWO KINDS: 1. Embryonic Stem Cells - Most undifferentiated - Pluripotent, can be induced to form specialized cells 2. Adult Stem Cells - Less differentiated - Found within organ or tissue - Limited self-renewal, and lineage potential may be limited to the cells of the organs they are found Factors that Influence Tissue Repair 1. Infection 2. Nutrition 3. Glucocorticoids/ Steroids 4. Mechanical Variables 5. Poor perfusion 6. Foreign Bodies 7. Location of Injury 8. Aberrations of Cell Growth End of Lecture Histopathologic and Cytologic Techniques LABORATORY Christian James R. Romawak, RMT Diagnostic Cytology - microscopic examination of cells from different body sites for diagnostic purposes - identify malignant and pre-malignant cells - Specimen may be derived from various sources: a. Exfoliative Cytology b. Fine Needle Aspiration c. Body Fluids Exfoliative Cytology Exfoliative Cytology - deals with the microscopic study of cells that have been desquamated from epithelial surfaces - COLLECTION TECHNIQUES: Lightly Scraping the surface Swabbing Aspirating Washing the Surface Exfoliative Cytology - APPLICATIONS: 1. Detection of malignant cells 2. Detection of pre-cancerous lesions in women 3. Assessment of female hormonal status in case of sterility and endocrine disorder 4. Determination of genetic sex 5. Detection of infectious agents  Smear Preparation Smear Preparation - should be made from fresh material, prepared in the doctor's office or radiology units - REQUISITION FORM: name, age, date, and type of specimen - SLIDES LABEL: Laboratory identification number Smear Preparation - LAB IDENTIFICATION NUMBER: Type of Specimen – Year in 2 digits – Accession No. S - Surgical C - Cytology A - Autopsy C-24-0001 1. Cervical Smear Cervical Smear - Detection and screening for cancer of the uterine cervix - Cell samples taken from ECTOCERVIX and ENDOCERVIX PAPANICOLAOU METHOD – collection, smearing, and staining with Pap’s Stain - Cervical Cytology is only a screening test. Cervical Smear - Patient Preparation a. Abstain from coitus b. Do not douche vagina for at least a day c. No intra-vaginal preparations at least one week prior Specimen should NOT be taken during menstrual bleeding. Cervical Smear - Collection a. Brush biopsies - more endocervical cell and blood may be present, leads to valuation difficulties a. Cotton Swab - discouraged, prone to drying of artefacts and loss of cells b. Wooden spatula - Preferable to plastic spatula due to its mildly rough surface 2. Impression Smear Impression Smear - often used for ulcerated surface lesions - preparations should be quickly air dried and then stained - taken by touching the cut surface with a clean slide and fixing immediately 3. Sputum Smear Sputum Smear - 3 consecutive morning specimen - deep cough in a wide -mouthed jar containing Saccomanno fluid (50% ethyl alcohol and 2% carbowax) INDUCED SPUTUM - If patient cannot cough spontaneously - inhalation of an aerosol solution for 20 minutes to produce a deep cough sample Sputum Smear - Minimum of 2-4 slides (if more extensive study is to be made) One - air dried for Giemsa staining At least two slides - stained by Papanicolaou method Sputum Smear - Solid particles crushed slightly in between slides and evenly distributed with the liquid portion - Spx. fixed with ALCOHOL must be delivered to the laboratory IMMEDIATELY due to its hardening effect ALVEOLAR MACROPHAGES – indicative of sputum specimen from a deep cough  4. Bronchoscopy Specimen Bronchoscopy Spx. BRONCHIAL BRUSHING - directly smeared into two slides via pull technique, - then fixed via spray fixative or 95% alcohol BRONCHIAL APIRATES - Aspirating into a glass suction apparatus, or - Washing bronchi with 1-2cc of saline  5. Smears of Gastric Secretions and Aspirates Gastrointestinal Spx. 1. Gastric Lavage 2. Gastric Brush 3. FNA (for sub-mucosal lesions) Smears of Gastric Secretions and Aspirates - Via simple irrigation and aspiration - Immediately processed - Delay more than 30 mins = cells are digested - FASTING: 8 hours 6. Smears of Breast Secretion Smears of Breast Secretion - potential detection of malignant cells in a patient with clinically undetected carcinoma - Low diagnostic yield for breast carcinoma Spontaneous nipple discharge - usually a result of hormonal imbalance in young patients Bloody Secretion - a benign intraductal papilloma should be considered clinically Smears of Breast Secretion - Collected via gently stripping the subareolar area and nipple using the thumb and forefinger - Immediately drop slide in a bottle of 95% isopropanol or use spray fixative. - Label with right or left, if from both breasts  Fine Needle Aspiration (FNA) Fine Needle Aspiration - study of cellular samples obtained from organs that do not shed cells spontaneously (breast, thyroid, lymph nodes, liver, lungs, skin, soft tissues and bones) - useful in lesions that are easily palpable - COLLECTION: - 25-gauge needle and a 10-ml syringe - needle is inserted into the lesion and repeatedly redirected to sample a number of areas while applying a small amount of suction on the syringe Fine Needle Aspiration IDEAL ASPIRATE: creamy consistency with numerous cells suspended in a small amount of tissue fluid without admixture with blood Solid lesion - usually a few drops from the tip of the needle has the most diagnostic material for cytologic evaluation Bloody Specimen - diagnostic cells are diluted and hard to find on a direct smear.  Slide Preparation Slide Preparation Bloody Specimen 1. Prepare a maximum 4 slides: using 1-2 drops on each slide and using slide-pull technique (similar to the technique used for peripheral blood smears). 2. Rinse the needle in a preservative solution such as Saccomano fluid, and process like any other body effusion specimen. Slide Preparation STAIN TREATMENT Hematological Air dried Smears not correctly made and stains dried quickly will produce artefacts Papanicolaou Rapidly fixed in If the smears are allowed to (Pap) or alcohol to show dry and not quickly fixed in hematoxylin nuclear details and alcohol, drying artefact can and eosin allow better occur, the cytoplasm will be (H&E) identification of more eosinophilic, and nuclear malignant cells details will appear fuzzy Body Fluids Body Fluids - cast light on the origin and type of primary tumors as opposed to reactive processes SEROUS EFFUSION - Fluids in the three serous cavities a. Pleural Fluid b. Pericardial Fluid c. Peritoneal Fluid - Presence of Malignant Cells: Metastasis Body Fluids 300 units of HEPARIN per 100mL aspirate - Added to prevent jelly-like clots Preferred: Freshly tapped spx. - Immediate processing not possible: Preserve on refrigerator (24-48hours), or pre-fix in 50% ethanol Body Fluids CYTOSPIN PREPARATION - Best method to collect cells from body fluids CENTRIFUGATION - Used in the absence of cytospin DISADVANTAGE IN THE USE HOW TO AVOID? OF CYTOCENTRIFUGE Distortion of cellular immediate fixation or by morphology due to air using an equal volume of drying artifacts polyethylene glycol.  Preparing Cytospin Slides Preparing Cytospin Slides 1. Centrifuge ASAP at 1000 rpm for 1 minute. 2. Remove supernatant 3. Make a smear on a slide coated with a thin layer of egg albumin. 4. Spread with another slide. 5. When edges begin to dry but the center is still moist, fix with 95% alcohol. Smears cannot be prepared immediately: Cover sediment with absolute alcohol and place in the refrigerator. 1. Urinary Tract Specimen Collection a. VOIDED URINE - first voided urine should be discarded, due to the overnight degeneration of cell/ prolonged bladded retention - PREFERRED SPX.: second urine - Delay in Transportation: refrigeration only, preservatives NOT recommended b. CATHETERIZED SPECIMEN c. WASHINGS FROM BLADDER OR PELVIS Collection MALE FEMALE Voided urine sufficient for Catheterized specimen is cytological evaluation recommended to prevent contamination of specimen with vulvar cells - VOLUME: At least 50 ml 2. Body Cavity Effusions Body Cavity Effusions - collected in a clean, non-sterile dry container - submitted fresh to the laboratory CEREBROSPINAL FLUID - Cells degenerate very quickly and are usually present in very low numbers - The addition of an equal amount of ethyl alcohol to the cerebrospinal fluid (CSF) is recommended if a delay in processing is anticipated. - minimum amount of 1 cc. is necessary for cytologic evaluation Adhesives Adhesives 1. Pooled human serum/plasma 2. Celloidin ether-alcohol 3. Leuconstoc culture Specimen Requiring Adhesives 1. Urinary Sediment 2. Bronchial lavage 3. Concetrated sputum 4. Lavage sample from GIT Fixation in Cytology Fixation - Process of preserving the specimen - Optimal Fixation: Dropping the smears in 95% ethyl- alcohol for 3-5 minutes (Use paper clip on every other slide to avoid slide surface contacts, and proper exposure to the fixative) - Exfoliated cells: Fix with a spray fixative or aqueous- alcoholic solutions containing polyethylene glycol or Carbowax. Wet Fixation - process of submerging of freshly prepared smears immediately in a liquid fixative ALCOHOL FIXATIVES a. 95% Ethyl Alcohol (Ethanol) - Ideal fixative recommended in most laboratories for cytological specimen - As a dehydrating agent, it causes enough cell shrinkage to yield optimal chromatin detail characteristics of cytological preparations. Wet Fixation b. Ether alcohol mixture - originally recommended by Papanicolaou. - equal parts of ether and 95% ethyl alcohol - ether is not used in most of the laboratories because of its safety hazards c. 100% Methanol - acceptable substitute for 95% ethanol - causes less shrinkage and is more expensive than ethanol. d. 80% Propanol and Isopropanol e. Denatured alcohol Wet Fixation NON-ALCOHOL FIXATIVES a. Carbowax (Polyethylene Glycol) fixatives - substitutes for wet fixatives - either aerosols applied by spraying the cellular samples or a liquid base dropped onto the slide - Prior to staining, the slides should be kept overnight in 95% alcohol to remove of the coating fixative. Wet Fixation NON-ALCOHOL FIXATIVES b. Carnoy’s fixative - special purpose fixative used to hemolyze the red blood cells in hemorrhagic samples - excellent nuclear fixative as well as preservative for glycogen but results in considerable shrinkage of cells and tends to produce over staining in hematoxylin - must be prepared fresh when needed and discarded after each use Precautions 1. Identify the slides before preparing smears. 2. Attach a paper clip to the identified end of the slide before preparing the smear. Paper clip prevents the slide from sticking together in the fixative 3. Smears should be placed into the fixative container immediately after preparations. 4. Place each smear in fixative by a single uninterrupted motion to avoid rippling of smeared material. 5. Avoid striking the bottom of the fixing container forcefully to prevent dislodging the material from the slide. End of Laboratory Histopathologic and Cytologic Techniques LECTURE Christian James R. Romawak, RMT  Classification of Disease According to Basic Etiologic Mechanisms, their Features and Laboratory Findings 1. Neoplasms Neoplasia - “New growth” - aka tumor ONCOLOGY – study of tumors - IMPORTANT FACTORS OF CARCINOGENESIS: Infectious agents Smoking, alcohol Diet, obesity Reproductive history Environmental carcinogens Basic Components of a Tumor 1. PARENCHYMA - Active elements of the tumor 2. STROMA - Connective tissue framework with lymphatic and vascular channels Classification based on Potential Clinical Behavior 1. BENIGN - Do not pd. death - microscopic and gross characteristics are considered to be relatively innocent, implying that it will remain localized - amenable to local surgical removal; 2. MALIGNANT - aka cancer, will pd. death - can invade and destroy adjacent structures and spread to distant sites (metastasize) Classification based on Potential Clinical Behavior BENIGN MALIGNANT Usually encapsulated Increase number of cells Grow slowly that accumulate Usually non-spreading Usually invade tissues With minimal mitotic Disseminate by lymphatic activity spread or direct seeding Resemble present tissue within cavity Characteristic nuclear feature Classification based on histological characteristics 1. MEDULLARY - More cells than supporting tissue - Soft ad very malignant 2. SCHIRROUS - More connective tissue than cells - Cell are trapped within connective tissues - Stony/hard Nomenclature 1. BENIGN - Use suffix –oma 2. MALIGNANT Sarcoma – if solid, mesenchymal/connective tissue (name is designated by cell) Carcinoma – if epithelial, regardless of tissue of origin Leukemias/ Lymphomas - arising from the mesenchymal cells of the blood EXAMPLES ONLY! Broder’s Classification - Based on differentiation of cells - Generally, well differentiated tumors are less malignant DIFFERENTIATED CELLS – resemble normal cells UNDIFFERENTITAED CELLS – resemble younger forms, anaplastic Broder’s Classification GRADE DIFFERENTIATED UNDIFFERENTIATED I 100-75% 0-25% II 75-50% 25-50% III 50-25% 50-75% IV 25-0% 75%-100% TNM System - Based on Size of primary tumor (T) Extent of spread to the lymph nodes (N) Presence of metastasis (M)  2. Hereditary Disorders and Congenital Anomalies Hereditary Disorders and Congenital Anomalies HEREDITARY DISORDERS - Derived from parents, transmitted in the gametes through generations; familial - Not all genetic disorders are congenital CONGENITAL - Present at birth - Some congenital disorders are not genetic Hereditary Disorders - NATURE: Mutations and Alterations in Protein- Coding Genes or Chromosomes - Examples: Hereditary Spherocytosis, Familial Hypercholesterolemia, Phenylketonuria’, Sickle Cell Anemia, Hemophilia A , Cystic Fibrosis Congenital Abnormalities 1. DOWN SYNDROME – Trisomy 21 2. EDWARDS SYNDROME – Trisomy 18 3. PATAU SYNDROME – Trisomy 13 Newborn Screening - Enables early detection and management of metabolic disorders, which if left untreated may lead to mental retardation and death - Performed after 24 hours of life but not later than 3 days from complete delivery - Newborn in intensive care: May be exempted from 3-day requirement but must be tested by 7 days of age Newborn Screening DISORDERS THAT CAN BE DETECTED: 1. Congenital Hypothroidism 2. Congenital Adrenal Hyperplasia 3. Phenylketonuria 4. Galactosemia 5. Glucose-6-phosphate Dehydrogenase Deficiency 6. Maple Syrup Urine Disease Expanded Newborn Screening - From 6 disorders to MORE THAN 28 Newborn Screening - Method of Collection: Heel Prick - Specimen: Blood Spot on Filter Paper/ Paper Blot 3. Circulatory Disorders Vascular Disease Principal Mechanisms 1. Narrowing or complete obstruction of vessel lumina occurring either progressively (e.g., by atherosclerosis) or acutely (e.g., by thrombosis or embolism) 2. Weakening of vessel walls, causing dilation and/or rupture Common Vascular Diseases 1. HYPERTENSION - major health problem in the developed world - increases the risk of stroke atherosclerotic coronary heart disease cardiac hypertrophy heart failure (hypertensive heart disease) aortic dissection multi-infarct dementia renal failure Common Vascular Diseases 1. HYPERTENSION - TYPES Idiopathic/ Essential Hypertension – 90-95% of cases Secondary Hypertension – due to primary renal disease, renal artery narrowing, or adrenal disorders Common Vascular Diseases 1. HYPERTENSION - RISK FACTORS Genetic – gene defects in enzymes in aldosterone metabolism, and mutations in proteins that affect sodium resorption Environmental - stress, obesity, smoking, physical inactivity, and high levels of salt consumption Common Vascular Diseases 2. ARTERIOSCLEROSIS - Hardening of arteries - generic term reflecting arterial wall thickening and loss of elasticity - THREE TYPES: a. Arteriolosclerosis b. Mönckeberg medial sclerosis c. Atherosclerosis Common Vascular Diseases 2. ARTERIOSCLEROSIS a. Arteriolosclerosis a. - affects small arteries and arterioles b. Mönckeberg medial sclerosis - presence of calcific deposits in muscular arteries - usually are not clinically significant. Common Vascular Diseases 2. ARTERIOSCLEROSIS c. Atherosclerosis - presence of intimal lesions called atheromas (atheromatous/atherosclerotic plaques). - Atheromatous plaques - raised lesions composed of soft grumous lipid cores (mainly cholesterol and cholesterol esters, with necrotic debris) covered by fibrous caps Common Vascular Diseases 2. ARTERIOSCLEROSIS - CONSTITUTIONAL RISK FACTORS for atherosclerosis : Genetics Age Gender – premenopausal women are relatively protected compared with age-matched men Common Vascular Diseases 2. ARTERIOSCLEROSIS - MODIFIABLE RISK FACTORS for atherosclerosis: Hyperlipidemia Hypertension Cigarette Smoking Type 2 DM Myocardial Infarction - MI, aka heart attack - Necrosis of heart muscle resulting from ischemia (loss of blood supply) - Ischemia can occur through: 1. Disruption of preexisting atherosclerotic plaque resulting to thrombosis 2. Coronary artery vasospasm leading to vasoconstriction Myocardial Infarction - CARDIAC MARKERS My Trop I CAL