Lecture 1 Pathology PDF

Introduction to Pathology Pathology: the study (logos) of suffering or disease (pathos). The study of the structural, biochemical, and functional changes in cells, tissues, and organs that are involved by disease. The science of causes & effects of diseases, especially the branch of m...

Introduction to Pathology Pathology: the study (logos) of suffering or disease (pathos). The study of the structural, biochemical, and functional changes in cells, tissues, and organs that are involved by disease. The science of causes & effects of diseases, especially the branch of medicine that deals with laboratory examination of samples of body tissue for diagnostic or forensic purposes A bridge between the basic sciences and clinical medicine. Uses morphologic, molecular, microbiologic, and immunologic techniques trying to reach a diagnosis and explanation. Pathologist: a physician who interprets and diagnoses the changes caused by disease in tissues and body fluids. How to reach diagnosis (most imp. part): 1) history 2) physical exam 3) investigation (involve pathology) Introduction General pathology: reactions of cells and tissues to abnormal stimuli. − Cell injury, inflammation and repair, hemodynamic disorders, genetic disorders, immune system diseases, infectious disease and environmental diseases. Systemic pathology: alterations in specialized organs and tissues in diseased status. Aspects of disease Achondroplasia: usually new mutation 1. Etiology/ cause: o Genetic: mutations (may be congenital or acquired) o Acquired: infectious, nutritional, chemical. 2. Pathogenesis: sequence of events in response of cells / tissues to the etiologic agent, from initial stimulus to ultimate expression of the disease. (mechanism). o include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. Classification of Pathology : Anatomical/ surgical pathology: (major part) Clinical pathology: Gross and microscopic examination to reach a diagnosis. (morphology of tissue and cell) hematology, microbiology, immunology, Includes: serology and biochemistry − Histopathology: tissue examination − Cytopathology: cellular examination − Autopsy: postmortem examination − Subspecialties: neuropathology, dermatopathology, oral pathology, (any organ) Diagnosis in Anatomical pathology Biopsies (tissue) excisional(whole tissue removal) incisional (part of tissue removal) Smears (cells): exfoliative (pap smear used for screening of Cervical CA) fine needle aspiration (breast/ thyroid) Examples: breast mass − Start by history, physical and investigation (mammogram/ US) then Take biopsy (true cut/ excisional) Type of biopsy advantage limitations Fine Needle Easy to obtain with ultrasound/CT guidance of peripheral adenopathy: Only a few cells.(limited use) Aspiration (FNA) Can identify carcinoma in LN. Can Identify infectious cause eg. TB. Can identify renal cell carcinoma, Willims tumor. Would likely not identify Lymphoma/leukemia Core biopsy (larger More tissue - more confident diagnosis. Won’t identify Hodgkins Lymphoma needle) Able to send flow cytometry to confirm lymphoma diagnosis Usually able to obtain 4 - 6 biopsies. Excisional Biopsy Most tissue. Most invasive, takes extra time to arrange Necessary for diagnosis of Hodgkin's ( only need core biopsy for RELAPSED Hodgkin's) EBUS/TANA Necessary for lung lesions that cannot be reached in any other way Same as FNA Ayah Bani Mostafa  Stages of tissue processing: processing and preservation of cells and tissues 1. Specimen identification and labeling: − Tissue specimens received in surgical pathology lab have a request form that lists patient information & history along with a description of the site of origin. − In pathology lab: The specimen is accessioned by giving them a number that will identify each specimen for each patient 2. Gross examination 3. Fixation: by 10 %formaldehyde (formalin), to prevent autolysis 4. Dehydration: by exposing the specimens to solutions of increasing alcohol concentration 5. Clearing: by immersing specimens in xylene or toluene 6. Impregnation 7. Embedding in molten paraffin 8. Section cutting 9. Staining: − Hematoxylin-eosin staining (H&E staining): Blue Nucleus Red: like cytoplasm and extracellular 10. Mounting CELLULAR RESPONSES AND ADAPTATIONS TO STRESS basic principles organ: differentiated structure (such as a heart, kidney, liver/stomach) consisting of cells and tissues, performing some specific function in an organism: − an organ is in homeostasis with the physiologic stress placed on it (homeo-stasis): the normal condition or − an increase, decrease , or change in stress on an organ can result in cellular responses. the standard environment that the cell looks to live in cellular responses : 1. adaptation: hypertrophy, hyperplasia, atrophy, metaplasia. 2. injury: reversible and irreversible (cell death). 3. apoptosis: programmed cell death 4. intracellular accumulation; calcification 5. cellular aging. whether a specific form of stress induces adaptation or causes reversible or irreversible injury depends on: − nature and severity of the stress: o Fast, severe change, prolonged > cell injury o Less severe> cellular adaptation o if the adaptive capability is exceeded or if the external stress is extremely harmful, cell injury will develop. − the involved cell itself. adaptation is a new steady state which the cells enter in response to stress or extracellular events, trying to preserve viability and function. 1. growth adaptations: reversible changes in size, number, phenotype, metabolic activity or function in response to changes in their environment. things that might change around the cell: ph, temp., electrolytes level, glucose. can be: − physiologic (e.g, uterine enlargement during pregnancy) or − pathologic (e.g, myocardial hypertrophy secondary to systemic htn), if stress is excessive or persistent , adaptations can progress to cell injury (e.g, significant lv hypertrophy → injury to myofibrils→hf) Ayah Bani Mostafa  a) hypertrophy left ventricle hypertrophy. − an increase in stress leads to an increase in organ size. o occurs via an increase in the size of cells (hypertrophy ) and/or the number of cells (hyperplasia). − hypertrophy involves gene activation, protein synthesis , and production of organelles. (in the same cell) − hypertrophy is an increase in cell size resulting in increase in the size of the organ. − mechanism: increased production of cellular structural proteins and organelles. − Due to increased functional demand (workload) or stimulation by hormones or growth factors. − there is a limit for hypertrophy. b) hyperplasia: − the production of new cells from stem cells. − increased number of cells resulting in increased mass of the organ or tissue. physiologic (hormone related or compensatory) pathologic (excessive hormones) examples: Examples: o uterine enlargement during pregnancy o hyperplasia of endometrium (excessive hormone stimulation) o female breast in puberty & lactation due to unopposed estrogen o compensatory hyperplasia in partial liver o prostate hyperplasia. (elderly males due to androgen) resection. o wound healing (effects of growth factors)> scars o infection by low-risk papillomavirus (skin warts). − hyperplasia can be a fertile soil for development of malignancy (pathological). o pathologic hyperplasia (e.g., endometrial hyperplasia) can progress to dysplasia and eventually , cancer. o A notable exception is benign prostatic hyperplasia (bph) , which does not increase the risk for prostate cancer. − hyperplasia and hypertrophy generally occur together (e.g. uterus during pregnancy ). o except: permanent tissues (e.g., cardiac muscle, skeletal muscle , and nerve) cannot make new cells and undergo hypertrophy only. o for example , cardiac myocytes undergo hypertrophy , not hyperplasia , in response to systemic hypertension c) atrophy − reduced size of cell, tissue or organ as a result from loss of cell substance (size and number). − cell size & function will be diminished but the cell is still alive and can at some point go back to normal status. physiologic : pathologic: o embryonic development. o decreased workload (disuse atrophy) in fractures o involuting gravid uterus. o loss of innervation (denervation atrophy) o diminished blood supply. o inadequate nutrition. (thyroid in iodine deficiency) o loss of endocrine stimulation. (early menopause) o aging. − a decrease in stress (e.g. decreased hormonal stimulation, disuse , or decreased nutrients/blood supply) leads to decrease in organ size (atrophy). I. occurs via a decrease in the size and number of organelles in cells. II. decrease in cell number occurs via apoptosis. III. decrease in cell size occurs via ubiquitin-proteosome degradation of the cytoskeleton and autophagy of cellular components. − mechanisms: o decreased protein synthesis and increased protein degradation. o reduced metabolic activity, which causes decreased protein synthesis also. o atrophy is mainly induced by ubiquitin-proteasome pathway: protein binds organelles → signals (kill me) → decrease # of organelles. o autophagy (self-eating) to find sources of protein. (starvation). undescended testis atrophy: high temp. > atrophy Frontal lobe atrophy: deeper sulci, thinner gyri: due to chronic ischemia/ neurodegenerative (e.g: Alzheimer disease) Ayah Bani Mostafa  d) metaplasia − a change in stress on an organ leads to a change in cell type (metaplasia). − most commonly involves change of one type of surface epithelium (squamous, columnar, or urethral ) to another − metaplastic cells are better able to handle the new stress. − → from mature cell type to another mature. − Examples: 1. Barrett esophagus is a classic example: o esophagus is normally lined by non-keratinizing squamous epithelium (suited to handle friction of a food bolus) o acid reflux from the stomach causes metaplasia to nonciliated , mucin producing columnar cells (better to handle the stress of the acid) o reprogramming of stem cells →replacement of one cell type by another that can adapt to a new stress. o new epithelium is better in dealing with the current stress or irritation. → but it will lose many functions. o persistence of factors causing metaplasia may lead to progression into malignant transformation. 2. replacement of ciliated columnar epithelium by stratified squamous epithelium in the respiratory tract of a smoker. 3. mesenchymal (connective) tissues can also undergo metaplasia. o classic example is myositis ossificans in which connective tissue within muscle changes to bone during healing after trauma. − metaplasia occurs via reprogramming of stem cells , which then produce the new cell type. − metaplasia is reversible, in theory , with removal of the driving stressor. o for example, treatment of gastroesophageal reflux may reverse Barrett esophagus. o under persistent stress, metaplasia can progress to dysplasia and eventually result in cancer: → barrett esophagus may progress to adenocarcinoma of esophagus. o a notable exception is apocrine metaplasia of breast, which carries no increased risk for cancer. (because it is physiological). dysplasia − disordered, precancerous epithelial cellular growth; not considered a true adaptive response. − characterized by loss of uniformity of cell size and shape (pleomorphism) ; loss of tissue orientation; nuclear changes. − most often refers to proliferation of precancerous cells − for example, cervical intraepithelial neoplasia(cin) represents dysplasia and is a precursor to cervical cancer. o Usually caused by high risk HPV − often arises from: o longstanding pathologic hyperplasia (e.g. endometrial hyperplasia) or metaplasia (e.g.,barrett esophagus) − dysplasia is reversible, in theory, with alleviation of inciting stress. − if stress persists, dysplasia progresses to carcinoma (irreversible). aplasia and hypoplasia − aplasia is failure of cell production during embryogenesis (e.g., unilateral renal agenesis) − hypoplasia is a decrease in cell production during embryogenesis, resulting in a relatively small organ: o (e.g., streak ovary in turner syndrome (XO). o Potter sequence: hypoplastic lung Ayah Bani Mostafa Ayah Bani Mostafa