Biol 282 Lec 1 PDF

What is Cellular Pathology? Histopathology diagnostic information from patient tissue samples focus on multicellular structures in tissues Cytopathology diagnostic information from cell preparations focus o...

What is Cellular Pathology? Histopathology diagnostic information from patient tissue samples focus on multicellular structures in tissues Cytopathology diagnostic information from cell preparations focus on cellular morphology Pathology – study (logos) of suffering (pathos) Aetiology, Pathogenesis, Morphology, Clinical Significance 1 Histopathology in disease diagnosis Histological changes may be either: Directly caused by the agent inducing disease Tissue response to causation. 3 types of changes: Modified - tissues become deranged or infiltrated e.g. Inflammation, abnormal presence of macromolecules Growth Abnormalities Degenerative e.g. atrophy and necrosis Proliferative e.g. hypertrophy, hyperplasia, metaplasia, dysplasia, neoplasia Foreign bodies e.g. bacteria, fungi, asbestos 2 Inflammation - Considered as pathology Acute = few hours to maximum of ~14 days Chronic = long-lasting - months/years Signs of acute inflammation rubor, calor, tumor (swelling), dolor + loss of function Which clinical symptoms can be seen by histologists? Rubor may be detected indirectly due to altered blood flow Tumor (swelling) masked by tissue shrinkage Presence of inflammation in histological sections is good indicator of disease – location and extent. 3 Acute inflammation characterised by: Vasodilation Increased vascular permeability Margination and Emigration Many neutrophils 4 Neutrophils – polymorphonuclear neutrophils (PMNs)/polymorphs Histological changes visible in acute inflammation (1) R NF M M N L Changes in the vascular system Presence of unusual cells and/or unusual numbers of By Department of Pathology, Calicut Medical College [CC BY-SA 4.0 cells in tissues 5 (http://creativecommons.org/licenses/by-sa/4.0)], via Wikimedia Commons Histological changes visible in acute inflammation (2) Degenerative changes Signs of necrosis, opaque cytoplasm, loss of cellular detail Pyknosis, karyorrhexis, karyolysis, cell debris Reactive changes Active tissue repair, cellular proliferation, mitosis, growing capillaries Outcomes of acute inflammation Recovery – tissue returns to normal Healing – tissue returns to healthy state but usually with scarring Progression to chronic inflammation 6 Chronic inflammation Distinct pathology - not simply continuation of acute inflammation Causes 1. Persistent infections 2. Non-degradable materials 3. Autoimmune disease Cardinal signs of acute inflammation are usually absent White cells mainly macrophages and lymphocytes (not PMNs) Prostrate chronic inflammation: note presence of Plasma cells indicative of strong immune plasma cells on the right, normal tissue on left. response By Nephron [CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0) 7 Chronic inflammation Macrophages Epithelioid cells Giant cells Langhan’s giant cells Tissue destruction by active macrophages induces repair mechanisms Tissue shows signs of healing – large numbers of active fibroblasts, new collagen formation and angiogenesis – can lead to fibrosis 8 Chronic vs acute inflammation - summary Acute Chronic Duration Short (days) Long (weeks – years) Cell types Neutrophils, macrophages Lymphocytes, plasma cells, macrophages, giant cells epithelioid cells, fibroblasts Vascular changes Vasodilation, increased permeability Angiogenesis (repair) Cardinal signs Strong Absent or weak Necrosis Usually limited Usually present Fibrosis Usually absent Usually present Systemic symptoms Fever, neutrophil leucocytosis Low grade fever, weight loss, variable white cell changes, increased plasma immunoglobulin 9 10 Healing Recovery – No tissue loss. Minor damage – tissue returns to normal. Regeneration – tissue loss, but replaced with new tissue that is same as original. Repair – scar tissue. Ability to repair or regenerate depends on tissue type: Labile tissue – epithelial Stable tissues normally non-mitotic but can become mitotic if there is damage or loss (e.g. liver may regenerate….up to a point). Permanent tissues –Repaired tissue lacks full functionality. 11 Degenerative tissue growth abnormalities Atrophy – organ shrinkage – pathological or physiological Physiological atrophy - involution Disuse atrophy Neurogenic atrophy Hormonal effects Ischaemic atrophy Pressure atrophy Brown atrophy Senile atrophy Generalised atrophy 12 Degenerative tissue growth abnormalities - necrosis ‘messy’ cell death – slow and destructive response to acute insult INTRINSIC PHASE Damage leads to lack of oxygen Normal aerobic metabolism distrupted ATP production via glycolysis [lactate] and [CO2] increased pH decreases Enzymes inhibited, glycolysis stops… 13 https://theartofmed.wordpress.com/2015/05/29/pathologic-cell-injury-and-cell-death-ii-necrosis/ Different forms of necrosis Coagulative necrosis in myocardium Caseous necrosis in lung Fibrinoid necrosis in a blood vessel. Note bright pink eosinophilic stain. 14 Different forms of necrosis Liquefactive necrosis in liver abscess Gangrenous necrosis in soft tissue and bone of toe Fatty necrosis in breast tissue: note infarcted (dead) fat cells and lipid rich macrophages. (www.pathologyoutlines.com) 15 16 Tissue overgrowth Hypertrophy – increase in cell size with no increase in cell numbers Hyperplasia – increase in cell number usually without any increase in cell size Metaplasia – transformation of one fully differentiated cell type into another Dysplasia – abnormality of differentiation 17 Neoplasia (tumours) Typical features of benign and malignant neoplasms Benign Malignant Size Small Large Borders Well defined Poorly defined Differentiation Resembles tissue of origin Variable Growth rate Slow Rapid Mitotic figures Rare Common Necrosis No Yes Invasion No Yes Metastasis No Yes 18 Nomenclature Tissue Benign Malignant Epithelium Papilloma (surface epithelium) Squamous cell carcinoma Adenoma (glandular epithelium) Adenocarcinoma Mesodermal Suffixed with ___oma (Fibroma/ Lipoma) Suffixed with ___sarcoma (Fibrosarcoma/ Liposarcoma) Key exceptions: 1) Melanoma – malignant skin tumour 2) Lymphoma – malignant haematopoietic tumour Pluripotent cell neoplasms: suffixed with ___blastoma Blood cell neoplasms: leukaemias 19 Dangers of neoplasms Invasiveness Metastasis To metastasise successfully cells must: (1) detach from original tumour (2) enter a suitable transport medium (lymph, blood), (3) survive in circulation (4) migrate into new tissue, (5) divide at new site Two mechanisms proposed to account for metastatic specificity Site of secondaries controlled by pattern of lymph or blood flow Seed and soil hypothesis – secondary site determined by cell growth requirements. 20 Histological recognition of malignancy – loss of uniformity Cellular changes Variation in nuclear size and shape – nuclei enlarged/irregular Increased nucleo-cytoplasmic ratio Increased chromatin content, disturbed distribution Altered staining – hyperchromatic, hypochromatic, polychromatic More frequent cell divisions observed Variation in cytoplasm size/shape – larger, may be vacuolated Abnormal staining Altered antigens Changes in tissue grouping Inflammation Abnormal maturation Invasion – cells breaking through normal tissue barriers Metastasis – the presence of tumour cells in other tissues 21 Grading of malignant neoplasms Histological assessment of the degree of malignancy mainly based on cell morphology and differentiation. Low grades - least malignant. High grades - most malignant. Histological grade of breast cancer 22 Staging of Malignant Neoplasms Generalised staging system TNM - Tumour, Node, Metastasis. T describes the size of the initial tumour (1 -4) N describes whether the cancer has spread to the lymph nodes (0-3) M describes whether it has metastasised (0 or 1) e.g. T2 N1 M0 - small cancer, spread to lymph nodes, no metastasis. Additional letters may be used to provide further info e.g. lung cancer stage M1a - has spread to the other lung, stage M1b lung cancer - has spread to other parts of the body. ‘p’ (pathological) describes surgically removed tissue e.g. pT4 The letter ‘c’(clinical) describes observation before surgery e.g. cT2 http://www.cancerresearchuk.org/about-cancer/what-is-cancer/stages-of-cancer 23 24 Ageing and senescence Ageing – how old a person has become Senescence – tissues become less effective, less active Every organ/system changes with increasing age – for the worse! Organ Tissue changes in senescence Diseases associated with advancing age Skin Atrophy, dryness Keratosis, carcinoma Heart Atrophy, amyloidosis, valve Heart disease calcification Respiratory Decrease ciliary activity, Carcinoma system emphysema Brain Cortical atrophy, accumulation of Alzheimer’s disease, Parkinson’s disease, lipofuscin, amyloidosis stroke Prostate Hyperplasia Carcinoma Breast Atrophy, fibrosis Carcinoma Immune Impaired immunity Infections, autoimmune disease system 25 Apoptosis (aka programmed cell death) Mechanism for eliminating unwanted or damaged cells via a precise suicide sequence leading to cell death without causing inflammation During apoptosis: Cells shrink and condense The cytoskeleton collapses The nuclear envelope disassembles and the nuclear chromtin condenses and breaks into fragments Caspases cleave intracellular proteins Endonucleases cleave between nucleosomes in chromatin Nucleus condenses – often forming a crescent-shaped structure The cell fragments and forms apoptotic bodies Apoptotic bodies have changes in membrane lipids and carbohydrates which mark them for phagocytosis 26 Comparison: Apoptosis vs Necrosis Apoptosis Necrosis Cells affected Isolated cells Groups of cells, tracts of tissue Morphology Chromatin margination Pyknosis, karyorrhexis, karyolysis Cell fragments into bound Coagulation of cell contents structures Shrinkage of cells and nucleus Swelling of cell Cell organelles (including Cell outline recognisable but cell contents lysosomes) remain intact disrupted Lysosomes rupture Inflammation Absent Present Phagocytosis Rapid: many cell types Slower – only ingestion macrophages as part of inflammatory process Occurrence Physiological and pathological Always pathological Mechanism Active Passive ATP used, ATP/ADP ratio Degradation by enzyme catabolism – ATP maintained. low, pH and ionic balance disturbed 27