--- module: 096-01 language: en chapter: 96 title: "General and Diagnostic Pathology: Patterns, Specimens, and Clinicopathological Reasoning" module_title: "Cellular adaptation, injury patterns, haemodynamic disturbance, and tissue outcome" source_sha256: 64da707fc425905a13a8759dddfe66016de15d4ecb8030c939bcf8bf2120565a --- # Adaptation, injury, haemodynamics, and tissue outcome ## Pathological reasoning ### Altered structure and function produce disease ### A pattern is not automatically a diagnosis #### One pattern, several causes #### One cause, patterns vary by dose and host ### Mechanism to morphology and back ## Cellular adaptation ### Hypertrophy enlarges cells #### Prominent where mature cells divide poorly #### Pressure overload raises oxygen demand and stiffness ### Hyperplasia adds cells in dividing tissue #### Hormonal, compensatory, or excessive stimulation ### Atrophy shrinks cells, sometimes numbers #### Less synthesis, more proteolysis, autophagy #### Prolonged loss reduces reserve ### Metaplasia swaps mature cell programmes #### Smoke: ciliated columnar to squamous #### Clearance and local defence decline ## Dysplasia and invasion ### Atypia, abnormal maturation, disordered architecture ### Mild dysplasia may regress when stimulus removed ### Severe dysplasia approaches carcinoma in situ ### Invasion crosses the basement membrane #### Access to lymphatics, vessels, nerves, stroma ## Reversible and irreversible injury ### Falling ATP weakens ion pumps #### Sodium and water enter, potassium lost #### Cells and organelles swell ### Anaerobic glycolysis lowers intracellular pH ### Lipid imbalance accumulates hepatic fat ### Irreversible: mitochondria fail, membranes break #### Calcium activates destructive enzymes #### Reactive oxygen species oxidise macromolecules ### Pyknosis, karyorrhexis, karyolysis ### Biomarkers need release, distribution, clearance ## Necrosis and regulated death ### Coagulative: ghost architecture in ischaemia ### Liquefactive: cerebral infarcts and abscesses ### Caseous: granular debris in granulomas ### Fat necrosis: fatty acids bind calcium ### Fibrinoid: vessel-wall immune pattern ### Gangrene is clinical, not a mechanism ### Apoptosis: caspases, contained fragments #### Less inflammation than necrosis #### Mitochondrial and death-receptor pathways ### Necroptosis, pyroptosis, ferroptosis ## Tissue outcome ### Dividing epithelia and marrow replace cells ### Stable cells re-enter the cycle ### Permanent cells: limited replacement ### Scar if injury extensive or matrix destroyed #### Fibrosis restores continuity, not architecture ## Congestion, oedema, and effusions ### Hyperaemia: active arteriolar inflow ### Congestion: passive impaired outflow #### Chronic lung: haemosiderin macrophages, fibrosis #### Chronic liver: centrilobular hypoxia ### Oedema: hydrostatic versus oncotic forces #### Heart failure raises venous pressure #### Protein loss lowers oncotic pressure #### Permeability and lymphatic obstruction ### Transudate protein-poor, exudate protein-rich #### Imperfect distinction, integrate context ## Haemorrhage, thrombosis, embolism ### Effect depends on rate, volume, site, reserve #### Skull makes small intracranial bleeds dangerous #### Repeated occult loss depletes iron ### Virchow's triad #### Arterial: plaque, high shear, platelet rich #### Venous: stasis, fibrin and red cells ### Thrombus fates: propagate, organise, embolise ### Emboli: thrombus, fat, gas, amniotic, tumour #### Paradoxical embolism via venous-arterial link ## Infarction and shock ### White infarcts: end-arterial solid organs ### Red infarcts: venous, loose, dual, reperfused ### Occlusion does not always infarct ### Watershed injury without one thrombus ### Shock: inadequate perfusion and oxygen use #### Hypovolaemic, cardiogenic, distributive, obstructive #### Compensation maintains pressure #### Normal pressure does not prove perfusion ## Practical sequence ### Name pattern, distribution, and age ### Identify the threatened structure ### Focal or diffuse, acute or chronic ### Explain morphology, physiology, timing together