Pathology PDF

General Pathology Pathology Etymology: pathos-suffering; logos- study -it is the study of the causes of disease and the associated changes at the levels of cells, tissues, and organs. Rudolf Virchow -- Father of Modern Pathology - He discovered the 5^th^ Cardinal Sign Aulus Cornelius Celsus...

General Pathology Pathology Etymology: pathos-suffering; logos- study -it is the study of the causes of disease and the associated changes at the levels of cells, tissues, and organs. Rudolf Virchow -- Father of Modern Pathology - He discovered the 5^th^ Cardinal Sign Aulus Cornelius Celsus -- He studied the First four signs of inflammation Etiology -origin of a disease -refers to Why a disease arises Pathogenesis - Steps in the development of disease - Describes how a disease develops Morphologic Changes - refers to the structural alterations in cells or tissues that are either characteristic of a disease or diagnostic of an etiologic process (PHYSICAL CHANGES) Functional Derangements and Clinical Manifestations - It is the end results of genetic, biochemical, and structural changes in cells snd tissues are functional abnormalities, which lead to the clinical manifestations of a disease (signs and symptoms) of disease, as well it's progress (clinical course and outcome). Signs and Symptoms Signs- observable changes Symptoms -- subjective Tissue Changes A. Retrogressive : Organs or tissues are smaller than normal 1. Aplasia -- incomplete or defective development Most commonly seen in one of paired structures such as kidneys, gonads, and adrenals 2. Atresia -- Failure to form an opening 3. Agenesia -- complete non- appearance of an organ 4. Hypoplasia -- Failure of an organ to reach its mature or adult size 5. Atrophy -- partial or complete wasting away or a part of the body Shrinkage in the size of the cell by the loss of cell substance 1. physiologic atrophy -- occurs naturally 2. Pathologic atrophy -- Occurs as a consequence of a disease 3. Endocrine atrophy -- Occurs due to lack of trophic hormone 4. Vascular Atrophy -- due to interruption or diminished blood supply 5. Starvation atrophy -- Lack of nutrition 6. Disuse Atrophy -- lack of nutrition 7. Exhaustion Atrophy -- too much workload 8. Pressure Atrophy -- caused by pressure B. Progressive: Organs or tissues are Larger than Normal 1. Hypertrophy -- increased tissue size due to increased cell size Ex: Hypertension (Pathologic Hypertrophy) 1. True Hypertrophy -- caused by increased workload and endocrine stimulus 2. Pseudohypertrophy -- caused by the accumulation of edema fluid and connective tissue proliferation 3. Compensatory -- When one of the paired organs compensate after the removal of its pair of or when the function is insufficient 2. Hyperplasia Ex: Fitting denture -- increased tissue size due to **increased cell number** 4. physiologic hyperplasia -- occurs as a natural mechanism 5. pathologic hyperplasia -- associated with disease C. Degenerative 1. Metaplasia -- transformation of one adult cell type to another adult cell type ( reversible) 2. Dysplasia -- literally means "disordered growth", enlargement of a tissue due to proliferation of abnormal cells ( reversible ). Cervical Dysplasia -- HPV Human papillomavirus, PapSmear -Koilocytes 3. Anaplasia -- transformation of adult cell type to a more primitive type ( irreversible) - Utilized as a criterion toward malignancy 4. Neoplasia -- Continuous abnormal proliferation of cells without control Oncology -- study of neoplasm Inflammation Etymology: Inflammare- to set a fire It is the overall reaction of the body to injury or invasion by an infectious agent. It is a series of biochemical and cellular changes that facilitate phagocytosis It is a defensive host eesponse, but it is itself capable of causing tissue damage Cardinal Signs of Inflammation 1. Rubor (Redness) -- The blood vessels dilate and the blood flow increases at the site of injury. Hyperemia -Blushing 2. Tumor (Swelling) -- The capillary permeability is increased leading to an increased flow of fluid and cells to the affected site. 3. Calor (Heat) -- The cellular metabolism and energy production is increased in the affected area 4. Dolor (Pain) -- The increased flow of fluid and cells (prostaglandins) causes tissue damage and pressure on nerve endings 5. Function Laesa (loss of function) -- The pain is interfered with nerve supply and destruction of the tissue functioning Inflammation according to duration 1. Acute Inflammation (days/week) -- Inflammatory reaction in which the dominant anatomic changes are vascular, usually of sudden onset Main cells: Neutrophils 2. Chronic Inflammation (Weeks/Months/years), (Severe, progressive) - Involves persistence of injurious agents for weeks to months due to proliferation. Main cells : Mononuclear cells ( Plasma Cell, Macrophages, Lymppcytes ) 3. Sub-chronic Inflammation -- **Intergrade** between acute and chronic inflammation Inflammation According to Character 1. Serous Inflammation -- extensive outpouring of watery, low-protein fluid derived from either the blood serum or secretions from serosal mesothelial cells 2. Hemorrhagic Inflammation- Mixture of large amount of blood and other exudate elements 3. Fibrinous Inflammation- Exudation of Large amount of fibrinogen and the precipitation of fibrin 4. Suppurative Inflammation -- production of large amount of purulent exudate and/or pus 5. Catarrhal Inflammation -- Hypersecretion of the mucosa with degenerative changes in the epithelium Ulcer An ulcer is a local defect, or excavation, of the surface of an organ or tissue that is produced by the sloughing (shedding) of inflamed necrotic tissue. Commonly encountered in: Mucosa of the mouth, stomach, intestines, or genitourinary tract The skin and subcutaneous tissue of the lower Helicobacter pylori -- Gastric Ulcer Tissue Repair Repair (Healing) -- refers to the restoration of tissue architecture and function after an injury Two types of Repair -- Regeneration and Scar formation Regeneration- The manner by which damaged tissues or cells are replaced to return to normal state ( must change to same tissue) Scar formation -- the laying down of connective (fibrous) tissue (must change/new) Cell Death 1. Apoptosis -- programmed cell death; "falling of" 2. Necrosis -- Pathologic cell death 3. Necrobiosis -- physiologic cell death 4. Pyknosis -- reduction of size and condensation of nucleus 5. Karyorrhexis -- Fragmentation of nucleus 6. Karyolysis -- Dissolution of nucleus 7. Autophagy -- Lysosomal digestion of the cell's own components; "self-eating" FEATURES OF NECROSIS AND APOPTOSIS Features Necrosis Apoptosis -------------------------------- ------------------------------------------- ------------------------------------------------- Cell size Enlarged (swelling) Reduced - shrinkage Nucleus Pyknosis -karyorrhexis- karyolysis Fragmentation into nucleosome -- size fragments Plasma Membrane Disrupted Intact Cellular Contents Enzymatic digestion; may leak out of cell Intact; may be released in apoptotic bodies Adjacent Inflammation With inflammation Without inflammation Physiologic or Pathologic Role Pathologic Necrosis Physiologic Apoptosis Hypoxia -- Oxygen deficiency, interferes with aerobic oxidative respiration and is an extremely important And common cause of cell injury and death Ischemia- loss of blood supply in a tissue due to impeded arterial flow or reduced venous drainage Deposition of Materials 1. Lipids Fatty change or Steatosis -- accumulation of free triglycerides in cells results from excessive intake or defective transport Cholesterol or Xanthoma -- result of defective catabolism and excessive intake happens in macrophages and smooth muscle cells of vessel walls in atherosclerosis 2. Proteins Cholesterol deposition -- reabsorbed proteins in kidney tubules (Protenuria -- nephrotic syndrome) 3. Pigments -are colored substances that are either exogenous or endogenous Exogenous pigments- come from outside the body (e.g., carbon) Endogenous pigments -- synthesized within the body itself (e.g., lipofuscin, melanin, derivatives of hemoglobin) Carbon -- most common exogenous pigment An example of coal dust Anthracos -- carbon accumulation -- blackening of lymph nodes and pulmonary parenchyma Lipofuscin -- "wear-and-tear pigment" An insoluble brownish-yellow granular intracellular material that Not injurious to the cell but is a marker of past free radical injury Melanin -- Endogenous, brown-black pigment Synthesized by melanocytes in the epidermis Acts as a screen against harmful ultraviolet radiation Hematogenous +-----------------------------------+-----------------------------------+ | Hemosiderin | -Iron containing pigment of | | | hemoglobin; oxygen rich. Most | | | common hemoglobin derivative | +===================================+===================================+ | Hematoidin | - Iron-free pigment of | | | hemoglobin; oxygen poor | +-----------------------------------+-----------------------------------+ | Hematin | -hemoglobin minus the globin; old | | | blood clots. Encountered in | | | malaria, pernicious anemia and | | | toxic hemolysis | +-----------------------------------+-----------------------------------+ | Hemozoin | Black granules formed by malarial | | | parasites in the red blood cells | +-----------------------------------+-----------------------------------+ | Hemofuscin | Iron-free brownish yellow pigment | | | that occurs with hemosiderin and | | | hemochromatosis | +-----------------------------------+-----------------------------------+ 4. Calcium Dystrophic Calcification- deposition of calcium at sites of cell injury and necrosis Metastatic Calcification -- Deposition of calcium in normal tissues, caused by hypercalcemia Necrosis 1. Coagulative Necrosis -- Occurs when the blood supply in arteries is cut off producing anemic and ischemic infarction "Tombstone Formation". (Heart) 2. Liquefactive Necrosis -- Occurs when there is a rapid enzyme dissolution of cells leading to pus production. (Brain) 3. Caseous Necrosis -- Caused by infections with mycobacterium tuberculosis;. "Friable Cheesy Masses". 4. Gangrenous Necrosis -- caused by interrupted blood supply to lower extremities Dry gangrene -- Arterial occlusion Wet gangrene -- Venous occlusion 5. Fat Necrosis -- seen in pancreatic degeneration, release of lipase that will degrade surrounding fats "Chalky Appearance". Fat tissue lipase/Amylase bind to calcium process called Saponification. 6. Fibrinoid Necrosis -- Deposition of fibrin-like material in arterial wall, seen in small blood vessels Cloudy Swelling -- First manifestation of almost all forms of injury to the cell. Grading of Tumors 1. Differentiated cells -- mature cells (less malignant) 2. Undifferentiated cells -- younger or primitive cells (most malignant) Broder's Classification Or Grading Grade Differentiated Cells Undifferentiated Cells ----------- ---------------------- ------------------------ Grade I 100% - 75% 0% - 25% Grade II 75% - 50% 25% - 50% Grade III 50% - 25% 50% - 75 % Grade IV 25% -0% 75% - 100 % T (Size of Tumor and its local extent) T (is) carcinoma in situ T(a) Non-invasive T(x) Cannot be evaluated T(0) tumor absent T1lesion is less than 2 cm T2 lesion is 2-5 cm T3 skin and/or chest wall involved by invasion T3a deep muscle T3b through organ T4 tumor invasion T4a adjacent organ T4b fixation to bladder or colonic wall in breast edema N (For regional lymph node involvement) Nx cannot be evaluated N0 no axillary nodes involved N1 one mobile axillary (regional) node involved N2 multiple, mobile regional nodes involved N3 Fixed regional lymph node involved N4 beyond regional node involvement M (Metastasis) ability to spread Mx distant metastases cannot be evaluated M0 metastasis absent M1 distant metastases are present Teratomas - Compound tumors - Greek: Monstrous Tumors (may contain hair, teeth, bones with heartbeat) Nomenclature of Neoplasms +-----------------------+-----------------------+-----------------------+ | Benign | Suffix used is -- oma | | +=======================+=======================+=======================+ | Benign | Benign neoplasm of | Benign neoplasm | | | epithelial tissue | mesenchymal or | | | origin: - Glands and | connective origin: | | | ducts -- Adenoma | | | | | Cartilage- Chondroma | | | Finger-like (warty) | | | | projections from | Adipose/fats -- | | | epithelial surfaces | Lipoma | | | -- Papilloma | | | | | Bone -- Osteoma | | | | | | | | Fibrous tissue - | | | | Fibroma | +-----------------------+-----------------------+-----------------------+ | Malignant | Mesenchymal/connectiv | Epithelial tissue | | | e | origin: | | | tissue origin: | | | | | Suffix used : | | | Suffix used : Sarcoma | Carcinoma | | | | | | | Cartilage -- | Glands and | | | Chondrosarcoma | adenocarcinoma | | | | | | | Adipose/Fats -- | | | | Liposarcoma | | | | | | | | Bone -- Osteogenic | | | | Sarcoma | | | | | | | | Fibrous tissue -- | | | | Fibrosarcoma | | +-----------------------+-----------------------+-----------------------+ Somatic Death Color of Death Certificate- White , 4 Papers It is the complete death or cessation of the functional and metabolic activities of the human body. Clinical Death -cessation of heartbeat and respiration but the brain is still alive but injured Brain Death -- cannot be revived anymore Primary Signs of Death 1. Circulatory Failure -- Occur when cardiac function ceases, absence of pulse and heartbeat 2. Respiratory Failure -- Absence of Oxygen and accumulation of Carbon dioxide 3. Central Nervous System Failure (CNS) -- loss of coordination of various body functions and loss of reflexes Secondary Signs of Death 1. Algor Mortis -- post-mortem cooling - Occurs at a rate of 7 °F per hour - Important in establishing the approximate time of death 2. Rigor Mortis -- Stiffening of muscles - First: neck and head, occur about 6-12 hours after death - Persists within 3-4 days 3. Livor Mortis -- lividity/suggillations - Purplish discoloration of skin in dependent portions of the body, due to stasis and eventual settling down into vessels 4. Post- Mortem -- Occurs slowly, immediately after death. Characterized as: Portions of clot assume a yellow "chicken fat" appearance Currant Jelly that assumes the shape of the blood vessel "Rubbery Consistency" Ante Mortem -- Occurs before Death Characterized as: Friable, Fibrin precipitation in tangled, irregular fashion. Usually, granular. Not Readily detachable Do not have rubbery consistency 5. Desiccation -- Drying and wrinkling of the anterior chamber of the eye 6. Putrefaction -- Production of foul-smelling gases due to invasion of saprophytic microorganisms 7. Autolysis -- self-digestion of cells Comparison of somatic death and molecular death: Somatic Death Molecular Death --------------------- ---------------------------------------------------------------------------------- --------------------------------------------------- Definition Complete irreversible cessation of function of brain and stoppage of circulation Death of individual tissues and cells respiration Response to stimuli Muscle responds to thermal, electrical Does respond not or chemical stimulus Confirmation Flat ECG and EEG and absent breath sounds Rigor algor mortis, mortis, postmortem lividity Autopsy Microscopic examination of tissues obtained from a dead body Gold Standard for the confirmation of medical disease Prosector -- one who dissects cadaver for anatomic demonstration and pathologic examination Diener -- A laboratory worker who assists in the performance of autopsies and maintenance of morgues Coroner -- an official whose duty is to investigate sudden, suspicious, or violent death to determine its cause Types of Autopsy According to: +-----------------------+-----------------------+-----------------------+ | Purpose | Routine/Hospital | When the family wants | | | Autopsy | to know the cause of | | | | death | +=======================+=======================+=======================+ | | Medico-legal autopsy | Done in NBI or any | | | | government | | | | institution for | | | | prosecution purposes | | | | (rape cases) | +-----------------------+-----------------------+-----------------------+ | Completeness | Complete autopsy | Examination of the | | | | whole body | | | | | | | | "head-to-tow" autopsy | +-----------------------+-----------------------+-----------------------+ | | Partial Autopsy | Examination of a part | | | | or a region of the | | | | body | +-----------------------+-----------------------+-----------------------+ | Manner of Incision or | Y-shaped (torso) | The cadaver is open | | Opening of Cadaver | | from both shoulder | | | | regions down to the | | | | xiphoid area then | | | | incised down to the | | | | pubis | | | | | | | | Commonly done in | | | | female cadavers | +-----------------------+-----------------------+-----------------------+ | | Straight cut | The Cadaver is open | | | | from the midline of | | | | the body from the | | | | suprasternal notch | | | | down to the pubis | | | | | | | | Commonly done in | | | | children or infants | +-----------------------+-----------------------+-----------------------+ Techniques of Autopsy Rudolf Virchow Technique -- Organs are removed one-by-one - Most widely used Carl Von Rokitansky Technique -- in situ dissection combined with en bloc technique Anton Ghon Technique -- en bloc technique Maurice Letulle Technique -- en masse technique