2 nd Practice. Cell injury, adaptation, storage disorders. Semmelweis University 2nd Department of Pathology

Transcription

1 2 nd Practice Cell injury, adaptation, storage disorders Semmelweis University 2nd Department of Pathology

2 Cell and tissue injury Cellular response to injury depends on the type, the duration and the severity of the injury Consequences depend on the type, the condition and the adaptability of the cell The most important attack points in the cell: plasma membrane, aerobic respiration, protein synthesis, genome The primary injury leads to secondary injuries in the cell Morphological changes follow the functional changes with delay

3 Cell and tissue injury Causes: 1. Oxigen and nutrition deficiency (ischemia, hypoxia) 2. Physical agents (mechanic, irradiation, electric, burn, thermic etc.) 3. Chemical agents (toxins, drugs, bacterial toxins) 4. Biological agents (microbes) 5. Genetic defects 6. Nutritional effects (qualitative/ quantitative malnutrition)

4 Hypoxia, ischemia Ischaemia hypoxia Ischaemia: deficient blood supply Hypoxia: deficient oxigen supply Ischemia also leads to deficient nutrition supply The most common cause of hypoxia is ischemia, but it can be caused by other pathological states, ex. decreased oxigen transport capacity of the blood (ex. anaemia)

5 Hypoxia, ischemia Pathomechanism: Large amount of ATP is needed for differentiated cell function The anaerobic ATP production (glycolysis) has low efficiency

6 Hypoxia, ischemia Reversible injury: structural and functional disorders possibly resolved by reperfusion Irreversible injury: disorders cannot be resolved by reperfusion Reperfusion injury: because of certain biochemical processes caused by hypoxia reactive oxigen species (ROS) are produced, which lead to additional injuries

7 Hypoxia, ischaemia NECROSIS

8 Necrosis DEFINITION: Pathological, irreversible cell or tissue death in a living organism

9 Morphology: Necrosis 1. Swelling: the transport mechanisms of the plasma membrane (ex. Na/K ATPase) are energy consuming increased ic. Na concentration enhanced cellular water uptake 2. Eosinophilia: Acidic metabolic products (ex. lactic acid) the ph of the cell decreases, BUT the mitochondria and the lysosomes swell; the membranes get descructed, so that lytic enzymes get released the ph gets neutral and eventually alcalic + the eosin binds to denaturated proteins

10 Necrosis 4. Diappearence of the nucleus 3. Formation of myelinfigures from degraded membranes 4. Calcifications: beacuse of the increased ic. Ca concentration Ca-soap is produced from fatty acids

11 Necrosis forms 1. Coagulative necrosis denaturation of proteins is the predominant during development Examples: infarction of most of the parenchymatous organs (except for brain),swallowing of acids (esophagus) Firm Dry (loss of water) Paleness, then yellowish color Demarcation zone Cellular outlines blurred Reddish (capillaries) Yellowish (neutrophils, macrophages)

12 Necrosis forms 1. Liquefactive necrosis Activity of proteolytic enzymes is predominant Examples: infectious lesion caused by bacteria and fungi, anemic or hemorrhagic infarction of the brain, tumors The necrotized tissue is softer than its environment Brain infarction Abscess (infectious agent) Absceding tumors

13 Necrosis forms Special forms Caseating necrosis A special type of coagulative necrosis At the central part of tuberculotic lesions due to the toxic peptidoglycolipid of Mycobacterium tuberculosis light amorphous granular, resembles to cheese Compared to classical coagulative necrosis the structure of the tissue is destructed, the borders of the dead cells are not visible. Inflammatory cells around the necrotic area T-cells Macrophages Epitheloid cells Langhans type giant cells See the details on the lecture titled Chronic inflammation and the practice titled The non-tumorous diseases of the lung

14 Necrosis forms of appearance Special forms Fat necrosis Special necrosis type of adipose tissue Examples: acute pancreatitis, injections given in fat tissue, traumatic injuries of organs that contain large amount of fat tissue (ex. breast) Tiny white, soap-like lesions Dead adipocytes with blurred borders Calcification Fibrinoid necrosis Special necrosis type of vessels, plasma proteins are insudated to the vessel wall Examples: malignant hypertonia (renal vessels), autoimmune diseases (immunocomplexes), vasculitis Proteins insudated to the vessel wall have hypereosinophilic staining (like fibrin)

15 Apoptosis DEFINITION: Programmed cell death, occurring in normal or pathological individual cells The process ensures tissue homeostases Regulated by pro- and antiapoptotic proteins 2 pathways: Intrinsic (mitochondrial) pathway Bcl-2 family proteins Extrinsic (death-receptor) pathway Fas and Fas-L interactions Final common pathway: activation of caspases activation of DNase and protease enzymes Causes: Physiological elimination of unnecessary cells Elimination of cells that have severe genetic and structural defects, so that the defects cannot be inherited to the next generation of the cells

16 Necrosis Apoptosis Strictly controlled step Compared to necrosis apoptosis is a strictly controlled process Morphological differences

17 Apoptosis Morphology: 1. Cytoplasmic eosinophilia The shape of the cell is round or oval Condensation of chromatin, -aggregation and margination 2. Karyorrhexis 3. Apoptotic bodies 4. Phagocytosis with inflammatory response

18 Adaptations of cellular growth and differentiation Adaptation: Reversible changes in size, number, phenotype, metabolic activity, or function of cells in response to changes in their environment. A. Atrophy B. Hypertrophy C. Hyperplasia D. Metaplasia

19 Atrophy DEFINITION: Pathological or physiological cellular or organ shrinkage Qualitative and quantitative decrease in function Physiologic atrophy (involution) e.g.: atrophy of embryonic structures during normal development (thyroglossal duct, thymus, Botallo duct) Pathologic atrophy local e.g.:diminished blood supply/oxigenation (renal atrophy), generalized e.g.: inadequate nutrition Decreased synthesis or increased metabolism of cellular structural components Initially reversible With long standing injury cell death occurs, these cells would be replaced by fat- and connective tissue Physiologic atrophy of the thymus Renal atrophy Malnutrition

20 Hypertrophy DEFINITION: Enlargement of an organ or tissue due to increase in cell size Nondividing cells (Striated muscle cells in the heart and skeletal muscles) respond only with hypertrophy The increased size of the cells is due to the synthesis of more structural components Physiologic hypertrophy e.g.: growth of uterus during pregnancy (also hyperplasia), skeletal muscle hypertrophy due to increased workload Pathologic hypertrophy

21 Hypertrophy Pathologic hypertrophy e.g.: Concentric myocardial hypertrophy (left ventricle) due to hypertension Hypertrophy of the urinary bladder muscular wall due to prostatic hyperplasia

22 Hyperplasia DEFINITION: Enlargement of an organ or tissue due to increase in cell number Increased number of functioning cells Response of cell populations that are capable of dividing Physiologic hyperplasia e.g.: growth of uterus during pregnancy (with hypertrophy), glandular proliferation during breast feeding Pathologic hyperplasia Excesses of hormones or growth factors May be induced by inflammation, tissue damage Pregnant uterus Following surgical resection (e.g. hyperplasia of remaining hepatic parenchyma following partial hepatectomy)

23 Hyperplasia Pathologic hyperplasia Hyperplasia of the adrenal cortex Benign prostatic hyperplasia Goiter

24 Metaplasia DEFINITION: Adaptive process of a tissue characterised by transformation to another type of matured tissue. Response to chronic irritation Adaptive substitution of cells that are sensitive to stress by cell types able to withstand the adverse environment

25 Intracellular Accumulations Manifestation of metabolic derangements in cells Normal cellular constituent or products of abnormal synthesis or metabolism Accumulation of exogenous substances Pigments The metabolism or removal of these substances are inadequate The overload may cause cellular injury

26 Intracellular Accumulations Lipids: Fatty degeneration of the liver: The liver has limited repertoire of cellular and tissue responses to injury (major organ involved in lipid metabolism) Diabetes with obesity Malnutrition, starvation Toxic agents: e.g.:alcohol Pathophysiology Excess accumulation of triglycerides Reduced synthesis of apoproteins Inhibition of fatty acid oxidation Mild forms may not harm cellular function, it can be reversible Severe cases may impair cellular function and may lead to cellular death

27 Intracellular Accumulations Proteins (defective transport and secretion of proteins, aggregation of abnormal proteins): Glycogen α1- antitrypsin deficiency Accumulation of Tau protein Alzheimer disease Glycogen storage diseases, Diabetes Mellitus

28 Intracellular Accumulations Pigments Exogenous pigments Anthracosis Tattoos

29 Intracellular Accumulations Pigments Endogenous pigments Hemosiderin chronic congestion Lipofuscin

30 Amyloidosis DEFINITION: Abnormal accumulation of specific extracellular proteins causing firmness, enlargement and malfunction of the involved organs Romhányi György Structure of protein deposites: Continuous, nonbranching fibrils Accumulation results from abnormal folding of proteins Associated with a number of hereditary diseases and chronic inflammation

31 Amyloidosis Amyloid material consists of aggregated fibril proteins that bind proteoglycans, glucosaminoglycans and plasma proteins (e.g. serum amyloid P-SAP) Amyloid: o the biochemical structure is heterogeneous, but the appearence is uniform enlarged, pale, wax-like o Diagnosed with Congo red staining and electron microscopy Congo red Cross beta-pleated sheet conformation of the non branching fibrils Congo red staining shows apple-green birefringence under polarized light Electron micrograph of 7,5-10 nm amlyoid fibrils

32 Amyloidosis Pathogenesis

33 a) Systemic: E.g..: Amyloidosis Classification Immunocyte Dyscrasias Reactive Systemic Amyloidosis (chr. inflammation) Hemodialysis-Associated Hereditary/ familial o Familial Mediterranean fever o Neuropathies associated with amyloidosis o senile systemic amyloidosis a) Localized: E.g.: Senile cerebral Alzheimer-disease Atrial Endocrine Amyloid o Medullary carcinoma o Type II Diabetes Mellitus

34 Amyloidosis Amyloidosis of the Kidney: the organ is enlarged, the glomerular architecture is almost totally obliterated by amyloid accumulation Spleen: splenomegaly, amyloid accumulation in follicules (sago spleen) or in the sinusoids (lardaceous spleen)

35 Amyloidosis Liver: hepatomegaly, amyloid accumulation withinin the space of Disse and in the parenchyme Heart: cardiomegaly, amyloid accumulation between the muscle fibers

36 Amyloidosis Systemic amyloidosis can occur in every organ Macroglossia

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