j0305257 General pathology General pathology I. Regressive changes (necrosis, atrophy, disorders of metabolism) Pigments and concrements j0305257 • apoptosis • necrosis • gangrene • • metabolic change • atrophy • • hyperplasia • hypertrophy • regeneration • repair • metaplasia • dysplasia • neoplasia • morphological and functional alteration Regressive changes (-) Progressive changes (+) j0305257 APOPTOSIS û process of programmed death, active process û û !! no inflammatory response (exceptions possible) û j0305257 APOPTOSIS in physiological situations ûembryogenesis (morphogenetic, histogenetic, phylogenetic) û û hormone-dependent involution ð endometrial cell breakdown during the menstrual cycle ð prostatic involution after castration ð û defence mechanisms during immune response ð death of neutrophils in an acute inflammatory response ð elimination of self-reactive T-lymphocytes during their maturation in the thymus, e.g. ð û elimination of damaged cells û û during aging û û û û û j0305257 APOPTOSIS in pathological conditions û pathological inhibiton of apoptosis ð tumors • follicular lymphoma • mammary, prostatic, e.g. , carcinomas with mutation in p53 gene) ð ðautoimmune diseases •SLE ð ð infections • herpes simplex virus • poxviruses • TBC û j0305257 APOPTOSIS in pathological conditions û pathological induction of apoptosis ð AIDS ð ð neurodegenerative diseases • m. Alzheimer, m. Parkinson, ALS • ð myelodysplastic syndrome • aplastic anemia • ð ischemic injury • acute myocardial infarction ð û j0305257 NECROSIS ûdeath of tissue in a living organism (irreversible process!!) → always with inflammatory reaction !! û û causes: ðischemia ð radiation ð toxins, … û ûnuclear changes: ð pyknosis with increased basophilia (hyperchromasia) ð karyorrhexis ð karyolysis (fading of basophilia of the chromatin) û û cytoplasmic changes ð hypereosinophilia ð breakdown of organellar/plasma membranes û j0305257 NECROSIS - types û Simple (rare) û û Coagulative (organs with protein predominance) ð ischemic = infarction ð secondary hemorrhage = hemorrhagic infarction (lung, bowel) ð caseous (cheese-like) –TBC û û Colliquative (organs with lipid predominance) ð brain ð pancreas û û Fibrinoid ð the base of the ulcer ð arterial wall û û ð ð ð ð û j0305257 NECROSIS - healing û→ inflammatory reaction = inflammatory infiltrate û (neutrophils, histiocytes….. lymphocytes) + afterwards nonspecific granulation tissue (fibroblasts, angiogenesis) → → maturation of the fibrous tissue → û û→ scar (within 6 weeks) + possible secondary alterations (dystrophic calcification, e.g.) û û → pseudocyst (colliquation of a necrotic tissue) û j0305257 GANGRENE û = modified necrosis with putrefaction û û types: ð dry • diabetic foot ð ð wet • decubitus • ð gas (Clostridium perfringens) û j0305257 coagulative necrosis – myocardial infarction IM j0305257 cardiomyocytes – norm 1 IM norma HE 200x j0305257 coagulative necrosis – myocardial infarction 2 IM přehled 20x 1 2 1 1 1 3 1 – coagulative necrosis 2 – partial necrosis 3 – granulation tissue, inflammatory infiltrate j0305257 coagulative necrosis – myocardial infarction 3 IM koagulační nekrosa 200x 1 1 2 3 1 - necrotic cardiomyocytes 2 - nuclear fragments 3 - necrotic interstitium j0305257 coagulative necrosis – renal infarction Renal infarkt j0305257 coagulative necrosis – renal infarction přehled 20x 1 1 1 1 2 2 2 3 1 – coagulative necrosis 2 - peripheral hyperaemia 3 - arteriosclerotic blood vessel 4 - normal tissue 4 4 j0305257 coagulative necrosis – renal infarction nekrosa 200x 1 2 2 3 1 - necrotic glomerulus 2 - necrotic tubules 3 - necrotic interstitium j0305257 hemorrhagic necrosis – pulmonary infarction Lung infarkt Lung embolus Pulmonary artery with embolus Wedge-shaped subpleural infarction j0305257 hemorrhagic necrosis – pulmonary infarction (review) Nekrosa 20x 1 1 1 2 1 - complete necrosis 2 - hemorrhagic area 3 - peripheral inflammatory infiltrate 2 2 3 3 j0305257 hemorrhagic necrosis – pulmonary infarction, destruction, nuclear detritus, erythrocyte hemolysis nekrosa 100x 1 - necrotic alveolar walls 2 - alveolar spaces (hemolyzed erythrocytes) 2 2 2 1 1 j0305257 caseous necrosis - TBC bronchopneumonia / miliary TBC LungTBC2 Lung TBC miliar 1 2 j0305257 caseous necrosis-lymph node-TBC granuloma Uzlík 100x 3 1 central caseation 2 epithelioid cells 3 multinucleated giant cell (Langhans cell) 4 peripheral lymphocytic rim 4 1 2 j0305257 caseous necrosis - lymph node - TBC granuloma, Langhans multinucleated giant cells Uzlík2 100x 1 2 3 4 1 - central caseous necrosis 2 - epithelioid cells 3 - multinucleated giant cell (Langhans) 4 - peripheral lymphocytic rim 3 j0305257 colliquative necrosis - encephalomalacia j0305257 colliquative necrosis (subacute) - encephalomalacia + pseudocyst formation Obrázek1.jpg j0305257 Colliquative necrosis – pseudocyst formation – white matter, subcortical area postmalatická pseudocysta 20x 1 2 3 1 - cavity of the pseudocyst 2 - area of macrophages 3 - brain tissue j0305257 encefalomalacie starší-ostrý.jpg colliquative necrosis - cerebral infarction, macrophages 1 - macrophages 2 - hemosiderin in macrophages 2 2 1 1 2 j0305257 fibrinoid necrosis - rheumatoid nodule revmat_uzlik_20x 1 1 3 3 1 Fibrinoid necrosis 2 Palisade of epithelioid cells 3 Fibrous tissue 2 3 1 j0305257 fibrinoid necrosis - rheumatoid nodule revmat_uzlik_200x 1 Fibrinoid necrosis of the fibrous tissue 2 Rim of epithelioid cells 1 1 2 2 2 j0305257 fibrinoid necrosis of renal arteriole ledvina 100x 1 Necrotic arteriolar wall 2 Perivascular leukocytic infiltrate 1 2 2 2 j0305257 fibrinoid necrosis - arteritis, Mallory trichrom (stains normal fibrous tissue blue) ledvina 2 100x 2 1 1 Fibrinoid necrosis of the whole arteriolar wall 2 Partial fibrinoid necrosis of a larger calibre vessel j0305257 ATROPHY û= pathologic shrinkage in the size of normally evolved organ û (X hypoplasia, aplasia) û û types: ð simple (reduction in cell size) ð numeric (reduction in cell numbers) ð ð ð û ð • • ð » û j0305257 ATROPHY •etiology: • û physiologic involution (thymus) û lack of nutrition ->> cachexia û pressure atrophy (compressed tissue) û loss of function (immobilisation of a limb) û loss of blood supply û loss of innervation û loss of endocrine stimulation û hormone-induced atrophy (in the skin after topically applied corticosteroids) û idiopathic û û û j0305257 Disorders of metabolism (dystrophy) û = regressive change due to abnormal metabolism of the cell û û disorders of metabolism of: ð1. Proteins ð2. Lipids ð3. Carbohydrates (glycogen, …) ð4. Mineral elements ð5. Water j0305257 Water+minerals distribution disturbances ûtype/localisation associated with the distribution of ions: ðEC: Na+, Cl-, HCO3-, Mg2+, sulphates ðIC: K+, phosphates ð A.extracellular changes: B. ð - → dehydration ð + → hyperhydration, oedema ü venous ü lymphatic ü hypoalbuminaemic ü inflammatory •anasarca = extreme generalised oedema of connective tissues ð û j0305257 Water+minerals distribution disturbances B.intracellular changes: ð (caused by ischemia, hyperaldosteronism, viral infections, toxic insults) ð ðSwelling - „intracellular oedema“, granulated cytoplasm • ðVacuolisation •cytoplasmatic vacuoles containing water→ foam appereance •specific subtypes – i.e. ballooning degeneration in hepatocytes (ischaemia, toxic, etc.) ð j0305257 Swelling of tubular cells in kidney ledvina_parenchymová dystrofie 400x epithelial cells of proximal tubules j0305257 Swelling of tubular cells in kidney ledvina vakuolární dystrofie HE 200x 1 - proximal tubulus 2 – epithelial cell cytoplasm 1 1 1 2 j0305257 Disorders of protein metabolism 1)IC and EC hyaline material deposition û (transformed proteins – collagen, keratin, usually in form of pink globules) 2)Inclusion bodies 3)Mucinous dystrophy 4)Amyloidosis 5)Gout 6) j0305257 Hyaline deposition in kidney tubules 200x ledvina hyalinní zkap 3 3 2 1 2 2 1 - glomerulus 2 - proximal 3 - distal tubulus j0305257 Hyaline change - intracellular ð ûMallory bodies ð inclusions found in the cytoplasma of hepatocytes ð associated with alcoholic liver disease û ûRussell bodies ð eosinophilic, immunoglobulin-containing inclusions ð usually found in a plasma cells undergoing excessive synthesis of immunoglobulin ð ð ð ûhyalin = intra- and extracellular homogenous eosinophilic substance, pink in HE staining ð j0305257 Mallory bodies (twisted-rope pink appearance) j0305257 Hyaline change - extracellular û= EC hyaline accumulation û û tendency to calcification û û diff.dg.: amyloid û ûHyaline change of the scars û ûHyaline change of the serous membranes ð coating of the organ with a fibrous hyaline -> sugar-coated spleen j0305257 Hyaline change – EC (sugar coated spleen) perisplen_kartilag_20x 2 1 – Hyaline thickened capsule 2 – Pulp of spleen 1 j0305257 Inclusion bodies û= pathologic intracellular particles û ûcytoplasmatic / nuclear ûvariable size ûeosinophilic or basophilic ûtypically represent sites of viral multiplication ð viral inclusion bodies: herpes simplex virus, CMV – owl eyes, rabbies - Negri bodies) û ûDiagnostic methods: special staining, IHC, in situ hybridisation, ELM j0305257 HIV-CMV-colitis202 CMV colitis (owl-eyes) j0305257 Mucinous change/accumulation û û1) epithelial û2) mesenchymal û û ûPAS (Periodic acid-Schiff) - neutral mucosubstances ûAlcian blue (acid mucosubstances) û û û j0305257 A) Mucinous change/accumulation – epithelial ûcystic fibrosis ð inherited metabolic disorder (AR - CFTR gen) ð abnormal mucous secretion – mucus plugs exocrine ducts -> parenchymal damage to the affected organs. ð clinically: • bronchiectasis • recurrent bronchopulmonary infections • pancreatic fibrosis – chronic pancreatitis • malabsorbtion due to defective pancreatic sekretions • ûalopecia mucinosa (follicular mucinosis) ð male pattern baldness due to irreversible loss of follicles ð accumulation of mucinous material in the damaged hair follicles and sebaceous glands creates an inflammatory condition and subsequent degenerative process j0305257 Cystic fibrosis cyst_fibr_pankr_lehka 1 1 accumulation of mucous material in pancreatic ducts and in acini. 2 thickened fibrous connective tissue septa 3 pancreatic acini 3 2 3 j0305257 cystic fibrosis (atrophy of pancreatic parenchyma) cyst_fibr_pankr_tezka 1 - overgrowth of connective tissue with chronic inflammatory infiltration 2 - persisting islets of Langerhans 2 2 1 1 j0305257 alopecia mucinosa (follicular mucinosis) alopec mucin HE 5x 3 1 epidermis 2 dermis 3 accumulation of mucinous material in the damaged hair follicles 1 2 j0305257 B) Mucinous change/accumulation - mesenchymal ûganglion ð pseudocyst formed by fibrous tissue, contains amorphous, often myxoid material ð localization near a joints or a tendon ð postraumatic û û myxoedema ð intradermal depositions of mucous substances ð associated with hypothyreoidism j0305257 Mucinous change/accumulation – depositions of mucinous substances in dermis Pretibialni myxedem HE 5x j0305257 Mucinous accumulation– depositions of mucinous substances in dermis ( Alcian blue staining ) Pretibialni myxedem alc m 5x 1 1 epidermis 2 intradermal depositions 2 2 j0305257 Amyloidosis ûamyloidosis refers to a variety of conditions wherein amyloid proteins are extracellularly abnormally deposited in tissues or organs û ûamyloid = group of pathological glycoproteins, fibrillary ultrastructure, β-pleated sheet microstructure, non-digestible. û û j0305257 Amyloidosis ðcan be classified according to: ð ûissue distribution ðsystemic – material is deposited in a wide variety of organs ðlocalised ð ûaetiology: ð hereditary ð acquired: AL, AA, etc û û chemical composition ð • ð û j0305257 Amyloidosis ûgross: ð in major deposition affected organs with waxy appearance, greyish-white, slightly hardened. û ûmicro: ð extracellular (often in BM) deposits of homogenous eosinophilic material (similar to hyalin, fibrin, etc.) -> „pressure“ atrophy -> parenchymal destruction -> organ dysfunction û ûhistochemical identification: ð congo red ð methylviolet ð yellow-green dichroism in polarising light ð ûelectron microscopy: ð fibrillar appearance û û j0305257 Amyloidosis - systemic û1) AL (primary) amyloidosis ð associated with B-cell tumorous proliferations •myeloma ð light chains Ig ð deposits: cardiovascular system, kidney, GIT, skin, tongue, peripheral nerve ð ð ð2) AA (reactive, secondary) amyloidosis ð associated with with chronic inflammation • rheumatoid arthritis • osteomyelitis • bronchiectasis • ð AA amyloid derived from SAA (serum associated amyloid) plasmatic acute phase reactant protein ð deposits: kidney, liver, spleen, lymph nodes, adrenal glands, intestine ð ð û û û j0305257 û3) AH amyloidosis ð long-term haemodialysis ð β2-microglobulin ð û4) hereditary amyloidosis ð Amyloidosis - systemic j0305257 Amyloidosis - localised û1) senile amyloid ð aorta, myocardium ð cerebral (Alzheimer‘s disease, old people) ð û2) tumor-associated amyloid ð in peptide hormones producing tumors (medullary thyroid carcinoma) û j0305257 (secondary) amyloidosis - liver jatra 40x 1 portobilium 2 central part of acinus – persisting trabeculae of hepatocytes 3 pink masses of amyloid 3 3 2 1 j0305257 (secondary) amyloidosis - liver jatra 200x 1 – sinusoidal lining cells 2 – Kupffer cells 3 – amyloid masses in perisinusoidal spaces 4 - atrophic trabeculae of hepatocytes 2 1 3 3 4 4 j0305257 (secondary) amyloidosis – liver congo red staining jatra kongo 40x 1 central part of acinus 2 amyloid depositions (red-orange) 2 1 1 j0305257 Gout (arthritis uratica) ûexcessive amounts of uric acid accumulated in tissues ð primary • 90%, enzyme defects ð secondary • overproduction of uric acid • increased cell lysis due to lymphoma or leukemia • decreased excretion of uric acid due to chronic renal diseases • ûurate crystals are stored in tissues: ð acute arthritis ð chronic arthritis ð gouty nephropathy ð j0305257 Gout (arthritis uratica) ûAcute form: ð gouty arthritis ð tophi formation (gouty pain in the big toe) û ûChronic form: ð chronic tophaceous arthritis •(recurrent episodes of inflammation) ð gouty nephropathy • urate deposition in the medullar interstitium, with surrounding granulomatous reaction, intratubular urate precipitions, renal calculi ð ð • û ð û j0305257 Kopie - urát, 200x.jpg 23 j0305257 dna1, přehled40x.jpg dna1, 200x2.jpg j0305257 0037_07.jpg j0305257 Disorders of lipid metabolism ûlipomatosis ð excess amount of fat tissue ð usually replacing atrophic functional tissue (pancreas, lymph node, kidney hilus, etc.) ð û lipidoses – storage disease ðinborn hereditary diseases ð usually single-gene enzymatic defect, blockage of metabolic chains ð accumulation of semi-products (sphingolipids) in macrophages (liver, spleen), nervous tissue ð û steatosis ð ð ð ð ð ð ð j0305257 Disorders of lipid metabolism û steatosis (fatty change) ð abnormal cytoplasmic accumulation of normal lipids (triglycerides, cholesterol) in form of droplets ð Liver, myocardium, skeletal muscle, neutrophils, etc. ð ûgross: ð yellowish, greasy û ûmicro: ð wash-out during embedding in paraphine (empty vacuoles) ð frozen sections – oil red, Sudan û j0305257 Disorders of lipid metabolism û intracellular steatosis: ð excessive fat intake • insufficient metabolism in normal cell ð pathological cell metabolism • hypoxia • toxins, • infections • starvation, etc. û ûextracellular steatosis: ð deposition in intercellular substance, commonly via macrophages (atherosclerosis) û j0305257 Fatty liver disease - steatosis ûgross: ð enlarged, paler, in extreme cases yellow, softer consistency ð ûmicro: ð small or confluent droplets in cytoplasm ð ûcauses: ð alcohol ð other toxins (drugs, organic substances) ð diabetes mellitus + metabolic syndrom ð excessive fat intake ð infection (hepatitis C, …) ð hypoxia ð û j0305257 sejmout0003 sejmout0004 Fatty liver disease - steatosis j0305257 Fatty liver disease - steatosis 1 macrovesicular steatosis 1 1 j0305257 Fatty liver disease - macrovesicular steatosis jatra 200x 1 (1) hepatocytes with intracytoplasmatic lipid droplets , displacing nucleolus (2) 2 2 1 j0305257 Fatty liver disease– microvesicular steatosis, oil red (frozen section) jatra olejovka 400x 1 – Hepatocytes filled with small vacuoles 1 1 j0305257 Disorders of sacharid metabolism û glycogenosis (hereditary, AR) û û intracellular glycogen deposits ð in tumors (renal cell carcinoma) û û diabetes mellitus ð primary impaired glucose metabolism – glucose intolerance, secondary. lipids + proteins, water and electrolytes homeostasis ð heterogennous group of diseases, multifactorial ð relative or absolute insufficiency of insulin, causing hyperglycaemia ð j0305257 Diabetes mellitus û insulin dependent (IDDM – type I): ð juvenile - onset diabetes (usually manifests before age of 20 years) ð insulin dependent ð insufficient insulin production ð genetic predisposition, viral and autoimmune factors û û non-insulin-dependent (NIDDM – type II): ð mature age ð connected with metabolic syndrom ð relative insulin insufficiency (↓ receptors) û û secondary diabetes mellitus ð chronic pancreatitis ð haemochromatosis ð hyperglycaemic hormones û ð û ð ð ð ð j0305257 Diabetes mellitus û complications: ð microangiopathy, ð neuropathy ð retinopathy ð accelerated AS ð hypertension ð immunodeficiency (susceptibility to pyogenic bacteria, fungi) ð diabetic nephropathy û j0305257 Diabetic nephropathy û clinically: ð proteinuria ð nephrotic syndrome ð chronic renal failure û ûmorphology: ð glomerulosclerosis ð hyalinizing arteriolar sclerosis ð tubulointerstitial lesions û j0305257 Diabetes mellitus and kidneys ûnonenzymatic glycosylation of proteins: ð accumulation of irreversible glycosylation products in BM of vessel walls, metabolic defect –> increased collagen synthesis, hemodynamic changes û ûdiabetic microangiopathy: ð in kidney (glomerulosclerosis) ð retina (diabetic retinopathy). ð diffuse thickening of capillary BM leads to ischemic changes, simultaneously increased plasmatic proteins permeability û j0305257 Diabetic glomerulosclerosis ûdiffuse glomerulosclerosis ð GBM thickening, increase in mesangial matrix û ûnodular glomerulosclerosis (Kimmelstiel-Wilson) ð after 10-15 yrs ð PAS+ nodular acellular material deposits at the tips of capillary loops ð leads to chronic renal insufficiency û j0305257 Diabetic glomerulosclerosis Diaibetes DiabetGS j0305257 Glycogenosis – liver jatra 40x 1 Portal vein 2 Hepatocytes with glycogen deposits 2 2 1 2 j0305257 Glycogenosis - liver PAS+ staining – hepatocytes with glycogen deposits jatra PAS 400x 1 Hepatocytes with glycogen deposits 1 1 j0305257 Renal cell carcinoma 40x j0305257 Calcification ûdystrophic ð depositions of calcium in formerly altered tissues, in: •necrosis •dystrophy •cell injury û ûmetastatic ð affects lungs, gastric mucosa, kidneys, artery walls ð caused by: • hypercalcemia • parathyroid hormone excess • chronic renal diseases û ûvisualization: von Kossa silver nitrate staining (black colour) û û û û j0305257 Dystrophic calcification - arterial wall with atheromatous plaque ceva 20x 1 - lumen with coagulated blood 2 - amorphous calcifications in atheromatous plaque 3 - calcificated ateromatous plaque 4 - endotelial fragments 5 - intima 6 - media 7 - adventitia 2 3 4 5 6 7 1 j0305257 Lithiasis (stones, calculi) û formation or presence of stony concretions, as calculi, in the body û û the most important risk factors: û 1.abnormal excess of the mineral 2.local conditions – inflammation, slower fluid flow rate 3.changes in pH û û locations: gallbladder, renal system (kidney, ureter, urinary bladder, urethra), salivary glands/ducts, pancreas û û etiology: ð calcium oxalate ð uric acid ð bile ð pigments û û 1. û û û û j0305257 Lithiasis (stones, calculi) û complications: ð irritation of nearby tissues, causing pain, swelling, and inflammation. ð obstruction of an opening or duct, interfering with normal flow -> > ð predisposition to infection ! û û medical conditions caused by stones: • gallstones (cholelithiasis) ð acute cholecystitis -> ascending cholangitis ð pancreatitis • • kidney stones (nephrolithiasis) ð hydronephrosis ð pyelonephrosis ð • urinary bladder stones (urolithiasis) – ð ð û ð ð ð û û û j0305257 PIGMENTATION ûpigments - naturally colored substances û ð endogenous: ð ð ð • • • • • • autogenous: melanin, lipofuscin • haematogenous: haematoidin, haemosiderin, haematin • ð exogenous • carbon based – dust • ink • metal • autogenous haematogenous j0305257 autogenous pigments û MELANIN ð brown / black pigment ð melanin is the primary determinant of skin color ð IHC: S-100, HMB-45, Melan A ð ð+: - lentigo and naevi ð - malignant melanoma ð - Addison´s disease ð - neurofibromatosis ð ð-: - albinism ð - vitiligo û û LIPOFUSCIN ð one of the aging or "wear-and-tear" pigments ð finely granular yellow-brown pigment granules (liver, myocardium) ð ð ð ð ð ð ð j0305257 vitiligo vitiligo1 j0305257 vitiligo 01341+ 1 – melanin in basement membrane of epidermis 2 – loss of melanin 1 2 COPY j0305257 Compound pigmented (melanocytic) nevus smíšený névus2, 200x.jpg smíšený névus, 400x.jpg 1 - nests of melanocytes in the junction area 2 - nests of melanocytes in the dermis 2 1 j0305257 Melanin (malignant melanoma) 01391+ COPY j0305257 Lipofuscin - cardiomyocytes lipofuscin myokard 200x 1 1 1 – cardiomyocyte lipofuscin deposits j0305257 Hematogenous pigments ûHemosiderin ð granular brown pigment ð IC i EC ð local hemosiderosis ← most often result from hemorrhage into tissue ð systemic hemosiderosis ← may result from hemorrhage, … ð ð ðhemosiderosis (without organ or tissue damage !!! ) X haemochromatosis ð û j0305257 HAEMOCHROMATOSIS ûserious disorder in which the presence of excess iron (as hemosiderin), is associated with a risk of progresion to cirrhosis û ûprimary (genetic) haemochromatosis ð excessive intestinal absorption of iron -> Fe (iron) overload -> haemosiderin accumulation in liver, spleen, pancreas, skin (bronze diabetes) → liver cirrhosis ð û secondary haemochromatosis ð repeated transfusions, alcohol + iron pots ð ð ð û j0305257 HAEMOSIDEROSIS - Perls j0305257 Hematogenous pigments – pulmonary siderophages siderofágy plíce 600x 1 1 – siderophages 2 - capillaries 3 - pneumocytes 4 – endothelial cells 5 – anthracotic pigment in macrophages COPY 1 1 2 2 3 4 5 j0305257 Hematogenous pigments – pulmonary siderophages (Perls reaction) - granules of hemosiderin stains blue siderofágy plíce Perls 400x COPY j0305257 Hematogenous pigments – bilirubin, cholestasis û BILIRUBIN ð breakdown product of haem moiety of haemoglobin ð ðCHOLESTASIS : ð- disturbance/stop of normal bile flow from the liver to the duodenum ð - conjugated icterus ð ð biliary obstruction •lithiasis, tumors incl. pancreatic, inflammation, congenital disorders – atresia • ð hepatocyte excretory dysfunction •viral hepatitis, toxins, drugs, etc. • ð inborn excretory defect •Dubin- Johnson syndrome • v GROSS : brownish green color of liver v MICRO: hepatocanalicular cholestasis, perivenous localisation, reactive canalicular hyperplasia v j0305257 obstr Hepatocellular carcinoma - cholestasis 1 1 - Bile retencion in pseudoglandular formations 2 - Bile pigment in the cytoplasm of the hepatocyte 1 2 j0305257 Exogenous pigments •anthracosis simplex û - black pigmentation in the respiratory tract, without peripheral fibrous reaction û •amalgam pigmentation ð - gingiva, mucous membranes, tongue; no inflammation! ð •tattoo j0305257 Exogenous pigments - tattoos (stable, inert pigment in dermis) 00408+ 1 1 - epidermis 2 – papillary dermis 3 – reticular dermis 4 – black pigment deposits in histiocytes 3 2 3 4 j0305257 Pneumoconioses û lung disease caused by inhaled dusts û û dusts: ð inorganic (mineral) ð organic ð û variable reaction changes: ð inert ð fibrous ð allergic ðneoplastic j0305257 Coal-workers pneumoconiosis (CWP) û1) Antracosis ðonly presence of coal dust in the lung ðnot associated with disability ð ð û2) Antracosilicosis (stages depends on amount of inhaled silica) ðmacular CWP •focal aggregates of dust laden macrophages in and around respiratory bronchioles, arterioles • ðnodular CWP •small nodules < 10mm in diameter, no significant scarring ð ð progresive massive fibrosis •large, irregular nodules with scarring, greater than 10mm, 1) ð ð ð j0305257 Silicosis ûchronic progressive pneumoconiosis û ûparts of silica -> terminal respiratory units -> ingestion by alveolar macrohpages -> toxic to macrophages -> focal necrosis -> fibrosis -> pulmonary hypertension -> cor pulmonale û ûgross: ð small nodules in upper lobes, later confluent nodes and scars, reactive emphysema ûmicro: ð silikotic nodule - concentric layers of hyalinised fibrotic tissue, commonly with anthracosis ð ûRTG – 3 stages: ð reticular fibrosis ð nodules ð diffuse fibrosis û û û ð ð ð û û j0305257 Silicotic nodule - lung j0305257 Silicotic nodule- lung silikosa 1 1 - concentric layers of hyalinised fibrotic tissue 2 – surrounding reactive emphysema 2 COPY 2 j0305257 Silicosis - confluent nodes, scarring of lung tissue silikosa plíce 20x 1 1 - concentric layers of hyalinized fibrotic tissue 1 1 j0305257 Asbestosis ûasbestos fibres (carcinogenic !!!) û ûlater encrusted with hemosiderin to form asbestos bodies û ûsymptoms: ð cough ð dyspnoe û ûprogression to: ð progresive massive fibrosis ð mesothelioma ð lung carcinoma j0305257 asbestosis – asbestos fibres (bodies) in lung tissue azbestoza plíce COPY j0305257 extrinsic alergic alveolitis (hypersensitivity pneumonitis) ûfarmer´s lung = most typical example ûinhalation of fungus present in poorly stored, mouldy hay û -> hypersensitivity reaction -> pneumonitis -> can leads to pulmonary fibrosis û ûother types: cotton fibres, bird faeces, … ð ð ð