Pathology PA Slides Summary PDF

Pathology PA slides 1 Acute pulmonary edema MICROSCOPIC ONLY & - 1. Lung parenchyma - 2. Congested ve...

Pathology PA slides 1 Acute pulmonary edema MICROSCOPIC ONLY & - 1. Lung parenchyma - 2. Congested vessels 3. Anthracotic pigment ORGAN: Lungs STAIN: Hematoxylin Eosin DIAGNOSIS: Acute pulmonary edema DEFINITION: Edema (from the greek oidaein = swelling) is an abnormal collection of fluid in: tissues —> in the intercellular compartment serosal cavities —> serous effusion PATHOGENESIS of EDEMA in general: 1. Increased hydrostatic pressure —> in the capillaries, due to venous thrombosis, congestion or heart failure (e.g. venous congestion, right heart failure) 2. Decreased blood osmotic pressure —> due to hypoproteinemia (e.g. nephrotic syndrome, liver function failure, hypoalbuminemia) 3. Increased vascular permeability —> inflammation, insect bites, allergies 4. Lymphatic obstruction —> removal of lymph nodes, parasites (Filaria bancrofti), tumoral surgery ETIOLOGY of ACUTE PULMONARY EDEMA: - acute left heart failure - shock - severe forms of pneumonia - inhalation of toxic gases - substitution acute pulmonary edema or ex vacuo - acute respiratory distress syndrome (particular form of pulmonary edema caused by (ARDS) rapid therapeutic evacuation of pleural effusion) - body over hydration (iatrogenic edema) CLASSIFICATION of EDEMA: 1. Venous edema —> heart failure, venous congestion; increasing hydrostatic pressure 2. Cardiogenic edema (heart failure) —> pitting edema (finger-shaped depression), depends on the gravitation; venous congestion + decreasing of kidneys filtration 3. Hypoalbuminemic edema —> areas with loose connective tissue (eyelid, periorbital, external genital organs); liver failure, kidney lesions, enteropathy, malnutrition, starvation, cachexia 4. Edema due to increased capillary permeability —> hypoxia, toxic and allergic factors, inflammatory edema 5. Angioneurotic edema (Quincke)—> severe, generalized, sudden onset, allergy-related, larynx, lungs 6. Lymphatic edema —> Filaria parasites, Surgical removal of the lymph nodes, Congenital, Milroy disease; It can lead to elephantiasis MORPHOLOGY of EDEMA: The macroscopic changes appear when the quantity of intercellular fluid increases with 10%: swollen and pasty tissues finger-shaped depression gelatinous aspect on section The tissues can be: - blue —> venous and cardiogenic edema - pale —> hypoalbuminemic edema - red —> inflammatory edema MACROSCOPIC DESCRIPTION: Lungs: distended, hyperemic, increased volume and weight, not collapsing on the autopsy table, pink-gray color, darker in dorsal and basal areas, pasty in consistency (similar to a wet sponge) Pleura: distended, thin, transparent, smooth, and shiny, with rib imprints on the pleural surface In case of Compression of the cut section surface → elimination of a pink-red foamy, frothy fluid, containing edema fluid, a few erythrocytes, and air bubbles MICROSCOPIC DESCRIPTION: 1. LUNG PARENCHYMA —>alveolar spaces filled with a homogenous or slightly granular, eosinophilic material = edema fluid —> 2 types of edema septal edema = edema fluid inside alveolar septa alveolar edema (edema fluid - transudate, quickly extravasated and therefore mixed with optically empty spaces - air bubbles, together with and rare cellular elements - desquamated alveolocytes, alveolar macrophages and leukocytes) 2. CONGESTED VESSELS —> Dilated capillaries 3. ANTHRACOTIC PIGMENT —> black color pigment resulted from inhalation of carbon particles, ingested by alveolar/interstitial macrophages and then accumulated in the connective tissue and/or regional lymph nodes  MACROSCOPIC and MICROSCOPIC 2 Lung infarction + Chronic pulmonary congestion 3 1. Infarcted area 2. Chronic pulmonary congestion 3. Hyperemic narrow rim 3. Trachea (macro) ORGAN: Lungs STAIN: Hematoxylin Eosin DIAGNOSIS: Lung infarction + Chronic pulmonary congestion DEFINITIONS: INFARCTION —> (from the latin in-farcire = stuffed) tissue death/ necrosis due to insufficient arterial/oxygenated blood supply, as result of sudden vascular occlusion, more frequent of an artery, within the living body CONGESTION —> Congestion is a passive process resulting from reduced venous outflow of blood from a tissue. It can be systemic, as in cardiac failure, or localized, as in isolated venous obstruction. PATHOGENESIS of CONGESTION in general: - heart failure - restriction of respiratory movement - compression of the cava vein ETIOLOGY of CHRONIC PULMONARY CONGESTION: - chronic left ventricular failure - mitral stenosis / incompetence CLINICAL FEATURES: CONGESTION —> dyspnea, cough, clubbing fingers (chronic hypoxia); —> on auscultation → crakles (air bubbling and fluid) INFARCTION —> pyramidal shape, wedge-shaped, triangular (occluded vessel located on the apex) EVOLUTION/COMPLICATIONS: CONGESTION —> superinfection, pulmonary fibrosis, chronic cor pulmonale INFARCTION —> organization / scaring, encapsulation, ulceration, superinfection, abscess CLASSIFICATION: CONGESTION —> Acute pulmonary congestion: alveolar capillaries engorged with blood, serum extravasation (due to increased intracapillary hydrostatic pressure and increased capillary permeability), alveolar and septal edema —> Chronic pulmonary congestion: pulmonary fibrosis, sclerosis (septa thickening) + intraalveolar and septal hemosiderin laden macrophages, brown induration of the lungs INFARCTION —> White / anemic infarct: in solid/compact tissues, such as Myocardium (heart attack), Spleen, Kidney, Brain (liquefactive necrosis), Liver (hepatic artery), Limb (gangrene) —> Red (hemorrhagic) infarct: in spongy tissues with dual or collateral circulation, such as Lungs and Intestine —> Zahn infarction: pseudo-infarction in the Liver, caused by portal vein obstruction; the area of congestion, atrophies, but no necrosis MACROSCOPIC DESCRIPTION: 1. Infarcted area (triangular shape, with the tip pointing towards the hilum -> occluded vessel, well defined, dark red color) 2. Chronic pulmonary congestion (increased weight, brown color due to the presence of siderophages, firm consistency = brown induration) 3. Trachea MICROSCOPIC DESCRIPTION: 1. Infarcted area —> well defined, red color, due to erythrocyte flooding, with preserved alveolar architecture, but loss of nuclei - “ghost-like appearance” or „Hiroshima effect“ indicating the necrosis 2. Chronic pulmonary congestion —> thick fibrotic interalveolar septa, due to hypoxia and reaction to deposited hemosiderin and cardiac cells/ heart failure cells/siderophages 3. Hyperemic narrow rim —> hypercellular area separating the infarcted tissue from the surrounding parenchyma, composed of congested vessels, extravasated erythrocytes and acute inflammatory infiltrate —> it is the area where the granulation tissue starts forming, so there are many macrophages, fibroblasts, fibrocytes and leukocytes  MICROSCOPIC ONLY. 3 Pulmonary thromboembolism 1. Bronchial lumen 2. Anthracotic pigment, lymph node 3. Large branch of the pulmonary artery, containing a thromb-embolus M ORGAN: Lung STAIN: Hematoxylin Eosin DIAGNOSIS: Pulmonary thromoembolism (deep vein thrombosis of the leg ) DEFINITION / PATHOMECHANISM of THROMBOEMBOLISM: 1. Thrombus detachment 2. Migration – usually anterograd 3. Lodge (fixation), which can result in a - blocking embolus - “saddle” embolus (across the bifurcation) CONSEQUENCES of THOMBOEMBOLISM: - acute respiratory and cardiac disorders - ischemia, necrosis (infarction) - congestion (lung) - sudden death (pulmonary embolism) - bacterial (infective) emboli - abscesses  MACROSCOPIC and MICROSCOPIC 4 Chronic hepatic congestion 1. Hyperemic areas in the center of the hepatic lobules 2. Normal, preserved hepatocytes 3. Portal space/triad ORGAN: Liver STAIN: Hematoxylin Eosin DIAGNOSIS: Chronic hepatic congestion DEFINITION: *See slide 2 of Chronic pulmonary congestion ! * ETIOLOGY: Right ventricular failure PATHOMECHANISM of HEPATIC CONGESTION: 3 stages 1. Acute congestion The central veins (CLV) of the hepatic lobules are dilated and filled with erythrocytes —> Macroscopic view: Enlarged liver on section alternance between yellow (hepatic parenchyma) and red areas (dilated central veins and surrounding sinusoid capillaries —> Microscopic view: distended central vein and sinusoids in hepatic lobules cockade appearance 2. Chronic congestion Sinusoid capillaries (C) are also dilated and the nutmeg liver aspect can be observed —> Macroscopic view: „Hemorragic bridges“ = alternation between yellow (hepatic parenchyma) and red color (dilated capillaries) —> Microscopic view: dilatation of the central veins and sinusoid capillaries and their fusion with neighboring lobules nutmeg liver 3. Persistent congestion or Cardiac Cirrhosis Pale areas of fibrosis (F) replace the congested areas (here the hepatocytes are destroyed) —> Macroscopic view: fibrosis (liver induration), followed by regeneration of the liver parenchyma (cardiac cirrhosis) fern (felce) appearance —> Microscopic view: Areas of fibrosis = connective tissue; Destruction of hepatocytes in those areas MICROSCOPIC DESCRIPTION: In the nutmeg liver we can observe fragments of hepatic parenchyma showing numerous hyperemic areas alternating with normal-looking areas. 1. Hyperemic areas in the center of the hepatic lobules: Dilated central veins of the hepatic lobules and sinusoid capillaries from which erythrocytes were extravasated; Hepatocytes suffer from hemorrhagic / coagulation necrosis 2. Normal, preserved hepatocytes at the periphery of the hepatic lobules, in the periportal areas 3. Portal space/triad  MACROSCOPIC and MICROSCOPIC 5 Acute renal infarction 1. Infarcted area 2. Normal renal parenchyma 3. Hyperemic narrow rim ORGAN: Kidney STAIN: Hematoxylin Eosin DIAGNOSIS: Acute renal infarction PROBABLE ETIOLOGY: Abdominal aorta atherosclerosis DEFINITION: INFARCTION —> (from the latin in-farcire = stuffed) tissue death/ necrosis due to insufficient arterial/oxygenated blood supply, as result of sudden vascular occlusion, more frequent of an artery, within the living body CLINICAL FEATURES: Pyramidal shape, wedge-shaped, triangular (occluded vessel located on the apex) EVOLUTION/COMPLICATIONS: 1. Organization / scaring 4. Superinfection 2. Encapsulation 5. Abscess 3. Ulceration CLASSIFICATION: —> White / anemic infarct: in solid/compact tissues, such as Myocardium (heart attack), Spleen, Kidney, Brain (liquefactive necrosis), Liver (hepatic artery), Limb (gangrene) —> Red (hemorrhagic) infarct: in spongy tissues with dual or collateral circulation, such as Lungs and Intestine —> Zahn infarction: pseudo-infarction in the Liver, caused by portal vein obstruction; the area of congestion, atrophies, but no necrosis MACROSCOPIC DESCRIPTION: 1. Infarcted area —> pyramidal, triangular shape, well contoured by the hyperemic rim, visible on the exterior surface of the kidney 2. Normal renal parenchyma 3. Hyperemic narrow rim MICROSCOPIC DESCRIPTION: 1. Infarcted area —> pale, with ghost-like appearance determined by the loss of nuclei, due to the „Hiroshima effect“ = necrosis 2. Normal renal parenchyma 3. Hyperemic narrow rim —> area separating the infarcted tissue from the surrounding parenchyma, composed of congested vessels, extravasated erythrocytes and acute inflammatory infiltrate  MACROSCOPIC and MICROSCOPIC 6 Mixed stratified thrombus 4. 1. Aortic intima 2. Atherosclerotic plaques 3. Mural thrombus (mixed stratified, adherent, matte, friable) 1. Arterial vessel wall 2. Thrombus, adherent to the arterial vessel wall 3. Calcified atherosclerotic plaque 4. Zahn lines ORGAN: Thoracic Aorta STAIN: Hematoxylin Eosin DIAGNOSIS: Mixed stratified thrombus (Aorta with mural thrombus and atherosclerosis) DEFINITION: Thrombosis ( from the greek thrombos = clotted material) means blood clotting in vessels, in the living body = blood necrosis in the living body. THROMBOGENESIS - VIRCHOW‘S TRIAD (3 possible reasons) 1. Abnormalities of the vessel wall/ Endothelial injury or lesions of intimal surface: - atherosclerosis - inflammations/vasculitis: arteritis, phlebitis - arterial hypertension - toxins: cigarette smoke - metabolic disorders: hypercolesterolemia 2. Abnormalities of the blood flow: - slowed flow velocity - stopped flow - turbulence in the blood flow - hyperviscosity (polycytemia) 3. Abnormalities of the blood elements/ Hypercoagulability: - increasing in the platelets number - platelet clumping - activation of the coagulation cascade CLASSIFICATION: Thrombi can be classified based on their TYPE: LOCALIZATION: mural (cardiac) veins (plebothrombosis) occlusive arteries broken (interrupted) cardiac thrombosis continuous (uninterrupted) EVOLUTION of THROMBI: 1. Dehydration 2. Growth, propagation into systemic circulation 3. Dissolution (enzyme lysis, resolution) 4. ORGANIZATION – transformation in a scar tissue 5. Recanalisation = dilation of vessels of the scarred connective tissue 6. Hyalinization and calcification 7. Septic dissolution (superinfection) 8. Migrating/ break off into the circulation —> EMBOLISM CONSEQUENCES of THROMBOSIS: Progressive growth of the thrombus Narrowing or obstruction of vessel’s lumen, followed by, depending on weather it is - Venous thrombus → congestion, edema, variceal ulcers, embolism, phlebothrombosis, deep vein thrombosis, migratory thrombosis (Trousseau syndrome) - Arterial thrombi → partial occlusion → ischemia → atrophy, sclerosis → total occlusion → infarction, even sudden death (e.g. in case of acute embolization of the pulmonary artery) MORPHOLOGY of THROMBI/ MICROSCOPIC CLASSIFICATION: 1. Fibrin thrombi —> in the microcirculation (Disseminated Intravascular Coagulation - DIC) —> fibrin + platelets 2. White (pale) thrombi (arterial thrombi) —> platelets + fibrin + leukocytes —> in case of continuous flow of circulation 3. Red thrombi (venous thrombi) —> fibrin + erythrocytes + leukocytes —>in case of vessel obstruction, circulation is stopped 4. Mixed thrombi (lamination, stratified) — > platelet clumping + erythrocytes —> lines of Zhan (white and red lines) 5. Composed thrombi —> they have a head – white thrombus body – mixed thrombus tail – red thrombus MACROSCOPIC FEATURES of THROMBI / DESCRIPTION: Thrmobi are solid, friable, matte, red mass, adherent to the vessel wall, completely or partially occluding the blood vessel. 1. Aortic intima 2. Atherosclerotic plaques 3. Mural thrombus (mixed stratified, adherent, matte, friable) MICROSCOPIC DESCRIPTION: 1. Arterial vessel wall 2. Thrombus - adherent to the arterial vessel wall 3. Calcified atherosclerotic plaque 4. Zahn lines: lightly eosinophilic layers (rich in platelets) alternating with red layers (rich in erythrocytes), all these cells being embedded in a fibrin network.  MACROSCOPIC ONLY 7 Saddle thrombus 1. Abdominal aorta and its bifurcation into the common iliac arteries 2. Common iliac arteries 3. Thrombus riding the aortic bifurcation = saddle thrombus ORGAN: Abdominal aorta STAIN: Hematoxylin Eosin DIAGNOSIS: Saddle thrombus DEFINITION: Thrombosis ( from the greek thrombos = clotted material) means blood clotting in vessels, in the living body = blood necrosis in the living body. *SEE THE DESCRIPTION OF THROMBUS ABOVE in MIXED STRATIFIED THROMBUS!* MACROSCOPIC DESCRIPTION: Thrombus - mixed stratified, adherent, matte, friable  MACROSCOPIC and MICROSCOPIC g Shock kidney 1. Pale renal cortex 2. Hyperemic renal medulla 3. Renal pelvis 4. The pale renal cortex is well delimited from the hyperemic medulla ORGAN: Kidney STAIN: Hematoxylin Eosin DIAGNOSIS: Shock kidney DEFINITION: A shock (cardiovascular collapse) is a systemic hypoperfusion caused by reduction either in cardiac output or in the effective circulating blood volume; a lack of balance between the vascular bed capacitance and volume of the circulating blood. CLASSIFICATION: 1. Cardiogenic shock (myocardial infarction – pump failure) 2. Hypovolemic shock (reduction in the effective circulating blood volume, due to loss of blood, plasma, water during burns, dehydration, trauma, hemorrhages 3. Septic (infective, endotoxic) shock (bacterial toxemia) 4. Anaphylactic shock (systemic vasodilation, increased vascular permeability due to allergic agents) 5. Neurogenic shock (paralytic vasodilation) —> trauma, lesions of CNS, spinal cord injury, pain, psychological factors CONSEQUENCES of SHOCK: Generalized venous congestion, followed by: plasma extravasation hypovolemia, hypoperfusion, hypotension progressive hypoxia metabolic disorders lactic acidosis MORPHOLOGY of SHOCK: - DIC = Disseminated intravascular coagulation (thrombosis, consumption coagulopathy) hypoxia → damaged endothelium → coagulation cascade triggered - Kidney (tubular necrosis) - Lung (alveolar damage) - Liver (centrilobular necrosis) - Pancreas (pancreatitis) - Gastro-intestinal tract (hemorrhages, necrosis) - Myocardium (hypotension, subendocardial focal necrosis), brain (neuronal injury) - Adrenal glands (hemorrhages) - Multiple system organ failure (MSOF) MACROSCOPIC DESCRIPTION: 1. Pale renal cortex 2. Hyperemic renal medulla 3. Renal pelvis 4. The pale renal cortex is well delimited from the hyperemic medulla MICROSCOPIC DESCRIPTION: Tubular necrosis = necrosis of the tubular lining epithelium —> no visible nuclei in the tubular epithelium; when looking at the slide, find the glomeruli and make sure that they have nuclei, whereas the tubules around don’t have any * A regeneration of the epithelium is possible with early treatment *  MACROSCOPIC ONLY 9 Cerebral hemorrhages/hematomas MACROSCOPIC DESCRIPTIONS: Subdural hematoma Subarachnoid hematoma Intraventricular and intracerebral 1. Sectioned skull 1. Brain hematoma 2. Meninges - dura mater 2. Subarachnoid hematoma 1. Brain 3. Subdural hematoma (localized between 2. Intraventricular and intracerebral (localized between dura arachnoid and pia mater) hematoma (+ blood accumulation mater and arachnoid) within the lateral ventricle) ORGAN: Brain DIAGNOSIS: Cerebral hemorrages/ hematomas DEFINITION: Hemorrhage = blood extravasation outside of vessels, in the living body CLASSIFICATION: Hemorrhages can be classified based on their BLEEDING LOCATION and BLEEDING DIRECTION cardiac hemorrhages External arterial hemorrhages Internal —> in tissues capillary bleeding —> in cavities venous hemorrhages CAUSES of HEMORRHAGES in general: 1. Rupture of the vessel wall —> trauma or spontaneously 2. Erosion of the vascular wall —> atherosclerosis, inflammations, tumors 3. Diapedesis (integral capillary wall)—> congestion, hypoxia, DIC, allergies, bacteria, viruses CONSEQUENCES/EVOLUTION of HEMORRHAGES: Depending on the following factors hemorrhages will have a different evolution: Rate of bleeding (rapid, slow) Volume of extravasated blood Site of hemorrhage: - brain (intracranial hypertension) - pericardium (cardiac tamponade) - respiratory tract (asphyxia) EVOLUTION of HEMATOMAS: 1. Lysis 2. Organization —> scarring 3. Capsuling —> pseudocyst (cavity) —> hyalinization, calcification 4. Dehydration / resorption 5. Superinfection —> abscess DENOMINATIONS of INTRACRANIAL HEMORRHAGES: Epidural hematoma = blood accumulation between bone (skull) and dura mater —> most often after trauma Subdural hematoma = blood accumulation between dura mater and arachnoid —> most often after aneurysm (congenital - young people) or systemic hypertension (HBP) and more rare after trauma Subarahnoidian hematoma = blood accumulation between pia mater and arachnoid —> especially in systemic hypertension (HBP) and rarely in aneurysms or vascular malformations; extremely rare in trauma Intraparenchymatous hematoma = blood accumulation inside the brain parenchyma —> especially due to HBP CAUSES of INTRACRANIAL HEMORRHAGES: 1. Hypertension → hyaline sclerosis of the deep penetrating arteries and arterioles, that weakens their walls (vulnerable) → formation of Charcot-Bouchard microaneurysms, finally resulting in their rupture 2. Trauma 3. Vascular malformations → arteriovenous malformations, cavernous malformations, capillary teleangiectasis (pons), venous angiomas 4. Tumors 5. Hemorrhagic conversion of an ischemic infarction 6. Cerebral amyloid angiopathy (amyloid deposits in the walls of medium- and small- caliber meningeal and cortical vessels) MACROSCOPIC DESCRIPTION (under the images on previous page)  MACROSCOPIC ONLY 10 Edema - Hydrocele MACROSCOPIC DESCRIPTION: 1. Testis - longitudinal section 2. Large cavity resulted from the accumulation of clear serous fluid between visceral and parietal layers of tunica vaginalis ORGAN: Testis DIAGNOSIS: Edema - Hydrocele DEFINITION: Edema = abnormal collection of fluid: - in tissues (intercellular compartment) - in serosal cavities (serous effusion) In this case (Hydrocele) it is the accumulation of transudate between the visceral and parietal layers of the tunica vaginalis of the testis. ! SEE ALL THE DESCRIPTION OF EDEMA IN SLIDE 1 (Acute Pulmonary Edema) !  MACROSCOPIC ONLY 11 Hemorrhoids MACROSCOPIC DESCRIPTION: 1. Anal canal 2. Inferior segment of the rectum 3. Hemorrhoids (prominent areas in the lumen - varicose veins / dilated hemorrhoidal veins) – blueish nodules, internal/external ORGAN: Anal canal + Rectus DIAGNOSIS: Hemorrhoids DEFINITION: ANORECTAL VARICES/ HEMORRHOIDS = abnormal downward displacement of the anal cushions, that causes venous dilation Hemorrhoids are part of the collateral circulation, that is a compensatory mechanism in ischemia or congestion, appearing in the venous system. —> e.g. in hepatic cirrhosis (portocaval anastomosis) - the hemorrhoidal veins are a natural path of collateral circulation for blood, trying to return to the heart from the rectum, due to portal hypertension  MACROSCOPIC and MICROSCOPIC 12 Fatty change of the liver 1. Liver ORGAN: Liver STAIN: Hematoxylin Eosin DIAGNOSIS: Fatty change DEFINITION: Fatty change = accumulation of tryglicerides in the cytoplasm of those cells which do not contain them in physiological conditions PATHOMECHANISM of INTRACELLULAR ACCUMULATION: 1. Unaffected metabolism = fatty infiltration, lipid accumulation —> cause: hyperlipidemia 2. Abnormal metabolism = fatty change —> causes: hypoxia/anoxia, toxins, infections LOCALIZATION of FATTY CHANGE: Liver —> - at the periphery of hepatic lobules (hyperlipidemia) - in the central area (hypoxia) - diffuse - fatty liver or steatosis (toxins, alcohol) Heart —> - striated fatty change in hypoxia yellow (fat) and brown (normal myocardium) bands, called «tigered effect» - diffuse fatty change, caused by toxins or infections Kidneys —> - fatty change in the renal tubular epithelial cells during hyperlipidemia, nephrotic syndrome, etc. EVOLUTION: Fatty change can be reversible or may lead to fibrosis MACROSCOPIC DESCRIPTION: The liver is enlarged, yellow, soft/friable consistency and greasy on the cut section surface MICROSCOPIC DESCRIPTION: We can observe small or large clear vacuoles (fat globules) in the cytoplasm, stained with Sudan III, IV or Oil Red Fragment of hepatic parenchyma with preserved architecture: visible portal spaces and central veins Both centrally and peripherally located hepatocytes show fatty change: they contain optically empty vacuoles of various sizes inside the cytoplasm (the lipids inside the vacuoles were lost during tissue processing) Hepatocytes contain optically empty vacuoles of various sizes inside the cytoplasm, vacuoles that push the nuclei to the periphery —> „Signet/engagement ring cells“ We can also observe some binucleated hepatocytes (as usual in the liver)  MACROSCOPIC (no image but description) and MICROSCOPIC 13 Hyperkeratosis (callosity) 1. Epidermis with thickened corneal layer 2. Normal dermis 3. Normal hypodermis 4. Thickened corneal layer, without the presence of the nuclei ORGAN: Skin STAIN: Hematoxylin Eosin DIAGNOSIS: Hyperkeratosis (Callosity) + Acanthosis DEFINITION: HYPERKERATOSIS = thickening of the stratum corneum, with preservation of the integrity of all epidermal layers Hyperkeratosis is a keratin disorder —> keratin is a simple protein (scleroprotein) located specifically in the epidermis: physiological keratinization = ortokeratosis of the skin, as evidenced by the lack of nuclei in the thickened stratum corneum KERATIN DISORDERS can be classified in: 1. Hyperkeratosis = thickening of the corneal layer 2. Parakeratosis and Dyskeratosis = pathological keratinization of the epidermis 3. Other abnormal location of the keratinization process e.g. Leukoplasia = abnormal keratiniztion on mucosal surfaces ETIOLOGY of HYPERKERATOSIS: Mechanical factors —> callosity, clavus, weft Congenital/ fetal/ harlequin ichthyosis —> generalized hyperkeratosis Sun exposure —> farmer's and sailor's skin Viruses —> verruca vulgaris, squamous papilloma ← HPV Skin tumors —> skin horn, basal cell papilloma DIFFERENTIAL DIAGNOSIS with other PATHOLOGICAL KERATINIZATIONS: 1. Parakeratosis= increased epidermal turnover —> Macroscopic aspect: pinkish red plaques with fine, silver scales —> Microscopic aspect: - lack of stratum granulosum and lucidum - retention of small nuclei in the stratum corneum Examples: Psoriasis Condilomas Syphilis (II) 2. Dyskeratosis = abnormal keratinization occuring prematurely in the inferior epidermal layers Example: Molluscum contagiosum (poxvirus, self-limited lesion in children), Squamous cell carcinomas 3. Abnormal location of keratinisation process: Leukoplasia (mucosal keratinisation) Cholesteatoma (tympanic cavity) MACROSCOPIC DESCRIPTION: The affected skin area is hard at palpation, thickened, and pale MICROSCOPIC DESCRIPTION: 1. Epidermis with thickened corneal layer: thickening of the stratum corneum (corneal layer), without nuclei in this layer; preservation of integrity of all epidermal layers 2. Normal dermis 3. Normal hypodermis 4. Thickened corneal layer, without the presence of the nuclei 5. ACANTHOSIS = abnirmally thick stratum spinosum  MICROSCOPIC ONLY 14 Compound melanocytic nevus 1. Normal epidermis 2. Proliferation of nevus cells 3. Normal adnexa (hair follicle, sebaceous gland) 1. Normal epidermis 2. The dermis and the dermoepidermal junction - interested by nevus cells proliferation 3. Normal dermis ORGAN: Skin STAIN: Hematoxylin Eosin DIAGNOSIS: Compound melanocytic nevus DEFINITION: Melanocytic nevi appear as a result of MELANIN ACCUMULATION, which is one of the possible pigments that can accumulate in some disorders. PIGMENT ACCUMULATION DISORDERS: Depending on the type of pigment we can classify them in Endogenous pigments —> synthesized by the body itself: - Hemoglobin pigments without iron: bilirubin and porfirin with iron: hemosiderin, hemomelanin (malaria pigment) and acid hematin - Non-hemoglobin pigments melanin, lipofuscin (aging pigment), lipochrom, lutein (carotenoid) Exogenous pigments —> from outside the body - Pneumoconiosis (dust accumulation in lungs; konis, gr. =dust) - Dietary pigmentations, skin pigmentations MELANIN ACCUMULATION: Melainin, from the greek melas, means black It can be emphasized with - H2O2 (hydrogen peroxyde) - AgNO3 (silver nitrate) - Histochemistry - Immunohistochemistry Conditions in which we have a - decreased quantity of melanin - Albinism - Vitiligo/leucoderma - increased quantity of melanin - Suntanning (Hyperpigmentation) - Ephelides (freckles) - Chloasma/Melasma during pregnancy on face - Addison disease + Peutz-Jeghers syndrome - Acanthosis nigricans - Xeroderma pigmentosum - Melanocytic tumors: nevi, benign and malignant lentigo, malignant melanoma NEVOCYTE = name of the melanocyte in the benign tumor (nevus/mole) Melanocytic nevi can develop in 3 different parts of the skin layers: 1. JUNCTIONAL NEVUS 2. COMPOUND NEVUS S more prone to become malignant 3. INTRADER,AL NEVUS with EXTENSIVE CELLULAR SENESCENCE MACROSCOPIC DESCRIPTION: Brown/tan, uniformly pigmented, symmetrical nodules/papules, 5 mm or less in diameter, with well defined rounded borders MICROSCOPIC DESCRIPTION: Round/oval cells that grow in nests (superficial) or cords (deeper), uniform and round nuclei, no mitotic activity. The cytoplasm may contain - brown granules of melanic pigment (also in stroma around) - melanin pigment can be released and phagocytosed by dermal macrophages (= melanophages) The nevus cells are round to oval cells, arranged in nests, cords or trabebeculae. Their nuclei are uniform and round, with inconspicuous nucleoli. Their mitotic activity is reduced or absent  MACROSCOPIC ONLY 15 Nephrolithiasis and Hydronephrosis MACROSCOPIC DESCRIPTION: Adipose perirenal tissue Kidney stones presenting a coraliform aspect Dilated renal calyces Atrophic renal parenchyma Hydronephrosis ORGAN: Kidneys DIAGNOSIS: Nephrolithiasis and Hydronephrosis DEFINITION of CALCULOSIS/ LITHIASIS: LITHIASIS/CALCULOSIS (from the greek lithos and latin calculus= stone ) = precipitation of solid materials either in the cavities covered with mucosal layer or in the excretory ducts of the glands PATHOMECHANISM: 1. Nucleation —> the nucleus can be bacteria, foreign matter, inflammatory cells,… 2. Precipitation of substances —> - crystal-like substances (radial structure on section) - colloid-like substances (concentric structure) - both type of substances (mixed structures) CAUSES of LITHIASIS: Systemic factors - metabolic disorders (hypercholesterolemia, hyperuricemia, hypercalcemia); - genetic predisposition (gout, cystinuria) Local factors - localized chronic inflammations - local stasis and increased secretion concentration - change in the pH of the secretion MORPHOLOGY: - Dimension: variable - Shape: round-oval, faceted, coral-shaped - Number: solitary or multiple - Consistency: friable, soft, or hard LOCATION: 1. GALLSTONES/ CHOLELITHIASIS = in the gallbladder and biliary ducts → composed of cholesterol, bile pigment, calcium carbonate, or mixed 2. URINARY CALCULI or STONES/ URO-, NEPHROLITHIASIS = in kidneys (pelvis, calyx), ureters or urinary bladder → urinary stones composed of uric acid, cystine, calcium oxalate/phosphate, struvite 3. Other organs(e.g. sialolithiasis = in the excretory ducts of the salivary glands, more commonly in the submandibular gland) POSSIBLE CONSEQUENCES of CALCULI: Latent lithiasis → asymptomatic Stone migration → pain (biliary, renal, ureteral colic) → elimination or → inclavation → obstruction → lumen dilation (biliary, ureter, pelvis) → mechanical jaundice Hydronephrosis Macroscopic hematuria Bacterial infections of the urinary tract Chronic inflammation with episodes of acutization High risk of developing a malignant tumor (e.g., gallbladder cancer)  MACROSCOPIC ONLY 16 Cholecystolithiasis 1. Gallbladder 2. Gallstones ORGAN: Gallbladder DIAGNOSIS: Cholecystolithiasis DEFINITION: LITHIASIS/CALCULOSIS (from the greek lithos and latin calculus= stone ) = precipitation of solid materials either in the cavities covered with mucosal layer or in the excretory ducts of the glands * See Lithiasis CLASSIFICATION and DESCRIPTION on slide 15 above! *  MACROSCOPIC and MICROSCOPIC 17 Amyloidosis - Systemic amyloidosis + Renal amyloidosis 1. Enlarged glomeruli, containing amyloid deposits 2. Renal tubes with amyloid deposits in the basal membrane 3. Blood vessels with thickened walls due to amyloid deposit 1. Glomeruli 2. Renal tubes 1. Kidney 2. Liver 3. Spleen 3. Blood vessels ORGANS: Kidney, Liver or Spleen STAIN: Hematoxylin Eosin DIAGNOSIS: Amyloidosis (Amyloid dystrophy) DEFINITION: AMYLOIDOSIS = the accumulation of amyloid/ extracellular amyloid precipitation, accompanied by tissue damage and functional disorders (e.g., renal failure, heart failure, memory loss, etc.) AMYLOID (from the greek amylon= starch) = homogeneous, clear, proteic substance, always accumulated extracellularly —> in pathological conditions associated with protein folding defects, which thus become insoluble, or with accumulations of protein fragments AMYLOID PRECURSORS: The amyloid is synthesized from different precursors, such as Serum Amyloid Protein A (SAA) Amyloid from Immunoglobulin light chanis (AL) Transthyretin Amyloid beta protein in the brain Beta-2-microglobulin Keratin Some hormones (procalcitonin and proinsulin) AMYLOID COMPOSITION: 1. Stable component: fibrillary protein P (SAP) 2. Labile component: serum glycoprotein PATHOGENESIS of AMYLOIDOSIS: Physiologically the monocyte can dissolve the amyloid precursors, after their endocytosis, but in the condition of monocyte-macrophage system disorders the amyloid precursors become insoluble proteins and due to exocytosis they get into the interstitium and are transformed in amyloid. CLASSIFICATION of AMYLOIDOSIS: - LOCALISED AMYLOIDOSIS 1. Nodular amyloidosis (pseudotumor) - in localized inflammations - lungs, larynx, skin, urinary bladder, tongue, periocular area 2. In endocrine tumors - procalcitonin (medullary carcinoma of the thyroid gland) - proinsuline (insulinoma) - adrenal glands (feocromocytoma) 3. Senile - heart (transthyretin) – isolated atrial amyloidosis - brain (beta-2-amiloid protein) – Alzheimer’s disease - SYSTEMIC AMYLOIDOSIS = affecting 2 or more organs 1. Secondary amyloidosis (type AA) – chronic inflammatory disorders, associated with tissue lysis 2. Primary amyloidosis - paramyloidosis (type AL) - plasma cell neoplasm —> multiple myeloma (paraproteins) 3. Hemodialysis -associated (beta-2-microglobulin) —> carpal tunnel syndrome - HEREDITARY AMYLOIDOSIS 1. Familial Mediterranean fever (SAA) 2. Familial amyloid polyneuropathy (transtiretin) 3. Systemic senile amyloidosis MACROSCOPIC DESCRIPTION: Amyloid is a homogenous, transparent insoluble substance The organ is increased in size, due to extracellular accumulation of amyloid and will appear lardaceus = white 1. KIDNEY —> Enlarged, pale (amyloid is white) kidney with prominent and retracted areas on the exterior surface; the consistency is hard 2. LIVER —> Fern leaf-like aspect, due to the amyloid deposits in the walls of the sinusoid capillaries 3. SPLEEN —> Sago spleen - amyloid deposits in the white pulp forms some nodules MICROSCOPIC DESCRIPTION: Depending on what Stain is used, amyloids deposits appear in different colours Under the microscope: - H&E: eosinophilic/pink - Van Gieson: yellow - Congo red: orange/red —> under polarized light the Congo Red-colored slide appears green birephringence - Immunohistochemistry: brown or red Under the electron microscope: - fibrilar structure 1. Enlarged glomeruli, containing amyloid deposits (eosinophilic,pinkish, acellular material) within the basal membrane of the glomerular capillary walls 2. Renal tubes with amyloid deposits in the basal membrane 3. Blood vessels with thickened walls due to amyloid deposit  MACROSCOPIC and MICROSCOPIC 18 Gouty arthritis 1. Subcutaneous tophi 2. Epidermis with hyperkeratosis ORGAN: Joints (Big toe joint) STAIN: Hematoxylin Eosin DIAGNOSIS: Gouty arthritis (tophi in the periarticular tissue) DEFINITION: GOUTY ARTHRITIS = accumulation of uric acid in the synovium and synovial fluid —> Plasma urate level are > 6.8 mg/dl CLASSIFICATION of GOUT: PRIMARY GOUT —> - genetic abnormalities of the metabolism of purines - especially in males SECONDARY GOUT —> - increased release of nucleic acids from the necrotic tissues (tumors) - increased nucleic acid turnover (polyglobulia, leukaemia) - decreased urinary excretion of uric acid (chronic renal disease) - high dietary purine intake (meat, alcohol) MORPHOLOGICAL CHANGES in GOUT: 1. ACUTE ARTHRITIS - inflammatory infiltrate in the the synovium and synovial fluid - synovium: clusters of urate crystals (long, needle-shaped, negatively birefringent) congestion, edema, scattered lymphocytes, plasma cells, and macrophages 2. CHRONIC TOPHACEOUS ARTHRITIS - evolves from the repetitive precipitation of urate crystals during acute attacks - the crystals encrust the articular surface and form visible chalky deposits in the synovium - the synovium becomes hyperplastic, fibrotic, and thickened, infiltrated with inflammatory cells, and forms a pannus → destroys the underlying cartilage 3. TOPHI in the ARTICULAR CARTILAGE, LIGAMENTS, TENDONS and BURSAE - pathognomonic of gout - large aggregations of urate crystals surrounded by an intense foreign body giant cell reaction 4. GOUTY NEPHROPATHY - urate crystals or tophi in the renal medullary interstitium or tubules - complications: uric acid nephrolithiasis, pyelonephritis MACROSCOPIC DESCRIPTION: Amputated great toe - white tophi (like chalk) located in the joints and soft tissues MICROSCOPIC DESCRIPTION: 1. Subcutaneous tophi —> - dissolved urate crystals - reactive fibroblasts surrounding the tophi - mononuclear inflammatory cells - giant multinucleated cells (foreign body giant cell reaction) 2. Epidermis with hyperkeratosis  MICROSCOPIC ONLY 19 Squamous metaplasia of the respiratory bronchial epithelium 1. Normal respiratory epithelium 1. Normal respiratory epithelium 2. Bronchial hyaline cartilage 2. Bronchial seromucous glands 3. Squamous metaplasia of the 3. Bronchial hyaline cartilage respiratory epithelium ORGAN: Bronchus STAIN: Hematoxylin Eosin DIAGNOSIS: Squamous metaplasia of the respiratory bronchial epithelium DEFINITION: METAPLASIA ( from the greek meta = after —> acquired disorder) = transformation of a mature, differentiated tissue, into another type of mature tissue, to become more resistant to the stress factor to which it is exposed It is one of the reversible cellular injuries (adaptive changes): - HYPERTHOPHY —> increase in the size and weight of an organ or tissue due to increase of cells in size/volume, without division not an increase in the number of cells, only cells enlargement it leads to an increase of tissue’s activity - ATROPHY —> decreasing of tissue or organ size with previous normal development - HYPERPLASIA —> enlargement of an organ or tissue due to the increase of cells number = increase of mitosis rate - METAPLASIA CLASSIFICATION of METAPLASIA: 1. SQUAMOUS METAPLASIA - of the respiratory epithelium lining the bronchi (due to exposure to cigarette smoke toxins or vitamin A deficiency) - of the endocervix 2. COLUMNAR (INTESTINAL) METAPLASIA —> Barett’s esophagus - metaplasia with gastric or intestinal epithelium of the squamous epithelium lining the lower third of the esophagus (in patients with gastroesophageal reflux) 3. BONE FORMATION - can sometimes be seen in the soft mesenchymal tissues affected by trauma CAUSES of METAPLASIA: chronic inflammation alteration of cellular environment chronic cellular injury cigarette smoking EVOLUTION of METAPLASIA: metaplasia can be reversible, if the irritating factor is removed, otherwise it will induce DYSPLASIA —> malignant transformation, abnormal growth of cells MICROSCOPIC DESCRIPTION: 1. Normal respiratory epithelium 2. Bronchial seromucous glands 3. Squamous metaplasia of the respiratory epithelium with dysplasia and carcinoma in situ - Dysplasia —> disorderly proliferation in 3 stages: 1. Mild dysplasia = abnormal cells formtion in the lower 1/3 of the epithelium 2. Moderate dysplasia = abnormal cells formtion in the lower 2/3 of the epithelium 3. Severe dysplasia/ in situ carcinoma = abnormal cells formtion in the entire thickness of the epithelium and leads to metaplasia - Carcinoma in situ —> - atypical dysplastic cells are identifiable in the entire thickness of the epithelium - squamous cells lack orderly differentiation - the basement membrane is intact (no tumor cells in the subepithelial connective tissue) - Squamous differentiation —> - intercellular bridges - keratin formation  MACROSCOPIC ONLY 28 Cardiac atrophy 1. Heart - decreased in size 2. Aorta with a normal calibre (large, compared to the small heart) 3. Coronary arteries present a winding aspect ORGAN: Heart DIAGNOSIS: Cardiac Atrophy DEFINITION: ATROPHY = decreasing of tissue or organ’s size in comparison to previous normal development —> When several cells suffer from atrophy, the entire tissue or organ (normally previously developed) decreases in size and becomes atrophic CLASSIFICATION of ATROPHY: - Depending on the cause, atrophy can be: Physiological ( involution) —> endometrial atrophy at menopause or senescence Pathological —> - Numerical atrophy (decreasing of cell number) - Simple or brown atrophy (lipofuscin accumulation) e.g., loss of innervation, malnutrition, lower limb muscle atrophy in patients immobilized for a long time in bed or due to reduced blood supply in those with chronic lower limb obliterative arteriopathy - Depending on the affected territories, atrophy can be: Generalized atrophy —> it affects the whole body e.g. cachexia, malnutrition, senile atrophy Localized atrophy —> decreasing in size of previously normally developed organ, vessels with winding/serpentine trajectory CAUSES of LOCAL ATROPHY: Mechanical – compression Chronic hypoxia or ischemia Radiation Immobility of the limbs, loss of innervation, hormonal insufficiency Aging MACROSCOPIC DESCRIPTION: 1. Heart - decreased in size 2. Aorta with a normal calibre (large, compared to the small heart) 3. Coronary arteries present a winding aspect (normally are linear)  MACROSCOPIC ONLY 21 Benign prostatic hyperplasia 1. Hyperplasia of the prostate gland, thus compression of the prostatic urethra at this level 2. Hypertrophy of Urinary bladder: thickened wall due to hypertrophy of the muscle layer 3. Penile urethra (longitudinal section) with a iatrogenic ulceration Nodules ORGAN: Prostate DIAGNOSIS: Benign prostatic hyperplasia DEFINITION: HYPERPLASIA = enlargement of an organ or tissue due to increase in number of the cells, through an increase in the mitosis rate in labile tissues —> the tissue’s structure is not affected CLASSIFICATION of HYPERPLASIA: - Depending on the cause, hyperplasia can be: Physiological —> caused by hormonal stimuli: - myometrium during pregnancy - breast tissue during puberty and pregnancy - erythrocytes produced in the bone marrow after increased erythropoietin secretion caused by life at high altitude —> compensatory hyperplasia: hyperplasia of the liver parenchyma remaining after subtotal resection, even reaching the initial preoperative dimensions  Pathological —> - Mechanical factors (thickening of the skin through hyperplasia of the stratum corneum of the epidermis - callosity) - Overproduction of hormones: Estrogen —> Endometrium, breast (gynecomastia) Dihydrotestosterone - DHT —> Prostate TSH —> thyroid – goiter (= enlarged thyroid) Somatotropin (STH) or hGH, produced by the pituitary gland —> bones, cartilages - acromegaly, gigantism - chronic hypoxia (erythrocyte hyperplasia, produced by the bone marrow) - chronic inflammations, tissue repair (wound healing-scar) - genetic factors (growth factors encoded by viral genes, e.g. HPV) CONSEQUENCES of HYPERPLASIA: Hyperplasia can be: - a reversible process (controlled by mechanisms that allow cell proliferation to stop, once the trigger signals stop) - malignant transformation ! (e.g., patients with endometrial hyperplasia have an increased risk of developing endometrial carcinoma) MACROSCOPIC DESCRIPTION: 1. Enlarged prostate gland => compression of the prostatic urethra at this level by the nodules formed due to the prostate hyperplasia (yatagan sword aspect) 2. Urinary bladder hypertrophy - thickened wall due to hypertrophy of the muscle layer (trabeculation of the urinary bladder) 3. Penile urethra (longitudinal section) + iatrogenic ulceration, caused by errors during catheterisation of the patient  MACROSCOPIC ONLY 22 Acute pancreatitis 1. Multiple small (2-6 mm) steatonecrotic areas in peripancreatic adipose tissue 2. Large hemorrhagic areas (dark appearance after formalin fixation) ORGAN: Pancreas DIAGNOSIS: Acute pancreatitis DEFINITIONS: NECROSIS = irreversible pathological death of cells or tissue in the living body; it always appears after an injury which leads to loss of membrane integrity and destruction of cell components —> associated with hostinflammatory response - Necrosis can be sudden or progressive - Morphological disorders can be observed only after a period of time (autolysis) - Particular forms of necrosis are Apoptosis and Cell aging APOPTOSIS = physiological or pathological programmed cell death - Usually involves single cellls - No host inflammatory response - Intact cell membrane MORPHOLOGY of NECROSIS: Under the microscope we can observe, after 15-20 hours !!: 1. Nuclear changes karyolisis —> - loss of nuclear staining - karyopyknosis (nucleus shrinkage) - karyorrhexis (fragmentation) → finally: disappearance of nucleus 2. Cytoplasm disorders —> - swelling, increased eosinophylia - loss of cytoplasmic details 3. Disorders of the interstitium —> - lysis - storage of detritus - dystrophic calcification At a ultramicroscopic level we can observe after 5-15 minutes: —> mitochondrial disorders CLASSIFICATION OF NECROSIS: 1. Coagulative necrosis (dry) —> infarction (except brain) 2. Caseous necrosis (TB, syphilis, tumors) 3. Liquefactive (colliquative) necrosis (wet) - brain infarction 4. Fat necrosis (steatonecrosis) - adipose tissue, pancreatitis 5. Gangrenous necrosis – legs, ombilicus 6. Fibrinoid necrosis EVOLUTION of NECROSIS: Isolated cells/small groups of cells: healing, complete resolution Expanded areas of necrosis: - scarring - capsuling: hyalinisation, calcification - auto-amputation, ulceration - superinfection CAUSES of ACUTE PANCREATITIS: Mnemonic: “I get smashed” MACROSCOPIC DESCRIPTION: 0. Edema —> caused by the acute inflammation of the pancreas 1. Multiple small (2-6 mm) steatonecrotic areas in peripancreatic adipose tissue: the lipase that was not able to leave the pancreas (e.g. cholestasis and gallstones blocking the papilla of Vater) starts acting on the pancreatic fat tissue 2. Large hemorrhagic areas (dark appearance after formalin fixation), caused by the elastase