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Pathology Lab 1

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					Lab 1: Cell Adaptation, Injury, Death, Inflammation, Repair - 8/24/05
1. Normal Histology: Overview a. Adipose Tissue: Large, bubble cells with nuclei on the edges b. Smooth muscle: Rounded nuclei c. Peripheral nerve tissue i. Wavy looking tissue ii. Serpentine nuclei iii. “Herring Bone” – spine with ribs coming off iv. Bulls eye – cross section of peripheral nerve – nerve (bulls eye), myelin is covering nerve fiber d. Skeletal muscle i. Eccentric nuclei (on the outside) ii. Striations in the cells as well…they run perpendicular to the fibers e. Blood i. RBC ii. platelets iii. White (leukocytes) 1. Neutrophils 2. Basophiles 3. Eosinophiles f. Difference between Guts and Arteries i. Guts have epithelial lining ii. Arteries, veins have endothelial lining (Arteries have much thicker walls than veins) iii. Layers of the arteries and veins (easier to see in arteries) 1. Tunica intima 2. tunica media 3. tunica adventia g. Cardiac muscle i. Centrally placed nucleus ii. Intercalated discs, and striations iii. Lipofuscion pigment: brown stuff in cardiac cells on slide h. Lymphocytes in spleen i. lymphocytes = dark round nuclei, almost no cytoplasm ii. lymphocytes = “black pepper” cells iii. White pulp - lymphocytes iv. Red pulp – RBC i. Thymus gland contains: i. Hassle‟s corpuscles ii. lymphoid cells j. Skin i. Two layers: Dermis (keratinized) and Epidermis ii. Contains Hair follicles iii. Epidermis has several layers 1. Stratum (S) corneum: most superficial, flat squamous cells packed with keratin filaments

iv. v. k. GI i. Mucosa – stratified squamous ii. Submucosa iii. Muscularis propria iv. Serosa l. Stomach i. Gastric pits and glands in the mucosa ii. Mucin glands – clear glands iii. Parietal cells in the mucosa m. Appendix i. Has lymphoid glands ii. Has chronic lymphocytes n. Colon i. Goblet cells ii. Lamina propria with lymphocytes o. Liver i. Is the hepatic lobular structure intact? That‟s what you have to ask yourself first to see if the liver is normal 2. Slide 53 – Atrophy of pancreas; Questions and answers a. Why did the endocrine cells survive? The endocrine cells survived because the enzymes are blocked in the gall bladder and pancreas, which digested the exocrine cells before the endocrine cells b. What are some possible causes of chronic pancreatitis? The most common cause is alcohol. Cystic fibrosis, hyperlipidemia are also causes c. Explain the mechanism of injury and death of the exocrine tissue. Mechanism is direct toxic effects of the enzymes d. Compare and contrast dystrophic and metastatic calcification. Dystrophic calcification is a degenerative change to dead tissue getting secondary calcification. Metastatic calcification is due to hypercalcemia that ends up killing the tissue 3. Slide 174 – Carbon Tetrachloride Injury (Liver); Questions and answers a. What is the estimated % of dead cells in the liver? There is probably about 80% b. What lesions account for yellow discoloration? Fatty change in the liver c. How do you explain the lack of regeneration? Continued exposure to CCl4 d. What criteria do you use to determine cell death in this slide? Necrosis a. Pyknosis – nucleus shrivels i. Karyorexis – nucleus breaks apart ii. Cytoplasm becomes fuzzy

2. S. lucidum: indistinct homogenous layer of keratinocytes present only in thick skin 3. S. granulosum: present in thick skin, keratinocytes 4. S. spinosum: contains Langhan’s cells, contains waterproofing keratinocytes 5. S. Basale (germinativum): deepest layer, tall cuboidal keratinocytes Subcutaneous – adipose tissue Sebaceous glands – contains lots of fat, stains similar to adipose

e. Compared to ischemia, what is the initial mechanism of cell injury caused by cabon tetrachloride? The initial mechanism of CCl poisoning: (fig 1.23) i. CCl4  CCl3 radical ii. Lipid radicals iii. Lipid peroxide 4. Slide 38 – Acute Appendicitis a. Elevated WBC (leukocytosis) = inflammation, maybe infection b. Elevated polymorphonuclear leukocyte (neutrophil) i. Tells us that this is an acute process ii. Other WBC‟s are more for chronic things iii. Also tells us that this is probably bacterial, not viral c. Mucosa is gone (ulceration), its been replaced by pepper (inflammatory cells – neutrophils) d. Questions and answers: i. Describe the sequence of events that allow leukocytes to move from the vessel lumen to the interstitial tissue. What is the process called? Extravasation – steps of “rolling and tethering” 1. Leukocyte margination on the outer part of the blood vessel 2. Rolls along margin 3. Diapedesis – Leukocytes traverses the margin of the blood vessel 4. Emigration to site of problem based on the chemotactic factors and complement ii. Explain the role of the fecalith (ball of feces) in the development of acute appendicitis. 1. Causes obstruction 2. Causes increased intra-luminal pressure 3. Causes some degree of ischemia 4. Bacterial proliferation and inflammation iii. Name the most feared complication of acute appendicitis. Perforation or rupture of appendix leads to peritonitis 1. Rebound tenderness is indicative of peritonitis 2. When you press the abdomen and hold it, the pain goes away 3. Letting go of the abdomen causes vibration in the peritoneum. If this causes pain, then you have peritonitis iv. Name a tumor that may present as the syndrome of acute appendicitis A tumor in the right lower quadrant may simulate appendicitis 1. Appendix cancer (rare) – carcinoid tumor 2. Colon cancer v. What causes rebound tenderness in the right lower quadrant? The abdominal muscle rigidity (guarding)? 1. Rebound tenderness is indicative of peritonitis a. When you press the abdomen and hold it, the pain goes away b. Letting go of the abdomen causes vibration in the peritoneum. If this causes pain, then you have peritonitis vi. Why is acute appendicitis particularly dangerous in the elderly? Dangerous in the elderly because the immune response in old folks is

inhibited, so they don‟t present early on, so they have a greater chance of perforating vii. What is the differential diagnosis of acute appendicitis? Differential diagnosis of right lower quadrant pain: 1. Appendicitis 2. Tumors 3. Middle Shmerts – ovaries and ovulation 4. Twisted ovaries (ectotorsion) 5. Ectopic pregnancy 6. Colitis – ascending (cecum) 7. Diverticulitis 8. Ureter stones 5. Slide 28 – Miliary Tuberculosis (TB) a. Dealing with infection in the lungs (probably bacterial) b. DIC – Disseminated intravascular coagulation c. Miliary TB – Millet (Bird seed) TB. Looks like bird seed in the lungs i. Granulomatous inflammation ii. Persistent chronic inflammation, particularly in response to a “nondigestible” substance may result in the formation of a granuloma. The principle cells involved in a granuloma are macrophages and lymphocytes. Macrophages undergo a characteristic change, transforming them into epitheliod cells. A nodular collection of these cells, with or without associated giant cells is the hallmark of Granuloma. d. Zeal-Neilson stain stains the bacteria and the cells e. INR – test of coagulation cascade f. Questions and answers: g. What is military TB? How does this form of TB spread? i. Miliary TB – TB spreading in the blood (hematogenous spread) [Miliary – bird seed, millit] ii. Primary TB – shows granulomatous, asymptomatic, over time this turns into scar tissue iii. Secondary TB – where primary is reactivated, and then you get lymph problems h. Name type of necrosis and the distinctive pattern of inflammation in this case. What kinds of cells comprise this type of inflammation? i. Caseating necrosis - you see granulomatous inflammation, have multinucleated giant cells (epitheliod histiocytes) i. Are sputum smears and PPD’s diagnostic of this disorder? Sputum smear and PPD are NOT diagnostic for this TB i. PPD is a skin test for TB antigen, look for induration (bump) on skin ii. Sputum smear – get sputum, put it on a slide in TB stain (Zeal-Neilson stain, AFB stain) 1. In about 80% of cases, you cant see the TB in these stains 2. You will actually do a culture to see the TB j. Which clinical test establish the etiology of this disease with certainty? Culture test, and molecular tests (PCR)

k. Name other organisms or agents that can cause similar lesions. The histologic lesion is a granuloma, other causes: i. Sarcoidosis ii. See notes on chapter 2 l. What is the mechanism of tissue injury? The mechanism is the formation of granuloma 6. Basic Stuff in Robbins… a. 4 Questions to ask yourself about every disease i. What is the cause of the disease? ii. What is the pathogenesis of the disease 1. Sequence of events leading to disease iii. What are the morphologic changes? (minimum thing to learn in lab) iv. What are the functional/clinical manifestations of the disease b. What are the major causes of disease i. Hypoxia – lack of Oxygen (due to CO, poisons) ii. Physical Agents (trauma, burns, radiation, etc.) iii. Chemical Agents (poisons, air pollution, abnormal levels of physiologic metabolites [increased glucose, etc]) iv. Infectious agents v. Immunologic reagents vi. Genetic abnormalities vii. Nutritional imbalance c. Mechanisms of cellular injury (broad categories, there will be some overlap) i. Not enough ATP ii. Damage to mitochondria iii. Influx of Ca++ iv. Accumulation of O2 derived free radicals v. Defect or change in cell membrane permeability d. Damage can be reversible or irreversible i. Neurons only takes a few minutes before damage is irreversible e. Cellular swelling is reversible f. Fatty Change is reversible g. Cell death is irreversible – necrosis (2 main types, the rest are subtypes) i. Coagulative – denatured proteins, but the outlines of the cells (cell membranes) are there 1. See it everywhere except the brain ii. Liquifactive – no cell membranes 1. In the brain 2. In infections (bacterial) 3. Whenever you get neutrophils iii. Enzymatic – usually fat necrosis 1. Has calcification 2. Get soponification 3. Usually only seen in the pancreas iv. Caseous – cheese-like, looks like cottage cheese 1. It‟s a combination of coagulative and liquifactive

2. Only seen in TB patients v. Gangrenous – necrosis due to ischemia 1. Diabetics get this because they have atherosclerosis 2. Dry Gangrene – coagulative 3. Wet Gangren – liquifactive h. Apoptosis i. Cell shrinks, nucleus shrinks ii. Membrane stays intact iii. Normal – shedding endometrium iv. Abnormal – Tumor cells have a decrease in apoptosis i. Intracellular accumulations i. Can have normal substances accumulate 1. Lipids – alcohol 2. Proteins – multiple myeloma (increased plasma cells) 3. Glycogen 4. Iron ii. Can have abnormal, endogenous substances 1. Enzyme deficiency of glycogen breakdown (increases your glycogen) iii. Abnormal, exogenous substances 1. Carbon pigment in the lungs j. Pigments i. Black pigment – carbon pigment ii. Brown pigment – all endogenous 1. Aging (lipofuscin) 2. Melanin 3. Hemocyderin – blood breakdown (bruising, black and blue) 4. Bile 7. TERMINOLOGY a. Atrophy – shrinking of size/number of cells b. Hypertrophy – increase in cell size c. Hyperplasia – increase in # of cells d. Metaplasia – change in the cell from type to another. Name it based on what it changes into: i. Columnar epithelium in bronchus changes to squemous, so you call it squemous metaplasia e. Dysplasia – (Dys = abnormal, plasia = growth) change in the morphologic appearance of the cell. This is precancerous f. Calcification – dystrophic and metastatic g. Hyaline – a homogenous, pink, eosinophilic appearance…non-specific

Lab 2: Hemodynamic Disorders - 8/31/05
Chapter 2: Inflammation 1. Inflammation – a complex reaction to injurious agents such as microbes and damaged, usually necrotic, cells that consists of vascular responses, migration and activation of leukocytes, and systemic reactions 2. Difference between arthralgia and arthritis a. Arth = joint b. itis = inflammation c. algia = pain 3. Exudate and Transudate a. Exudate is caused by a change in vascular permeability i. Exudate has high protein content, lots of cells, high specific gravity ii. When exudates has lots of neutrophils (pus) you call it purulent exudate b. Transudate is an ultrafiltrate of plasma, results from imbalance between pressure pulling things into fluid (osmotic), and pressure pushing things out (hydrostatic) i. Too much hydrostatic or not enough osmotic ii. Has low specific gravity b/c you have low cells and low protein 4. Edema – swelling, too much fluid in the interstitium (stuff that surrounds the cells) or body cavity 5. Acute inflammation – vasodilation (vasodilatation), blood vessles are expanded and full of blood a. Migration/emigration - White cells go to where the injury because of chemotaxis (LTA, etc) b. Phagocytosis - Once in the tissue, the white cells phagocytose the bacterium c. Neutrophils respond first (6-14h), then monocytes, others (24-28h) 6. Phagocytosis – cell eating a. Recognizing and attaching of WBC to bacteria b. Engulfing the bacteria c. Killing the bacteria i. Oxygen dependant ii. Oxygen independent d. In chronic granulomatous disease, patients (children usually) cant kill bacteria properly by phagocytosis 7. Chemical mediators of inflammation a. Preformed chemical mediators – histamines b. Newly synthesized chemical mediators – prostaglandins, leukotrienes, etc c. Constant chemical mediators in an inactive form i. Synthesized in liver as inactive precursors ii. Kinin system (kininogen  kinin) iii. Complement cascade iv. Coagulation cascade (XII (inactive) to XIIa (active)) 8. Major chemical mediators a. Vasoactive amines – 5HT, active in acute inflammation

b. Plasma proteases – kinin, complement, coagulation c. Arachodonic acid metabolites – acted on by cyclooxygenase or lipooxygenase i. cyclooxygenase  prostagandins  thromboxane (platelet aggregation) or prostacyclin (platelet deaggregation) ii. lipooxygenase  leukotrienes, lipoxins (inhibit leukocyte recruitment) d. Lysosomal constituents e. O2-free radicals f. Platelet activating factor (PAF) g. Cytokines – (cyto = cell, kine = substance produced) substance produced by cells. Examples include: Interleukins, chemokines, TNF h. Nitric Oxide – potent vasodilator 9. Chronic Inflammation – takes weeks or months a. Lymphocytes b. Monocytes (blood) or macrophage (tissue) i. Histocyte = macrophage ii. Monocyte half-life = one day iii. Macrophage half-life = several months c. Plasma cells d. Fibroblasts = Scarring – fibrosis i. Organization – at the step of inflammatory process where the fibroblasts and new vessels are forming e. Then there is a scar left after organization f. Granulation Tissue – the chronic inflammatory cells + organization (this is a good sign, means its healing) 10. Lymphatics – secondary barrier to prevent the spread of infection a. Inflammation of the lymphatics = Lymphadenitis b. Lymphadenopathy = enlarged LN c. Lymphangitis = inflammation of LN 11. Granulomatous Inflammation (Granuloma) a. Don‟t confuse with granulation tissue (highly vascularized tissue that is part of the scarring process) b. Granuloma = a collection of macrophages or histiocytes, especially epitheliod macrophages c. Multi-nucleated Giant cells (histiocytes) i. Langhan‟s Giant cells – associated with TB infection d. Clinical Example: If you do a lung biopsy and see a granuloma i. You know you‟re dealing with chronic inflammation ii. You also know there are only a few things that cause granulomatous inflammation 1. TB – looks like cheese (caseous necrosis) 2. Foreign body reaction (if you get a sliver and get a nodule around it if its stuck) 3. Fungi

4. Sarcoidosis – granulomatous inflammation that is of unknown etiology 12. Terms a. Serous – clear fluid (transudate and exudates) b. Fibrinous – has to do with fibrin (acute, comes from clotting factors in acute inflammatory process) c. Fibrous – has to do with fibrosis, scarring (chronic) d. Supprative [perulent] – pus, neutrophiles and necrosis e. Abscess – pocket of pus, well-circumscribed collection of neutrophils i. Body may wall this off with fibrosis f. Ulcer – loss of the mucosa, not the submucosa or muscularis 13. Systemic effects of inflammation a. Fever is an effect i. Macrophages produce prostaglandins which cause vasoconstriction of vessels in the skin 1. To get rid of heat, you dialate blood vessels b. Acute phase reactants – plasma proteins that are produced in the liver that go up with inflammation i. C reactive protein increases 1. You use a sedimentation rate to measure C-reactive proteins in your patient ii. Fibrinogin increases c. Leukocytosis – increase in leukocytes i. What kinds of leukocytes? 1. neutrophils – neutrophilia (bacterial infection or acute inflammation) 2. lymphocyte – lymphocytosis (virus infection) 3. monocyte – monocytosis (Mononucleuosis) 4. eosinophils – eosinophilia (parasites and allergies) 5. basophils – basophilia (leukemias) d. Leukopenia – decrease in leukocytes Chapter 3 (Healing and Repair) 14. Regeneration versus scarring of tissue a. The tissue type determines how much regeneration there is b. Labile, stabile and permanent cells determine if you do regeneration or scarring c. Labile cells – proliferate through life (blood cells and epithelial cell) i. Chemotherapy 1. hair loss – epithelial 2. N/V – GI epithelial d. Stabile cells – can proliferate if need be (organ cells, muscle, vessels) e. Permanent cells – don‟t proliferate at all (neurons, skeletal and cardiac muscle)

15. Slide #7: Organizing Thrombus, Left Atrium a. Rheumatic fever – after a strep infection, you get a cross reaction from strep and this reacts with the valves of the heart and causes damage b. You get damage to flow, more turbulent flow c. Makes you tired easily d. Dyspnea – difficulty breathing i. Has fluid backing up into pulmonary veins ii. This backup causes pulmonary edema (congestion) iii. This is because of left sided heart failure e. Irregular pulse – abnormal heart rhythm (arrhythmia) due to atrial fibrillation i. This is due to the rheumatic fever ii. Most atrial fibrillation is idiopathic, however f. The turbulent blood flow, and fibrillation cause more thrombus g. Neck vein distension (congestion) is a problem of congestive heart failure (right sided heart failure) h. Increased S1, open snap = mitral stenosis, confirmed by catheterization i. Commisurotomy – opening the mitral stenosis j. Slides of the thrombus a. Thrombus – interaction of the vessel wall, platelets, and clotting factors b. Lines of Zahn are formed from these layers (sometimes hard to see) layering of platelets, fibrin, and blood cells c. Embolus – an intravascular mass that travels to a distant site d. Infarct – ischemic necrosis of tissue e. Hemostasis – maintaining proper bloodflow…results from interaction between vessel wall, platelets and coagulation cascade i. If coagulation factors aren‟t working, you will be constantly bruising and bleeding ii. If coagulation factors are overactive, you will get lots of thrombi that you don‟t want f. Causes of thrombi – only 3 (Verkow’s Triad) i. Injury to endothelium – atherosclerosis is most common ii. Alteration in normal bloodflow (stasis of bloodflow) 1. in this case we had atrial fib and damage to valve iii. Hypercoaguable state (coagulation factors are messed up) b. Terms i. Mural Thrombus – thrombus in a chamber (usually the heart) ii. Vegetation – infected mural thrombus, usually on a valve c. How do you distinguish a post-mortem thrombus from a pre-mortem thrombus i. Pre-mortem = lines of Zahn ii. Post-mortem = chicken fat, jelly looking d. Clinical implications of a thrombus i. Arterial Thrombus – causes infarction (stroke, etc) 1. not red infarct, because blood is blocked off ii. Venous Thrombus – infarction is rare (still have arterial supply)

1. causes stasis of blood 2. hemorrhagic infarction – this is red because you have bloodflow e. Prevention of Thrombus i. Aspirin and persantin – blocks platelets ii. Heparin, coumadin – blocks clotting factors iii. Fibrinolytic – breaks up the clots k. Question answers i. Mitral stenosis due to rheumatic fever ii. Rheumatic fever, turbulent bloodflow, atrial fibrillation iii. Embolus going to pulmonary (right heart), or systemic (left heart) iv. Coronary arteries, cerebral blood vessels, iliac, femorals v. Pre-mortem = attached to vessel wall lines of Zahn, Post-mortem = chicken fat, jelly looking, not attached to vessel wall vi. Embolus, stenosis, removal by fibrinolytics, organization of thrombus 16. Slide 44: Chronic Passive Congestion of Liver With Centrilobular Necrosis a. Aortic insufficiency – valve doesn‟t completely close, there is blood backing up into the atrium b. dyspnea and cough is due to pulmonary congestion c. Liver congestion is caused because Right atrium backs up into the SVC and IVC, which backs up into hepatic vein, which backs up into the central veins, which back up into the sinusoids, then portal vein….this is chronic passive congestion of liver d. Coughing up blood tinged sputum doesn‟t have anything to do with the liver…the sputum is caused by a DVT that embolized and went to the lung (PE), and then got a pulmonary infarct e. There are two types of congestion (hyperemia) i. Passive (congestion) – due to impaired venous drainage, has a blueish color to it grossly ii. Active (hyperemia) – dilated arteries, usually reddish color f. Scarring of the liver – cirrhosis, if you have long-standing congestion in the heart you will get cardiac cirrhosis g. Question answers i. Dead cells = no nucleus, live cells have nucleus ii. Prominent nucleolus is a sign of regeneration iii. Explanation of sudden cough is probably pulmonary embolus from a DVT because of the CHF iv. pulmonary emboli and maybe some congestion and edema 1. congestion is a backup of blood, pulmonary arteries 2. edema is increased hydrostatic pressure v. Pulmonary infarct from the PE vi. Hepatomegaly is due to right sided heart failure because of the left sided failure

17. Slide #23: Hemorrhagic Infarct, Lung a. Digoxin increases contractility b. Blood-tinged sputum = PE and pulmonary infarcts c. Pulmonary Thrombosis – rare, seen in pulmonary HTN d. Pulmonary Embolism – third most common cause of death i. 95% come from deep veins ii. Saddle embolus – sits over right and left pulmonary artery, plugs one or both of these arteries (sudden death) 1. Patient dies of hyperacute right sided heart failure – blood cannot get into the lungs iii. Paradoxical embolus – hole between right and left side of heart causes a DVT embolus to go from venous system, into arterial system and you can get a systemic embolus (stroke) e. Different sizes cause different problems i. Small – no problems ii. Medium – pulmonary infarct iii. Large – death f. Embolus i. 10% cause infarction ii. 5% resolve iii. 10% cause death g. Question answers i. DVT is the cause ii. Heart failure compromises the bronchial circulation  necrosis iii. Small to medium ones cause embolus iv. Bed rest, stasis of blood, clotting (thrombosis)/DVT, Embolus v. Left anterior descending artery 18. Intravascular Water a. A 70kg man has 42L, 28L intracellular, 14L extracellular b. 3-4L in vasculature c. 11L in the interstitium (between the cells) d. Oncotic pressure keeps water in e. Hydrostatic pressure pushes water out 19. Edema – excess fluid in the interstitium or in a body cavity a. Anasarca – edema everywhere b. Ascites – edema in peritoneal cavity c. Pleural effusion – edema in the pleural cavity 20. Systemic Edema vs. Localized Edema a. Localized – increased vascular permeability b. Systemic (all over the body) 21. Systemic Differential Diagnosis a. Heart failure - Not enough blood flow ( hydrostatic pressure) b. Liver disease - Not making enough albumin in the liver ( oncotic pressure) c. Kidney failure – losing albumin, you‟re making enough and excreting it (Periorbital edema is renal failure)

d. Cerebral Edema – the surrounding tissue (outside the necrosis) will become edematous  can cause focal lesions 22. Congestion – Read Robbins 23. Hemorrhage – RBC outside of the blood vessels a. Hematoma – bruise, massive area of hemorrhage b. Hemothorax – thorax hemorrhage c. Hemopericadium d. Hemoperitoneum 24. Bleeding in the skin a. Purpura – problem with clotting b. Petechia – little red dots; looks like a rash, small popped capillaries, due to platelet problem c. Ecchymosis – bruise, black and blue due to breakdown of RBC and hemoglobin 25. DIC – disseminated intravascular coagulation (clotting all over the place) a. Signs/symptoms: patient will come in with bleeding problems, all the coagulation factors get used up, so you don‟t have any more, and you get bleeding problems 26. Embolus a. PE, systemic E, Thrombo E b. Air embolus – when you dive, if you come up really fast, you end up with air (the bends) c. Fat embolus – fractures of long bones, little fat gets into the circulation d. Amniotic fluid embolus – baby dies, but this is very rare 27. Infarction – Read in Robbins 28. Shock – state of inadequate perfusion of tissue, not enough blood flowing a. Stages of shock i. Compensated hypotension (non-progressive phase) – 1. heart pumps faster (tachycardia) 2. vasoconstriction of the skin (cold and clammy) 3. Renin-Angio-Aldosterone kicks in ii. Tissue hypoperfusion (progressive phase) 1. hypoxia 2. lactic acid builds up (lactic acidosis) iii. Irreversible cell death (necrosis) b. Major causes of shock i. Cardiogenic: heart is not pumping out enough blood (MI, arrhythmias, CHF) ii. Hypovolumic: blood loss, fluid loss iii. Infection (gram negative endotoxins): vascular collapse, so fluid spills everywhere iv. Anaphylaxis: IgE mediated, type I hypersensitivity v. Neuropathic: spinal cord injury

Lab 3: Neoplasia – 9/7/05
1. Neoplasia - Introduction a. Neoplasia – new growth, usually abnormal b. Tumor – new growth, neoplasia c. Cancer – subcategory under tumor/neoplasia i. Malignancy – will kill you ii. Benign – won‟t kill you d. Desmoplasia – stromal reaction to tumor cells, particularly to malignant cells. You get a fibrous reaction to tumor – fibrous tissue grows around the malignant tumor cells e. Neoplasia is a usually a result of a genetic alteration, arises in general from a single cell, or single clone of cells (monoclonal) 2. How do we classify tumors? Benign and malignant a. Malignant classification i. Epithelial origin = carcinoma. Cellular cohesion is #1 identifying marker of epithelial carcinoma 1. subclasses are based on which kinds of epithelial cells: 2. squamous = squamous cell carcinoma (keritinization and intercellular bridges) 3. columnar/cuboidal (glandular = adeno) = adenocarcinoma 4. transitional = transitional cell carcinoma ii. Mesenchymal (supporting tissue, connective tissue, etc) = sarcoma Fibroblasts Smooth Muscle Fibrosarcoma Leiomyosarcoma Blood vessels Rhabdomyosarcoma Skeletal muscle Angiosarcoma Fat, adipose Nerves Liposarcoma Neurosarcoma iii. Lymphoid = lymphoma, malignant by definition, originates from a lymphocyte iv. Melanoma = malignant by definition, melanocytes in the skin v. These 4 things comprise about 94% of malignancies (leukemia is the other 6%) b. Benign classification i. Epithelial origin 1. adenoma = glandular 2. papilloma = microscopic, finger-like projection, covered in epithelium 3. polyp = projection into the lumen ii. Mesenchymal origin Fibroblasts Smooth Muscle Fibrcoma Leiomyoma Skeletal muscle Blood vessels Rhabdomyoma Angioma Fat, adipose Nerves Lipoma Neuroma iii. Lymphoid hyperplasia – the counterpart to lymphoma, but it‟s not really neoplasia because lymphoid neoplasia is always malignant iv. Nevus – benign cell of melanocytes c. Hepatoma – hepatocellular malignancy

3.

4. 5. 6.

7.

d. Semnoma - benign testicular neoplasia e. Teratoma – neoplastic process that arises from more than one germ cell lines (endoderm, mesoderm, ectoderm) i. Dermoid cyst – ovarian teratoma that has teeth, hair, lung tissue, brain tissue f. Hamartoma – benign, disorganized, normal, mature tissue in a particular site i. In the lung, you get a benign tumor that has lung tissue all jumbled up ii. Clinically, you take a chest X-ray, and see a tumor in there and you have to distinguish between the hamartoma and a carcinoma g. Choristoma – benign, ectopic presence of normal tissue Criteria for malignancy – how do we decide if its benign or malignant; two ways: a. Cytology – looking at the properties of the individual cells i. Increased nuclear/cytoplasmic ration in M ii. Increased nuclear pleomorphism in M iii. Hypochromasia in M iv. Abnormal mitosis in M b. Histology – looking at the properties of the tissues i. Architecture – is it sheets, is it glands, is it clumped ii. Polarity – what happens to the epithelium as it moves from the base to the apex iii. Differentiation in the tissue – how much the M tissue resembles the normal tissue 1. if it‟s well differentiated, then it looks like the normal tissue 2. if it‟s not well differentiated, then it won‟t look like the normal tissue 3. Anaplasia – lack of differentiation, a malignant cell 4. Dysplasia – abnormal cell, loss of cell structure, etc c. Rate of growth - Malignant grows faster d. Invasion – Malignant invades more e. Metastasis – if the cancer moves to another part of the body i. Direct seeding – spreads to adjacent tissues ii. Bloodstream – hematogenous, goes thru liver iii. Lymphatic – breast cancer, spreads in a predictable fashion In Situ carcinoma – epithelial tumor cells that are preinvasive, they haven‟t invaded the basement membrane Infiltrating carcinoma – epithelial tumor cells that have invaded the basement membrane Grading – the pathologist determines the grade a. The level of differentiation in the tumor cells based on cytology and histology b. Grading is based on differentiation (well, moderate, low, no) c. Sometimes you cant tell Staging – the oncologist determines the stage

a. The extent of the spread b. TNM classification of staging i. Tumor size ii. Nodes – presence or absence of cells in nodes iii. Metastasis to other tissues 8. Slide #25 – Squamous metaplasia and carcinoma of the bronchus a. Most weight loss is due to people being on a diet b. Blood-tinged sputum and cough ~ malignancy in the lung i. Blood-tinged sputum due to erosion of blood vessels into the bronchial tree c. Tumor is centrally located, which is important because there are different types of lung tumors: i. Based on the different tissue types ii. Most of the lung tumors are carcinomas iii. Squamous metaplasia is caused by smoking, so squamous cell carcinoma is the most common type d. Sputum test is a non-invasive way to determine if you have cancer cells e. Endoscope is another way f. Bronchial-alveolar lavage – where you inject NaCl water and swish it around and hopefully get some cancer cells when you suck the water back out g. We will use H&E stain in histology h. We will use Pap or Geimsa stain for cytology i. Small cell carcinoma is inoperable because its of neuroendocrine origin j. If the cancer has spread to the lymph nodes, then you cant surgically remove it, and you have to do palliative care (treat the symptoms – radiation, chemotherapy) k. Adenocarcinoma in the lung is more peripherally located in the lung l. Number 1 criteria for something being a carcinoma is cellular cohesion (forming islands of cells) i. Next step is determining the type of carcinoma ii. Squamous cell has karitenization, and intercellular bridges m. Question answers i. Bronchogenic carcinoma is the same thing as lung carcinoma, but this is not the same lung cancer because lung cancer (malignant neoplasia) can be something other than a carcinoma. Smoking is the number 1-50 risk factor, radiation exposure, immunosuppression (AIDS), asbestos. Second hand smoke is associated with increased risk of bronchogenic carcinoma ii. There is an increase in the number of women smoking iii. Squemous and small cell is more often central. Adenoma is peripheral 9. Slide #39 – Adenocarcinoma of the Rectum a. Adenocarcinoma is going to arise from the mucosa because that‟s where the glands are b. There is obstruction of the colon, which will lead to

c. d. e. f. g.

h.

i.

j.

i. Decreased caliber of the stool ii. Constipation iii. Cramping abdominal pain – indicative of obstruction of a hollow viscous The increased fatigue is due to bleeding, which means you‟re losing iron, becoming anemic, and thus becoming more fatigued Obstipation – obstructive constipation…completely obstructed 3+ blood in the stool is because she has hemorrhoids in this case…but it is indicative of cancer Sigmoidoscopy failed because of the obstruction Colon cancer i. 2nd most common cancer, 50% of cases in US ii. older people, males more than females iii. lots of different causes iv. pathogenesis is important: colonic mucosa can just proliferate (hyperplasia), can cause a protuberance into the lumen (polyp, hyperplastic polyp) v. Neoplastic proliferation of cells and glands (tubular adenoma)…these are benign, but they can develop into malignancies vi. Villus Adenomatous polyps – when you have villus architecture, you increase the chance of having a malignancy vii. Carcinoma – adenocarcinoma Question answers i. Sites of tumor: 1. Left side is most common 70% (rectal 60%, sigmoid 15%) 2. 30% are throughout the rest of the colon 3. Left side lesions cause obstruction a. annular (napkin ring) (early obstruction) b. more solid, smaller stool on left side c. smaller diameter 4. Right sided are more polyploid – obstruction is more uncommon because of larger diameter and looser stool ii. Use of stool for occult blood tests for blood in the stool, it‟s a sensitive test, but not very specific (most common cause of blood is hemorrhoids, so (+) test not always cancer) iii. Hyperplastic and adenomatous polyps. Villus has increased risk of carcinoma iv. Single most important prognostic indicator of colorectal cancer is the stage of the tumor (TNM) (Tumor size, Nodes, Metastasis) Types of colon cancers i. 98% are carcinomas ii. most of the carcinomas are adenocarcinomas iii. Metastasis – regional lymph nodes, liver, lung, bones CEA – carcino-embryonic antigen. A substance in the blood to screen the world population for colon cancer. You can have elevated CEA in other

malignancies (lung, brain, etc), and in non-malignant conditions. Lacks specificity, we use this in following patients after you have treated the cancer surgically…if the CEA goes up after surgery, then you‟re thinking recurrence or metastasis 10. Slide #341: Leiomyosarcoma, uterus a. Fibroids = leiomyoma, benign tumors, more common than adenocarcinomas…leiomyosarcoma is the rarest b. Spindle cell malignancy has increase pleomorphism, increased N/C ratio…etc i. Diffuse proliferation of spindle cells = sarcoma ii. This is leiomyosarcoma because of the characteristics of the cells, they look more like smooth muscle cells, thus you have the leiomyosarcoma iii. Uterine sarcoma is most likely leiomyosarcoma because there isn‟t a lot of other tissues in the uterus c. Question answers i. Mesenchymal (supportive tissue) is where sarcomas are derived ii. Leiomyosarcoma characteristics: Aggressive, high incidence of local recurrence, widespread metastasis iii. Will see these wherever there is smooth muscle like in your GI track and in the uterus, sometimes retroperitoneum, anywhere there‟s smooth muscle iv. Single most reliable criterion for leiomyosarcoma is the mitotic rate of the cells (0-5 is benign, 10+ is malignant) v. Most common type of tumor is leiomyoma. A benign metastasizing tumor that is still benign, and its rare 1. Atypical leiomyoma has a decreased mitotic rate, but it otherwise looks malignant vi. The likelihood of transforming from leiomyoma to leiomyosarcoma is very rare because leiomyosarcoma is very rare, even though leiomyoma is common d. Gastrointestinal stromal tumors have a different prognosis than the leiomyosarcoma because it is of neural origin. Marks with CB117 11. Slide #62: Squamous Cell Carcinoma, metastases to lymph nodes a. Question answers i. Metastatic squamous cell carcinoma ii. Lymphatic spread iii. These cells don‟t belong here: 1. Increased nuclear/cytoplasmic ration in Malignant (M) 2. Increased nuclear pleomorphism in M 3. Hypochromasia in M 4. Abnormal mitosis in M

Lab 4: Dermatopathology – 9/28/05 -Sorry guys, I didn‟t have my computer for this one… Lab 5: Bone and Soft Tissue Tumors - 9/21/05 1. Introduction – Big broad categories of bone and soft tissue diseases (different from book) a. Developmental/congenital b. Abnormal matrix i. Osteogenesis imperfecta ii. Osteoporosis c. Osteoclast disfunction i. Too little – osteopetrosis ii. Too much – Paget‟s Disease (Eating of the bone, there is a rebound of osteoblasts…but osteoclast function is main problem) d. Abnormal Calcium i. Osteomalacia ii. Hyperparathyroidism (PTH pulls Ca out of bone  hypercalcemia) iii. Renal Osteodystrophy – with renal disease, you have a decrease in Ca, parathyroid gland will increase PTH, then you get similar problems to hyperparathyroidism e. Fractures f. Osteonecrosis – avascular necrosis – often a result of trauma, loss of blood to bone g. Infections – the „itis‟ i. Osteomyelitis – bone infection ii. Arthritis - joints h. Neoplasia i. Joints i. Ganglands - cyst j. Tumor, tumor-like lesions i. Lipoma, liposarcoma 2. Bone a. Consists of calcium and osteoid b. Osteoid – bone matrix c. Types of cells in bones i. Osteoblasts – makes bone ii. Osteocytes – cells in the bone iii. Osteoclasts – resorb (break down) bone (increase Ca in blood) iv. Collagen – 90% of bone is collagen d. Lamellar Bone – stronger bone, mature bone, has regular structure e. Woven Bone – weaker bone, new bone, has less regular structure i. A fracture will give you woven bone initially ii. Fractured bones will have woven turn into lamellar f. Spongy – looks like a sponge, has holes in it (inside of bone) g. Compact/Cortical bone – dense bone (outside of bone)

h. Epiphysis, Diaphysis, metaphysic i. Epiphysis – the end of the bone ii. Metaphysis – area between epiphysis and diaphysis iii. Diaphysis – main part of a long bone i. Bone remodeling – 2 main types i. Enchondral bone formation – how long bones get longer ii. Intramembranous bone formation – skull formation 3. Slide 347: Osteogenic Sarcoma a. Primary bone tumors – what cells? i. Osteoblasts, cartilage, marrow (leukemia, multiple myeloma), fibroma(sarcoma), angioma(sarcoma), lipoma(sarcoma) ii. Most are benign, across all age groups iii. Adults: malignant are most common iv. Kids: only 20% malignant b. The big four malignant bone tumors: i. Osteosarcoma (osteogenic sarcoma) – most common 1. happens in kids 2. around knee 3. doesn‟t involve joint space (epiphysis) ii. Chondrosarcoma 1. middle age /older adults 2. involves epiphysis 3. involves trunk of body (ribs) iii. Ewing‟s sarcoma 1. Kids 2. diaphysis 3. doesn‟t involve epiphysis or joint space 4. has immature looking cells iv. Giant cell tumor 1. Middle age 2. involves epiphysis 3. similar to chondrosarcoma c. The big benign tumors i. Osteochondroma – bone and cartillage ii. Fibroma iii. Benign giant cell d. Need age of patient, exact location of tumor, X-ray findings as well as what‟s under the microscope to determine the type of tumor e. Now the case: i. The fact that its around the knee important because most bone cancers are around the knee ii. Age of patient is also important iii. Elevated periosteum – codman‟s triangle iv. Increased osteoblastic activity = high serum alkaline phosphatase 1. you get high serum alkaline phos in normal kids and pregnant women

2. alkaline phosphatase also give increase from liver pathology 4. Bone Tumors – More Detail a. Osteoma – benign tumor of bone b. Osteoidosteoma – very painful, different from osteoma c. Osteosarcoma i. Malignant mesenchymal tumor ii. Second most common form of malignant bone tumor behind bone marrow tumors iii. Two situations: 1. primary (classic): arises in normal bone, happens in younger patients 2. Secondary: occur in older adults, occurs in a bone with an underlying disease (e.g. Paget‟s or osteomyolitis) d. Genetics i. Is there a cytogenic mutation involved in this? Not really ii. The p53 gene mutation decreases apoptosis (Rb gene also leads to more bone tumor 100% increase vs. people that don‟t have osteogenic sarcoma) e. 60%-70% around the knee f. rarely involves joint space or epiphysis g. Bad tumor to have, aggressive, lots of blood metastasis i. Lung > bones > brain h. Clinical presentation i. Pain, swelling to affected area i. Treatment i. Surgery, chemo, radiation ii. Poor prognosis j. Benign Chondromatous Tumors i. Osteochondroma (exostosis) – overgrowth of bone and cartilage ii. Enchondroma – benign carilage T 1. Ollier‟s Disease: multiple Enchondroma‟s in childhood 2. Mafucci 3. skin hemangioma iii. chondroblastoma: most common epiphyseal tumor in kids iv. Fibromyxoid chondroma k. Malignant – Chondrosarcoma i. Better prognosis than osteogenic sarcoma ii. Peaks in 60-70 yo iii. Involves epiphysis iv. Appears as large, bulky, gelatinous mass (has cartilage) v. Grows more slowly, has ability to metastasize l. Unknown cell origin tumors i. Ewing‟s sarcoma – primitive neuroectodermal T (PNET) 1. If in bone = Ewings 2. If in soft tissue = PNET

3. second most common in kids behind osteogenic sarchoma 4. pain, swelling, cytogenic abnormality (translocation between 11 and 22, results in abnormal oncogene proliferation) 5. Don‟t know where it originates 6. Doesn‟t involve epiphysis 7. Small, round, blue-cell tumor 8. tends to form a Codman‟s triangle 9. really bad, wide-spread mets 10. chemo, radiation, surgery ii. Giant cell sarcoma m. Most bone tumors are NOT primary, they are mets from somewhere else i. Prostate > Breast > kidney > lung ii. Kids: neuroblastoma, Wilms, osteogenic sarcoma, Ewings, rhabdomyosarcoma iii. Mets are most often going to the axial skeleton followed by proximal femur iv. Most are lytic (destroy bone), occasionally they are blastic mets (adenocarcinoma of the prostate) n. Question answers i. Malignant mesenchymal tumor ii. Knee iii. Triangle resulting from elevation of the periostium iv. Lungs v. No (maybe p53 mutation or Rb gene). Cytogenetic abnormality can be seen at the chromosomal level (so we cant see p53) 5. Slide 86 – Gouty Tophus a. This has 3 manifestations: i. Elevated uric acid ii. Nodule (gouty tophus) iii. Arthritis – inflammation in the joints 1. what is the differential diagnosis of arthritis 2. osteoarthritis = most common a. tends to be asymmetric b. involves hands (distal interphalangeal joint DIP), hips, knees 3. rheumatoid arthritis a. symmetrical b. involves small joints of hands (PIP proximal interphalangeal joints) and feet c. autoimmune disease – antibodies against the IgG (an IgM antibody to IgG) i. use a blood test, rheumatoid factor 4. sero-negative spondyloarthopathies a. Sero-negative = no rheumatoid factor

b. Ankylosising spondylitis (arthritis of the sacro-iliac joint) is associated with HLA-B27 c. Reiter’s Syndrome = arthritis with conjunctivitis, with non-gonococcal urethritis d. Inflammatory Bowel arthritis 5. Crystalline arthritis – deposition of crystal and you get an inflammatory reaction to it a. Gout = uric acid deposits b. Chondrocalsinosis (pseudo-gout) = calcium deposits 6. Infectious arthritis – has neutrophils in the joint spaces b. Presentation of Gout i. Transient, persistant attacks of arthritis  inflammatory response  gouty tophi ii. Most gout is primary (enzyme defect) iii. Secondary gout (10% of cases) associated with: 1. increase turnover of nucleic acid (leukemia, malignancy from chemo) 2. problem excreting uric acid in the kidney 3. problem in conversion of purines to uric acid 4. Lesch-Nighan syndrome – where you get an increase in uric acid because of a problem in the enzyme metabolism (patients end up chewing on their hands) hypozanthineguanine-methyl-transferase deficiency iv. Gouty Tophi happen around the elbows and knees, but can occur anywhere (olecrenon and patellar bursa) and the ear v. There is one part of the body where you don‟t get Gouty Tophi (the brain b/c of the blood-brain barrier) c. Treatment i. Colchicines – anti-inflammatory ii. Zanthine-oxidase inhibitor – allopurinol iii. Inhibit reabsorption in the kidney – probenecid d. Question answers i. Pathonomonic = specific for some pathology….here it‟s the gouty tophus (nodule made of uric acid and inflammatory cells [multinucleated giant cells]) ii. Around any joint, but specifically in olecrenon and patellar bursa and ear, and big toe iii. No, because of the blood brain barrier, no uric acid crossing iv. Lots of uric acid in the blood, gets to the kidney, causes kidney stones v. Gouty arthritis, renal colic, renal failure 6. Slide 263 – Rhabdomyosarcoma a. Bladders have transitional cell carcinoma, or a leiomyosarcoma (smooth muscle) b. Alveolar rhabdomyosarcoma – looks like alveolar cells

c. Soft Tissue Tumors i. Benign versus malignant (100 Benign:1 malignant) ii. We‟ll see malignant in the clinic because benign wont cause problems iii. Rhabdomyoma – benign skeletal muscle tumor (very rare, usually in the heart) iv. Rhabdomyosarcoma – malignant, most common soft tissue sarcoma of childhood (bad cancer, it metastasizes early) 1. embryonal– occur in kids <10years old, in the head and neck a. botryoid - “cluster of grapes” when in the bladder or vagina (uro-genital); happens in infants 2. alveolar – t2:13 translocation 3. pleomorphic – adults over 45 years old, extremities and trunk deep soft tissues 4. 2/3 are embryonal or botryoid d. Question answers i. Myoglobin, myogenin, actin ii. t(2:13)(q34;q14) iii. Yes, but only about 20% of cases (lungs > LN > Bone Marrow) iv. Embryonal (about 2/3 of cases) 7. Slide 256: Giant Cell Tumor of Bone a. Epiphyseal end, 35 years old, swelling = chondrosarcoma b. Has multi-nucleated giant cells, spindle cells, stromal cells c. Could be benign or malignant – you decide by looking at the small cells, the stromal cells to see if they have hyperchromatic nuclei, increased N:C ratio, increased mitosis in sarcoma i. The giant cells are fused histiocytes d. Small, round, blue cell is the Ewing‟s sarcoma in kids e. Tend to arise in the epiphysis, involve the joint space f. More the 50% arise around the knee g. Age: adults (~45) h. Presentation similar to other tumors (pain, tenderness, swelling) i. Question answers i. Knee, epiphyseal of long bones ii. Stromal cells iii. 10-30% are malignant (anaplasia of stromal cells) iv. Chondrosarcoma for malignant, chondroblastoma v. Other lesions that show multi-nucleated 1. Infection – TB 2. Foreign body reaction 3. Chondroblastoma 4. Hyperparathyroidism – bone broken down by osteoclasts (which are also multi-nucleated giant cells) 5. Pigmented nodular synovitis – inflammation of the synovium

Cardiovascular Pathology Lab 6 November 2, 2005 1. Intro a. Heart weighs 300g b. LAD c. Posterior wall MI comes from RCA d. LCx feeds lateral portion of the left ventricle e. Multiple bypasses are bypassing the branches of the three main arteries 2. Congestive Heart Failure (CHF) a. Not the same as MI, MI is a manifestation of CHF b. Definition: pathologic state in which the tissues are not getting enough blood flow and oxygen. c. Causes: decreased contractility, regurgitation (insufficiency), occlusion, conduction problems d. Compensatory mechanisms: hypertrophy, dilatation (will increase contractility), RAAS, norepinephrine (NE) 3. Left Sided Heart Failure a. Patient presents with dyspnea b. Look up pathway of how blood backs up 4. Right Sided Heart Failure a. Most common cause is left sided failure b. Look up pathway of how blood backs up c. Leads to anasarca, activates RAAS 5. Major types of heart disease a. Ischemic (greater than 90% of all HD) b. Hypertensive c. Congenital d. Valvular e. Non-Ischemic, Primary myocardial disease, cardiomyopathy 6. Ischemic heart disease (atherosclerotic heart disease) a. There is an imbalance between the O2 used and the O2 needed b. Due to underlying atherosclerosis c. 4 clinical presentations of people with atherosclerosis i. angina (chest pain); reversible injury to myocardial cells ii. MI; irreversible injury to myocardial cells iii. Chronic ischemic heart disease; tiny MI‟s that cause fibrosis iv. Sudden death due to an arrhythmia d. Complicated atherosclerosis – you have sclerosis on top of a plaque 7. More on MI a. Biochemical abnormalities – enzyme leakage i. Increased enzymes  dead myocardial cells that leak these enzymes b. EKG changes c. Functional changes  CHF 8. Morphology of an MI

a. Subendocardial MI – under the endocardium b. Transmural MI – in between the layers of the endocardium c. LAD = 40-50%, RCA = 20-30%, LCx = 10-20% 9. ON TEST: If I squeeze your coronary artery, what happens to the heart from a gross standpoint and microscopic standpoint a. Microscopic is easier to determine because it follows what we learned in inflammation b. At 6-8 hours after death you see cells dying c. At 12-14 hours you see neutrophils infiltration for the next 2-3 days d. At 5-7 days you see macrophages e. At about a week or 2, you begin to see chronic inflammatory cells, fibroblasts  granulation tissue f. After a few weeks, you end up with a scar g. Grossly, you don‟t see much for the first 12 hours h. Then after a day or 2, you see a yellowish discoloration with hemorrhage around it 10. What are the 3 criteria for MI when you‟re working in the hospital a. Clinical b. EKG changes c. Enzymes; cardiac markers i. Troponin I or Troponin T – stays up for about a week ii. CKMB – goes up within 4-8 hours, peaks at 24, gone after 3 days iii. Myoglobin – least specific (also in skeletal muscle), but its sensitive, has good negative predictive value 11. Complications of MI a. CHF b. Arrhythmia c. Hole in the heart (myocardial rupture) d. Pericarditis e. Mural Thrombus f. Ventricular aneurism 12. Slide #2: Recent Infarction a. Cardiomegaly can be caused by dilatation or hypertrophy b. MI associated with N/V, angina has no associated of N/V c. MI  CHF  decreased blood flow, so you could faint if you don‟t get enough blood to the brain d. High WBC is a sign of acute inflammation e. Death was most likely do to an arrhythmia f. Question answers: i. No because there are neutrophils and coagulative necrosis. After 7 days you‟d see macrophages and granulation tissue ii. They appear normal because they are normal…in the acute MI, you haven‟t necrosed off those cells yet iii. The hemorrhage is caused by rupture of the blood vessels because you‟re necrosing off the blood vessel cells iv. It‟s a very acute (new) infarct, after a few days they will infiltrate

v. The acute stage (4-7days) 13. Slide #3: Organizing MI a. You will probably see fibrous tissue in an old MI (scar) b. Question answers i. About a week for granulation tissue, fibrosis would be weeks to months ii. Not enough myocardial cells to keep up with the demand, so you get heart failure iii. Lipofuscin, not important, its seen in wear and tear iv. No because it happened so long ago v. Hypertrophy is the significance vi. Atherosclerosis lesion vii. You have fibrous tissue replacing the myocardial cells 14. Slide #106: Acute Rheumatic Pancarditis a. This is acute rheumatic fever that causes pain in the knees b. Rheumatic heart disease presents two ways i. Chronic rheumatic heart disease decades after the acute fever ii. Acute rheumatic fever c. Aschoff bodies are made of: i. Anitschkow‟s cells – have long, bar-looking nuclei ii. Aschoff cells – rounded nuclei d. You have rheumatic heart diseases, acute infective endocarditis, nonbacterial thrombotic (usually due to pancreatic cancer), lupus all cause vegetations of the valves e. Patients with acute rheumatic fever develop regurgitation more commonly than stenosis f. Question answers i. Inflammatory process causes damage to the valve and signs of insufficiency ii. Idiopathic pericarditis, probably a virus iii. More often regurgitation due to inflammation iv. The joints, the kidneys, the lungs v. Fibrosis vi. No bacteria in the vegetation because vegetations have clotting, fibrin, and platelets. If it was inflammatory, then you would see inflammatory cells. 15. Slide #105: Acute Infective Endocarditis a. This is aortic valvular disease b. Drug users will usually have endocarditis (and vegetations) in the tricuspid c. Infective endocarditis is almost always caused by bacteria i. Causes vegetations ii. Occurs on a normal valve d. Caused by strep. pyogenes, staph. aureus i. Subacute caused by strep. viridians e. Question answers

i. Acute endocarditis caused by staph aureus and other skin contaminants ii. Most frequent outcome = 60-80% mortality iii. CHF, disseminated infection, embolus, arrhythmias iv. The minimum number of cultures is 2 cultures 15-60 minutes apart during a clinical episode (spiking fever) v. Marantic endocarditis (hypercoaguable vegetations, in pancreatic cancer  has fibrin and platelets, but no inflammation or bacteria) 16. Slide #5: Atherosclerosis, Aorta a. Complicated atherosclerosis – has ulceration and calcification b. Non-complicated atherosclerosis – no ulceration or calcification c. Aneurysm is a common problem stemming from atherosclerosis d. Question answers i. Fatty streak is the earliest morphologic state ii. A complicated plaque is: ulceration, calcification, thrombosis, hemorrhage, aneurysm iii. Lipid iv. LDL, HDL, triglycerides, total cholesterol…we isolate the HDL and measure the amount of cholesterol from the HDL, we can then calculate the LDL from HDL and triglycerides (LDL = HDL – TAG/5), we can also measure total cholesterol v. Complications of atherosclerosis include: CVA, aneurysm, embolism, renal failure, peripheral neuropathy (due to ischemia of femoral arteries and lactic acid build-up) called intermittent claudication, atherosclerosis of the mesenterics  GI pain after eating

Hematopathology Lab 7 November 16, 2005 1. Lymphocytes a. B and T lymphocytes b. B are in the follicles which consists of a germinal center and a mantle zone and a marginal zone c. T are in the interfolicular areas, and in the medulla of the hilus of the node d. Lymphocytes come through the afferent arterioles, this is where malignancies come into the LN (so you look under the capsule) e. Circulating lymphocytes are T (70%), B (30%) f. Most lymphocytes originate from marrow, go to thymus (T cells) or LN‟s (B cells) g. Other WBC‟s are myeloid cells (eosinophil, neutrophil, basophil, monocytes 2. White cell disorders a. Classifications: Decreases and increases i. Decreases – leucopenia ii. Increases – reactive (inflammatory), neoplastic b. Leucopenia – the only significant one is Neutropenia (agranulocytosis), two categories: i. Ineffective granulopoeisis (not enough production)  leukemias, lymphoma of bone marrow, bone tumors, certain drugs ii. Neutrophils are destroyed after they‟re made  auto-immune, splenomegaly, certain drugs 1. passive congestion of the liver from R heart failure  splenomegaly  neutropenia iii. Infection can also cause a Neutropenia iv. Patients with Neutropenia will present with bad-ass infections c. Reactive (inflammatory) Increases of WBC (leukocytosis) i. Increased eosinophils (eosinophilia) – significant because of parasitic infections and allergies ii. Basophilia (least likely)  CML is the only situation where you see basophilia iii. Neutrophilia (granulocytosis) – inflammation, usually acute iv. Monocytosis – chronic inflammation, viral infection v. Lymphocytosis – chronic inflammation, viral infection d. Reactive increases of WBC in LN‟s (lymphadeno-) i. Acute lymphadenitis – increased lymphocytes and increased neutrophils 1. occurs in bacterial infections that drain into LN ii. Chronic lymphadenitis – usually B cells in the germinal centers (follicular hyperplasia) 3. Neoplastic increases in WBC‟s a. Classification done by the type of WBC, but from an origin standpoint (Lymphoid, myeloid, histiocytic, but histiocytic rarely used)

i. Lymphoid – CML, CLL, ALL AML ii. Myeloid – neutrophils, eosinophils, basophils, RBC, platelets iii. Leukemias – proliferation of different blood cells, present with abnormal RBC production, abnormal platelet production iv. Lymphomas present with enlarged lymph nodes everywhere v. Multiple Myeloma presents in a unique way as well (not talking about it) b. What is the relationship between lymphoid and myeloid neoplasms? i. Lymphoid: which lymphomas and leukemias are lymphoid 1. leukemias - ALL, CLL 2. lymphomas - Non-Hodgkin‟s, Hodgkin‟s, multiple myeloma ii. Myeloid: 1. leukemias – AML, CML 2. lymphomas – myeloproliferative disorders, myelodysplastic disorders c. Classification of lymphomas (Hodgkin‟s, non-Hodgkin‟s) i. Morphology – you have diffuse or follicular lymphomas 1. diffuse in general has worse prognosis ii. Size of the cell 1. small cell lymphomas have better prognosis than large cell lymphomas iii. Are cells cleaved (indented)? 1. cleaved cells have better prognosis iv. Immunology - Look for certain markers or do flow cytometry to differentiate what type of cancer 1. 85% of non-Hodgkin‟s lymphomas are B cell v. Molecular – the molecular arrangements are also useful 4. Slide 207: Follicular (non-Hodgkin’s) lymphoma a. Non-tender and diffuse points toward lymphoma, not inflammation/infection – infection would be painful b. CD19, CD20 are B-cell precursors, CD10 is a B and T cell precursor c. Monoclonality is more kappa light chain than lambda light chain (this case is monoclonal) d. In follicular lymphoma there is no mantle zone e. In follicular lymphoma the follicles are disordered, they are throughout the lymphoma, normal follicles are concentrated on the outside of the LN f. Subclassification of Non-Hodgkin‟s lymphomas i. There are 4 major subcategories ii. B-cell neoplasms 1. precursor B cell neoplasm – most of these turn out to be ALL (leukemia) 2. mature (peripheral) B cell neoplasm – multiple myeloma (BIG CATEGORY) iii. T-cell

1. precursor T cell neoplasm – most of these turn out to be lymphomas (medialstinal lymphomas) 2. mature (peripheral) T cell neoplasm – pretty rare g. Subcategories of peripheral B-cell neoplasm i. Small lymphocytic lymphoma 1. a.k.a. Chronic lymphocytic leukemia – CLL ii. Follicular lymphoma 1. (most common, 45% of all B-cell proliferations) 2. comes from the follicle 3. has a translocation 14:18  over expression Bcl-2 gene – bcl-2 inhibits apoptosis iii. Diffuse large cell B-cell lymphoma 1. Aggressive, BAD 2. happens in all ages 3. responds well to treatment, but will eventually kill you iv. Burkitt‟s lymphoma 1. associated with EBV – often seen in Africa 2. sometimes associated with HIV 3. translocation 8;14 4. happens in young 5. has associated abdominal mass or a mass in the jaw v. Multiple Myeloma – presents very differently from these other peripheral B-cells vi. Marginal zone lymphomas 1. a.k.a. maltomas 2. not a big deal, can be treated with antibiotics h. Subcategories of peripheral T-cell neoplasm – READ IN ROBBINS i. For the most part, we don‟t see them ii. Mycosis fungoides and ceseary syndrome are skin associated peripheral T-cell neoplasm i. Question answers i. Follicular has better prognosis ii. Older iii. 14;18 translocation  bcl-2  over-expression of bcl-2  inhibits apoptosis 5. Hodgkin‟s Disease (Hodgkin‟s lymphoma) a. Arises in a single LN or a chain of LN‟s and spreads in a very predictable fashion (non-Hodgkin‟s doesn‟t present predictably) b. Hodgkin‟s is in its own category even though it‟s a B-cell process c. Reed-Sternberg cell is the malignant cell in Hodgkin‟s lymphoma; there are different types: i. Classic type: Bi-nucleated cell with prominent nuclei that look like owl‟s eyes ii. Lacunar cell: single nucleus, looks like its sitting in a hole because the cell stains very pale iii. Lymphocytic/histiocytic LH cell – looks like a kernel of popcorn

1. negative for CD15 and CD30 markers d. R-S cells are the malignant cell, and you cannot make a diagnosis unless you see these R-S cells e. Classical i. Most are classical ii. RS Cells are positive for CD15 and CD30 iii. 4 subcategories 1. Nodular sclerosis (most common – 66%) with lacunar R-S cells – good prognosis 2. Mixed cellularity (25% of cases)– you will see all kinds of reactive cells, plasma cells, eosinophils, etc; need the classical R-S cell for diagnosis, prognosis is not as good, its more aggressive 3. Lymphocyte rich – lots of lymphocytes, but need R-S cells 4. Lymphocyte depleted – not many lymphocytes, made up of atypical cells (could be a large cell non-Hodgkin‟s lymphoma), has R-S cell CD15 and CD30 positive f. There is only one type of non-classical – Nodular lymphocyte predominant i. lots of lymphocytes and nodules ii. R-S cells are the L/H type which are negative for CD15 and CD30 g. Ann Arbor Staging of Hodgkin‟s Disease i. Stage 1 – one group of lymph nodes ii. Stage 2 – 2 or more groups of LN on one side of the diaphragm iii. Stage 3 – 1+ group of LN on both sides of the diaphragm iv. Stage 4 – LNs everywhere h. In Hodgkin‟s disease, the mesenteric nodes and Waldeyer‟s ring (around the tonsil) are rarely involved i. In non-Hodgkin‟s these are more often involved…extra-nodular involvement is more common on non-Hodgkin‟s i. When non-Hodgkin‟s involves the BM its para-trabecular (near the bone, outside of the marrow) 6. Slide #64: Nodular Sclerosis Hodgkin’s a. Wide mediastinum = Lymphadenopathy b. Has a fleshy, nodular appearance on gross specimen 7. Slide #66: Plasma cell myeloma (multiple myeloma) in BM a. MM falls into the category of plasma cell neoplasm b. Plasma cell is a terminally differentiated B-cell c. You end up with a single clone of plasma cell secreting a single monoclonal immunoglobin called an M-protein (para-protein) d. Bents-Jones protein is in this myeloma – this is monoclonal light chains and monoclonal light chain dimers e. Plasma cytoma has a monoclonal increase in immunoglobins f. Waldenstroms macroglobinemia – plasma-cell like lymphoma (associated with IgM) g. Heavy chain disease – all heavy chains, no light chains

h. Amyloidosis – amyloid is pink amorphous stuff, sometimes its immunoglobins, so sometimes you have a proliferation of these cells i. MGUS – mono-clonal gamopathy of undeterminant significance, these people didn‟t have any problems initially (~5 years) but after 10-15 years these patients developed worse symptoms j. MM involves multiple BM sites, presents with multi-focal boney lesions, bone pain, MM bone marrow has an increase in plasma cells or plasma cell precursors, hypercalcemia, bone fractures, recurrent infections, renal involvement (due to Bents-Jones proteins ending up in renal tubules and causing damage) k. Russel bodies in the cytoplasm l. Dutcher bodies are in the nucleus m. MM happens in older patients (50-60 years old) n. Bents-Jones will only present in the urine…99% of patients will have something in blood or urine…In 70% of cases you will find intact immunoglobulin in the blood and urine, in 20% you will only see BentsJones protein in the urine o. IgG is the most common, followed by IgA…usually if you have IgM, its not multiple meloma, it‟s the Waldenstrom‟s p. The plasma cells don‟t get into the peripheral blood in MM (if they do, you‟re dealing with a very rare dz – plasma leukemia)…you have increased Roulleaux formation in the peripheral blood  as a result of the increased Ig in the blood, you have RBC‟s sticking to each other like a stack of coins q. MM patients have anemia because the cancer is taking over the bone marrow…ruins RBC production r. Elevated urea nitrogen  poor kidney function because of the Bents-Jones poisoning the renal tubules s. Question answers i. Increased plasma cells in the BM >30%, lytic bone lesions, frequent bacterial infections ii. More the axial skeleton (pelvis, ribs, verts, skull) iii. Increased total protein, increased Ig, serum protein electrophoresis, IFE, urine protein electrophoresis for a monoclonal band, then do IFE on urine (immuno fixation electrophoresis) iv. 70% have Bents-Jones protein v. amyloidosis 8. Slide 335: Acute Myelogenous (Myeloid) Leukemia a. Leukemia – malignant neoplasm of hematopoeitic stem cells characterized by diffuse replacement of bone marrow by neoplastic cells…this usually spills into the blood, but not necessarily b. Liver, Spleen, and LN‟s are the tissues infiltrated by leukemia c. Divided into acute and chronic i. Acute – very rapidly progressing course ii. Chronic – more slowly progressive dz

d.

e.

f. g.

h.

iii. Acute has a problem with a block in differentiation (lots of blast cells) iv. Chronic has a problem with too much differentiation (over production of blood cells) The four types of leukemia and their associated ages: i. Kids – ALL = precursor B ii. 15-40 – AML iii. 25-60 – CML iv. 60+ - CLL = peripheral B Myelodysplasia and myeloproliferative disorders are related to AML and CML i. Myelodysplasia (pre-leukemia) – you have blasts and some atypical changes ii. Myeloproliferative disorders 1. CML is a subcategory of this disease 2. instead of blocking differentiation, the myeloid stem cell differentiates like crazy 3. This gives rise to an increase in 3 different cell lines a. Neutrophils (CML) – can confuse with infection b. Basophils c. Eosinophils 4. Polycythemia vera (increased RBC) 5. Idiopathic myelofibrosis with myeloplasia ALL involves the CNS (so you will do a spinal tap whenever you make this diagnosis) ALL is a precursor B-cell neoplasm (pre-cursor T cell is a lymphoma – mediastinal mass) i. You distinguish between ALL from AML because a lymphoblast has 1. less cytoplasm 2. fewer nucleoli 3. no granules 4. no hour-rods 5. negative for most of histochemical enzymes (stains) ii. ALL can be subclassified morphologically, but we don‟t use that so much anymore – there are certain cytogentic abnormalities that are associated with AML more than ALL iii. Prognosis is pretty good, this is the one leukemia that has had a good outcome for a while CLL is the same disease as small lymphocytic lymphoma, peripheral B cell neoplasm i. There are lots of CD markers (look in Robbins) ii. Clinically 1. older people, asymptomatic 2. if they become symptomatic, they will present with anemia, thrombocytopenia (if it infiltrates the bone marrow)

3. they could be symptomatic with hepatosplenomegally or enlarged LNs iii. Treatment – you don‟t treat them until they manifest the cytopenias or megaly i. AML – mnyeloid proliferative dz i. Age: 15-40 ii. There are 2 classifications: FAB classification (M0-M7), Genetic classification 1. M0 – undifferentiated blasts 2. M1 – bunch of myeloblasts, barely differentiated (9;22 – bcr-abl) 3. M2 – slight differentiated myeloblasts (8;22 translocation) 4. M3 – all promyelocytes ( 5. M4 – myelomonocytic (inversion of chromosome 16) 6. M5 – monoblasts (acute monoblastic leukemia) 7. M6 – erethroleukemia (RBC) 8. M7 – megakaryocytic leukemia (platelets) iii. 9;22 was first discovered in CML – better prognosis, in AML, 9;22 is worse prognosis j. CML – subcategory of myeloproliferative disorders i. Going crazy with differentiation ii. If you don‟t treat CML, they will go into a blast crisis (acute leukemia crisis – cant tell between this and AML at this stage) iii. In about 30% of cases you get a lymphoblast crisis, which means this dz could be do to a precursor even before myeloid precursors k. Question answers i. Amount of cytoplasm, granules, auer rods, etc ii. Interrupted erethropoeisis, granulopoeisis, thrombocytopenia iii. They progress to AML, these used to be pre-leukemias iv. If they go untreated, they can lead to a blast crisis, which is similar to AML crisis


				
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