5-25-15 Pathology Inflammation apoptosis Necrosis Cell injury Ischemia: susceptl areas Infarcts: red vs pale Shock Atrophy Inflammation Leukocyte extravasation Free radical injury Wound healing Granulmoatus dx Exudate vs transudate ESR Iron poisoing Amyloidosis On histological exam, a dying cell is noted to lack signs of acute inflammation in its vicinity. What type of cell death has likely occurred? Apoptosis Western blot is used to study this killer T cell efector molc that degrades DNA and is involved in extrinsic pathway? Granzyme What immune cells utilize perforns and granzymes? Killer (cytotoxic) T cells Changes in the proprotions of what 2 factors lead to increasd mitochondria permeability and conseuqnetly cytochrome c release? Bcl-2 or Bax Pro-aptotic factor Bax (pro-apoptoic factor Anti-apoptoic factor? Bcl-2 An increase in Bax and/or a decrease in Bcl-2? Induces apoptosis Nuclear shrinkage is due to? Pyknosis Where as nuclear fragmentation is due to? Karyorrhexis Pro-apoptoic gene? Bax Anti-apoptoci gene? Bcl-2 Western blot is used to study this killer T cell effector molc that punchesw hols int eh plasma membrane? Perforin Under what conditions does intrinsic apoptosis occur? Embryogenesis Hormone induction (i.e. mensturation) Menopause Atrophy (injurious stimuli) Radiation HYPOXIA Toxins Before the formation of apoptoci bodies, what 4 proccess occur in a cell underoing apoptosis? Cell shrinkage; pyknosis and basophilia, membrane blebbing and karyorrhexis What is the final common pathway of the intrinsic and extrinsic pathway of apoptosis? Activation of cytosolic caspases What are the 2 extrinsic apoptoic pathways? 1) ligand-receptor interactions Fas ligand binding to Fas receptor (CD95) (death receptor) 2) cytocic T cells release of granzyne B and performins Which pathway or pathways of apoptosis requires ATP (intrainsic and/or extrinsic) Both intrinsic and extrinsic APOPTOSIS (Dr. Gojan) always require energy What is apoptosis? Programmed cell death. Give an example of how withdrawing a growth factor can lead to apoptosis via the intrinsic pathway? Withdrawal of IL-2 after an immune response lead to apoptosis of proliferating effector cells. What type of necoris is a/w with TB? Caseous USMLE: An alcoholic has sveral bouts of acute pancreatiis. If he does not stop rinking, watht yep of necrosis can you expect in hs pancrease? Fatty necoriss (saponification via lipase) They can ask peripancreatic fat which is the fat necoriss Which parenchymal will be liquefactive according to firecrackers enzymatic degradation and protein denaturalizing caused by exogenous cell injury results itn eh relase of intracell component? Necrosis Liquefactive necoriss occurs most commonly in what organ? Brain What is the main difference between dry and wet gangrene? Ischemic coagulation gangrene? Dry gangrene Necrosis superimposed with a bacterial infection? Wet gangrene Ischemia happens with both of them the same cause and when infection happens you get wet What type of necoriss limbs and GI tract? Gangrenous necrosis What morphologic type of necoriss MC occurs in the blood vessels? Fibrinoid necoriss Coagualtive necoris soccurs msotc ommonly in what organ? Heart, liver and kidney USMLE: 49 yo male has a sudden onset chest pain diagnosed as MI. what type of necoris would b eseen? Cogaulative necoriss Pervuian immigrant peresnts with a productive cough. Culture stain acid fast. If he is not rx, what type of necoris do you expect Pt has TB not treated he will develop casious necoris (also seen with? Systemic fungi 50 yo man with pneumonia develosp a parapneumonic effusion. What type of necoriss occurs in this effucsion? Liquifactive nencorsis What ist he main dif between necoris asnd apotposi? Necoris s a/w inflammation Regarding cell injury, is plasma membrane damage reversible or irreversible? Irreversible Regarding cell injury, are nuclear pyknosis, karylosy and karyhexis reversible or irreverabile? Irreversible regardingClel injyr, is glycogen depletion? Reversible Calcium influx that leads to capsse activation R or I? Irrersible (caspse activation leads aptosis, which is irreversible ) Lack of ATP leads ot cellular swelling. Reverislbe w/o ATP, Na/K/ATPase pumps do not work ledas to massive sliudm and H2O influx. swelling is fatty change R or I? R Increased mitochondrial permaiblity R or I? I Is lysoomsal rupture R or I? I Ncuelar chromatic clumjkping R or I? R Ribosomal detachment R or I? R USMLE Pts cell shows nuclear clumping and fragmentation. Is this R or I signs of cell injury? Irreversible: pyknosis (nuclear clumping) and karyolysis (nuclear framgantion) are irrersbiel changes What part of the kidney is most suscpeti to hypoxia? Proximal tuble (cortex) and thick ascending limb (medulla) Because they are the watershed areas. Hypoxic ischemic ecneaplophaty primarily affects which cells of the hippocampus? Pyramidal cells (purkinje cells are affected as well) Liver (most suscpetile to ischemia) Zone 3 Area around the central vein USMLE A man with arterial stenosis often has left upper quandra pain after eating a large meal. What watershed area is most likely affected? Splenic flexure Which parts of the brain are more suscpeti to hypoxia? Bounadaires Anteria, middle, posteiroe cerebral artery Watershed areas What part of the hear tis most suscpet to hyposxia? Subendocardial tissue MOA? Watershed area An area that receives dual blood supply fromt eh most distal branches of two arteries? Watershed area 3 organs manifest irrerbisl eishema with a pale infarction? Heart, spleen kidney This colored infarct can occur after reperfusion b/c it suggests hemorrhage Red infarct Can los tissue with collateral circulation? Red Occur in soldi tusses with asingle blood supply? Pale 3 organst manifest irrersibel ishcmeia with a red infarction? Liver, lungs, intestines, Why can reperfusion of an organ lead to more dmanage? Injury is due to dmange ffree radicals USMLE: A man with a gunshot wound is rushed to the ER. HE is cold, clammy and has a low BP and high TPR. What state is this? Hypovolemic shock Cardiaonci shock Low cardiac OUTput failure Pt with sepetic shock can be warm to the touch. Penhomnomen? Dilated arterials TPR? Low In pts with septic shock, there is TPR? Dfecreased Hypovolemic shock? Cradiac output failure? Low Pt admitted to the ICU is cold and clammy. Hypovolemic or dardiogneic In a pt with hypovolimc/cardiogenic shock, TPR? Incrase To componste for low CO Pt expierences widespread bactermia. He is warm to the touch. CO to be? High Septic shock Septic shock CO state? High Reduction in the size or number of cells? Atreophy Causes? Decrase in hromones Blood flow, Innervation, Nutrients Occlusion of secretary ducts Incrase in pressure A man severs his right bracial pleux can cannot more his arm. He develops vast mucsuclar atrophy, unepxoed by lack of use alone. MOA? Dnervation fo msucles in his right arm accelerated the atrophy Why does the endoemetrial ining of the uterus undero atrophy after menopause? It loses of growth signals from endogenous hromeons A man is diagnosed with CF. What sithe pathogenesis of his pancreatic atrophy ove rtthe long term? Occlusion fo secretary ducts 40 yo man has PF. Wha type cell type in his lugns will repdomiante in cuasing the pathologic hanges? Fibroblasts 50 yo man has left lower lobe exudative inflammation from bacterial pneumonia. What sepcts of the inflammatory process led to this? Increased? Vascular permability Vasodilation Endothelial injury Abnormal ocmmuicatnion between 2 epitheliaized surfaces Fisutal Present? Resolution phase of inflammation What is the ce3lularl component of the inflammatory process? Neutrophil extrvation (circulation to the in injured tissue) to mediate? Phagocytosis; Degranulation Inflammatory mediator release What cells and proteins mediate acute inflammation? Neutrophils, esoinphopls And antibodies Chronic inflammation? Persistent destruction and repair Charc of granulation tissue? Highly vascularized fibroti citssue Present? Resolution phse of inflammation Inflammation: What should normally happen in the resoluation phase of inflammation? Restoration Normal tissue structure What is an abscess? Fibrosis surrounding pus When are abscess present? Resolution phase of inflammation USMLE: Chronic inflammation is mediabed by cells? Mononuclear cells W What are the pathological charc of such an inflammation? Persistent destruction and repair Nodular collecitons of epithelioid macorphages and giant cells? Granuloma Chronic phase of inflammation 4 main cytokinase Triggered by bacterial prodcuts) that guide leukocytes to a site of injury or infection (CILK) C5a IL-8 LTB4 Kallikrein Tight binding is mediated by? ICAM-1 On the vascular endotheium And by binding to what? Ont eh leukyoctyes LFA-1 (integrin) 4 steps involved in leukocyte extrvation: Rolling Tight binding Diapedesis Migration Leucokcytes travel between endotehliuc cells adne xits the blood vessel? Diapedesis Mediated by ? Ont eh vascular endothium? PECAM-1 And binding to on the leukocytes? PECAM-1 The cell travesl to the site of infection or injury with tethe guidance of chemotactic signals? Migration Rolling is medicated by what ont eh vascular endoium? E and P selectins By binding on the leukocytes Sialyl Lewis Name 3 pathays for free radical degradation? Antioxidants (vitamins, ACE) Enzymes (i.e.? Catalase, superoxide dismutase) Spontaneous degradation (decay) Free radical damage by carbon tetrachlrodi causes what pathlogic change int eh uman body? Fatty change in the liver Some enzyems that degrade free radicals: Catalase Glutathione peroxidase Superoxide dismutase Via what mechiansid do free radicals damage cells? Membrane lipid peroxidation, Protein modification DNA breakage 3 vit with antioxidants properties that involve in degrading free radicals? E, A, C Fat soluble vitamins? DEAK USMLE: An infant is born at 22 weeks gestation. Exposure to free radicals predispose him towha tpathological processes in his eyes and lung? Bronchopulmonary dyslplaisa (lungs) Retionphaty of prematurity (eyes ) Pt undergoes thrombolysis for acute limb ischemia. What type of fre radical injury is of most concern? Reperfusion injury MI pt that had fibrinolysis: why do troponin rise again? Free radiacl injury can be induced by expose to what substances and processes? Radiation Heavy metals Metabolism of drugs (phase 1) Redox reactions NO Leukocyte oxidative burst Wound healing Which phase of wound healing has infiltration of paltelets, neutorphils and macrophages at the site of injury? Inflammatory phase!!! Has infiltration of fibroblasts, myofibrblyasts, endotehlic cells, and keratinocytes at the site of injury? Proliferative phase Which cells are most important in mediating the remodling process of wound healing? Fibroblasts In which phase of wound healing is type III collagen replaed by type I collagen? Remodeling phase MOA? To increase tensile strength of tissue . What are the 3 phases of wound healing, in order?

Inflammation, proliferative, remodeling Whend eos the prolifeative phase of wound healing occur? 2 to 3 dyas After wound In which phase is the wound healing process one week after an injury? Remodeling phase What are the charc of the inflma phase? Clot formation Incrased vessel permability Neutrophil migrate into tissue Macoprhage clearance of debris two days later Which wound healing phase has collagen deposition, angioegeniss, clot dissolution, epitheliuc cell rplofieration and wound contraction? Prlofieratif phase When does the ifnlammaotyr phase of wound healing occur? Immediatlye after injury Granlumotase dixses Why must you check for granulmostu dx before starting an anti-tumor necoriss factor medication? b/c these medication break down granulomas and can predispose to dissiminated disease Th1 cells secrete gamma-interfern activagin macrophages, macropahgese secrete TNF-alpha, inducing/maintain granulmona formation? Granuloma forms G dxs: TB Fungi (histoplasmosis) Syphilis (T. pallidum) M. leprae (leprosy) Cat scrath fever (B. henselae) Sarcoidosis Crohns berylliosisUSMLE a Mexican immigrant not up to date on vaccines presents wth liver granulmoas secondary to a productive cough. What cuased his granuloma? TB Does increased fluid pressure cause formation of a transudate or exudate? Transudate Serous exudate TransudateTypes[edit] Purulent or suppurative exudate consists of plasma with both active and deadneutrophils,fibrinogen, andnecroticparenchymal cells. This kind of exudate is consistent with more severe infections, and is commonly referred to aspus. Fibrinous exudate is composed mainly offibrinogenandfibrin. It is characteristic of rheumatic carditis, but is seen in all severe injuries such asstrep throatandbacterial pneumonia. Fibrinous inflammation is often difficult to resolve due to blood vessels growing into the exudate and filling space that was occupied by fibrin. Often, large amounts of antibiotics are necessary for resolution. Catarrhal exudate is seen in the nose and throat and is characterized by a high content of mucus. Serous exudate (sometimes classified as seroustransudate) is usually seen in mild inflammation, with relatively low protein.[6]Its consistency resembles that of serum, and can usually be seen in certain disease states liketuberculosis. (See below for difference between transudate and exudate) Malignant (or cancerous) pleural effusion is effusion wherecancer cellsare present.[7]It is usually classified as exudate.Exudates vs. transudates[edit]Transudatevs.exudate view talk edit

TransudateExudate

Main causesIncreasedhydrostaticpressure,Decreasedcolloidosmotic pressureInflammation-Increased Vascular Permeability

AppearanceClear[8]Cloudy[8]

Specific gravity1.020

Proteincontent2.9 g/dL[9]

fluid protein/serum protein< 0.5> 0.5[10]

Differenceofalbumincontentwith blood albumin> 1.2 g/dL< 1.2 g/dL[11]

fluidLDHupper limit for serum< 0.6 or 0.6[9]or >23[10]

Cholesterolcontent< 45 mg/dL> 45 mg/dL[9]

There is an important distinction betweentransudatesand exudates. Transudates are caused by disturbances ofhydrostaticorcolloid osmotic pressure, not by inflammation. They have a low protein content in comparison to exudates. Medical distinction between transudates and exudates is through the measurement of thespecific gravityof extracted fluid. Specific gravity is used to measure the protein content of the fluid. The higher the specific gravity, the greater the likelihood ofcapillarypermeabilitychanges in relation tobody cavities. For example, the specific gravity of the transudate is usually less than 1.012 and a protein content of less than 2g/100mL (2g%).Rivalta testmay be used to differentiate an exudate from a transudate. It is not clear if there is a distinction in the difference of transudates and exudates in plants. Trausndate can occur in the setting of excess sodium ? Retention Transudate are protein poor compared to exduates Sepcfici gravity < less than 1.012

Transudates are characted by few cells, little protein and specfici gravity? < 1.012 Exudates many cells, much protein, specfici gravity? > 1.020 USMLE: A pt with decompensated CHF has a pelural effusion.l Is the fluid more likely to be T or E? Transudative Increased hydrostatic pressure A 40 yo man with bacterial pneumonia has a pleural effusion on chest xray. Exudative Damage to endothelium 2 pathologica processes that lead to the formation fo exudates: Lympathic obsturciton and inflammation Transudate can result from Oncotic pressure in the vasculature? Decreased ESR (erythrocyte sedimentation rate) Least 2 conditions that can predispose pts to a lower ESR Sickle cell anemia Polycythemia CHF USMLE: A med student worries a pregnant women has an b/c of her high ESR. Do you agree? No. ESR can naturally be increased in pregnancy w/o superimposed infection Name at least 3 conditions that can cause an elevated ESR Infection, inflammation, cancer, pregnancy SLE SOAP BRAIN MD SEROSITIS ORAL ULCERS ARTHRITIS PHOTOSENSITIVTY RAYNAUDS PHENOMENOM Anti-histones SHIPP Q-chimppps Quinidine Chlorpromazine Hydralzine Isoniazide Methyldopa Procainamide Phenytoin Penicylamine Sulfonamides What is the Mecnahims of cell death iron poisoing? Membrane lipid peroxidation In what population are your particularly worried about iron poisoing? Children Why? Iron poisoining is one of the MCC of death in children secondary to toxco.lgoci agents What is the acute sign of iron poisoining? Gastric bleeding What are the isgns of chronic iron poisoing? Metabolic acidosis scarring leading to GI obstruction USMLE: A man with no surgical history decides to take 5 iron supplemnts a day. He later develops a small bowle obstctruion? MOA? Chronic iron poisoing cause scarring leads to the gastrointestinal obstruction. USMLE: A 5 yo is rushed to the ER after swallowing 10 mutlivtamin pills. He has acute gastric bleeding. Likely cause? Iron poisoing from the MVs Amyloidosis Tissue affected by amyloidosis may have? Waxy appearance What protein is depsoisted in mayloidoss in pts with medullary carcinoma of the thyroid? A-CAL What ist he precursor protein? Derived rom calcitonin Dialysis-asosicated amylidsoi is charac by dpeostion of what protein? B2-microglobulin What is the name of its precursor protein? Derived from Major histocopatiblity complex class 1 protein (MHC1) 2ndary maylodiss is charc by the deposition of AA rptoein. From what protein is AA rpteoin derived? Serum amyloid-accoisted rptoein. High serum levels chornic inflammation USMLE USMLE Pt suffers from RA. If her tisseus are found to have amyloid deposition. Expect? Secondary amylodis Pt suffers from horrible form of cardiac and neurological amylodis.s wha mutation is responbile The pt has ATTR neurlogic/carida amylodiss, due to transthyretin (TTR or prealmbumin) gene mutation ATTRtransthyretin

ransthyretin is a protein that is mainly formed in the liver that transports thyroxine and retinol binding protein.[4]A mutant form of a normal serum protein that is deposited in the genetically determinedfamilial amyloid polyneuropathies. TTR is also deposited in the heart insenile systemic amyloidosis.[11]Also found inleptomeningeal amyloidosis.

Pt suffers from a heritable form of cardiac and neurlogica amyldoisis Gene mutation? Primary amlydoiss is charac by the dpeosion of AL protein. Form what priteoin is this AL derived from? Ig Light chain Which type of amylidos is charc by AL protein derived from Ig light chain? Bence jones amyloidosis What dx can cause amyloidsi from an cexcess of Ig light chain? Multiple myeloma What is charc hisotlogica finding in tissed affected by amlyodis? B pleated sheet that show apple green birefreingche when stain with Congo red and viewed under polarized light Amyloidosis in AD pts is charac by deposition of what protein? B-amyloid What is the name of its precursor protein? Derived from ? Amyloid precursor protein Senile cardiac amyloidosis sis characterized by the depsitn of what protein? tr

Transthyretin What is the name of its repcurs protein? Derived from AF AF Amyloidosis Amyloidosis Center | Boston Universitywww.bu.edu/amyloid/research/laboratory.../af-2/ Boston UniversityAF Amyloidosis. Studies on the familial forms of systemic amyloidosis are aimed at understanding the pathogenetic mechanism by which normally soluble... Describe the pathophyskogy fo age related (senile) systemic amlyodis)