Pathology Lecture 1-8 PDF

PATHOLOGY A, 1ST LESSON PA LANG, PATHOLOG NA AKO LECTURER: DOC DARYL REQUISO, PISO PO (1.00), ‘WAG SINGKO Unahan ko na kayo, marami dinagdag galing sa book sa trans na ‘to, hindi...

PATHOLOGY A, 1ST LESSON PA LANG, PATHOLOG NA AKO LECTURER: DOC DARYL REQUISO, PISO PO (1.00), ‘WAG SINGKO Unahan ko na kayo, marami dinagdag galing sa book sa trans na ‘to, hindi Basta promoters (initiate) sobrang based sa PPT ni Doc, kasi panay sabi siya na maglibro, basahin sa libro. kaya nga nasa unahan, Disclaimer lang para ‘di kayo magtaka bakit dami nakalagay, ayon lang bahala tapos enhancers na kayo sa mga buhay niyo, at unang trans pa lang pagod na ako batch 2026… (modulate) – THEY ARE SEND GCASH PAMPAGANA SA AMIN BUONG SEM NAMAN!!!! JOKE NOT JOKE! MAG-ARAL KAYO! PATHO = PHYSIO X PHYSIO X PHYSIO ANG EQUATION NITO OKAY!? THE BINDING SITE FOR TRANSCRIPTION WHAT IS PATHOLOGY??? FACTORS. GENETIC VARIATIONS (POLYMORPHISMS) PATHOLOGY Study of suffering (pathos); study of disease Many genetic variations (polymorphisms) associated with Cellular disturbances arise from alterations in molecules (genes, diseases are in NON-CODING PROTEIN REGIONS of genome. proteins, and others) that influence the survival and behavior of Any two humans are typically >99.5% DNA-identical. cells Individual variation, including differential susceptibility to diseases What is Pathology? This is Physio with high mortality daw according sa higher and environmental exposures, is encoded in B o Loss of endocrine stimulation ▪ Muscle to Bone o Pressure ▪ Myositis ossificans - Not considered a true adaptation Decreased workload, wala ka nang kwenta, ano pang silbi mo? Pababain na rather more of a repair mechanism natin number mo. Example panay buhat ka for 1 week tapos huminto ka ng 1 Metaplasia, magpapalit ng anyo lol from one cell type to another. Tulad nung month, imbis na nagka-muscles ka na, nawala siya, atrophy. Loss of innervation picture sa next page, si columnar to squamous like sa yosi. Need kasi mag-adapt ‘yung stroke patients madalas if sa left may problema (supratentorial or ng baga mo kakahipak mong hinayupak ka kaya nagpapalit ng structure or cell infratentorial – STOP NEUROANA), liliit si left mo ‘di ba. Diminished blood supply type, kaso nga lang ‘yung dating columnar na may cilia para maka-expel or more on syempre walang napapadala, edi walang nutrients. Loss of endocrine maka-secrete, ‘di na nangyayari kasi squamous na, kaya prone sa sakit sab aga stimulation kasi si endocrine ang may responsibility sa pagpapalaki usually sa old ang mga naninigarilyo. TANDAAN SI MYOSITIS OFFICANS NA HINDI ADAPTATION women. Kapag pressure, kapag pressed ang organs gano’n din walang delivery PERO MORE ON REPAIR MECHANISM, BONE FORMATION IN MUSCLE ‘YAN. or blood flow. Ayan si atrophy. IPAPAPUTOL KO DALIRI KO KAPAG ‘DI TINANONG ‘YAN KUMUNOY’S IMPROPERTY 4  PATHO QUACK QUACK QUACK LECTURER: DOC TAGAYUNA, TAGAYMUNA BAGO TURO Myositis ossificans Metaplasia a. hypertrophy b. hyperplasia AGAIN, SIYA AY METAPLASTIC BUT NOT ADAPTIVE CHANGE c. metaplasia d. atrophy OKAY Stretch of the cell is stimulatory Hypertrophy a. hypertrophy b. hyperplasia Stretch, increased size boi c. metaplasia d. atrophy Which of the following transcription factors GATA4 is/are involved in hypertrophy? Transcription sina PI3K at CELLULAR ADAPTATIONS TO STRESS – SUMMARY NA HINDI a. PI3K/AKT b. GATA4 GPCR ha??? Signal Increased CELL AND ORGAN SIZE, often in c. All of the given options d. GPCR transduction silaaa response to INCREASED WORKLOAD Induced by GROWTH FACTORS produced in What is the adaptive mechanism involved Hormonal HYPERTROPHY response to MECHANICAL STRESS or other when thyroid gland increases its functional hyperplasia stimuli capacity when TSH level is increased? Iha, what is TSH? Anong nginingiti-ngiti mo iha, INCAPABLE OF CELL DIVISION a. Compensatory hyperplasia sagutin mo ako. Hay Increased CELL NUMBERS in response to b. Hormonal hyperplasia nako iha paano ka hormones and other growth factors c. Hypertrophy nakapasa sa physio B? HYPERPLASIA HORMONE SI TSH, FUNCTIONAL Occurs in tissues whose cells are ABLE TO d. Metaplasia CAPACITY NAMAN DIVIDE or contain ABUNDANT TISSUE STEM CELL TANONGGGG DECREASED cell and organ size What type of cell are the target of increased Mature and DECREASED nutrient supply or disuse growth factors in hyperplasia? stem cells ATROPHY a. All of the given options b. Senescent cells SENESCENT NA NGA, DECREASED synthesis of cellular building blocks Increased breakdown of cellular organelles c. Mature cells d. Stem cells STOP NA, WALA NA SIYA KWENTA, PAANO PA SIYA and autophagy (decreased pa rin kasi sira) e. Mature and stem cells MAG-PROLIFERATE? CHANGE IN PHENOTYPE of differentiated cells, In hypertrophy signal transduction generally Cytoplasm often in response to chronic initiation occurs in which part of the cell? Cell membrane si METAPLASIA Makes cells BETTER ABLE TO WITHSTAND STRESS a. Nucleus b. Cell membrane integrated actions Nucleus si transcription Induced by altered differentiation pathway of c. Chromatins d. Cytoplasm factors tissue stem cells Which of the following is a form of pathologic Benign prostatic hyperplasia? hyperplasia Which of the following adaptive change is a. Breast enlargement in puberty HUY MAY SAKIT NGANG observed in the smooth endoplasmic Hypertrophy b. Enlarged uterus of a pregnant woman BPH SA LALAKI ANUBA COMPENSATORY reticulum of the hepatocytes in the presence Protein synthesis, kapag c. Benign prostatic hyperplasia MECHANISM SI dumami proteins, of increase protein synthesis? dadami pwede d. Post hepatectomy liver HEPATECTOMY, a. hypertrophy b. hyperplasia magpalaki ng size HORMONAL SINA A, B c. metaplasia d. atrophy Evidence of atrophy EXCEPT perinuclear Accelerated proteolysis via ubiquitin- a. residual bodies hemosiderin proteasome pathway is a mechanism in Atrophy b. perinuclear hemosiderin May nabasa ba kayong perinuclear hemosiderin? which adaptive change? LYSIS, SIRA, SISIRA c. vacuolated cytoplasm Wala ‘di ba? Kaya ayan PROTEINS, LILIIT SIZE, d. decrease in cellular components a. hypertrophy b. hyperplasia ATROPHYYY except HAHA c. metaplasia d. atrophy Most common etiology of hyperplasia Hormone a. Hormone imbalance imbalance Which adaptive change is a fertile soil of Hyperplasia b. Increased workload B – HYPERTROPHYY cancerous proliferation? PROLIFERATION NA NGA C – Wala??? OH, INCREASED NUMBER c. increased blood supply D – Yes pwede viral infections a. hypertrophy b. hyperplasia OF CELLS DIN SA caused by hyperplasia, pero d. Microbiologic agents c. metaplasia d. atrophy CANCER most si hormone Example of columnar metaplasia Match the statements to the adaptive changes a. Respiratory tract with cigarette smoking Esophageal Stem cells divid Hyperplasia b. Deficiency of vitamin A on respiratory changes with a. hypertrophy b. hyperplasia Can divide po, can proliferate siya epithelium gastric reflux c. metaplasia d. atrophy c. Stones in excretory ducts A, B, C - Epithelial Loss of endocrine stimulation Atrophy d. Esophageal changes with gastric reflux a. hypertrophy b. hyperplasia Decrease nanaman, paano magpapalaki o TRUE OF ADAPTATIONS usually due to c. metaplasia d. atrophy magpaparami??? a. usually due to chronic injury chronic injury Senile brain atrophy b. seen only in stable cells B – BAKIT AADAPT KUNG STABLE NA? a. hypertrophy b. hyperplasia GAGU MERON KA NITO, MENTAL DECLINE HAHA c. Cannot return to normal C – CAN RETURN TO NORMAL c. metaplasia d. atrophy DECREASE SO ATROPHY d. mediated by cytokines, hormones, etc D – HINDI CYTOKINES ANG ALAM KO KUMUNOY’S IMPROPERTY 5  PATHO QUACK QUACK QUACK LECTURER: DOC TAGAYUNA, TAGAYMUNA BAGO TURO Not considered a true adaptation rather more REMEMBER, KAPAG REVERSIBLE CELL INJURY: CELLULAR SWELLING AND FATTY Myositis Ossificans CHANGE!!! ANTABA NI REVER, NAGMANAS ‘YUNG KATAWAN. Kapag reversible, of a repair mechanism Epithelial metaplasia syempre mababalik sa dati, maaayos pa kapag nawala ‘yung damaging a. Involution b. Barrett esophagus si Barrett stimulus. Syempre kapag and’yan ‘yung toxic na naninira, magiging maayos ba? c. Myositis Ossificans d. Wart Magiging prolonged at progressive lang ‘yung damage, MAGIGING Adaptation which may be progress to IRREVERSIBLE, HINDI NA MAAAYOS, HINDI NA BABALIK SA DATI, ‘WAG KA NANG malignant transformation Hyperplasia UMASA, MAY CELL DEATH NA. Kapag cellular swelling, dahil ‘to sa influx ng tubig. a. all adaptations may undergo malignant Mga plasia Kasi nag-fail ka sa exam este nag-fail ‘yung sodium-potassium ATPase pump kasi transformation malignant nga ‘di ba bumaba ATP dahil reduced ang oxidative phosphorylation. So kung b. hypertrophy c. atrophy d. hyperplasia walang ATP, walang pump, si 3 sodium hindi makalabas, edi susunod si water sa loob, water influx, swelling ng cell, kaya nagmamanas. Itong si fatty change sa Metaplastic but not an adaptive change? organs ‘to na involved ang lipid metabolism. Kapag ‘yung injury na toxic nasisira a. Myositis ossificans Myositis rin ‘yung metabolic pathways tapos namumuo ‘yung mga triglyceride-filled lipid b. Barrett esophagus Ossificans vacuoles (ayan oh lipid kaya fatty change). AYANG DALAWA ANG MAIN HA c. columnar to squamous change in KAPAG REVERSIBLE ANG CELL INJURY: ANTABA NI REVER, NAGMANAS KATAWAN. PLASTIC MO, ‘DI phenotype of the respiratory tract KA TOTOO Ultrastructural Changes d. cervical squamous metaplasia o Plasma membrane alterations Papillomaviruses result into which of the epithelial ▪ Blebbing, blunting, loss of microvilli following changes? o Mitochondrial changes a. atrophy hyperplasia ▪ Swelling and the appearance of small amorphous b. epithelial metaplastic change Papi na playboy densities c. hypertrophy of involved muscle Papilloma or viral infection po hyperplasia o Dilation of the ER, with detachment of polysomes; d. epithelial hyperplasia intracytoplasmic myelin figures may be present Which pathway is involved in exercise- phosphoinositide o Nuclear alterations, with disaggregation of granular and induced hypertrophy? 3-kinase pathway fibrillar elements a. ubiquitin-proteasome pathway Exercise induced ay b. phosphoinositide 3-kinase pathway Dizk physiological PI3K sa Physio c. p53-dependent pathway Mechanical sensors in hypertrophy is Increased triggered by which of the following? workload a. Increased workload B – Signal b. Activation of PI3K/AKT pathway transduction po c. All of the given options D – Mechanism d. Synthesis of muscle proteins Ayan daw kapag overview ng morphologic changes ng reversible cell injury, Which of the following is/are transcription may swelling ‘di ba tama, tapos may membrane blebs or parang bilog-bilog sa factor/s seen in hypertrophic adaptive gilid, sa microscopic (3rd pic) kapag may cell injury nag-iincrease eosinophilia ng changes? All of these cytoplasm, may blebs din, tapos may swelling. Normal ‘yung nasa gitna. TraGaMeN a. GATA4 b. NFAT c. MEF2 d. All of these CELL INJURY CAUSING CELL DEATH Cell Death o Continuing damage becomes irreversible cell → cannot TYPES OF CELL INJURY recover →dies REVERSIBLE CELL INJURY Early stages or mild forms of injury, the functional and NECROSIS morphologic changes are reversible if the damaging stimulus is Severe damage to membranes, lysosomal enzymes enter the removed cytoplasm and digest the cell, LEAKAGE OF CELLULAR CONTENTS Hallmarks of Reversible Injury: Always a pathologic process o Reduced oxidative phosphorylation with resultant depletion Denaturation of intracellular proteins and enzymatic digestion of of energy stores in the form of adenosine triphosphate (ATP) the lethally injured cell o Cellular swelling caused by changes in ion concentrations May take hours and water influx Morphology: Features: o Increased eosinophilia – loss of cytoplasmic RNA and o Cellular swelling – Hydropic change – Vacuolar accumulation of denatured cytoplasmic proteins degeneration o Glassy homogenous appearance ▪ Vacuoles in the cytoplasm o Cytoplasm vacuolated, moth-eaten ▪ Failure of energy-dependent ion pumps o Myelin figures – whorled phospholipid derived from damaged o Fatty change – Steatosis cell membranes ▪ In cells involved in and dependent on fat metabolism o Calcification of fatty acid residues – calcium soaps – calcified dead cells KUMUNOY’S IMPROPERTY 6  PATHO QUACK QUACK QUACK LECTURER: DOC TAGAYUNA, TAGAYMUNA BAGO TURO Cheese like – friable white appearance of NUCLEAR CHANGES the area Faded basophilia of chromatin Collection of fragmented or lysed cells and KARYOLYSIS Loss of DNA due to degradation by CASEOUS amorphous granular debris enclosed within endonucleases NECROSIS a distinctive inflammatory border APOPTOTIC CELL DEATH Most often in foci or tuberculous infection Nuclear shrinkage and increased basophilia CASE-CHEESE Focus of inflammation known as a PYKNOSIS Chromatin condenses into a solid, shrunken na friable granuloma basophilic mass white KARYORRHEXIS Pyknotic nucleus undergoes fragmentation appearance Ang nuclear changes, pwedeng one of three patterns, pero laaht dahil sa boi BREAKDOWN OF DNA. Kapag fading ng basophilia dahil sa enzymatic degradation ng endonucleases, karyoLYSIS (LYSIS = SIRA). Pyknosis kapag solid, shrunken (PYK, SHRUNK). Dito si chromatin nag-c’condense into dense and shrunken basophilic mass. Kapag karryohexis, fragmentation. Tandaan niyo karryoHExis, fragMENtation. Focal areas of fat destruction PATTERNS OF TISSUE NECROSIS Not a specific pattern Architecture of dead tissues preserved FAT NECROSIS Release of activated pancreatic lipases into COAGULATIVE Firm texture of affected tissues Mga fatty acids + pancreas and peritoneal cavity calcium (fat NECROSIS Denaturation of structural proteins and saponification), Dapat tandaan, si enzymes, PROTEOLYSIS IS BLOCKED!!!! kaya may mga Coagulative necrosis, ischemia Eosinophilic, anucleate cells chalky white EXCEPT SA BRAIN. Necrotic cells removed by phagocytosis areas diyan, Tapos preserved Ischemia may lead to coagulative necrosis ayan ‘yung fats ang architecture of dead tissues dahil of the supplied tissue in all organs except the proteolysis is brain blocked (Walang Infarct-localized area of coagulative Special form of necrosis usually seen in sumisira, edi goods necrosis immune reactions involving blood vessels pa rin ‘yung itsura). ‘Yang kidney, may FIBRINOID Complexes of antigens and antibodies dilaw ‘di ba? Ayan NECROSIS deposited in arterial walls ‘yung infarcted Fibrinoid – bright pink and amorphous part, pero ang outlines niya AUTOIMMUNE, immune complexes with fibrin that has ANTIGEN-ANTIBODY preserved, dahil COMPLEX, KAPAG leaked out of vessels WALA NGA OR MAY SLE O SYSTEMIC BLOCKED ANG LUPUS PROTEOLYSIS. ERYTHEMATOSUS, BASTA IMMUNE Digestion of the dead cells REACTIONS LIQUEFACTIVE Liquid viscous mass TANONG, IBIGAY NECROSIS Necrotic material frequently creamy yellow KAY FIBRINOID Pus – presence of dead leukocytes Kapag focal Seen in focal bacterial or fungal infections bacterial Accumulation of leukocytes liberating infection, enzymes Dami nangyayari kay necrosis. Pathological siya ha, unregulated, ‘di organized liquefctive gano’n, MAY LEAKAGE NG CELLULAR CONTENTS, may denaturation ng cellular CNS hypoxia – manifest as liquefactive agad. Tapos proteins, LOCAL INFLAMMATION, at enzymatic digestion. Morphological change, necrosis kung si reversible cell injury ay cellular swelling at fatty change (paulit-ulit na ako ito, umaabot ah), si necrosis ‘yung pyknosis, karyorrhexis, at karyolysis tapos more on na sa CNS kasi breakdown ng plasma membrane, may abundant myelin figures, at leakage si coagulative and enzymatic digestion ng cellular contents. Please memorize ‘yang deins. coagulative to fibrinoid, benta ‘yan sa tanungan sa exam… Viniolet ko na ‘yung mga importanteng dapat tandaan ha, ang magkamali, tanga. Non-specific pattern of cell death GANGRENOUS Digestion of the dead cells NECROSIS Generally the lower leg APOPTOSIS Alam niyo na ‘yan, ‘yung parang Lost its blood supply, necrosis (typically Induced by tightly regulated suicide program → cells destined to sumabog na ewan, coagulative necrosis) die activate intrinsic enzymes that degrade cells’ genomic DNA tsaka LOWER EXTREMITIES Wet gangrene – bacterial infection and nuclear and cytoplasmic proteins. TANDAAN superimposed with liquefactive necrosis KUMUNOY’S IMPROPERTY 7  PATHO QUACK QUACK QUACK LECTURER: DOC TAGAYUNA, TAGAYMUNA BAGO TURO Nuclear dissolution, fragmentation of the cell without complete Pathological siya kapag hindi nakakatulong pala ‘yung cell death. Example DNA loss of membrane integrity, and rapid removal of the cellular damage, kailangan mo si DNA, pero sinira siya ng mga radiation at cytotoxic anticancer drugs. Mabubuhay ka ba ng walang DNA??? Kapag hindi agad debris naayos ‘yung damage, mag-tr’trigger ng apoptosis, kaya medyo masasaktan Serves many normal functions and is not necessarily associated ka in the process (pathological). Pineprevent naman ni apoptosis ‘yung maka- with cell injury survive ‘yung cells na may DNA mutations kasi syempre panget ‘yan, malignant Pathway of cell death induced by tightly regulated suicide ‘yan. Pero akala mo lang nakakatulong si apoptosis, nasasaktan ka nga in the program process… Kapag pathological, more on may abnormality na pinipigilan si Cells destined to die activate enzymes that degrade the cells’ apoptosis (ELIMINATES CELLS INJURED BEYOND REPAIR). own nuclear DNA and nuclear and cytoplasmic proteins MORPHOLOGY OF APOPTOSIS Cell death by this pathway does not elicit an inflammatory Cell size is reduced, cytoplasm is dense, reaction eosinophilic and organelles, relative normal, Cell Shrinkage Cell membrane remains intact are more tightly packed. Structure altered SWELLING IN NECROSIS, SHRINKAGE IN Avid target for phagocytes APOPTOSIS Rapidly cleared Most characteristic feature of apoptosis Absent inflammatory reaction The chromatin aggregates peripherally, INTRACELLULAR ACIDOSIS PREVENTS PROTEOLYSIS Chromatin under the nuclear membrane, into dense Kabaligtaran ni apoptosis si necrosis, regulated dito eh, organized, and mostly Condensation masses of various shapes and sizes. The physiologic din ‘to, para maitapon natin ‘yung mga wala nang kwenta sa buhay nucleus itself may break up into two or natin. ABSENT INFLAMMATORY REACTION, kaya ‘di siya ‘yung sobrang lalang cell more fragments. - injury, pero oo cell death pa rin siya, programmed nga lang. May mechanism Formation of cytoplasmic blebs and kasi siyang kakaiba, mas marami nga lang ganap dito. apoptotic bodies. Causes: Formation of The apoptotic cell first shows extensive o Physiologic – to remove unwanted or potentially harmful cells Cytoplasmic surface membrane blebbing, which is ▪ Causes: blebs and followed by fragmentation of the dead ✓ During embryogenesis – critical for involution of apoptotic bodies cells into membrane bound apoptotic primordial structures and remodellng of maturing tissues bodies composed of cytoplasm and tightly ✓ Hormone-dependent involution – endometrial cell packed organelles, with or without nuclear breakdown during menstrual cycle; ovarian follicular fragments. atresia in menopause; regression of lactating breast after Phagocytosis of apoptotic cells or cell weaning bodies, usually by macrophages. The ✓ Cell deletion in proliferating cell population – immature Phagocytosis apoptotic bodies are rapidly ingested by lymphocytes that fail to express useful antigen receptors; phagocytes and degraded by the and epithelial cells to maintain constant cell number phagocyte’s lysosomal enzymes. (homeostasis) ✓ Death of host cells that have served their useful purpose – neutrophils (acute inflammatory response); lymphocytes (end of immune response) ✓ Elimination of potentially harmful self-reactive lymphocytes ✓ Cell death induced by cytotoxic T-cells Kapag nga kasi namatay ang cell through apoptosis, normal ‘yon, tinatanggal ‘yung mga hindi na kailangan sa buhay mo. Imagine kung hindi natatanggal ‘yung mga hindi na maganda sa katawan mo, ‘yung hindi na nakakatulong sa’yo, ‘yung sinisira na ‘yung buhay mo, mamamatay ka lang. Kaya magpasalamat ka sa apoptosis, mas magiging okay ka. Lahat ng cells nag- uundergo ng apoptosis kasi need nila maka-survive at maging maayos. o Pathologic – removed cells damaged beyond repair Mechanisms: ▪ Causes: o Initiation Phase Cell death produced by a variety of injurious ▪ Caspases become catalytically active stimuli ▪ Signals from 2 pathways: o Cell death in tumors (DNA DAMAGE) 1. Extrinsic or receptor-mediated Accumulation of misfolded proteins (ER STRESS) 2. Intrinsic or mitochondrial Cell injury in certain viral infections o Execution Phase Pathologic atrophy in duct obstruction ▪ Caspases act to cause cell death o Adaptive KUMUNOY’S IMPROPERTY 8  PATHO QUACK QUACK QUACK LECTURER: DOC TAGAYUNA, TAGAYMUNA BAGO TURO FEATURE NECROSIS APOPTOSIS Cell Size Enlarged (swelling) Reduced (shrinkage) Pyknosis, Karyorrhexis, Fragmentation into Nucleus nucleosome-size fragments Karyolysis Plasma Intact; Altered Structure; Disrupted Orientation of Lipids Membrane Cellular Enzymatic Digestion; Intact; may be released in may leak out of cell apoptotic bodies Contents Adjacent Frequent No Inflammation Often physiologic, means of Physiologic Usually Pathologic eliminating unwanted cells; may (Culmination of be pathologic after some forms or Pathologic irreversible cell injury) of cell injury, especially DNA Kapag mitochondrial, increase permeability Role damage ng outer membrane ng mitochondria tapos rerelease ng mga pro-apoptotic molecules papunta sa cytoplasm (nasa loob si NECROPTOSIS mitochondria, tapos nagpapalabas siya, edi NECROSIS + APOPTOSIS sa cytoplasm) Isang na-r’release ng It resembles apoptosis, both characterized by loss of ATP, swelling mitochondria ay cytochrome c na kapag of organelles, generation of reactive oxygen species (ROS), rinelease mo sa cytoplasm, nag-iinitiate ng release of lysosomal of reactive oxygen species (ROS), release of suicide program ng apoptosis. Tapos lysosomal enzymes, and ultimately rupture of the plasma magkakaroon ng caspase activation para membrane. magkaroon ng apoptosis. Usually nangyayari ‘to kapag lack of survival signals and Resembles necrosis morphologically, apoptosis genetically since it irradiation na mag-c’cause ng DNA damage. is a controlled form of cell death. Basta mitochondrial, intrinsic (malamang nasa o Morphologically (membrane rupture) – necrosis loob nga mitochondria). Basta apoptotic o Mechanistically (genetically programmed) – apoptosis pathway ang ending ng pathway na ‘to. Necroptosis is TRIGGERED BY LIGATION OF TNFR1 and by proteins found in DNA and RNA viruses So ayan si Fas, ‘yang dilaw FasL. Death receptor si Necroptosis is CASPASE-INDEPENDENT, NO CASPASE ACTIVATION Fas. Kapag may FasL na, bibind siya, magiging 3 or and depends on RIPK1 and RIPK3 complex. marami si Fas (kaya nga from 1, naging tatlo ‘yung RIPK1-RIPK3 signaling leads to phosphorylation of MLKL → forms receptor). Nag-f’form ‘yan ng binding site sa isang pores in plasma membrane adaptor protein, si FADD (Fas-associated death domain), kapag nakakabit na si FAS kay FADD, si Release of cellular contents evokes an inflammatory reaction as FADD b’bind sa caspase 8, tapos aactivate na. ang in necrosis. ending lang din niyan ulit ay apoptosis. Basta sa Examples: plasma membrane kapg extrinsic. o Ischemic and Hypoxic Injury Fash Fast o Ischemia-Reperfusion Injury becomes 3 Fas o Chemical Injury Mitochondrial (Intrinsic) Pathway FaFADspace ▪ Direct o Is triggered by loss of survival signals, DNA damage, and ▪ Indirect accumulation of misfolded proteins (ER STRESS) → Leakage of pro-apoptotic proteins from mitochondrial membrane into PYROPTOSIS cytoplasm and subsequent caspase activation Form of apoptosis that is accompanied by the release of FEVER- o Can be inhibited by anti-apoptotic members of BCL2 family, INDUCING CYTOKINE IL-1. which are induced by survival signals including growth factors. Inflammasome – microbial products entering infected cells are recognized by cytoplasmic innate immune receptors and Death Receptor (Extrinsic) Pathway activating this multiprotein complex. o Eliminates self-reactive lymphocytes and is a mechanism of Inflammasome ACTIVATES CASPASE-1 (Interleukin – 1 – B cell killing by cytotoxic T lymphocytes converting enzyme) I B-converting o Initiated by engagement of death receptors in the plasma membrane (members of TNF receptor family) FERROPTOSIS o Responsible ligands can be soluble or expressed on surface of IRON-DEPENDENT PATHWAY of cell death induced by lipid adjacent cells peroxidation. FERRO NA NGA, IRON ‘YAN. KUMUNOY’S IMPROPERTY 9  PATHO QUACK QUACK QUACK LECTURER: DOC TAGAYUNA, TAGAYMUNA BAGO TURO Which of the following is likely to be seen Write A if the statement is associated to A. fibrinoid necrosis in a patient with systemic lupus Write B if the statement is associated to B. KOYA AUTOIMMUNE erythematosus? Write C if the statement is associated to BOTH A and B. DISORDER ‘YAN, a. gangrenous b. fibrinoid Write D if the statement is NOT associated to A nor B. FIBRINOID AUTOMATIC! c. gangrenous d. coagulative Often physiologic B B – APOPTOSIS LANG Inflammation in necrosis is mostly A. necrosis B. apoptosis PHYSIO leakage of cellular attributed to which of the following Stimulus to inflammation in cell death A – APOPTOSIS NGA, contents circumstances? A. release of cellular contents A WALANG kaya nga a. anaerobic glycolysis B. fragmentation of cells in apoptosis INFLAMMATION nagkakaroon ng b. increase in cytosolic calcium Antioxidant mechanism B – Fenton reaction ay c. hypoxia inflammation dahil sa release ng contents A. Fenton reaction & -action oxidation ng organic d. leakage of cellular contents B. glutathione peroxidase contaminants Dissection of lung lobe sent to the Reversible injury C C BOBOTH laboratory reveals a cheesy white lesion. A. fatty change B. cellular swelling After fixing and staining, it caseous Cellular aging f microscopically appears as an A. Decreased cellular replication ~ C – sa dulo pa ‘to eh, amorphous area surrounded by a rim of necrosis B. Accumulated metabolic and genetic pero tama both fibroblasts, lymphocytes and epithelioid damage - Cheese-case cells. The diagnosis is Match the pattern of necrosis to the statements a. gangrenous b. caseous Coagulative necrosis proteolysis is blocked c. liquefactive d. coagulative a. bacterial infection Liquefactive A – liquefactive - Proteolysis in coagulative necrosis is inhibited by which of the following? intracellular b. saponification c. autoimmune patient * Fibrinad B – fat C - fibrinoid a. water influx b. hypoxia c. lipase d. intracellular acidosis acidosis d. proteolysis is blocked ↑ Gangrenous necrosis What is considered a marker of presence of active a. bacterial infection coagulative necrosis in apoptosis? caspases b. saponification the lower extremity a. absence of inflammation Necroptosis ang caspase-independent c. autoimmune patient sa mga limbs b. cytochrome C d. coagulative necrosis in the lower ‘di ba c. formation of apoptotic bodies A - necrosis extremity g d. presence of active caspases Liquefactive necrosis a. bacterial infection ~ Which of the following is consistent with necroptosis? caspase- bacterial infection b. saponification ‘Yung focal bacterial a. there is widespread peroxidation of independent c. autoimmune patient infection, liquefactive lipids d. coagulative necrosis in the lower ‘yaaan A - Ferroptosis b. caspase-independent extremity C – Pyroptosis c. interleukin I release is characteristic Enzymatic fat necrosis d. prevented by iron-chelation D - Ferroptosis Saponification a. bacterial infection Opo, sina fatty acids + Salmonella-infected macrophages b. saponification ~ activate caspase 1, which activates IL-1, Pyroptosis c. autoimmune patient calcium undergo causing cell death in the presence of saponification kaya IL-1, INFLAMMATION d. coagulative necrosis in the lower inflammation and fever. may chalky white AND FEVER, extremity a. ferroptosis b. necroptosis PYROPTOSIS Fibrinoid necrosis c. pyroptosis d. apoptosis a. bacterial infection autoimmune patient Seen in cells which are undergoing b. saponification FIBRINOID NGA apoptosis ~ NUCLEUS FRAGMENTS c. autoimmune patient AUTOIMMUNE ANG a. nucleus fragments B – NECROPTOSIS d. coagulative necrosis in the lower KULIT MO NAMAN b. plasma membrane is disrupted Y C – NECROSIS extremity D – REVERSIBLE CELL INJURY c. inflammatory cells respond Y In reversible cellular injury this/these cellular swelling it d. cells becomes swollen Y is/are observed. cellular swelling + fatty When a stimulus is removed in a setting a. cellular swelling of cell injury, the functional and Reversible b. aerobic phosphorylation is favored change; kapag denaturation, morphologic changes are restored. What c. denaturationTof intracellular proteins Restored po, bumalik sa irreversible na is this type of injury? dati, nagkabalikan, d. All of these a. permanent b. compensated maaayos natin ‘to kuno c. reversible d. None of these KUMUNOY’S IMPROPERTY 10  PATHO QUACK QUACK QUACK LECTURER: DOC TAGAYUNA, TAGAYMUNA BAGO TURO Which of the following is/are direct activation of Microscopic findings showed chromatin consequence/s of mitochondrial apoptotic pathways condensed into a solid, shrunken Pyknosis damage? Apoptosis na intrinsic pathway ‘yang basophilic mass are consistent with Karyolysis – liquefied si mito Karyorrhexis - fragmentation a. activation of apoptotic pathways B – apoptosis naman, pero siguro a. Karyolysis b. Pyknosis c. Karyorrhexis b. Cell shrinkage need pa kasi pati extrinsic pathway Pathologic apoptosis. ma-activate bago mag-shrink c. enzymatic digestion of proteins talaga? Haha ewan basta A raw ~a. accumulation of misfolded proteins accumulation of Yasi d. All C – Necrosis ‘yan b. observed in embryogenesis misfolded proteins What is the effect of defective apoptosis? increased cell survival c. apoptosis of cells that have served B, C, D – physiologic a. increased cell death rate A – Kuya cell death nga si apoptosis, their purpose defective tanong, may mamamatay b. increased cell survival pa ba? d. cell death induced by cytotoxic T-cells MAS MARAMING CELL NA NAKAKA- c. dysplastic changes SURVIVE MAPA-GOODS OR Programmed cell death where the cell Necroptosis d. All of these DEFECTIVE membrane is disrupted, and caspase is CASPASE IS NOT Ruptured cell membrane without ACTIVATED AGAD CLUE, caspase activation. Necroptosis not activated. a. necrosis b. pyroptosis NECROPTOSIS AY NECRO + WALANG CASPASE APTO a. Necrosis b. Necroptosis ACTIVATION, CASPASE c. apoptosis ~d. necroptosis c. Apoptosis d. none of these INDEPENDENT Which of the following statement reversible injury In the process of apoptosis what is indicates failure of adaptation to a transient pa naman typically expected to happen to the None of these transient injurious stimulus? IR-sevent daw, mild na transient nuclei? -a. reversible injury b. necrosis reversible; severe, Hoy necrosis ‘yang a. Karyorrhexis b. Karyopyknosis mga ‘yan c. homeostasis d. apoptosis progressive irreversible c. Karyolysis d. none of these Y Which is/are of reversible hallmark/s of Cellular swelling and fatty change are reversible injury? cellular swelling seen in which of the following Reversible a. apoptosis APOPTOSIS AY CELL conditions? b. cellular swelling ~ DEATH NA BALIW a. Irreversible injury b. Reversible injury injury c. increased oxidative phosphorylation c. Necrosis d. Apoptosis d. All of these In cell injury denaturation of intracellular Which of the following statements best Necrosis the membranes are - proteins and enzymatic digestion of the explains why inflammation is usually lethally injured cell pertain to which of present in necrosis? disrupted releasing the Basta may denaturation of the following? a. the swelling of the cell in necrosis cellular contents proteins and enzymatic ~a. Necrosis b. Metaplasia exposes receptors for the neutrophils LAGING LEAKAGE NG digestion, necrosis na ~ b. the membranes are disrupted CELLULAR CONTENTS c. Apoptosis d. Hydrophobic change DAHILAN KAYA MAY releasing the cellular contents What type of necrosis is typically ischemis observed in infarct? Coagulative - c. the cells are fragment resulting into the INFLAMMATION SA NECROSIS, OKAY??? lower chey white lasio Ischemia si coagulative a. Gangrenous b. Caseation release of inflammatory mediators bauterist ‘di ba c. Liquefaction ~ d. Coagulative Why is the architecture of dead tissues Which of the lesions is composed of preserved in coagulative necrosis? proteolysis is antigen-antibody complex? a. digestion of the dead parenchymal a. Enzymatic fact necrosis Fibrinoid necrosis cells blocked Ag-Ab complex, ~ b. proteolysis is blocked WALA PONG PROTEOLYSIS, -b. Fibrinoid necrosis immuneeee WALANG SUMISIRA KAYA c. Granuloma c. affected tissues usually have firm WALANG NASISIRA, KAYA d. Coagulation necrosis texture OKAY PA SILA Which best explains why the architecture d. inflammation does not ensue of dead tissues is preserved in Proteolysis is blocked Which pertains to the point of -no return in Inability to reverse coagulative necrosis? due to denaturation of cell injury? mitochondrial damage P a. Proteolysis is blocked due to proteases and a. increase in extracellular calcium Si failure of Na-K pump, cellular swelling ‘yan, reversible pa. Si denaturation of proteases and structural structural proteins b. failure of Na-K pump increase extra calcium, anong proteins Blocked proteolysis ~c. inability to reverse mitochondrial injury niyan? b. Because intracellular contents remain dahilan, meaning walang damage sumisira sa proteins, kaya inside the cell Which is likely to be seen in a pulmonary Cheese-like area ang architecture or c. Bacterial infection usually leads to this TB lesion? Barterial-Liquefo structure ng tissues, - of necrosis form of necrosis oks pa rin a. Creamy white necrosis Lol Chalky white – fat d. Due to free radicals present in b. Yellowish pus at the center of the Yellow – liquefactive reperfusion injury lesion Y Creamy white – c. Cheese-like area of necrosisit caramel great taste lol O d. Chalky-white deposits fat Calcium KUMUNOY’S IMPROPERTY 11 Ect Enzymatio  PATHO QUACK QUACK QUACK LECTURER: DOC TAGAYUNA, TAGAYMUNA BAGO TURO Enzymatic fat necrosis is typically seen in ATP PRODUCTION which of the following conditions? Oxidative phosphorylation of adenosine diphosphate Acute o a. Acute cholecystitis o Glycolytic pathway in the absence of oxygen b. Acute perotinitis Tissues with a greater glycolytic capacity survive loss of O2 and pancreatitis c. Acute pancreatitis decreased oxidative phosphorylation better than tissues with d. Acute fasciitis limited capacity for glycolysis Tuberculous lesions are most likely to Effects of ATP depletion to Full > c. granule release d. platelet adhesion - - to Fibrin ↳ Fibrinogen Thrombin cleaves circulating fibrinogen into insoluble fibrin, secondary hemostasis creating a fibrin meshwork, and also is 1st si vasocons, 2nd si a potent activator of platelets, leading primary, 3rd si to additional platelet aggregation at secondary, 4th si clot, the site of injury. This sequence is referred to as sundan niyo lang. a. clot stabilization and resorption4 Madali lang ‘to if alam b. secondary hemostasis 3 niyo c. arteriolar vascoconstriction 1 The next step is clot stabilization and resorption. d. primary hemostasis 2 The Fibrin and platelet aggregates undergo contraction. In the phase of secondary hemostasis, fibrin They form a solid permanent plug ➔ preventing the stabilization of the clot is expected. Which among the choices polymerization hemorrhage. Fibrinolysis refers to this step. Stabilize, eh si thrombin Counter Regulatory mechanism like t-Pa which now lyses activation cl’cleave pa a. thrombin activation the cloth. Fiban b. fibrin polymerization lang si fibrinogen to fibrin, Thrombomodulin will block coagulation cascade. c. phospholipid complex expression hindi pa stabilize lol Normal endothelial cells express anti-coagulant factors ➔ d. secretion of tissue factor inhibits platelet aggregation and coagulant -> promotes In secondary hemostasis, the endpoint creating fibrin meshwork T-pAfibrinolysis and releases procoagulant activities. Thrombomodelin a. vasoconstriction platelet plug formation Procoagulant vs anticoagulant: balance changes based b. platelet aggregation ang endpoint ni primary c. activation of clotting factors on need for clot formation or clot lysis hemostasis d. creating fibrin meshwork Endothelium can be activated by microbial pathogens, AKO LANG BA OR BAKIT PARANG ANDALI NG TANONG NIYA RITO, hemodynamic forces and pro-inflammatory mediators. TAPOS SAMPLEX PA, NAGBUBURA AKO TANONG KUMUNOY’S IMPROPERTY 8  PATHOLONG, PATHOLOGIN NIYO AKO MGA 1 SEM HEMODYNAMIC, THROMBOBO, GULAT LECTURER: DOC ESGUERRA, SAMPLEX PO O GERA? MAMILI KA DOC TY PO Which of the following is the process Normal endothelium shield by which blood clots form at sites of coagulation from tissue factor in vascular injury? Hemostasis vessel walls and expresses factors ina a. Embolism b. Hyperemia actively opposing coagulation c. Congestion d. Hemostasis Heparin like molecules: cofactors Which of the following are disc- shaped anucleate cell fragments that that interact with antithrombin 3 to are shed from megakaryocytes in the bone marrow into the bloodstream? Platelets inactivate thrombin, factor Xa & other coagulation factors commen a a. Stem cells b. Red blood cells Thrombomodulin: binds to thrombin c. Platelets d. White blood cells ANTICOAGULANT converting it from a procoagulant In primary hemostasis, the platelets EFFECTS w/c can activate protein C which bind via this receptor to vWF on inhibits clotting by proteolytic exposed extracellular matrix and are glycoprotein Ib HEPARIN AT cleavage of Va and Factor VIIIa activated THROMBOMODULIN a. endothelin b. glycoprotein IIbIIIa Heparin like molecules suppress TANDAAN NIYO. c. ADP d. glycoprotein Ib formation of fibrin, they oppose Hemorrhages that measure more Ecchymoses HEPANTITHROMBIN 3 coagulation when no longer than 1 cm Can be small like needed. Bound thrombin loses its ANTIPLATELET ‘YON ability activate because of a. Purpura b. Ecchymoses petechiae/ purpura or big SINA PGI2, NO, ADP. c. Petechia d. Hematoma like ecchymosis (1-2 cm) MAY MGA TANONG SA Thrombomodulin. SAMPS NA WHICH OF Thrombin can't activate THE FF IS NOT AN coagulation factor and platelets. ANTICOAG OR Endothelium Instead they would cleave to ANTIPLATELET AH Balance between ANTICOAGULANT AND PROCOAGULANT Protein C & S, vitamin K dependent ACTIVITIES OF ENDOTHELIUM determines whether clot protease (requires co-factor). formation, propagation, or dissolution occurs Protein C & S are coagulation Endothelial cells maintain an environment conducive to inhibitors. blood flow Endothelium is also a source of protein S and tissue factor pathway ANTITHROMBOTIC PROPERTIES inhibitor Endothelium serve as barrier that TPA-cleares plasminroger Cell surface protein that directly plasmin inhibits tissue factor VIIA and Xa PLATELET shields platelets from subendothelial > - ↳Cares Fibrir vWF and collagen activities Ebain-degrade thrombin INHIBITORY PGI2, NO, ADP – inhibit platelet FIBRINOLYTIC t-PA cleaves plasminogen to form activation and aggregation EFFECTS PLASMIN which cleaves FIBRIN to EFFECTS PGI2 (Prostacyclin) – produced by degrade thrombi Cyclooxygenase 1 Rineregulate ng TRUE OR FALSE: Hyperemia is an katawan mo na hindi magkaroon ng platelet NO (Nitric Oxide) – product of endothelial nitric oxide synthase erros active process and is often seen True aggregation kung Non-activated platelets do not grossly as erythematous Hyperactive, PassCon hindi naman kailangan, adhere to the endothelium appearance of tissues. lalo na kung ‘di sila Activated platelets are inhibited In secondary hemostasis, the activated. Tsaka kung activated man sila, form the binding to uninjured endpoint expected is which of the hindi sila mag-b’bind sa endothelium following? Fibrin entanglement hindi naman injured Express ADPase - degrades ADP & a. Fibrin entanglement in kasi blood clot lang in between the ‘yan na mag-l’lead sa contributes to inhibition of platelet between the platelets 3 b. Lysis of clot 4 platelets disorder aggregation c. Vasoconstriction 1 d. Formation of platelet plug 2 KUMUNOY’S IMPROPERTY 9  PATHOLONG, PATHOLOGIN NIYO AKO MGA 1 SEM HEMODYNAMIC, THROMBOBO, GULAT LECTURER: DOC ESGUERRA, SAMPLEX PO O GERA? MAMILI KA DOC TY PO False aspirit T/F: Heparin is a drug that inhibits Platelets cyclooxygenase, a enzyme that is required for platelet False Play a critical role in hemostasis by forming the primary hemostatic plug ASPIRIN!!!!!! o typically disc-shaped, they undergo conformational thromboxane A2 synthesis. change as they adhere to the endothelium glat PSA T/F: The balance between the o derived from megakaryocytes from the bone marrow , spikey Trueantithrombic and prothrombotic TRUE Two types of granules: activities of endothelium o Alpha granules determines whether thrombus ▪ express P-selectin (adhesion molecule) formation, propagation, or ▪ contains fibrinogen, fibronectin, factor V & VIII, PF-4, dissolution occur. PDGF, & TGF-beta Platelets bind via which receptor o Gamma Granules (Dense Bodies) to von Willebrand factor? a. GpIb b. GpIIa-IIIb GpIb ▪ ADP (promotes aggregation) & ATP, ionized calcium, histamine, serotonin, & epinephrine c. GpIa d. GpIIb-IIIa Which of the following mediators Formation of a Platelet Plug AS GRA does not exert an anti-platelet 1. Platelet adhesion effects that maintain an Thrombomodulin a. platelets adhere to the endothelium via the protein von environment conducive to blood Silang tatlong una lang Willebrand factor, and this is mediated by the platelet flow. ang antiplatelet surface receptor GpIb. Pol a. ADPase b. prostacyclin i. DEFICIENCY is called von Willebrand disease & c. nitric oxide d. thrombomodulin Bernard-Soulier syndrome, respectively No BSS "Giant Platelety" 2. Conformational Change Endothelium Procoagulant Properties a. After adhesion, platelets undergo conformational Production of vWF - essential cofactor for platelet binding change. Disc-shaped to a “spiky” appearance. to collagen & other surfaces b. Accompanied by conformational changes on cell o deficiency of vwF can cause primary hemostasis surface glycoproteins GpIIb-IIIa. Ap2b-39 Complex disease called von WIllebrand Disease VWD i. increases affinity to fibrinogen o Patient has small bleeds in skin/mucosal membrane c. (-)-charged particles, specifically phosphatidylserine, seen as petechiae, small 1-2 mm hemorrhages or are translocated to the platelet surface—binds calcium. purpura (3 mm or more) i. serve as nucleation sites for the assembly of o mucosal and skin capillaries are prone to rupture coagulation factor complexes following minor trauma which is normally sealed by the platelets 3. Granule release (secretion) nosebleeding o Mucosal bleeding without vWF can also cause epistaxis, a. often referred to as platelet activation, along with the GI bleeding or menorrhagia (excessive menstruation) conformational change. b. triggered by a number of factors, including thrombin and Procoagulant effects - induced by endotoxins or cytokines ADP (TNF, IL-1) to synthesize tissue factor leading to extrinsic c. Thrombin activates platelets via the g-protein coupled cascade clotting activation receptor: proteases activated receptor (PAR1) o For a coagulation factor defect (e.g. no thrombin or 4. Recruitment factor V)the manifestation would be bleeding into soft a. ADP acts by binding two g-protein coupled receptors: tissue muscles or joints ➔ hemarthrosis. It is 12 P2Y1 & P2Y12. Payl Pay characteristic of hemophilia b. Thromboxane A2 is produced by activated platelets, o Hematoma: a palpable mass of blood and induces aggregation. c. Aspirin inhibits platelet recruitment and aggregation by Antifibrinolytic effects - inhibitors of plasminogen activator inhibiting cyclooxygenase—an enzyme required to (PAIs) produce Thromboxane A2. KUMUNOY’S IMPROPERTY 10  PATHOLONG, PATHOLOGIN NIYO AKO MGA 1 SEM HEMODYNAMIC, THROMBOBO, GULAT LECTURER: DOC ESGUERRA, SAMPLEX PO O GERA? MAMILI KA DOC TY PO 5. Aggregation Coagulation Cascade a. RECEPTOR: GpIIb-IIIa. Conversion of inactive proenzymes into activated enzymes i. deficiency is called Glanzmann thrombasthenia. leads to formation of Thrombin, which converts fibrinogen to b. Prior conformational change of receptor, allows binding fibrin. of receptor to fibrinogen—forms bridges between Each reaction in the pathway is an assembly of the ff: ESL adjacent platelets, leading to aggregation. (reversible o Enzyme (activated coagulation factor) step) o Substrate (proenzyme form of coagulation factor) c. Thrombin converts fibrinogen into insoluble fibrin. o Cofactor (reaction accelerator) (irreversible step) Components are typically assembled on a phospholipid i. cements and stabilizes the platelets in place. complex, and are held together by calcium ions. ii. promoting platelet contraction, dependent on o binds to carboxylated glutamic acid residues present in cytoskeleton. Factors II, VII, IX, & X 2, E , 9 10 Vit-K , WBCs adhere to platelets via P-selectin and to endothelium via adhesion receptors Thrombin directly stimulates neutrophil and monocyte adhesion & generates chemotactic fibrin split products from the cleavage of fibrinogen. FSP Von Willebrand disease – malamang walang vWF Bernard-Soulier syndrome – GP1b deficiency bbbernard Glanzmann thrombasthenia – GpIIB-IIIa complex deficiency (2mbas3nia) MADALAS ITANONG SA SAMPLEX ‘YUNG TATLO. Para kasi magkaroon ng platelet