Team CELL INJURY Insight of Cell Injury ‘© The most common cause of cel injury is Hypoxia ‘© Themost common cause of Hypoxia is ischemia ‘© Themost sensitivecell to Hypoxia isthe brain/neurons. ‘© Themostresistant cell to Hypoxiaisa fibroblast. Cellinjury Injury 4 Adaptation [ails Reversible cell injury {injury continues Irreversible (cell death) cell injury ‘Types of Cell Injury ‘ona3a8 ‘There are two types of cell injury 1, Reversible Cell Injury 2. Imreversible Cell Injury Reversible Cell Injury onset ‘Mitochondrial Dysfunction occurs causing the decrease in ATP production, ‘The process of ATP failure includes: 1, Failure of Na’ K"ATPase Pump NORMAL FAILURE /REVERSAL 3Na! CELLULAR HO. ‘SWELLING! INFLUX HYDROPIC a weg CHANGE Pr FRsT MORPHOLOGICAL Nokia CHANGE In cELINIURY © There is 120 influ. © Itisreferred toas Hydropie Change, # Thisisresponsible for the following: © Cellularswelling © Endoplasmic reticulumswelling © Flattening ofthe microvilli ‘© Formation of cytoplasmic blebs Telegram : © GlobalNet www. Distia.co © Formation of Myelin Figures, also called Concentric Lamellation —>+ Composition: Phospholipids (primarily) and Ca! 2, Anaerobic Glysolysis: ‘© ThepH will become acidic, causing the nuclear chromatin to clump. 3; Decrease in Protein Synthesis The ribosome detachment is seen, leading to a decrease in protein synthesis, © This isalso associated with fatty change Irreversible Cell Injury nana The two defining moments of reversible cell injury are: 1, Severe Membrane Damage: The inflow of calcium occurs causes the activation of three enzymes: a. Phospholipase b. Protease ©. Nuclease 2. Severe Mitochondrial Damage: The calcium sits on the ‘mitochondria causing Amorphous Flocculent Densities & Important Information Myelin Figures: © Myelin Figures arealsocalled concentric lamellation. ‘© Myelin figuresare seen in reversibleas wellas ireversible cell injuries. ‘More Myelin figures are seen in irreversible cell injury 1 @teamglobalchatNuclear Changes in the Cell Inju The three stages of nuclear changes in cell injury are: ‘© Pyknosis: The nucleus becomes small and dark due to the nuclear chromatin edit = condensation ‘+ Karyorrhexis: There will be Nuclear Fragmentation, ‘© Karyolysis: The nucleus gets dissolved. Cell (acess) ucuBaie CHANGES NORMAL PYKNOSIS — KARVORRHBAS KARVONSSS eat Nc Scie enn framatin Pscrtaon vitae ©) (eo) ( Prins KK Norma Nucleus Kaxyortexis Karyohsis Death-Necrosis, onasia Definition eu -u Pathological Cell Death, is associated with inflammation Microscopie Examination oh appears pink (Eosinophilic) ‘© Amorphous © Inflammation ‘Types of Necrosis 1. Coagulative Necrosis: Itisthe most commonly occurring Necrosis. ‘There is denaturation of the proteins. Mtoceursin the solid organs (kidney, liver, heart) Occurrence of infarct (Wedge shaped structures) in the organs. Leading tothe formation of multiple ghost cells, causing a Tombstone Appearance. ‘The tissue architecture is preserved even after the death of thecells. © Team GlobalNet www. Distia.co EE important information Ghost Cells: ‘© Ghost cells are associated with coagulative Necrosis, © Occurs onaskin-generated tumor, Pilomatrixoma, ‘The row of Tombstone appears in the Pemphigus (Pemphigus Vulgaris) 2. Liquetactive Necrosi © Itmostly occurs in CNS and Panereas. © This occurs because they ar rich in Hydrolytic Enzymes. © Mtisals called Colliquative Necrosis. © Thetissue architecture is not preserved. 3. Caseous Necrosis: Associated withthe high lipid content inthe cel walls. ‘Thereis cheese-like appearance of he organs. It is the combination of Coagulative Necrosis and Liquefactive Necross Most common examples include tuberculosis, fungal infection (histoplasmosis; coccidioidomycosisis), syphilis, et Fat Necrosis: © Ttoccurs inthe fat-rich organs e.g, breasts; omentum, ete 6 Iteauses the breakdown of fas into fatty acids. © AChalky White appearance is seen. (© Italso occurs around the pancreas due to the presence of peripancreatic fat. Fat Fat cally Write (cas) Telegram : @teamglobalchatoid Necrosis: ‘© Associated with the antigen-antibody reactions (immune complex deposition). © Someexamplesare: > Polyartertis Nodosa (PAN) > Rheumatic Heart Disease (RHD) > SLE > Malignant Hypertension (HTN) 6. Gangrene: (©. Blackish discoloration of the organs. © Foulsmelting. (©. Dry gangrene is classified as Coagulative Necrosis with a line of demarcation. © Wet gangrene is classified as Liquefactive Necrosis without any line of demarcation, 7. Zenker's Degeneration: © Itisatype of Coagulative Necrosis © Itoccursiintyphoid or Enteric fever, © Itisa complication seen inthe skeletal muscles > Rectus Abdominis ~> Diaphragmatic Muscle McQ: Q. Myelin figures are derived from? @. Cytoplasm b. Nucleus . CellMembrane Ribosomes Q.A 61-YEAR-OLD female patient presents with left-sided chest pain radiating to the left arm and jaw. The patient explains that the pain has inereased severely over the past 40, ‘minutes. She is immediately rushed to the hospital. Cardiae enzymes are elevated, The patient was admitted and started ‘on thrombolytic therapy. However, on the fifth day of observation, she suddenly collapses and dies. Which of the following Necrosis are you most likely to find in the heart of this patient? © Team GlobalNet www. Distia.co a, Liquefactive Necrosis b. Congulative Necrosis ©. FatNecrosis 4. Fibrinoid Necrosis Q. A45-year-old female patient complained of being hit in the chest by a football while passing by a garden 4 weeks back Initially, her left breast was tender and swollen. But over the weeks, the tenderness has subsided. However, she now notices a lump in the peri-areolar region which is firm tohard, in consistency. Radiological investigations reveal calcific deposits. Which of the following best describes the phenomenonabove? Liquefaetivenecrosis Coagulativenecrosis Fatnecros Fibrinoidnecrosis Cell Death—Apoptosis, Definition: Apoptosis isagreck word that means "falling off." tisboth physiological as wel aspathological cell death Mitochondria play a pivotal role in apoptosis. It is @ programmed cell-death, now known as Caspase Depetident Programmied Cell Death, oxouas ATP Usage: # There willbe the usage of ATP. # Oveutsas anActive Process Jnflammation: * Noinflammation will occur. Examples of Apoptosis + Physiological Apoptosis (© Onganogenesis (Embryogenesis), For example, fingers and hand formation (© Neutrophils Clearance (© Endometrial Shedding + Pathological Apoptosis © Councilman Bodies, seen in viral Hepatitis (Hepatitis C- Virus) © Civatte/Colloid’ Cytoid Bodies, seen in Lichen Planus. €& important information ‘Chemotherapy: ‘© Itcausescancer cell death, ‘* Itsacombination of Apoptosis (80%) and Necrosis(20%). Telegram : @teamglobalchatCaspase ‘= Ttconsistsof Cysteine Residue. ‘+ Itbreaks after aspartic acid residues. © ItisanEnzyme. Mechanism of Apoptosis ‘The mechanism is classified into two processes. 1. Initiation 11 is dependent on Caspase 8, 9, and 10, There are two pathways toapoptosis initiation, a. Extrinsic Pathway: Ithappens on the surface of the cell. ‘The cell wanting to die will have CD9S / Fas, and the supporting T cell will have CD95 Ligand / Fas Ligand, i. I leads to the occurrence of Trimerisation of CD9S/ Fas iv. The Fas Associated Death Domain (FADD) will activate Procaspase 8, 10 into Caspase 8,10. . The process is inhibited by FLIP (anti-apoptotic molecule) vi. Itisalso called Death receptor pathway. b, Intrinsic Pathway i. Itisalso called Mitochondrial Pathway Ithappens within the cel. i, toccurs whenthe cells undergo stress. iv. The stress is detected by the stess sensors: BIM, BID, BAD, NOXAand PUMA. ¥. The sensor increases the pro-apoptotic factor and decreases the anti-apoptotic factors, vi. The Apoptosome activates Procaspase 9 into Caspase 9 ‘@) PivOTOL ROLE OF APOPTOSIS ‘saci DIABLO (wheet tke PQ « hexamer mn ‘APOPTOSOME 7 apoptosis Apaf 1 sctivating Factor Proc © ps3 © BCI? * BAC * MCIL + BAX © BCIXL. © BCLXS Team GlobalNet www. Distia.co © 2. Execution: ‘© Ioceursafter the Initiation process, ‘= Itisdependenton Caspase3,6,and 7. ‘© Itactivatesthree enzymes: © Phospholipase © Protease E& Important Information Endonuclease: ‘© Itbreaks the DNA after 180-200 bp ‘© Itis called Internucleosomal Cleavage Once the execution takes place, the cell falls off into small bodies called apoptotic bodies. These apoptotic bodies give an "Eat me" signal lo Macrophages, causing Phagocytosis. Efferocytosis ons ‘© The apoptotic bodies giving the eat-me signals, expressed in the form of Clq, Thrombospondin, and PS (Phosphatidyl Serine) ‘+ In the normal cell, the Phosphatidyl Serine is present in the inner leaflet, but in the apoptotic cell, the Phosphatidyl Serine comes out ‘There is Phosphatidyl Serine Flipping, ‘© Theflipping is known as the signal given tothe Macrophage. Onemajordefect of fipping is Scott Syndrome. ‘+ The Macrophage engulfs the apoptotic bodies, which is called Efferoeytosis. Defeets in Efferosome SLE copp Bronehiectasis Cystic fibrosis & Important Information Survival of Cancer ells: Cancer cells express CD47 to Macrophages. ‘© C47 isa"Do not Eat me" Signal. Update Robbins 10c- oiass ‘+ Proapoptotic molecules [BAC, BAX, BCLXS]: BH 1-3 ‘© Anti-apoptotic molecules [BCL2, MCL, BCLXL]:BH 1-4 ‘* Stress sensors (BIM, BID, BAD, NOXA, PUMA]: BH 3 only ‘+ SMAC/DIABLO : Proapoptotie ‘© Glucocorticoids: Proapoptotie '* Sex Steroids: Antiapoptotic 4 Telegram : @teamglobalchatTeam GlobalNet Q www. Distia.co 1 Meter Aman ater Pig) "| EB? Amportant Information ‘+ Molecular Marker: CD9S/ Fas caer ‘+ Microscopic Examination: Nuclear Chromatin ‘+ Smearingis seenonly in Necrosis. Condensation. (The cytoplasm willbe pink and Nucleus will | « Step Ladderisseen both in Apopiosis and Necrosis. be blue, long withcellularshrinkage) ‘© Stain: Tunel Stain (TdT dUTPNick End Labelling) © Positive: Apoptosis, © Negative: Necrosis © GelEleetrophoresis: Step Ladder Apoptosis 5 + Telegram : @teamglobalchat2 PREVIOUS YEAR QUESTIONS (Q. Whatis the first changein the cell injury? Mitochondrial Dysfunction Q. Whichisthe first morphological change inthe cell injury? The cellular swelling or Hydropic Change. Q. Whatis the composition of Myelin Figures? Primarily made up of phospholipids and a minor presence of calcium, Q. What is the composition of Amorphous Flocculent Densities? Caleium, Q. The injury with which the Amorphous Flocculent Densities areassociated? Ineversible Cell Injury. Q. The three stages of nuclearchange inthe cel injury? Pyknosis Karyorthexis Karyolysis © Team GlobalNet www. Distia.co 6 ‘Whatis the most common type of Necrosis? Coagulative Necrosis Which are the most common organs affected by Coagulative Necrosis? Heart ‘Which necrosis happens inside the pancreas? Liquefaetive Necrosis Which necrosis happens around the pancreas? Fat Necrosis ). Zenker’s Degeneration be seentin which skeletal muscles? Reetus Abdominis Diaphragmatic Muscle Telegram : @teamglobalchatTeam © GlobalNet www. Distia.co > I jp 2__| NEWER CELL DEATHS Newer Cell Deaths + Necroptosis ‘© Pyroptosis © Ferroptosis © Anoikis Necroptosis Necrosis + Apoptosis makes Necroplosis Definition: Caspase independent programmed cell death Necrosis. ‘© Morphology © Inflammation Apoptosis ‘© Programmed cell death ‘Necroptosis: ‘© Physiological © Growth Plate Formation in Human Body ‘= Pathological © Steatohepati © Pancreatitis © Reperfusion Injury (MI) s(faty Fiver) Updates: Robbins 10th Edition ‘© Programmed Necrosis (New terminology fo necroptosis) cmv ‘© Itdoes not undergo apoptosis due fo the presence of caspase inhibitors. ‘© Itundergoesnecroptosi (caspase independent) Mechanism of Necroptosis = 123death © Step 1: TNF comesandbindto TNF receptor © Step 2: due to binding trio oceurs -RIPK 1, RIPK 3 (RECEPTOR INTERACTING PROTEIN KINASE,) PROCASPASES © Step 3: MLKL phosphorylation which results in Cell Death Pyroptosis Pyromeans Fever +tosismeanscell death, 4 Associated with microorganisms. Examples: ‘© Initially studied for Shigetla and salmonella Telegram : Bactes enters thebody Binds toNOD Receptors (gest activated) 4 Inflammasomes 1 activates CASPASE I—vactivates IL-1» fever ‘ =f canton i Amik ‘Type of apoptosis- why isitdifferent? ‘© Lack ofnatural environment © Example: 6 Cells keptin an unnatural! environment celldies. Choose the iieorrect statement about Necroptosis ? Isitacaspaseindependent cell death RIP1&3 is formed Caspase is required Growthplate formation follow neeroptosis arse ‘Choose the incorrect statement about pyroptosis ? Seen in response to shigella ) TLRisused Caspase 1 isrequited ILL activated ee eFO Cell Injury-Cellular Adaptations «Hypertrophy Hyperplasia Atrophy Metaplasia Dysplasia-PRECANCER, Healthy cll Hyearvaphy Hyperplasia feat @teamglobalchatHypertrophy + When te size of cells is inereasing but the number remains Hyperplasia ‘¢ Number of cells increases, size remains same Differentiation between Hypertrophy and Hyperplasia ene Pee Basic Difference Increase in Size of cells Increase the number of eells Mechanism Increase in -Transcription Happens by Factors division/mitosis *GATAS Increases the number of © NFAT cells * MEF 2 Are being elevated. * More RNA. © More Protein Henee the size increases, *DNA —___ RNA Tamra = Protein ‘Common Examplesare: ‘Common examples of hypertrophy and hyperplasia are 1. Gravid uterus shows hypertrophy (more commonly) as well, ashyperplasia, 2. Breast development during puberty and pregnancy shows both hypertrophy as wellas hyperplasia more commonly) Examples of Hypertrophy (only) 1, Bodybuilders - Skeletal Muscle Hypertrophy 2. Obstruction Proximalto Obstruction Q. How will the body adapt to obstruction?” Answer: The body is going to adapt to hypertrophy. Example: Aortic stenosis lel ventricular hypertrophy Examples of Hyperplasia (only condition) For Females ‘© Endometrial Hyperplasia > Increased Estrogen is responsible. Q.Name one condition whereestrogen increases? Ovarian Tumors -Granulosa Cell Tumor Produces estrogen —> it will cause endometrial hyperplasia + Riskof Endometrial cancertype 1 © Team GlobalNet www. Distia.co 8 ForMales © BENIGN PROSTATICHYPERPLASIA © Now called Nodular Hyperplasia of the Prostate © Testosterone DHT ~ Dihydrotestosterone Salers (retaholite) hyperplasia F inhibits steride Atrophy © Cellsize decreases © Cellnumberdecreases Mechanism faction UPP-UBIQUITINPROTEASOME PATHWAY Examples: © Disuse Atrophy ~ Fracture — cast for six weeks —+ muscle atrophy © DenervationAtrophy © Polio ‘Ischemic Atrophy © Senile» Alzheimer's Disease © Malnutrition © Endometrial atrophy o Lessofesirogen More estrogen —> Less estrogen —rendometrial endometrial hyperplasia atrophy © Endometrial Cancer» Endometrial Cancer Type 2 Type} # Worst prognosis Metaplasia Alllcellular adaptations are Reversible. Toughest o revertis Atrophy. Q.Whatmetaplasiais © 100%reversible © Onetissue = another tissue © Epithelial = epithelial (© Mescnchymal = mesenchymal Mechanism of action + Reprogramming ofthe Stem Cells Examples: © Epithelial epithelial Most common metaplasi 1) Squamous metaplasia -most common condition Pseudostratified ciliated columnar epithelium Chronic Smoker ‘Vitamin A (deficiency/excess) squamous (end result) epithelium Telegram : @teamglobalchat2) Barrett's Esophagus - Precancerous adenocarcinoma of the esophagus (cancer) Squamous epithelium —> intestinal columnar epithelium Cons goblet cls L Acidic mucin Aleian blue positive (special stan) Q. Hallmark of Barrett Esophagus. © Gobletcells, Q. Where do yousee Mesenchymal metaplasia ‘© Myositis(muscle) +ossificans(caleium/bone) ‘© Muscle changes to bone—voccurs due to trauma, Breast is one such organ where all he adaptation happens. ‘© In Puberty & Pregnancy Hypertrophy and Hyperplasia both occurs, M/C is hyperplasia, ‘© Atrophy occurs in postmenopausal occurs —+oldage ladies © Metaplasia~ ‘© Squamous Metaplasia ofthe lactferous Ducts (SMOLD) © Mostcommonly seenin chronic smokers female © Team GlobalNet www. Distia.co McQs event Q. Allaretrue formetaplasia except? Slow growth, Reversible with treatment Irreversible Canbe precancerous eeee e Histopathological difference between Barret’s epithelium and gastric mucosa? Barrett's mucosa is acidic and stains alcian blue positive Barret’sisalkaline and stains prussian blue positive Barrett’salcian blue negative because its neutral Gastric mucosa is alkaline and stainsaleian blue positive ese 2 ‘A47-year old man visits an outpatient elinie with complaints of heartbur and chest pain forthe past 6 months. His pain is retrostemal and was initially only associated with intake of solid foods, but it now oceurs with liquid as well. Antacids dont relieve his pain anymore. He is worried about the pain as it is getting Worse-physical examination including abdominal examinations normal. Hehas ost2.7kg(61bs). Laboratoryinvestigation reveals.: Hgb- 10 gm Platelet count-168* 10.911. Esophagogastroduodenoscopy reveals an exophytic mass in the lower third of the esophagus. Which of the followings the most likely diagnosis in the patient? a, Squanious Cell Carcinoma b, Leiomyoma , GastricUleers 4. Adenocarcinoma Telegram : @teamglobalchatTeam GlobalNet www. Distia.co OS ae © a *) CROSS WORD PUZZLES @ aS Crossword Puzzle Across 3._ Initially studied for Shigella andsalmonetla 4, Allcellular adaptations are REVERSIBLE. Down 1. When the size of cels is increasing but the number remains 2, Number ofcells increases sizeremains same a TTTT) Fale ay Jala] C1 10 + Telegram : @teamglobalchatTeam GlobalNet Q www. Distia.co INTRACELLULAR ACCUMULATIONS @ $3] rent + Thebluish colorstainis knownas the Sehmor! sta, Melanin onaoss ‘© Present in, skin, hair & eyes ‘© Inthe brain, melanin ispresentin the substantia nigra, (> Important Information ‘© InParkinson’s disease, there isa decrease in dopaminergic neurons, which causes a decrease in dopamine and ‘melanin, causing the appearance of a pale substantia nigra, ‘Melanin Stain ‘+ Inthe skin, there is brownish stain around the basale layer, which iscalled stratum basale ‘© The best stain that we have for melanins the Dopa Oxidase, Kisalso known as the enzyme histochemical stain. ‘© Immunohistochemistry - HMB 45 and 100, Hemosiderin: 20 ‘© The blackish color image representation of the melanin stain isknownas the Masson Fontana Silver stain, + Itconsists ofany existence of hemorthageor hematoma. + Yellow. Brown, efactle Shiny) + Pec'sstainor Prussian Bue stzincan be seen. © Itconssts of Fe3+ ‘In the case of any iron overload, Hemosiderin will be appearing, (3 Important Information © Lillie's stain will done forFe2+ 1 Telegram : @teamglobalchat ~nano Iisalso defined as wear and tear pigment: © Senile Atrophy © Brownatrophy telltale sign offre radical injury (moreinold age) Ifa free radical injury increases, lipofuscin will increase because free radicals do lipid peroxidation, which causes the formation of Tipofuscin, As it is present around the nucleus, it is also called perinuclear, Q.Whatarethe special stains? Oiled O, ZN stain (Acid Fast) Certain criteria regarding pigments: ‘= Copper: ‘© Increased copper will cause Wilson's disease. ‘© The special stain that is related to copper is Rhodanine ‘and Rubeanic acid. (© However, Rhodamine is related to mycobacterium TB (fluorescent) (©. The copper-associated protein is ceruloplasmin. Orcein sain is related to ceruloplasmin, It is the stain for the HBsAgand Elastin. * Hematin: ©. Italso shows Hamazoin, whieh comes up in the disease of malaria, ‘© Anthracotie pigment: (© This pigment consists of carbon, (© Therefore, individuals that smoke a lot show these varieties of pigment. 12 © Team GlobalNet www. Distia.co © Homogentisicacid: © Itis also a black-colored pigment that gets deposited in the disease of ATkaptonuria, Lipids: ‘© The most common organ where the fat wll get deposited is the fatty liver/steatosis, © When the fat gets deposited inthe heat, itis called the tigered effector tabby cat. + Some conditions forthe deposition of fat in the heart are: © Cellinjury 0 ARVCM (Arthythmogenieright ventricular cardiomyopathy) Diphtherial Myocarditis Inthe case of atherosclerosis, some empty spaces can be seen in the image. These empty spaces are called cholesterol clefts, InH&E stain: © Due to the processing with alcohol, the fat is washed off, Which causes the formation of Cholesterol Cleft ‘+ The tiny yellow color dots are called Cholesterolosis of the ‘gallbladder. Itis also called the strawberry gallbladder. © Italso shows foamy macrophages. ‘© Therefore, the representation where md has engulfed all the cholesterol, Telegram : @teamglobalchatThe red color stain iscalled the i red The black color stainis called Sudan Black B ‘The orange colorstainis called Sudan 4. One ofthe otherstains is knownas the osmium tetroxide, Cryostat or frozen section machine. This machine is used for the identification ofthe il red O. Protein: ‘© There are two conditions of protein accumulation: ©. Either there willbe an accumulation of too much protein. (© However, there must be another condition which is called the misfolding protein, © Some examplesare: © Mallory hyaline/denkbodies: onasa7 © Team GlobalNet www. Distia.co ~> They are mostly seen in alcoholic liver disease. > Itis composed ofeytokeratin 8/18. © Multiplemyeloma: — Itisalsoknownas the tumorofplasina cells >It is caused due to the increased production of antibodies. — Russell bodies are: intracytoplasmic collections of immunoglobulins > Dutcher bodies are intranuclear collections of immunoglobulins Crooke Hyaline Change: > Itis seen inthe pituitary gland, > Itis caused due to Cushing disease > Itis composed of eytokeratin. err Perera Cores) LDL Re ‘Alzheimers disease AATD (Hypercholestrolemia Abeta (Alpha 1 Deficiency) CFTR (Mutation.) Prion disease PrP Tay Sachs Disease (exosaminidase deficiency. ) 13 Telegram : @teamglobalchatTeam GlobalNet Q www. Distia.co (> Important information ‘© The alpha-1 deficiency causes panacinar emphysema in the lungs (Caused due to the deficiency of the protein.) and citrhosis in the liver (Caused due to the misfolding protein), Glycogen: nasa? ‘© Glycogen will be accumulated only inthe caseof © Glycogen storage disease, © Itispresentasaconcentriclamellations © Diabetes Mellitus. (Diabetienephropathy.) © Itshowsanonion peel appearance. ~ Glycogen goes into the PCT (Proximal convoluted ‘© Thepsammoma bodies areseen in Tubule),thenitiscalledan Armani Ebstein Lesion, > Papillary Carcinoma (© Some special stainsare: — Prolactinoma > PAS (Peer lodic acid Sehift) + SomatoStatinoma > Itwillbe pink incolor. > Serous Ovarian Tumor > PAS + Diaslase Sensitive shows that if you add the > Meningioma diastase, the glycogen will vanish. Hence, the pink > Mesothelioma ‘color will disappear. (© Metastatic calcification. > Seen in normal tissues. Calcification: > Thebloodcalcium leveliselevated ‘© Types ofcalciication: ~The most common organ alfected due to metastatic © Dystrophiccaleifieation: calcifications thelungs > Dead ordegenerating tissues are seen Some Examples: > There will bea normal blood calcium levels. * Hyperparathyroidism: It occurs due to the increase — Some examples: ‘of the parathyroid hormone, Caused by the increase * Dead Parasite inthecalcium “1B * Cancer: RCC and Breast cancer shows an increase + Atheroma ofealeium. + Monckeberg Sclerosis: * Vitamin D intoxication + Milkalkali syndrome, Multiple myeloma: It shows bony Iytic causing the increase of ealcium level in the blood. Sarcoidosis: It shows non-caseating granuloma, ‘causing the inerease of vitamin D3. Henceforth, increasein the calcium level. Stains for ealeium: onsi:s0 © Von Kossa:Itwillgive usablack color. isalso called caleific medial degeneration, Ithappens inthe tunica media. Caleium occursblue incolor, occurs only as an old age phenomenon and there is no clinica significance. © Psammoma Bodies: 14 + Telegram : @teamglobalchat© Itwill giveus ared color © Itisusedto represent when the minute amount of caleium ispresent, © Calcein © AZANstains: © Itisused for differentiating between the mineralized bone andosteoid, One-liner: Q. Whatis the first place of deposition of the caleium? Ans. Mitochondria (However, inthe history of kidney deposition, the calcium goes into the basement membrane) McQs: (Q. Elderly female patient presented to the outpatient depertnient with the presence of @ lump in the right breast measuring ‘Sxdem. The lump was firm to hardin consistency. The right auillary group of lymph nodes isalso palpable and shows the presence of tumor deposits. Thee is the deposition of an amorphous material noted which stains positive with von statements is incorrect 8, Grossly ealeium appears chalky white in color b. Von Kossa gives ablack colorto caleium c. Stains for picking up minute quantities of caleium include alizarin red S The first site of deposition of calcium is the endoplasmic reticulum 4 Ans: d, The first site of deposition of calcium is the endoplasmic reticulum © Team GlobalNet www. Distia.co Q.A.S4-year-old male patient presented witha pigmented lesion measuring 4x3cm on the right cheek. A biopsy of the lesion shows the presence of atypical cells with prominent nucleoli. Mitotic figures are noted. Histopathological diagnosis of ‘malignant melanoma is made. Which ofthe following stains cannot be used for the diagnosis? Masson Fontana Schmorls stain HMB4s Masson trichrome ‘Ans: d. Masson trichrome Qi Incorrectabout the pigment shown, a, Defined asyellow-brown in appearance b, Formed due tolipid peroxidation ©. Canbe positive for oil red Seen more commonly in infants ‘Ans: d. Seen more commonly in infants Q. Which Of The Following Stains Is Best Suited For The Diagnosis OFGlycogen? a. OilredO b. Perl'sstain ©. PAS 4. Congored Ans:e.PAS 15 Telegram : @teamglobalchatTeam GlobalNet www. Distia.co CROSS WORD PUZZLES & Crossword Puzzle Across 3. He is said to be the father of modern Pathology. His contributions are as follows: 4. Thisiscaused by integrins in Leukocytes. Integrins Down Fy 1. Vasoconstriction First even, Transient even lasting fr few Ly seconds, Reflex) 2. Leukocytes Mediated Injury: It is done by WBC, end CLOUT ITT TI I 0 Leukocytes by releasing Enzymes. 1 I 0 16 Telegram : @teamglobalchat © Q —-+ © Aulo="Self" and Phagy = "Eating.” ‘© Othername: Cell Cannibalism. ‘© A Japanese scientist named "Yoshinori Ohsumi", © Gaveall the mechanisms of autophagy in2016, © Received aNobel prize forthe discovery. Examples of Autophagy ooansa © Senile = Malnutrition © Cancers ‘# Neurodegenerative Conditions © Alzheimer's disease © Parkinson's disease ‘Types of Autophagy oanas Four types of mechanisms 1, Macro-Autophagy 2. Miero-Autophagy 3. Chaperone Mediated Autophagy (CMA) 4, Mitophagy srautophagy: General outline of Macro-Autophagy Refer Image 4.1 Macro-Autophagy ‘© Autophagosome formation occurs. Q.Which is the autophagy in which the phagophore or autophagosome or the plate formation occurs? Answer: Macro-Autophagy LK COMPLEX > BECLIVA (grt enain 3) APIS © Team GlobalNet www. Distia.co 17 4 AUTOPHAGY AND FREE RADICAL INJURY @ + Bating of Endoplasmic Reticulum and Ribosomes occurs. © ULKI COMPLEX starts the formation of the plate called Phagophore. ‘© Plate will gradually elongate and become bigger. © BECLIN-1 helps in elongation ‘© LC3 (Light Chain 3) completes the full plate formation and now the plate is called Auto-Phagosome (APS). © Auto-Phagosome fuse with the lysosome to form Autophagolysosome (APLS). ‘© Finally al the substrates are broken inside the APLS. ‘Complexes Involving in Macro-Autophagy ULK1—+BECLIN-1+Le3 Q. What isthe marker of Autophagy? Ans.LC3 Advanced Points o/ RITOR decides the fate of autophagy. ‘© Ata well fed stage mTOR is activated and it will inhibit ULKL © Inmatnutrition, mTOR isinhibited. © mPOR« 1/Autophagy. 2.. Micro Autophagy on1000 Simplest process. ‘© Direct uptake by lysosomes via endocytosis, MA nse (CMA stands for Chaperone Mediated Autophagy. CChaperon corrects misfolded protein. Examples of Chaperone © H1SP(Lteat Shock Proteins) Mechanism of CMA, ‘© Chaperone binds with misfolded protein. ‘© The complex enters the lysosome via LAMP 2A (Lysosome Associated Membrane Protein 2A) for autophagy. Q. LAMP24 isused in which mechanism? Ans.CMA, Mitophagy Atype of Macro- Autophagy. Autophagosome formation, Only eating of mitochondria occurs 1696 seen Telegram : @teamglobalchat +www. ‘© Old mitochondria are represented by PINK and PARKIN molecules on their surface. ‘© Itconfirms eating up of old mitochondria, Important Marker of autophagy LC3 (Light Chain 3) Most important gene for autophagy ATGI ATGS gene mutation Increased risk to get tuberculosis (TB) ATGI6L gene mutations Increased risk of Crohn's Disease (Inflammatory Bowel Disease) Cellular Ageing Causes of Cellular Ageing: ‘© Free radical injury (via chemicals, poisons and pollution) is themost common cause of ageing. Telomere shortening. ‘© Insulinresistance ‘+ DNArepairdetects ‘Telomere Shortening oa ‘© Thousands of telomeres are present at the terminal end of chromosomes from human birt, One telomere sequence: TTAGGG, With each cell division, telomeres’ become shorter, thus ageingoceurs, ‘Thiscanbe prevented by "Telomerase": Telomerase isa RNA Dependent DN Polymerase enzyme. ‘Telomerase is very famously known as "Immortality Gene”, Telomeres ZN © 0 WV IN 0000 - AVIV AN \N crvaresone OOOOOOOO — Cell division XKXK Telomere shortening 18 © Team GlobalNet Distia.co Don'thave telomerase? 1 Toa om t “ & ; es Cel divisions — Somatic cell Drops down. Stem cell Gradual decrease Germ cell No change Maximum telomerase activity is seen Cancer-cell Reactivate telomerase Survive longer Hayflick Limit ‘© Acell undergoes 40-60 cell divisions before it gets old. ‘© In some books 60-70 cell divisions are the average cell divisionsperformedbefore ageing of cell. How to Prolong Lifespa SIRT Genes (SIRT 1-6) produces SIRTUIN proteins inthe human bod. SIRTUIN proteinsare the histone deacetylases High levels of SIRTUIN proteins can show anti-ageing Properties. Role of SIRTUINS © Anti-ageing ‘© Promote cell repair, therefore, being used in cancer treatment ‘© Used in the treatment of diabetes as it increases insulin sensitivity How to Increase SIRTUINS Levels + Caloriedeticit © Redwine consumption Telegram : @teamglobalchat© Team GlobalNet www. Distia.co . Lamina d, LaminB Free Radical Injury oosas + Most common cause ofageing Werner Hutchinson Gilford Cockayne Syndrome or Syndrome or Syndrome FreeRadical Adult Progeria Laminopathy + Also knownas ROS (Reactive Oxygen Species). Syndrome © They areof thee types: © Superoxide Oceurs in Cacheria © Hydrogen peroxide adulthood GSlaete, occurs in © Hydroxyl (most potent ree radical) pean '® Allofthem cause lipid peroxidation. + Lipofisein pigment is generated, @ tclbiae sign of free radical injury Free Radical Formation o, Fenton's RXN Chemicals Toxins Poisons] S10 Ferrous Ferre Reperfusion _|Dismutase Fe Fe Later onset Early Childhood Onset - Injury wok disease 0, $25 10, =) on Superoxide Hydrogen Hydroxyl DRAB |LMNA (amin Ajgme | /ERCE a Hydrogen Hyd defect defect where the nucleus is gene not developed properly defect Medical Therapy for Hutchinson Gilford Syndrome: Lonafarnib -A famesyl transferase inhibitor is under tial, His supposed to correetthe nucleus. Note MEN (Multiple Endocrine Neoplasia) I Syndrome Adult progeria syndrome under premature ageing, Q. WemerSyndromeis defectin? ‘Oxygen — Superoxide due tothe environmental chemicals, ‘toxins, poisons, and reperfusion injury. Superoxide > Hydrogen Peroxide by Superoxide Dismutase (SOD). Hydrogen peroxide > Hydroxyl (most potent) and the reaction is called Fenton's Reaction. ‘© InFenton's Reaction the ferrousion — ferricion, Free Radical Injury - Protection Diet should have antioxidants like vitamin A,C, and E. ‘Transpor proteins © Transferrin-Transports Fe © Ceruloplasmin- Transports Cu Protective Enzymes a DNAHfticase b. NER gees Free radical injury ~ Proteetion? © IMR sone dL Allotheabose 0, SOP, 140.——§+ou coaua [Ciuatione Q. Hutchinson-Gilford Progeria syndrome is due to the peroxidase a. Kein to Mo b. KentinB 4 19 Telegram : @teamglobalchat© Superoxide Dismutase (SOD). © Catalase acts on Hydrogen Peroxide > Water and oxygen. © Glutathione peroxidase acts on both Hydrogen Peroxide and Hydroxyl —» Waterand oxygen. Clinical Correlation ‘+ Superoxide Dismutase (SOD) is of two types: © Team GlobalNet www. Distia.co Ferroptosis + lronmediated cell death, * Glutathione Peroxidase Type isthe master regulator, + Mitochondria changes are very similar to necrosis: © Lossofcristae ©. Rupture of Membrane onsise Q. Which ofthe following pigments arc involved in free radical © Cytoplasmic SOD (Cu-Zn SOD) injury? © Mitochondrial SOD (MnSOD) Lipotuscin ‘+ SOD 1 gene mutation can cause ALS (Amyotrophic Lateral, Melanin Sclerosis- Microscope studies show Bunina Bodies) «Bilirubin ‘ ALSisboth upperand lower motor neuron disorder. 4. Hematin ‘© Stephen Hawking had ALS. Image 4.1 Initiation complex ta @ | <@ Nucleation ‘compen INITIATION ELONGATION Recydting of metabolites @x = 2 Bevo MATURATION OF AUTOPHAGOSOME FUSION WITH LYSOSOME DEGRADATION 20 Telegram : @teamglobalchatOS t ay og f Crossword Puzzle OW © Team GlobalNet www. Distia.co *) CROSS WORD PUZZLES Across 3. Adultprogeria syndrome under premature ageing 4. Reactivate telomerase TT TTT Down 1, WernerSyndromeisdefect in E fetes fee es ll 2. Dropsdown immediately 0 21 Telegram : @teamglobalchat- PREVIOUS YEAR QUESTIONS poe> 2 onR> © 2 SOR> © Team GlobalNet www. Distia.co Alllare features of reversible cel injury EXCEPT? (AIIMS 2019) \- Endoplasmic reticulum swelling Dense deposition of mitochondria Bleb formation Detachment ofibosome Avwedge shaped are inthe adrenal glandis affected. On HPE. nucleus is not seen but cellular outlines are intact, Which typeofnecrosisis being described? (JIPMER ~ Nov - 2018) - Coagulative Liquefactive Fibrinoid Caseous BCL2proteinis located in which ofthe following site? (JIPMER ~ May - 2018) Cell membrane Mitochondria Nucleus Cytosol 22 Q 2 DOSP © DOR> pomp APAF 1 is involved in the activation of which of the following caspases (AIMS = June-2020) Caspase Caspase9 Caspase3 Caspase 10 Staining of lipids is best seen in which of the following conditions? (INICETNov2020) . Frozen ection Liquid parafin Formalin fixed Karnovsky stain Dystrophic calcification Seen in which of the following conditions? (AIMS ~ May -2019) Myositis ossificans Paget's disease Metastasis Sarcoidosis Telegram : @teamglobalchat