NFNF1612 Cell Survival, Injury, Death & Autophagy 2021 PDF

Dr. Nor SyafinazYaakob Fakulti Farmasi, UKM [email protected]  50% of knowledge retention via discussion  75% of knowledge retention via practice doing  90% of knowledge retention via teaching others  At the end of this topic students should be able to: ▪ Explain possible fate...

Dr. Nor SyafinazYaakob Fakulti Farmasi, UKM [email protected]  50% of knowledge retention via discussion  75% of knowledge retention via practice doing  90% of knowledge retention via teaching others  At the end of this topic students should be able to: ▪ Explain possible fates of a cell following an injury or stress ▪ Describe the mechanism of different types of cell adaptations ▪ Describe the mechanisms of reversible and irreversible cell injury ▪ Describe the mechanistic changes at the cellular critical points that can lead to cell injury/death ▪ Describe & differentiate the mechanism of apoptosis and necrosis ▪ Describe the mechanism of cell autophagy  Cell Adaptations  Cell Injury  Cell Death  Cell Autophagy  Cells → Tissue → Organ → System  Cell pathology: general, can occur in any tissue  Homeostasis : normal, steady state, equilibrium conditions in physiological environment Precise control of physiological processes are very crucial!! Otherwise → Disease Can be the pathologic stimuli http://image.slidesharecdn.com/cellhomeostatis-150316064951-conversion-gate01/95/cell-homeostatis-3-638.jpg?cb=1426506685  Cellular swelling Fatty change Hypertrophy Hyperplasia Atrophy Metaplasia Robbins Basic Pathology, 9th Ed  What is “Adaptation”?  What is the difference between: ▪ Physiologic adaptation ▪ Pathologic adaptation  Increase in SIZE OF CELLS → Increase ORGAN SIZE  Due to increased workload (eg. hypertension)  Occurs when cells have limited capacity to divide  No new cells, more protein and organelles  Physiologic hypertrophy example: estrogen- stimulated smooth muscle hypertrophy → enlargement of uterus during pregnancy  WHAT IS THE GOAL OF THE ADAPTATION??  Pathologic hypertrophy example http://www.abcam.com/ps/CMS/Images/Hypertrophy_Image05.jpg  Increase in NUMBER OF CELLS → Increase ORGAN SIZE  cell proliferation and differentiation  Occurs in cells capable of replication  Induced by hormones and growth factors  Can occur together with hypertrophy  Physiologic hyperplasia example?  Pathologic hyperplasia example? WHAT IS THE GOAL OF THE ADAPTATION?? https://edc2.healthtap.com/ht-staging/user_answer/avatars/341279/large/open-uri20120805-28563-18r4c0f.jpeg?1386592149  Shrinkage in cell size by loss of cell substance  Can diminish the organ size when a lot of cells involved  Triggers (eg.) : reduced blood supply, nutritional imbalance  Cells still alive but with reduced function  Protein synthesis , Protein degradation , Autophagy  WHAT IS THE GOAL OF THE ADAPTATION?? http://www.rayur.com/wp-content/uploads/2012/09/Atrophy.jpg  Replacement of one adult cell type with another adult cell type  Change in phenotype of differentiated cells  Reversible change  Stress-prone cell type → resistant cell type  Reprogramming of stem cells to a different pathway  Pathologic from smoking habit WHAT IS THE PROCESS AND THE GOAL OF THE ADAPTATION??  Survival advantage, but compromised protective mechanism Causes :  Hypoxia → O2 deprivation  Chemical agents  Infectious agents  Immunologic agents  Genetic factors  Nutritional imbalances  Physical agents  Aging **Robbins Basic Pathology 9th Ed, pg. 7 2 main morphology:  Cellular swelling: due to failure of energy-dependent ion pumps, unable to maintain ionic and fluid homeostasis  Fatty change: accumulation of lipid vacuoles (fatty liver disease) http://pathol.med.stu.edu.cn/pathol/fileUpload/imageUpload/Diagrams/Ch1Injury/113-2FattyChang-2CellularMorphology.jpg  Adaptive cells and reversibly injured cells CAN PROGRESS TO IRREVERSIBLE INJURY if the pathologic stimuli continues significantly, exceeds the limit/capacity of the cells 1. Cellular response to injury depends on the type of injury, its duration and its severity 2. Consequences of injurious stimulus depends on the type, status, adaptability and genetic makeup of the injured cell 3. Cell injury can be caused by one or more functional and biochemical abnormalities of essential cellular components 4. Multiple biochemical alterations can be triggered by any one injurious insult Critical points!!  Cell death  Loss of membrane integrity  Leakage of cellular contents  Elicit inflammation response  Different patterns may hint the underlying cause  Coagulative necrosis  Liquefactive necrosis  Gangrenous necrosis  Caseous necrosis (Robbins Basic Pathology 9th Ed. Pg. 10-11)  Cell death pathway (cell suicide)  Cells activate enzymes that degrade their own nuclear DNA and cytoplasmic proteins  Intact cell membrane, but altered in a way that it triggered phagocytosis  Phagocytosed before cellular contents leakage  Do not elicit inflammation Physiologic Pathologic Feature Necrosis Apoptosis Cell size Nucleus Plasma membrane Cellular contents Adjacent inflammation Physiologic or pathologic role Dr. Nabila Hamdi  What will happen to the mature autophagosome if there's no vATPase at the lysosomal interface? Will it stay in our body and be harmful?  Do we need to memorize everything from the initiation process until fusion process under macroautophagy topic ?  is there any critical point where or when metaplasia & dysplasia will stop being reversible? If yes, what is the effects on body once they stopped being reversible?  Under what circumstances can the cell reverse from dysplasia to metaplasia, and finally back to normal cell again? *Extra Ref: Metaplasia: tissue injury adaptation and a precursor to the dysplasia–cancer sequence https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5998678/  in apoptosis,the remnants of death cell will be eaten by phagocytes,so what will happen to the remnants of necrotic cell? Does the remnants stay in the body for a long time and affects neighbouring cells continuously?  How stratified squamous epithelial tissues can help the cell to survive in cigarette smoking? And is there any consequences of the switching of ciliated columnar epithelial tissues to stratified squamous epithelial tissues to our lungs in cigarette smoking?  I am curious why do we still need to take medication in Gastroesophageal Reflux Diseases when cells can survive with ability of columnar mucosal epithelium to secrete more mucus to protect the cell from acid?  I am still confused why callouses can be an example for hyperplasia.  Could Dr explain more on mechanism of Necrosis? I am quite confused....  Robbins Basic Pathology 9th Ed