Cell injury, adaptation, and death can occur through various stimuli and stresses. Cells may undergo reversible or irreversible changes. Reversible changes include cellular adaptation through hypertrophy, hyperplasia, and metaplasia to stressors. Irreversible changes result in cellular atrophy and eventually cell death through necrosis or apoptosis. The morphology of reversible injury includes cellular swelling, fatty change, and changes to organelles. Necrosis is the degradative process of cell death where cellular contents are digested by enzymes.
Dear all, Pathologybasics is out with a new series of power point presentations on general Pathology.. Following is link presentation on seventh and the most difficult to understand chapter of robbins.. chapter 7,neoplasia. Any suggestions/feedback/constructive criticism are welcome on facebook.com/pathologybasics or pathologybasics@gmail.com
Difference between reversible and irreversible cell injury,Mechanism of cell ...Rukhshanda Ramzaan
Cell Injury: Any change resulting in loss of the ability to maintain the normal or adapted homeostatic state.
Agents that cause cell injury
• Hypoxia / Ischemia (loss of blood supply)
• Microbial
• Parasitic
• Chemical
• Physical
• Trauma
• Genetic
• Nutritious
• Environmental
Types of Cell injury
Reversible Cell Injury
Pathologic changes that can be reversed in mild cellular injury when the stimulus is removed. Cell injury is reversible only up to a certain point otherwise it will be irreversible.
Changes in reversible cell injury
Cellular Swelling: Due to accumulation of intracellular water and endoplasmic reticulum & mitochondria.
Clumping of chromatin.
Irreversible Cell injury
Pathologic changes that are permanent and cause cell death, they cannot be reversed to normal state.
Changes in irreversible cell injury
Irreversible injury is marked by severe mitochondrial vacuolization, extensive damage to plasma membranes, detachment of ribosomes from the granular endoplasmic reticulum (ER). Injury to lysosomal bodies leads to leakage of lysosomal enzymes into the cytoplasm and condensation, fragmentation and lysis of nuclei.
Dear all, Pathologybasics is out with a new series of power point presentations on general Pathology.. Following is link presentation on seventh and the most difficult to understand chapter of robbins.. chapter 7,neoplasia. Any suggestions/feedback/constructive criticism are welcome on facebook.com/pathologybasics or pathologybasics@gmail.com
Difference between reversible and irreversible cell injury,Mechanism of cell ...Rukhshanda Ramzaan
Cell Injury: Any change resulting in loss of the ability to maintain the normal or adapted homeostatic state.
Agents that cause cell injury
• Hypoxia / Ischemia (loss of blood supply)
• Microbial
• Parasitic
• Chemical
• Physical
• Trauma
• Genetic
• Nutritious
• Environmental
Types of Cell injury
Reversible Cell Injury
Pathologic changes that can be reversed in mild cellular injury when the stimulus is removed. Cell injury is reversible only up to a certain point otherwise it will be irreversible.
Changes in reversible cell injury
Cellular Swelling: Due to accumulation of intracellular water and endoplasmic reticulum & mitochondria.
Clumping of chromatin.
Irreversible Cell injury
Pathologic changes that are permanent and cause cell death, they cannot be reversed to normal state.
Changes in irreversible cell injury
Irreversible injury is marked by severe mitochondrial vacuolization, extensive damage to plasma membranes, detachment of ribosomes from the granular endoplasmic reticulum (ER). Injury to lysosomal bodies leads to leakage of lysosomal enzymes into the cytoplasm and condensation, fragmentation and lysis of nuclei.
This is a presentation on the topic of Adaptations, Cell injury and cell death, prepared by Dr Ashish Jawarkar, he is MD in pathology and a teacher at Parul institute of Medical sciences and research Vadodara.
This is a presentation on the topic of Inflammation and repair, prepared by Dr Ashish Jawarkar, he is MD in pathology and a teacher at Parul institute of Medical sciences and research Vadodara.
Cellular Adaptation
as cells encounter stresses they undergo functional or structural adaptations to maintain viability / homeostasis.
Injury - altered homeostasis
if limits of the adaptive response are exceeded or if adaptation not possible, a sequence of events called cell injury occurs.
Reversible Cell Injury
removal of stress results in complete restoration of structural & functional integrity.
b) Irreversible Cell Injury / Cell Death
if stimulus persists or is severe enough from the start, the cell suffers irreversible cell injury and death.
2 main morphologic patterns: necrosis & apoptosis.
Adaptations are reversible changes in the size, number, phenotype, metabolic activity, or functions of cells in response to changes in their environment.
Physiologic adaptations are responses of cells to normal stimulation by hormones or endogenous chemical mediators
Pathologic adaptations are responses to stress that allow cells to modulate their structure and function and thus escape injury.
Hypertrophy refers to an increase in the size of cells, that results in an increase in the size of the affected organ
The hypertrophied organ has no new cells, just larger cells.
Types:
a) physiologic b) pathologic
Causes:
a) increased functional demand b) hormonal stimulation
“Inflame” redirects here. For the 2017 Turkish film, see
Inflame (film).
Toes inflamed by chilblains
Inflammation (from Latin inflammatio) is part of the
complex biological response of body tissues to harmful
stimuli, such as pathogens, damaged cells, or irritants,[1]
and is a protective response involving immune cells,
blood vessels, and molecular mediators. The function of
inflammation is to eliminate the initial cause of cell injury,
clear out necrotic cells and tissues damaged from
the original insult and the inflammatory process, and to
initiate tissue repair.
The classical signs of inflammation are heat, pain, redness,
swelling, and loss of function. Inflammation is a
generic response, and therefore it is considered as a mechanism
of innate immunity, as compared to adaptive immunity,
which is specific for each pathogen.[2] Too little
inflammation could lead to progressive tissue destruction
by the harmful stimulus (e.g. bacteria) and compromise
the survival of the organism. In contrast, chronic
inflammation may lead to a host of diseases, such as hay
fever, periodontitis, atherosclerosis, rheumatoid arthritis,
and even cancer (e.g., gallbladder carcinoma). Inflammation
is therefore normally closely regulated by the body.
Inflammation can be classified as either acute or chronic.
Acute inflammation is the initial response of the body to
harmful stimuli and is achieved by the increased movement
of plasma and leukocytes (especially granulocytes)
from the blood into the injured tissues. A series of biochemical
events propagates and matures the inflammatory
response, involving the local vascular system, the
immune system, and various cells within the injured tissue.
Prolonged inflammation, known as chronic inflammation,
leads to a progressive shift in the type of cells
present at the site of inflammation, such as mononuclear
cells, and is characterized by simultaneous destruction
and healing of the tissue from the inflammatory process.
Inflammation is not a synonym for infection. Infection
describes the interaction between the action of microbial
invasion and the reaction of the body’s inflammatory response
— the two components are considered together
when discussing an infection, and the word is used to imply
a microbial invasive cause for the observed inflammatory
reaction. Inflammation on the other hand describes
purely the body’s immunovascular response, whatever the
cause may be. But because of how often the two are
correlated, words ending in the suffix -itis (which refers
to inflammation) are sometimes informally described as
referring to infection. For example, the word urethritis
strictly means only “urethral inflammation”, but clinical
health care providers usually
The study of the blood flow is called hemodynamics.
Thus hemodynamics deals with the dynamics of blood flow. The circulatory system is controlled by homeostatic mechanisms, much as hydraulic circuits and are controlled by control systems.
Hemodynamic response continuously monitors and adjusts to conditions in the body and its environment. Thus hemodynamics explains the physical laws that govern the flow of blood in the blood vessels.
This is a presentation on the topic of Adaptations, Cell injury and cell death, prepared by Dr Ashish Jawarkar, he is MD in pathology and a teacher at Parul institute of Medical sciences and research Vadodara.
This is a presentation on the topic of Inflammation and repair, prepared by Dr Ashish Jawarkar, he is MD in pathology and a teacher at Parul institute of Medical sciences and research Vadodara.
Cellular Adaptation
as cells encounter stresses they undergo functional or structural adaptations to maintain viability / homeostasis.
Injury - altered homeostasis
if limits of the adaptive response are exceeded or if adaptation not possible, a sequence of events called cell injury occurs.
Reversible Cell Injury
removal of stress results in complete restoration of structural & functional integrity.
b) Irreversible Cell Injury / Cell Death
if stimulus persists or is severe enough from the start, the cell suffers irreversible cell injury and death.
2 main morphologic patterns: necrosis & apoptosis.
Adaptations are reversible changes in the size, number, phenotype, metabolic activity, or functions of cells in response to changes in their environment.
Physiologic adaptations are responses of cells to normal stimulation by hormones or endogenous chemical mediators
Pathologic adaptations are responses to stress that allow cells to modulate their structure and function and thus escape injury.
Hypertrophy refers to an increase in the size of cells, that results in an increase in the size of the affected organ
The hypertrophied organ has no new cells, just larger cells.
Types:
a) physiologic b) pathologic
Causes:
a) increased functional demand b) hormonal stimulation
“Inflame” redirects here. For the 2017 Turkish film, see
Inflame (film).
Toes inflamed by chilblains
Inflammation (from Latin inflammatio) is part of the
complex biological response of body tissues to harmful
stimuli, such as pathogens, damaged cells, or irritants,[1]
and is a protective response involving immune cells,
blood vessels, and molecular mediators. The function of
inflammation is to eliminate the initial cause of cell injury,
clear out necrotic cells and tissues damaged from
the original insult and the inflammatory process, and to
initiate tissue repair.
The classical signs of inflammation are heat, pain, redness,
swelling, and loss of function. Inflammation is a
generic response, and therefore it is considered as a mechanism
of innate immunity, as compared to adaptive immunity,
which is specific for each pathogen.[2] Too little
inflammation could lead to progressive tissue destruction
by the harmful stimulus (e.g. bacteria) and compromise
the survival of the organism. In contrast, chronic
inflammation may lead to a host of diseases, such as hay
fever, periodontitis, atherosclerosis, rheumatoid arthritis,
and even cancer (e.g., gallbladder carcinoma). Inflammation
is therefore normally closely regulated by the body.
Inflammation can be classified as either acute or chronic.
Acute inflammation is the initial response of the body to
harmful stimuli and is achieved by the increased movement
of plasma and leukocytes (especially granulocytes)
from the blood into the injured tissues. A series of biochemical
events propagates and matures the inflammatory
response, involving the local vascular system, the
immune system, and various cells within the injured tissue.
Prolonged inflammation, known as chronic inflammation,
leads to a progressive shift in the type of cells
present at the site of inflammation, such as mononuclear
cells, and is characterized by simultaneous destruction
and healing of the tissue from the inflammatory process.
Inflammation is not a synonym for infection. Infection
describes the interaction between the action of microbial
invasion and the reaction of the body’s inflammatory response
— the two components are considered together
when discussing an infection, and the word is used to imply
a microbial invasive cause for the observed inflammatory
reaction. Inflammation on the other hand describes
purely the body’s immunovascular response, whatever the
cause may be. But because of how often the two are
correlated, words ending in the suffix -itis (which refers
to inflammation) are sometimes informally described as
referring to infection. For example, the word urethritis
strictly means only “urethral inflammation”, but clinical
health care providers usually
The study of the blood flow is called hemodynamics.
Thus hemodynamics deals with the dynamics of blood flow. The circulatory system is controlled by homeostatic mechanisms, much as hydraulic circuits and are controlled by control systems.
Hemodynamic response continuously monitors and adjusts to conditions in the body and its environment. Thus hemodynamics explains the physical laws that govern the flow of blood in the blood vessels.
Cellular adaptations, injury and death.. Lecture 1Ashish Jawarkar
This is a series of lectures on general pathology useful for undergraduate and postgraduate pathology students. The ppts here have are enriched with explanatory pictures as well as useful video links.. hope you find them useful
Inflammation is a fundamental process for human survival, this lecture covers the basics of the process, its components and affects. Developing an understanding of this process will enable the student to comprehend this omnipresent process and how it is directly linked to our survival.
This is the brief overview on the topic CELL INJURY. After reading this you will get to know about adaptations, types, etiology, pathogenesis of cell injury.
Elevating Tactical DDD Patterns Through Object CalisthenicsDorra BARTAGUIZ
After immersing yourself in the blue book and its red counterpart, attending DDD-focused conferences, and applying tactical patterns, you're left with a crucial question: How do I ensure my design is effective? Tactical patterns within Domain-Driven Design (DDD) serve as guiding principles for creating clear and manageable domain models. However, achieving success with these patterns requires additional guidance. Interestingly, we've observed that a set of constraints initially designed for training purposes remarkably aligns with effective pattern implementation, offering a more ‘mechanical’ approach. Let's explore together how Object Calisthenics can elevate the design of your tactical DDD patterns, offering concrete help for those venturing into DDD for the first time!
Essentials of Automations: Optimizing FME Workflows with ParametersSafe Software
Are you looking to streamline your workflows and boost your projects’ efficiency? Do you find yourself searching for ways to add flexibility and control over your FME workflows? If so, you’re in the right place.
Join us for an insightful dive into the world of FME parameters, a critical element in optimizing workflow efficiency. This webinar marks the beginning of our three-part “Essentials of Automation” series. This first webinar is designed to equip you with the knowledge and skills to utilize parameters effectively: enhancing the flexibility, maintainability, and user control of your FME projects.
Here’s what you’ll gain:
- Essentials of FME Parameters: Understand the pivotal role of parameters, including Reader/Writer, Transformer, User, and FME Flow categories. Discover how they are the key to unlocking automation and optimization within your workflows.
- Practical Applications in FME Form: Delve into key user parameter types including choice, connections, and file URLs. Allow users to control how a workflow runs, making your workflows more reusable. Learn to import values and deliver the best user experience for your workflows while enhancing accuracy.
- Optimization Strategies in FME Flow: Explore the creation and strategic deployment of parameters in FME Flow, including the use of deployment and geometry parameters, to maximize workflow efficiency.
- Pro Tips for Success: Gain insights on parameterizing connections and leveraging new features like Conditional Visibility for clarity and simplicity.
We’ll wrap up with a glimpse into future webinars, followed by a Q&A session to address your specific questions surrounding this topic.
Don’t miss this opportunity to elevate your FME expertise and drive your projects to new heights of efficiency.
GraphRAG is All You need? LLM & Knowledge GraphGuy Korland
Guy Korland, CEO and Co-founder of FalkorDB, will review two articles on the integration of language models with knowledge graphs.
1. Unifying Large Language Models and Knowledge Graphs: A Roadmap.
https://arxiv.org/abs/2306.08302
2. Microsoft Research's GraphRAG paper and a review paper on various uses of knowledge graphs:
https://www.microsoft.com/en-us/research/blog/graphrag-unlocking-llm-discovery-on-narrative-private-data/
Key Trends Shaping the Future of Infrastructure.pdfCheryl Hung
Keynote at DIGIT West Expo, Glasgow on 29 May 2024.
Cheryl Hung, ochery.com
Sr Director, Infrastructure Ecosystem, Arm.
The key trends across hardware, cloud and open-source; exploring how these areas are likely to mature and develop over the short and long-term, and then considering how organisations can position themselves to adapt and thrive.
Accelerate your Kubernetes clusters with Varnish CachingThijs Feryn
A presentation about the usage and availability of Varnish on Kubernetes. This talk explores the capabilities of Varnish caching and shows how to use the Varnish Helm chart to deploy it to Kubernetes.
This presentation was delivered at K8SUG Singapore. See https://feryn.eu/presentations/accelerate-your-kubernetes-clusters-with-varnish-caching-k8sug-singapore-28-2024 for more details.
Generating a custom Ruby SDK for your web service or Rails API using Smithyg2nightmarescribd
Have you ever wanted a Ruby client API to communicate with your web service? Smithy is a protocol-agnostic language for defining services and SDKs. Smithy Ruby is an implementation of Smithy that generates a Ruby SDK using a Smithy model. In this talk, we will explore Smithy and Smithy Ruby to learn how to generate custom feature-rich SDKs that can communicate with any web service, such as a Rails JSON API.
Epistemic Interaction - tuning interfaces to provide information for AI supportAlan Dix
Paper presented at SYNERGY workshop at AVI 2024, Genoa, Italy. 3rd June 2024
https://alandix.com/academic/papers/synergy2024-epistemic/
As machine learning integrates deeper into human-computer interactions, the concept of epistemic interaction emerges, aiming to refine these interactions to enhance system adaptability. This approach encourages minor, intentional adjustments in user behaviour to enrich the data available for system learning. This paper introduces epistemic interaction within the context of human-system communication, illustrating how deliberate interaction design can improve system understanding and adaptation. Through concrete examples, we demonstrate the potential of epistemic interaction to significantly advance human-computer interaction by leveraging intuitive human communication strategies to inform system design and functionality, offering a novel pathway for enriching user-system engagements.
Dev Dives: Train smarter, not harder – active learning and UiPath LLMs for do...UiPathCommunity
💥 Speed, accuracy, and scaling – discover the superpowers of GenAI in action with UiPath Document Understanding and Communications Mining™:
See how to accelerate model training and optimize model performance with active learning
Learn about the latest enhancements to out-of-the-box document processing – with little to no training required
Get an exclusive demo of the new family of UiPath LLMs – GenAI models specialized for processing different types of documents and messages
This is a hands-on session specifically designed for automation developers and AI enthusiasts seeking to enhance their knowledge in leveraging the latest intelligent document processing capabilities offered by UiPath.
Speakers:
👨🏫 Andras Palfi, Senior Product Manager, UiPath
👩🏫 Lenka Dulovicova, Product Program Manager, UiPath
UiPath Test Automation using UiPath Test Suite series, part 4DianaGray10
Welcome to UiPath Test Automation using UiPath Test Suite series part 4. In this session, we will cover Test Manager overview along with SAP heatmap.
The UiPath Test Manager overview with SAP heatmap webinar offers a concise yet comprehensive exploration of the role of a Test Manager within SAP environments, coupled with the utilization of heatmaps for effective testing strategies.
Participants will gain insights into the responsibilities, challenges, and best practices associated with test management in SAP projects. Additionally, the webinar delves into the significance of heatmaps as a visual aid for identifying testing priorities, areas of risk, and resource allocation within SAP landscapes. Through this session, attendees can expect to enhance their understanding of test management principles while learning practical approaches to optimize testing processes in SAP environments using heatmap visualization techniques
What will you get from this session?
1. Insights into SAP testing best practices
2. Heatmap utilization for testing
3. Optimization of testing processes
4. Demo
Topics covered:
Execution from the test manager
Orchestrator execution result
Defect reporting
SAP heatmap example with demo
Speaker:
Deepak Rai, Automation Practice Lead, Boundaryless Group and UiPath MVP
State of ICS and IoT Cyber Threat Landscape Report 2024 previewPrayukth K V
The IoT and OT threat landscape report has been prepared by the Threat Research Team at Sectrio using data from Sectrio, cyber threat intelligence farming facilities spread across over 85 cities around the world. In addition, Sectrio also runs AI-based advanced threat and payload engagement facilities that serve as sinks to attract and engage sophisticated threat actors, and newer malware including new variants and latent threats that are at an earlier stage of development.
The latest edition of the OT/ICS and IoT security Threat Landscape Report 2024 also covers:
State of global ICS asset and network exposure
Sectoral targets and attacks as well as the cost of ransom
Global APT activity, AI usage, actor and tactic profiles, and implications
Rise in volumes of AI-powered cyberattacks
Major cyber events in 2024
Malware and malicious payload trends
Cyberattack types and targets
Vulnerability exploit attempts on CVEs
Attacks on counties – USA
Expansion of bot farms – how, where, and why
In-depth analysis of the cyber threat landscape across North America, South America, Europe, APAC, and the Middle East
Why are attacks on smart factories rising?
Cyber risk predictions
Axis of attacks – Europe
Systemic attacks in the Middle East
Download the full report from here:
https://sectrio.com/resources/ot-threat-landscape-reports/sectrio-releases-ot-ics-and-iot-security-threat-landscape-report-2024/
2. Normal cell is in a steady state
“Homeostasis”
Change in Homeostasis due to stimuli -
Injury
Injury - Reversible / Irreversible
Adaptation / cell death
3. CELLULAR ADAPTATION TO STRESS
Adaptations are reversible changes in the number, size, phenotype,
metabolic activity or functions of cells in response to changes in their
environment
• Physiologic adaptations are responses of cells to normal stimulation by
hormones or endogenous chemical mediators
• Pathologic adaptations are responses to stress that allow cells to
modulate their structure and function and thus escape injury
4. Hypertrophy
•is an increase in the size of cells & consequently an increase in the
size of an organ.
•the enlargement is due to an increased synthesis of
structural proteins & organelles
•Occurs when cells are incapable of dividing
Types:
a) physiologic
b) pathologic
Causes:
a) increased functional demand
b) hormonal stimulation
8. Hyperplasia
•is an increase in the number of cells in an organ or tissue
•an adaptive response in cells capable of replication
•a critical response of connective tissue cells in wound healing
Types:
a) physiologic hyperplasia
1) hormonal
ex. Proliferation of glandular epithelium of the female
breast at puberty & during pregnancy
2) compensatory – hyperplasia that occurs when a portion
of
a tissue is removed or diseased
e.g. partial resection of a liver > mitotic activity 12 hours
later
b) pathologic hyperplasia
Caused by excessive hormonal or growth factor
•
stimulation
11. Atrophy
• Shrinkage in the size of the cell by the loss of cell substance
•Results from decreased protein synthesis and increased protein degradation
in cells
•Is accompanied in many situations by increased autophagy with resulting
Increases in autophagic vacoules
Causes:
•
Decreased workload
•
Loss of innervation
•
Diminished blood supply
•
Inadequate nutrition
•
Loss of endocrine stimulation
•
Aging (senile atrophy)
12. Atrophy of the brain in an Normal brain of a 25-year-old
82-year-old man man
14. Metaplasia
•a reversible change in which one adult cell type ( epithelial or
mesenchymal) is replaced by another adult cell type.
• is cellular adaptation whereby cells sensitive to a
particular stress are replaced by other cell types better
able to withstand the adverse environment
Epithelial metaplasia
Examples
•
Squamos change that occurs in the respiratory epithelium in
habitual cigarette smokers ( normal columnar epithelial cells
of trachea & bronchi are replaced by stratified squamos
epithelial cells
•
Vitamin A deficiency
•
Chronic gastric reflux, the normal stratified squamos
epithelium of the lower esophagus may undergo metaplasia
to gastric columnar epithelium
15. A.Schematic diagram of columnar to squamos epithelial
B. Metaplastic transformation of esophageal epithelium
Mesenchymal metaplasia Ex. Bone formed in soft
tissue particularly in foci of injury
18. CELLULAR INJURY
Cell Injury- pertains to the sequence of events when cells have no
adaptive response or the limits of adaptive capability are
exceeded
Types of Cell Injury
1. Reversible Injury- injury that persists within certain limits, cells
return to a stable baseline
2. Irreversible Injury- when the stimulus causing the injury persists
and is severe enough from the beginning that the affected
cells die
a. necrosis
b. apoptosis
19. Causes of Cell Injury
1. Hypoxia
Causes:
a. Ischemia
b. Inadequate oxygenation of the blood
c. Reduction in the oxygen-carrying capacity of the blood
2. Chemical Agents
a. glucose, salt or oxygen
b. poisons
c. environmental toxins
d. social “stimuli”
e. therapeutic drugs
3. Physical agents- trauma, extremes of temperature, radiation, electric
shock, & sudden changes in atmospheric pressure
4. Infectious agents
20. 5. Immunologic reactions
Example: anaphylactic reaction to a foreign protein or a drug
reaction to self antigens
6. Genetic defects
Examples are genetic malformations associated with Down Syndrome,
sickle cell anemia & inborn errors of metabolism
7. Nutritional Imbalances
21. MORPHOLOGY OF CELL AND TISSUE INJURY
• All stresses & noxious influences exert their effects first at the
molecular or biochemical level
• Cellular function is lost far before cell death occurs and the
morphologic changes of cell injury (or death) lag far behind both
•
Ultrastructural Changes of Reversible Cell injury
• Alteration in plasma membrane reflecting disturbance in ion
and volume regulation induced by loss of ATP
2. Mitochondrial changes
3. Endoplasmic reticulum changes
4. Nuclear alterations
22. PLASMA MEMBRANE ALTERATIONS
•Cellular swelling
•Formation of cytoplasmic
blebs
•Blunting and distortion of
microvilli
•Deterioration and loosening
of intercellular attachments
23. Mithochondrial Changes
Early it appears condensed as a
result of loss of matrix protein
following loss of ATP
Followed by swelling due to
ionic shifts
Amorphous densities which
correlate with the onset of
irreversibility
Finally, rupture of membrane
followed by progressing
increased calcification
24. Endoplasmic Reticulum Changes
•Dilation
•Detachment of
ribosomes and
dissociation of
polysomes with
decreased protein
synthesis
•Progressive
fragmentation and
formation of
intracellular
aggregates of myelin
figures
26. Two Patterns of Morphologic Change Correlating to
Reversible Injury that can be recognized under the light
Microscope: cellular swelling and fatty change
Cellular Swelling
●
Is the result of failure of energy-dependent ion pumps in the
plasma membrane leading to an inability to maintain ionic
& fluid homeostasis
●
first manifestation of almost all forms of injury to cells
•microscopically small, clear vacoules may be seen within
the cytoplasm
•sometimes called hydropic change or vacoular
degeneration
•swelling of cells is reversible
27. Hydropic degeneration: kidney
Cloudy swelling & hydropic change reflect failure of membrane
ion pumps, due to lack of ATP, allowing cells to accumulate
fluid
28. Fatty Change
* occurs in hypoxic injury & various forms of toxic( alcohol
& halogenated hydrocarbons like chloroform ) or
metabolic injury like diabetes mellitus & obesity
•manifested by the appearance of lipid vacoules in the
cytoplasm
•principally encountered in cells participating in and
involved in fat metabolism e.g. hepatocytes &
myocardial cells
•also reversible
29. Morphologic Alterations in Reversible Cell Injury
Cell swelling
•
Fatty change
•
Plasma membrane blebbing and loss of microvilli
•
Mitochondrial swelling
•
Dilation of the ER
•
Eosinophilia (due to decreased cytoplasmic RNA)
•
30. NECROSIS
•Refers to a series of changes that accompany cell
death, largely resulting from the degradative action of
enzymes on lethally injured cells
•The enzymes responsible for digestion of the cell
are derived either from the:
1) Lysosomes of the dying cells themselves or from
2) lysosomes of leukocytes that are recruited as
part of the inflammatory reaction to the dead
cells
31. Morphologic alterations in Necrosis
✔
Increased eosinophilia (pink staining from eosin dye)
✔
Myelin figures ( whorled phospholipid masses)
✔
Nuclear changes assume one of three patterns all due to
breakdown of DNA & chromatin:
1) Karyolysis
2) Pyknosis characterized by nuclear shrinkage and
increased basophila
3) Karyorrhexis – fragmentation and dissolution
✔
Breakdown of plasma membrane and organellar
Membranes
✔
Leakage and enzymatic digestion of cellular contents
32. Patterns of Tissue Necrosis
Coagulative Necrosis
➢
A form of tissue necrosis in which the component cells are
dead but the basic tissue architecture is preserved for at
least several days
➢
It is characteristics of infarcts ( areas of ischemic
necrosis) in all solid organs except the brain
A wedge-shaped kidney
Infarct (yellow) with
preserva
tion of the outlines
33. Liquefactive Necrosis
➢
Seen in focal bacterial or occassionally fungal infections
because microbes stimulate the accumulation of
Inflammatory cells and the enzymes of leukocytes digest
( “liquefy”) the tissue
➢
This necrosis is characteristic of hypoxic death of cells
witnin the CNS
➢
Associated with suppurative inflammation (accumulation
of pus)
➢
The areas undergoing necrosis are transformed into a
Semi-solid consistency or state (liquid viscuous mass)
Example: abcess
35. Caseous Necrosis
➢
Encountered most often infoci of tuberculous infection
➢
Characterized by a cheesy yellow-white appearance of
the area of necrosis
➢
It is often enclosed within a distinctive inflammatory
border
A tuberculous lung with a large
area of caseous necrosis
containing yellow-white and
cheesy debris
36. Fat Necrosis
➢
Refers to focal areas of fat destruction, typically resulting
from release of activated pancreatic lipases into the
substance of the pancreas and the peritoneal cavity
➢
Occurs in acute pancreatitis
Fat necrosis in aqcute pancreatitis. The areas of white chalky deposits
represent foci of fat necrosis with calcium soapformation (saponification)
at sites of lipid breakdown in the mesentery
37. Fibrinoid necrosis
➢
A special form of necrosis usually seen in immune
reactions involving blood vessels
➢
This pattern of necrosis is prominent when complexes of
antigens and antibodies are deposited in the walls of
Arteries
➢
Deposits of these immune complexes together with fibrin
that has leaked out of vessels result in a bright pink and
amorphous appearance called 'fibrinoid”
Fibrinoid necrosis in an artery
in a patient with Polyarteritis
Nodosa. The wall of the
artery
shows a circumferential bright
pink area of necrosis with
protein deposition and
inflammation
38. Gangrenous Necrosis
➢
This is not a distinctive pattern of cell death
➢
It is usually applied to a limb, generally the lower leg, that
has lost its blood supply involving multiple tissue layers
➢
Types:
✔
Wet gangrene
✗
Occurs in naturally moist areas like mouth, bowels lungs
✗
Characterized by numerous bacteria
✔
Dry gangrene
✗
begins at the distal part of the limb due to ischemia and
often occurs in the toes and feet of elderly
patients due to arteriosclerosis
✗
This is mainly due to arterial occlusion
✗
There is limited putrefaction and bacteria fail to
survive
39.
40. SUBCELLULAR RESPONSES TO INJURY
• Autophagy
•Refers to lysosomal digestion of the cell's own
components
•It is thought to be a survival mechanism in times of nutrient
deprivation
•Organelles are enclosed in vacoules that fuse with
lysosomes
Heterophagy a cell usually a macrophage ingests
substances from the outside for intracellular destruction
41.
42. • Hypertrophy of Smooth Endoplasmic Reticulum
Cells exposed to toxins that are metabolized in the SER show
hypertrophy, a compensatory mechanism to maximize
removal of the toxins
• Mitochondrial Alterations
* alterations in size, number, shape & function
Ex. Mitochondria assume extremely large & abnormal
shapes (megamitochondria) in hepatocytes in various
nutritional deficiencies & alcoholic liver disease
Cellular hypertrophy > # of mitochondria in cells
Atrophy < # of mitochondria
• Cytoskeletal Abnormalities
some drugs & toxins interfere with the assembly & functions
of Cytoskeleton filaments or result in abnormal
accumulations of filaments
43. General Principles Relevant To Most Forms Of Cell Injury
• The cellular response to injurious stimuli depends on the type of
injury, its duration, and its severity
• The consequences of an injurious stimulus depend on the type ,
status , adaptability , and genetic makeup of the injured cell
•Cell injury results from functional & biochemical abnormalities in
• one or more of several essential cellular components
The most important target of injurious stimuli are:
1) cell membrane integrity, critical to cellular ionic and osmotic
homeostasis
2) mitochondrial, the site of adenosine triphosphate (ATP)
generation
3) protein synthesis
4) integrity of the genetic apparatus
5) cytoskeleton
44. MECHANISMS OF CELL INJURY
➢
ATP depletion: failure of energy-dependent functions
reversible Injury necrosis
➢
Mitochondrial damage: ATP depletion failure of energy-
dependent cellular functions ultimately necrosis;
under some conditions, leakage of proteins that causes apoptosis
➢
Influx of calcium: activation of enzymes that damage cellular
components and may also trigger apoptosis
➢
Accumulation of reactive oxygen species: covalent modifications of
cellular proteins, lipids, nucleic acids
➢
Increased permeability of cellular membranes: may affect plasma
membrane, lysosomal membranes, mitochondrial membranes;
typically culminates in necrosis
➢
Accumulations of damaged DNA and misfolded proteins triggers
apoptosis
45. Accumulation of Oxygen-Derived Free radicals (Oxidative
Stress)
Free radicals are chemical species with single unpaired electron
in an outer orbital. In such a state the radicals are extremely
unstable & readily react with inorganic or organic chemicals.
Free radicals may be generated within cells by
• Reduction-oxidation (redox) reactions
• Nitric oxide (NO)
• Absorption of radiant energy (e.g. ultraviolet light, x-rays)
• Enzymatic metabolism of exogenous chemicals (e.g. carbon
tetrachloride)
• Inflammation, because free radicals are produced by leukocytes
that enter tissues
46. Mechanisms that remove Free radicals
●
Action of superoxide dismutases (SODS)
●
Glutathione (GSH) peroxidase
●
Catalase present in perixisomes
●
Endogenous or exogenous antioxidants (e.g. vitamins E, A
and C, and beta-Carotene may either block the formation of
free radicals or scavenge them once they have formed
●
Iron and Copper can catalyze the formation of Reactive
Oxygen Species (ROS)
47. APOPTOSIS (“FALLING OFF”)
➢
Is a pathway of cell death that is induced by a tightly
regulated suicide program in which cells destined to die
activate enzymes capable of degrading the cells own
nuclear DNA and nuclear and cytoplasmic proteins
➢
It differs from necrosis in the following characteristics
1) Plasma membrane of the apoptotic cell remains
intact
2) Has no leakage of cellular contents
3) Does not elicit an inflammatory reaction in the host
➢
Sometimes coexist with necrosis
➢
Apoptosis induced by some pathologic stimuli may
progress to necrosis
48. Causes of Apoptosis
Apoptosis in Physiologic Situations
Death by apoptosis is a normal phenomenon that
serves to eliminate cells that are no longer needed and to
maintain a steady number of various cell populations in tissues
Programmed destruction of cells during embryogenesis,
Including implantation, organogenesis, developmental
involution, and metamorphosis
Involution of hormone- dependent tissues upon hormone
deprivation such as endometrial cell breakdown during the
menstrual cycle and regeression of the lactating breast after
Weaning
Cell loss in proliferating cell populations, such as intestinal
Crypt epithelia
49. Death of cells that have served their useful purpose, such
as neutrophils in an acute inflammatory response and
Lymphocytes at the end of an immune response
Elimination of potentially harmful self-reactive lymphocytes
Either before or after they have completed their maturation
Cell death induced by cytotoxic T lymphocytes, a defense
mechanism against viruses and tumors that serves to kill
eliminate virus-infected and neoplastic cells
50. Apoptosis in Pathologic Situations
Apoptosis eliminates cells that are genetically altered or
Injured beyond repair without eliciting a severe host reaction,
thus keeping the damage as contained as possible
DNA damage
Radiation, cytotoxic anticancer drugs, extremes of
temperature and even hypoxia can damage DNA either
directly or via production of free radicals
Accumulation of misfolded proteins
✔
These may arise because of mutations in the genes
encoding these proteins or because of extrinsic factors
such as free radicals
✔
Excessive accumulation of these proteins in the ER leads
to a condition called ER stress
51.
Cell injury in certain infections particularly viral infections
Pathologic atrophy in parenchymal organs after duct
obstruction such as in pancreas, parotid gland and kidney
Morphologic Alterations in Apoptosis
●
Nuclear chromatin condensation
●
Formation of apoptotic bodies ( fragments of nuclei and
cytoplasm)
The fundamental event in apoptosis is the activation of enzyme
called caspases
52. Two Major Pathways in the Initiation of Apopotosis
1) Mitochondrial ( intrinsic) pathway
Triggered by loss of survival signals, DNA damage
and accumulation of misfolded proteins (ER stress)
2) Death receptor (extrinsic) pathway
Responsible for the elimination of self-reactive
lymphocytes and damage by cytotoxic T lymphocytes
53. INTRACELLULAR ACCUMULATIONS
THREE MAIN PATHWAYS OF ABNORMAL INTRACELLULAR
ACCUMULATIONS
●
A normal substance is produced at abnormal or an increased
rate, but metabolic rate is inadequate to remove it
Example. Fatty change in the liver
●
A normal or abnormal endogenous substance accumulates
because of genetic or acquired defects in its folding,
packaging, transport or secretion
Example. Accumulation of of proteins in anti-trypsin deficiency
●
An abnormal exogenous substance is deposited and
Accumulates because the cell has neither the enzymatic
Machinery to degrade the substance nor the ability to transport
It to other sites.
Example. Accumulation of carbon or silica particles
54. Fatty Change (Steatosis)
Refers to any abnormal accumulation of triglycerides within
✔
parenchymal cells
Most often seen in the liver but may also occur in the heart,
✔
Skeletal muscle, kidney and other organs
May be caused by toxins, protein malnutrition, diabetes
✔
mellitus, obesity and anoxia
Alcohol abuse and diabetes associated with obesity are
✔
the most common causes of fatty liver
56. Cholesterol and Cholesteryl Esters
✔
Result of defective catabolism and excessive intake
Present in lipid vacoules of smooth muscle cells and
✔
macrophages in atherosclerosis (hardening of the aorta)
Give atherosclerotic plaques their characteristic yellow color
✔
and contibute to the pathogenesis of the lesion
✔
Xanthomas are hypercholesterolemic tumurous masses
found in the connective tissue of the skin or tendons
57. Proteins
✔
Less common than lipid accumulations
✔
Occur because excess are presented to the cells or
because the cells synthesize excessive amounts
✔
Examples:
1) Nephrotic syndrome there is heavy protein leakage
across the glomerular filter due to a much larger
reabsorption of albumin
2) accumulation of newly synthesized imunoglobulins
in RER of some plasma cells forming rounded,
eosinophilic Russell bodies
3) Mallory body or “ alcoholic hyalin” is an eosinophilic
cytoplasmic inclusion in liver cells highly characteristic
of alcoholic liver disease
4) Neurofibrillary tangle found in the brain in Alzheimer
disease
59. Glycogen
✔
Accumulations of these are associated with abnormalities
in the metabolism of either glucose or glycogen
✔
Ex.
1) In poorly controlled diabetes mellitus, glycogen
accumulates in renal tubular epithelium, cardiac
myocytes, and β cells of Islets of langerhans
2) Glycogen storage diseases or glycogeneses are
Genetic disorders where glycogen accumulates in
macrophages of patients with defects in lysosomal
enzymes
60. Pigments
➢
colored substances that are either exogenous or
endogenous
●
Exogenous – coming from outside the body
1) Carbon ( ex. Coal dust)
➔
Most common air pollutant
➔
Aggregates of the pigment blacken the
draining lymph nodes and pulmonary
parenchyma (Anthracosis)
➔
Heavy accumulations may induce emphysema
or a fibroblastic reaction that can result in a
serious lung disease called coal workers
pneumoconiosis
61. ●
Endogenous – synthesized within the body itself
1) Lipofuscin or “wear-and -tear pigment or lipochrome
✔
an insoluble brownish-yellow granular intracellular
material that accumulates in the heart, liver, & brain as
a function of age or atrophy
✔
represents complexes of lipid & protein that derive
from the free radical-catalyzed peroxidation of
polyunsaturated lipids
✔
it is not injurious to the cell but is important as a
marker of past free-radical injury
✔
the brown pigment when present in large amounts,
imparts an appearance to the tissue that is called
brown atrophy
62. The pale golden brown finely granular pigment seen here in nearly
all hepatocytes is lipochrome (lipofuscin).
63. 2) Melanin
✔
An endogenous, brown-black pigment synthesized
exclusively by melanocytes when the enzyme tyrosinase
catalyzes tyrosine to (DOPA) dihydroxyphenylalanine
located in the epidermis
✔
Acts as a screen against harmful ultraviolet radiation
✔
Basal keratinocytes in the skin can accumulate the
pigment (e.g. in freckles)
65. 3) Hemosiderin
✔
A hemoglobin-derived granular pigment that is
golden yellow to brown and accumulates in tissues
when there is a local or systemic excess of iron
✔
Iron is normally stored within cells in association with the
protein apoferritin, forming ferritin micelles
✔
Iron can be identified by the Prussian blue reaction
66. Local excess of iron & consequently of hemosiderin result
✔
from hemorrhage
Ex. Bruise
The original red-blue color of hemoglobin is
transformed to varying shades of green-blue by the
local formation of biliverdin (green bile) and bilirubin
(red bile) from the heme moiety
✔
The iron of hemoglobin accumulate as golden- yellow
hemosiderin
67. Hemosiderosis
✔
a condition where hemosiderin is deposited in many
organs and tissues whenever there is systemic overload
of iron
✔
It occurs in the following settings
•Increased absorption of dietary iron
•Impaired utilization of iron
•Hemolytic anemias
•Transfusions
Hereditary Hemochromatosis
✔
A condition where there is extensive accumulations of iron
with tissue injury like liver fibrosis, heart failure and
diabetes mellitus
✔
Characterized principally by
1) the deposition of hemosiderin in the following organs (in
decreasing order of severity):liver, pancreas,
myocardium, pituitary, adrenal, thyroid, joints & skin
2) cirrhosis and 3) pancreatic fibrosis
68. PATHOLOGIC CALCIFICATION
➢
implies the abnormal deposition of calcium salts, together
with small amounts of iron, magnesium, and other minerals
TYPES
A. Dystrophic calcification
✔
deposition of calcium in dead or dying tissues
✔
occurs in the absence of calcium metabolic
derangements ( with normal serum levels of calcium)
✔
Local deposits of calcium may occur in
1) necrotic tissue which is not absorbed
●
old infarcts
●
tuberculous foci
●
old collection of pus
●
dead parasites
●
acute pancreatic necrosis
69. 2) Tissue undergoing slow degeneration
●
Hyaline areas in benign tumors
●
Fibroids
●
In arteries due to atheromatous degeneration or old age
●
Old thrombi
●
Diseased or abnormal heart valves
Pathogenesis
➢
Initiation ( or nucleation)
➢
Propagation
Both may be intracellular or extracellular with calcium
phosphate as the end product
70. B. Metastatic Calcification
✔
deposition of calcium salts in normal tissues
✔
almost always reflects some derangement in calcium
metabolism ( hypercalcemia)
Four major causes of hypercalcemia
1) Increased secretion of parathyroid hormone, due to either
parathyroid tumors or production of parathyroid hormone-
Related protein by other malignant tumors
2) Destruction of bone due to the effects of accelerated
turnover (e.g. Paget disease),immobilization, or tumors
(increased bone catabolism associated with multiple
myeloma, leukemia or diffuse skeletal metastases)
3) Vitamin D-related disorders like vitamin D intoxication and
sarcoidosis ( in which macrophages activate a vitamin D
precursor
4) Renal failure, in which phosphate retention leads to
secondary hyperparathyroidism
71. CELLULAR AGING
➢
results from combination of accumulating cellular damage
(e.g., by free radicals), reduced capacity to divide (replicative
senescence), and reduced ability to repair damaged DNA
Cellular senescence
➢
Aging of a person is intimately related to cellular aging
Mechanisms known or suspected to be responsible for cellular
aging
●
DNA damage
✔
defective DNA repair mechanisms
DNA repair may be activated by calorie restriction (known
to prolong aging in model organisms)
72. ●
Replicative senescence
✔
Reduced capacity of cells to divide because of decreasing
amounts of telomerase and progressive shortening of
chromosomal ends (telomeres)
Telomeres
➔
are short repeated sequences of DNA present at the
linear ends of chromosomes
➔
Importance
* for ensuring the complete replication of chromosome
ends
* and for protecting the ends from fusion & degradation
●
Progressive accumulation of metabolic damage
✔
Repeated environmental exposure to radiation
✔
Progressive reduction of antioxidant defense mechanism
Like Vit. E & glutathione peroxidase
●
Possible roles of growth factors