This document provides an overview of cell injury and cell death processes presented by Dr. Marc Imhotep Cray. It discusses reversible cell injury mechanisms including hydropic swelling, intracellular accumulations, and cellular adaptation processes. It also covers irreversible cell injury mechanisms of necrosis and apoptosis. Necrosis types such as coagulative, liquefactive, caseous, and fat necrosis are described. The document provides histological images and discusses the cellular and molecular mechanisms involved in different types of cell injury and death.
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.
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
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.
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
Definition of inflammation, Causes, Signs of inflammation, Types of inflammation, Triple response, Phagocytosis, Transudate or Exudate, Difference between transudate and exudate, Granuloma and Granulomatous inflammation
“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
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
INTRODUCTION
HISTORY
CAUSES OF INFLAMMATION
CLASSIFICATION
ACUTE INFLAMMATION
CHEMICAL MEDIATORS OF INFLAMMATION
OUTCOMES OF ACUTE INFLAMMATION
CHRONIC INFLAMMATION
INFLAMMATORY DISEASES
REFERENCES
Definition of inflammation, Causes, Signs of inflammation, Types of inflammation, Triple response, Phagocytosis, Transudate or Exudate, Difference between transudate and exudate, Granuloma and Granulomatous inflammation
“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
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
INTRODUCTION
HISTORY
CAUSES OF INFLAMMATION
CLASSIFICATION
ACUTE INFLAMMATION
CHEMICAL MEDIATORS OF INFLAMMATION
OUTCOMES OF ACUTE INFLAMMATION
CHRONIC INFLAMMATION
INFLAMMATORY DISEASES
REFERENCES
this is a series of notes on general pathology, useful for undergraduate and post graduate pathology students. Notes have been prepared from standard textbooks and are in a format easy to reproduce in exams.
This report, prepared by the student at the College of Dentistry, Hassan Atheed , in the third phase discusses scientific topics, but it maybe did not be 100% complete.
Cell injury (cell death): it is the variable changes in morphological and functional properties of cell occurs due to internal or external causes (ex. Chemical, physical, infectious and genetic agents), that obligate cell to respond for preserving normal hemostasis (adaptation) or death (necrosis) when the injury factors sever cell unable to adept, cell may also killed by another pathway even when it have the ability to adept for saving other cells and tissue by programed cell death (apoptosis).
حسن عضيد
CONTENTS,
Introduction
Necrosis
Fates of necrotic cells
Patterns of tissue necrosis
Causes of cell injury
The biomechanism of cell injury
Clinicopathological correlations; examples of cell injury and necrosis
Apoptosis
Causes of apoptosis
Apoptosis in physiologic conditions
Apoptosis in pathologic conditions
Mechanism of Apoptosis
The Mitochondrial pathway of Apoptosis
The Death receptor pathway of Apoptosis
Clearance of Apoptotic cells
Examples of Apoptosis
Summary
References
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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Cell Injury and Cell Death
1. Cell Injury and Cell Death:
A Capsular Review
Prepared and presented by
Marc Imhotep Cray, M.D.
Companion Notes:
General Concepts in Pathology
(Q & A Rapid Review)
3. PowerPoint
General Pathology Concepts & Diseases_ A Global Overview
eNotes
IVMS General Pathology Lecture Notes.pdf
Images
IVMS-Gross Pathology, Histopathology, Microbiology and
Radiography High Yield Image Plates.pdf
WebPath Website
http://www-medlib.med.utah.edu/WebPath/webpath.html
Companion learning tools and resources:
4. Marc Imhotep Cray, M.D.
Stages of cellular response to stress & injurious stimuli
4
Kumar V and Abbas AK. Robbins and Cotran Pathologic Basis of Disease 8th ed.
Philadelphia: Saunders, 2014
5. Marc Imhotep Cray, M.D.
Ultrastructural features of reversible cell injury
5
Endoplasmic reticulum (ER): cisternae of the ER are
distended by fluid in hydropic swelling
Mitochondria: In some forms of acute injury,
particularly ischemia (lack of adequate blood flow),
mitochondria swell
Plasma membrane: Blebs of plasma membrane-
that is, focal extrusions of cytoplasm
Nucleus: reflected mainly by segregation of fibrillar
and granular components of nucleolus
These changes in cell organelles are reflected in
functional derangements (e.g., reduced protein
synthesis, impaired energy production)
After withdrawal of stress that caused reversible
cell injury, by definition, cell returns to its normal
state
Copstead LC, Banksia JL. Pathophysiology, 5th Ed. St. Louis,
Missouri: Saunders-Elsevier, 2013.
6. Marc Imhotep Cray, M.D.
Reversible Cell Injury: Hydropic Swelling
Cellular swelling in kidney tubule epithelial cells. A, Normal
kidney tubule with cuboidal cells; B, early ischemic changes
showing surface blebs and swelling of cells.
Copstead LC, Banksia JL. Pathophysiology, 5th Ed. St. Louis, Missouri: Saunders-Elsevier, 2013. 6
7. Marc Imhotep Cray, M.D.
Reversible Cell Injury: Intracellular Accumulations
Copstead LC, Banksia JL. Pathophysiology, 5th Ed. St. Louis, Missouri:
Saunders-Elsevier, 2013. 7
Intracellular accumulations may be
categorized as
(1) excessive amounts of normal intracellular
substances such as fat
(2) accumulation of abnormal substances
produced by cell b/c of faulty metabolism or
synthesis, and
(3) accumulation of pigments and particles that
cell is unable to degrade
Lipids may contribute to atherosclerotic
diseases and accumulate in blood vessels,
kidney, heart, and other organs
Fat filled cells tend to compress cellular
components to one side and cause tissue
to appear yellowish and greasy
Fatty liver showing large intracellular vacuoles of lipid.
8. Marc Imhotep Cray, M.D.
Reversible Cell Injury
Roles of chaperone proteins in protein refolding and ubiquitin in protein
degradation after stress-induced protein damage
8
9. Marc Imhotep Cray, M.D.
Reversible Cell Injury
Intracellular Accumulations (1)
9
Accumulations of silicon dust in tissues
of the lung.
Copstead LC, Banksia JL. Pathophysiology, 5th Ed.
St. Louis, Missouri: Saunders-Elsevier, 2013.
Excess accumulations of substances in
cells may result in cellular injury b/c
substances are toxic or provoke an
immune response, or
merely b/c they occupy space needed for
cellular functions
In some cases, accumulations do not in
themselves appear to be injurious but
rather are indicators of cell injury.
10. Marc Imhotep Cray, M.D.
Reversible Cell Injury
Intracellular Accumulations (2)
10
Intracellular accumulations may be categorized as:
(1) excessive amts. of normal intracellular substances such as fat
Abnormal metabolism as in fatty change in liver
(2) accumulation of abnormal substances produced by cell b/c of
faulty metabolism or synthesis
Mutations causing alterations in protein folding and
transport so that defective proteins accumulate
Deficiency of critical enzyme responsible for lysosomal
degradation
(3) accumulation of pigments and particles that cell is unable to
degrade
an inability to degrade phagocytosed particles such as coal
dust
Copstead LC, Banksia JL. Pathophysiology, 5th Ed.
St. Louis, Missouri: Saunders-Elsevier, 2013.
11. Marc Imhotep Cray, M.D.
Reversible Cell Injury
KEY POINTS
• Hydropic swelling is an early indicator of cell injury. It results from Na+-
K+ pump dysfunction at cell membrane.
• Intracellular accumulations of abnormal endogenous or exogenous
particles indicate a disorder of cellular metabolism.
• Damage from accumulation of abnormal intracellular protein is limited
by chaperone proteins that attempt to refold the protein into its correct
shape and by the ubiquitin-proteosome system that digests targeted
proteins into fragments.
11
12. Marc Imhotep Cray, M.D.
Cellular Adaptation
Adaptive cellular responses of atrophy, hypertrophy, hyperplasia,
metaplasia, and dysplasia
Copstead LC, Banksia JL. Pathophysiology, 5th Ed. St.
Louis, Missouri: Saunders-Elsevier, 2013.
12
13. Marc Imhotep Cray, M.D.
Cellular Adaptation (2)
13
A, Normal brain of a young adult.
B, Atrophy of the brain in an 82- year-old male with atherosclerotic cerebrovascular
disease, resulting in reduced blood supply.
Kumar V and Abbas AK. Robbins and Cotran Pathologic Basis of Disease 8th ed.
Philadelphia: Saunders, 2014.
14. Marc Imhotep Cray, M.D.
Cellular Adaptation (2)
A, Hypertrophy of cardiac muscle in left ventricular chamber.
B, Compare with the thickness of normal left ventricle.
This is an example of cellular adaptation to an increased cardiac workload.
Copstead LC, Banksia JL. Pathophysiology, 5th Ed. St. Louis, Missouri: Saunders-Elsevier, 2013.
14
15. Marc Imhotep Cray, M.D.
Cellular Adaptation
KEY POINTS
• Adaptive cellular responses indicate cellular stress caused by altered
functional demand or chronic sublethal injury.
• Hypertrophy and hyperplasia generally result from increased functional
demand.
• Atrophy results from decreased functional demand or chronic ischemia.
• Metaplasia and dysplasia result from persistent injury.
15
16. Irreversible Cell Injury: Necrosis
Type of necrosis is dependent on nature, intensity and duration of injurious
agent, and type of cell involved
N.B.-initial membrane damage allows Ca+2 leakage with subsequent activation of Ca-
dependent phosphatases and lipases
Coagulative necrosis – cytoplasm of necrosed cells becomes eosinophilic and
persists for many days (myocardial infarction)
Liquefactive necrosis – cells undergo lysis rapidly (brain infarcts)
Caseous necrosis – Mycobacterium tuberculosis interacts with macrophages
Gangrenous necrosis – primary (bacterial toxins) or secondary (ischemia,
infection)
Fibrinoid necrosis – smooth muscle necrosis, fibrin release (malignant
hypertension)
Fat necrosis – inflammatory response to liberated fat fibrosis (pancreas)16
17. Irreversible Cell Injury: Necrosis (2)
17
There are also nuclear changes related to necrosis:
Margination of chromatin chromatin condensing around
periphery of nucleus
o Chromatin clumping is reversible, but dissolution of entire nucleus
is not reversible when nucleus is lost cell will die
Pyknosis – small and dense nuclei
Karyolysis – complete lysis of the nuclei
Karyorrhexis – fragmented nuclei (generally seen in apoptosis)
18. Irreversible Cell Injury: Necrosis (3)
18
Irreversible cell injury is typically accompanied by:
Release of intracellular enzymes:
o Cardiac muscle – troponin, creatine kinase (MB isoform), aspartate
(AST) transaminase, lactate dehydrogenase (LDH)
o Hepatocytes – alanine transaminase
o Striated muscle – creatine kinase (MM isoform)
o Exocrine pancreas – amylase
Loss of membrane selectivity – may be helpful in diagnosis through
uptake of dyes
Inflammatory response – initiated by products (mediators) of the
necrotic cells
19. Marc Imhotep Cray, M.D.
Coagulative necrosis / Dry gangrene
Gangrene is a term used to describe cellular death
involving a large area of tissue
Gangrene usually results from interruption of major
blood supply to a particular body part such as toes, leg,
or bowel (ex. Diabetes mellitus patients)
Depending on appearance and subsequent infection of
necrotic tissue it is described as dry gangrene vs wet
gangrene vs gas gangrene
Dry gangrene is a form of coagulative necrosis
characterized by blackened, dry, wrinkled tissue that is
separated from adjacent healthy tissue by an obvious
line of demarcation (as see in illustration)
Copstead LC, Banksia JL. Pathophysiology, 5th Ed.
St. Louis, Missouri: Saunders-Elsevier, 2013.
19
20. Marc Imhotep Cray, M.D.
Gangrene cont.
Liquefactive necrosis may result in wet gangrene typically found in
internal organs, appears cold and black, and may be foul smelling b/c of
invasion of bacteria
Rapid spread of tissue damage and release of toxins into bloodstream
make wet gangrene a life-threatening problem
Gas gangrene is characterized by formation of bubbles of gas in damaged
tissue
Gas gangrene is result of infection of necrotic tissue by anaerobic
bacteria Clostridium perfringens
o bacteria produce toxins and degradative enzymes that allow
infection to spread rapidly through necrotic tissue
Gas gangrene may be fatal if not managed rapidly and aggressively
21. Marc Imhotep Cray, M.D.
Coagulative necrosis
21
Coagulative necrosis is most common
Manifestations of coagulative necrosis are
same, regardless of cause of cell death
In general, steps leading to coagulative
necrosis may be summarized as follows:
(1) ischemic cellular injury leading to
(2) loss of plasma membrane’s ability to
maintain electrochemical gradients, which
results in
(3) an influx of calcium ions and
mitochondrial dysfunction, and
(4) degradation of plasma membranes and
nuclear structures
Two large infarctions (areas of coagulative
necrosis) are seen in this sectioned spleen
http://library.med.utah.edu/WebPath/CINJHTML/CINJ018.html
22. Marc Imhotep Cray, M.D.
Coagulative necrosis (2)
A. Normal heart. All myocytes are nucleated, and striations are clear.
B. Myocardial infarction. The heart from a patient following acute myocardial
infarction. The necrotic cells are deeply eosinophilic and most have lost their nuclei.
Rubin R and Strayer DS Eds. Rubin’s Pathology: Clinicopathologic Foundations of Medicine, 6th Ed. Baltimore: LLW, 2012
22
23. Marc Imhotep Cray, M.D.
Mechanisms by which ischemia leads to
cellular death by necrosis
23
1. Loss of oxygen due to vascular occlusion
impairs mitochondrial function resulting
in decreased energy (adenosine triphosphate
[ATP]) production by aerobic processes
2. Decreased ATP impairs ATP-dependent ion
exchangers
3. Loss of aerobic processes causes anaerobic
glycolysis to predominate, with consequent
intracellular acidosis, eventually leading to
increased cytosolic [Ca2+]
4. Ca2+-dependent phospholipases are then
activated, causing loss of cell membrane
integrity and necrosis
Rubin R and Strayer DS Eds. Rubin’s Pathology: Clinicopathologic
Foundations of Medicine, 6th Ed. Baltimore: LLW, 2012
24. Marc Imhotep Cray, M.D.
Liquefactive necrosis
When rate at which necrotic cells dissolve
greatly exceeds rate of repair resulting
appearance is termed liquefactive necrosis
PMN cells of acute inflammatory reaction contain
potent hydrolases capable of digesting dead cells
A sharply localized collection of these acute
inflammatory cells (generally in response to
bacterial infection) produces rapid cell death
and tissue dissolution
Result is often an abscess a cavity formed by
liquefactive necrosis in a solid tissue
Liquefactivenecrosisinanabscessoftheskin.
Rubin R and Strayer DS Eds. Rubin’s Pathology: Clinicopathologic
Foundations of Medicine, 6th Ed. Baltimore: LLW, 2012
Copstead LC, Banksia JL. Pathophysiology, 5th Ed.
St. Louis, Missouri: Saunders-Elsevier, 2013.
24
25. Marc Imhotep Cray, M.D.
Fat necrosis
Copstead LC, Banksia JL. Pathophysiology, 5th Ed. St. Louis,
Missouri: Saunders-Elsevier, 2013.
25
Fat necrosis refers to death of adipose tissue
usually results from trauma or pancreatitis
Process begins with release of activated digestive
enzymes from pancreas or injured tissue
Enzymes attack cell membranes of fat cells
causing release of their stores of triglycerides
Pancreatic lipase can then hydrolyze triglycerides to
free fatty acids and glycerol which precipitate as
calcium soaps (saponification)
Fat necrosis appears as a chalky white area of tissue
26. Marc Imhotep Cray, M.D.
Caseous necrosis
Copstead LC, Banksia JL. Pathophysiology, 5th Ed. St. Louis, Missouri:
Saunders-Elsevier, 2013.
26
Caseous necrosis is characteristic of
lung tissue damaged by tuberculosis
Areas of dead lung tissue are white,
soft, and fragile resembling
clumpy cheese
Dead cells are walled off from rest of
lung tissue by inflammatory WBCs
In center, dead cells lose their
cellular structure but are not totally
degraded
Necrotic debris may persist
indefinitely
27. Marc Imhotep Cray, M.D.
Caseous necrosis (2) tuberculous lymph node
27
Hilar lymph node from a
patient with active tuberculosis
Irregular pink areas of caseous
necrosis (arrow) are evident
against a background of
lymphocytes
Inset: Granulomas on the
periphery of necrotic areas
show epithelioid macrophages
and multinucleated giant
(Langhans) cells (arrows)
Rubin R and Strayer DS Eds. Rubin’s Pathology: Clinicopathologic Foundations of Medicine,
6th Ed. Baltimore: LLW, 2012
28. Marc Imhotep Cray, M.D.
Apoptosis
28
Cell death can also occur through apoptosis
it may be physiological deletion of selected cells (e.g.
morphogenesis, cyclic hyperplasia of reproductive processes) or
it may occur in response to a pathological stimuli
Number of cells in tissues is tightly regulated by controlling rate of
cell division and rate of cell death
If cells are no longer needed they activate a cellular death
pathway resulting in cell suicide
Note: there are no gross structural changes involved with apoptosis
29. Marc Imhotep Cray, M.D.
Apoptosis (2)
29
In contrast to necrosis, which is messy and results in inflammation and
collateral tissue damage
apoptosis is tidy and does not elicit inflammation
Apoptosis is not a rare event large numbers of cells are continually
undergoing programmed cell death as tissues remodel
For example:
During fetal development more than half of nerve cells that form
undergo apoptosis
It is estimated that more than 95% of T lymphocytes that are
generated in bone marrow are induced to undergo apoptosis after
reaching thymus
30. Marc Imhotep Cray, M.D.
Apoptosis (3)
30
The initiation of apoptosis requires two processes:
Priming – a reversible stage in which specialist machinery for apoptosis
(e.g. transglutamase, calcium/magnesium endonucleases) are activated
Triggering – the irreversible point which leads to a sustained rise in
cytosolic calcium, and induction of new mRNA species for c-fos, c-myc
and heat-shock proteins
Apoptosis then proceeds:
1. Cytosol and nucleus lost half their volume
2. Fragmentation of nucleus and cytosol ( activation of transglutamase that forms an
insoluble layer beneath the intact cell membrane)
3. Condensation of chromatin (pyknosis)
4. Macrophages bind to cell fragments prior to phagocytosis (non-specific mechanism)
31. Marc Imhotep Cray, M.D.
Comparison of cellular changes in necrosis and apoptosis
Copstead LC, Banksia JL. Pathophysiology, 5th Ed. St. Louis, Missouri: Saunders-Elsevier, 2013.
Pathological cell death is more
often due to necrosis
process releases intracellular
enzymes (useful diagnostically)
and
mediators that stimulate
inflammation followed by
healing by repair, scarring,
contracture & distortion of
tissue architecture
33. Marc Imhotep Cray, M.D.
Necrosis and Apoptosis
KEY POINTS
• Necrosis occurs when the injury is too severe or prolonged to allow adaptation and is
usually a consequence of disrupted blood supply.
• Local and systemic indicators of cell death include pain, elevated serum enzyme levels,
inflammation (fever, elevated WBC count, malaise), and loss of function.
• Different tissues exhibit necrosis of different types: heart (coagulative), brain (liquefactive),
lung (caseous), and pancreas (fat).
• Gangrene refers to a large area of necrosis that may be described as dry, wet, or gas
gangrene. Gas gangrene and wet gangrene may be rapidly fatal.
• Apoptosis is cell death resulting from activation of intracellular signaling cascades that
cause cell suicide. Apoptosis is tidy and not usually associated with systemic manifestations of
inflammation.
33
34. Marc Imhotep Cray, M.D. 34
THE END
Further study tools and resources on last slide.
35. Marc Imhotep Cray, M.D.
Further study:
35
eLearning:
IVMS General and Systems Pathology Cloud Folder
Internet Pathology Laboratory for Medical Education
http://library.med.utah.edu/WebPath/webpath.html#MENU
Textbooks:
Kumar V and Abbas AK. Robbins and Cotran Pathologic Basis of Disease 8th ed.
Philadelphia: Saunders, 2014
Rubin R and Strayer DS Eds. Rubin’s Pathology: Clinicopathologic Foundations of
Medicine, 6th Ed. Baltimore: Lippincott Williams & Wilkins, 2012