Pathophysiology
• JP Advis DVM, Ph.D.
Bartlett Hall, Animal Sciences, Cook,
932 - 9240, advis@aesop.rutgers.edu
01
• Course website: rci.rutgers.edu/~advis
• Lectures, tests, grades, office hours, textbook,
Lectures 1-2: Introduction to Pathophysiology (2)
Lectures 3-4: Mechanisms of Self-Defense and Stress (2)
Lectures 5-8: Endocrine and Nervous System Dysfunctions (4)
Lecture
9: Alterations of Skeletal Muscle Function (1)
REVIEW AND TEST #1
Lectures 12-18: Cardiovascular, Respiratory and Renal Dysfunctions (7)
REVIEW AND TEST #2
Lectures 21-24: Alterations of Digestive Function and Intermediary Metabolism (4)
Lectures 25-26: Alterations of the Reproductive System (2)
REVIEW AND TEST #3
• Material to
be covered:
• About
lecture
slides:
•
•
•
•
There are not intended to be the sole source for studying the course material !!!!!!!!!!!!!!!!
Slides are good to review the course material after you have study your course textbook
Slides are a good indicator of the relative importance of lecture topics (see slide # per topic)
Group slides by titles when using them to review course material. Match lectures and text.
Introduction to Pathophysiology
Physiology is best learned in a systematic approach, by
understanding cellular and macroscopic body processes.
What is a disease
life, death, suspended life,
cell as a patient, terms and
definitions, cell adaptations
Cell injury and its types
cell injury, intracellular
accumulations
Cell injury & its systemic
manifestations
systemic manifestations,
cell death
Rather than memorizing individual relationships, student
should strive to learn the underlying rationale, such as:
“The cell membrane allows passage of some molecules
and not others based on lipid solubility, size of molecules,
concentration gradient, and electrical charge.
Since cell membranes are formed by lipid bilayers, liposoluble molecules pass through more easily. Smaller
molecules and those without an electrical charge also
transfer more easily.
Finally, the concentration gradient “drives” the molecular
transport, with larger gradient providing a greater “force”.
The use of “punch – lines” in an active learning mode is the
best way to learn physiology and pathophysiology.
Page 1
Introduction to Pathophysiology
What is a disease
life, death, suspended life,
cell as a patient, terms and
definitions, cell adaptations
Cell injury and its types
cell injury, intracellular
accumulations
Cell injury & its systemic
manifestations
systemic manifestations,
cell death
A rationale understanding of disease and plan for
treatment are best acquired by learning about the normal
physiological process on a basic science level; similarly
being aware of how disease alters normal physiological
process is best understood on a scientific level.
Physiology also requires the ability to appreciate the
normal working of the body, whereas pathophysiology
focus on how disease or disruption of the normal state
affects the same mechanisms.
The student should strive to learn the reason a disease
manifests as certain symptoms or signs.
The use of “punch – lines” in an active learning mode is the
best way to learn physiology and pathophysiology.
Introduction to Pathophysiology
What is a disease
life, death, suspended life,
cell as a patient, terms and
definitions, cell adaptations
Cell injury and its types
cell injury, intracellular
accumulations
Cell injury & its systemic
manifestations
systemic manifestations,
cell death
There are six key questions that help stimulate the
application of basic science information in the clinical
setting:
1.- what is the likely mechanism for the clinical findings ?
2.- what is the likely cellular response to a certain change
in the environment ?
3.- what is the biochemical finding noted, what clinical
processes are expected ?
4.- given physiological readings, what is the likely disease
process ?
5.- what is the likely mechanism for the medication effect ?
6.- what graphic data best depict the physiological
principle ?
The use of “punch – lines” in an active learning mode is the
best way to learn physiology and pathophysiology.
Page 2
Introduction to Pathophysiology
What is a disease
life, death, suspended life,
cell as a patient, terms and
definitions, cell adaptations
For every tissue there are standards of form and
function, with some allowance for acceptable
variance; any deviation from those limits implies
disease.
For example, at tissue level, normal, mucus secreting,
bronqui ciliated epithelium, becomes non secretory
squamus stratified epithelium in smokers, a
pathological condition.
Cell injury and its types
cell injury, intracellular
accumulations
Cell injury & its systemic
manifestations
systemic manifestations,
cell death
Diseases at the individual level is more difficult to
define because the boundaries are vague and shifting.
But we can use this old definition as starting point:
Disease is any condition of the body or mind
that decreases the chances of survival of
the individual or the species.
What is a disease ?
Two diseases that favor propagation:
What is a disease
life, death, suspended life,
cell as a patient, terms and
definitions, cell adaptations
achondroplasia of the basset hound
(inborn defect) and the Rembrandt or
broken tulip (mosaic type viral infection).
Cell injury and its types
Brain death (“electrocerebral
silence”) in a head injured man.
cell injury, intracellular
accumulations
Cell injury & its systemic
manifestations
systemic manifestations,
cell death
Page 3
What is a disease ?
What is a disease
life, death, suspended life,
cell as a patient, terms and
definitions, cell adaptations
Cell injury and its types
cell injury, intracellular
accumulations
Cell injury & its systemic
manifestations
systemic manifestations,
cell death
Portrait of Sebastian de Morra,
Jester in the Spaniard court of
Philip IV, by Diego Velazquez
Sebastian de Morra was crippled from birth and the subject of mockery and abuse from the
noblemen at the court. Velázquez portrays his whole body, sitting on the ground, wearing a
rich cloak and with his short legs pointing forward in an inelegant position reminiscent of a
marionette. He looks directly at the viewer, motionless, making no hand gestures, in
denunciation of the court’s treatment of himself and other dwarfs. His expression is severe
and sad, contrasting with his profession of jester and reflecting the torment of man.
What is a disease ?
What is a disease
life, death, suspended life,
cell as a patient, terms and
definitions, cell adaptations
Cell injury and its types
cell injury, intracellular
accumulations
Two examples of suspended life:
Commercial dried brine shrimp eggs.
After 3 days in a suitable medium the
shrimp have hatched. The Tardigrade
(water bear or slow walker), survive a
vacuum of a millionth of a mm, heating to
151°C, cooling to near 0°K, for 120 years.
Cell injury & its systemic
manifestations
For the purpose of this course we
will define disease as any condition
in which a chronic deviation of the
steady state is unable to regain its
homeostatic value.
systemic manifestations,
cell death
Page 4
Terms and Definitions
What is a disease
life, death, suspended life,
cell as a patient, terms and
definitions, cell adaptations
Cell injury and its types
Pathophysiology is the study of the underlying changes in
body physiology that results from disease or injury. It seeks to
provide an understanding of the mechanisms of disease and
how and why alterations in body function lead to sign and
symptoms of disease. This understanding is basic to plan, to
select and to evaluate disease’s therapies and treatments.
Among some main “terms” used in pathophysiology are:
cell injury, intracellular
accumulations
Pathology & pathogenesis: structural alterations & its development
Cell injury & its systemic
manifestations
systemic manifestations,
cell death
Etiology: disease cause, known, idiopathic, iatrogenic, nosocomial
Signs & symptoms: objectives alterations & subjective experiences
Diagnosis and prognosis: disease and its expected outcome
Manifestations: acute, chronic, remission, exacerbation, complication
Cellular Injury and its Types
What is a disease
life, death, suspended life,
cell as a patient, terms and
definitions, cell adaptations
Cell injury and its types
cell injury, intracellular
accumulations
Cell injury & its systemic
manifestations
systemic manifestations,
cell death
Most diseases start with cell injury, which
occurs when the cell is unable to maintain
homeostasis, in the face of injurious stimuli
(chemicals, hypoxia, free radicals, infection,
physical/mechanical factors, immunologic
reactions, genetic and nutritional factors).
TYPES OF PROGRESSIVE CELL INJURY:
Adaptation
Active cell injury
Reversible cell injury
Irreversible cell injury
Necrosis
Apoptosis
Chronic cell injury
Accumulations or Infiltrations
Pathologic Calcification
Body response to progressive cell injury.
Page 5
TYPES OF
PROGRESSIVE
CELL INJURY:
Adaptation
Active cell injury
Reversible cell injury
Irreversible cell injury
Necrosis
Apoptosis
Chronic cell injury
Accumulation/Infiltration
Pathologic Calcification
Cellular Adaptations
CELL ADAPTATION:
What is a disease
life, death, suspended life,
cell as a patient, terms and
definitions, cell adaptations
Cell injury and its types
cell injury, intracellular
accumulations
CELLS ADAPT TO THEIR ENVIRONMENT:
to escape and protect themselves from injury.
An adapted cell is neither normal nor injured.
Common and central to many disease states.
Atrophy:
decrease in cell size
Hypertrophy: increase in cell size
Hyperplasia: increase in cell #
Cell injury & its systemic
manifestations
systemic manifestations,
cell death
Metaplasia: reversible change of a
mature cell by a less mature cell
Dysplasia: deranged cell growth,
an atypical hyperplasia
Body response to progressive cell injury.
Page 6
Cellular Adaptations
What is a disease
life, death, suspended life,
cell as a patient, terms and
definitions, cell adaptations
Cell injury and its types
cell injury, intracellular
accumulations
Cell injury & its systemic
manifestations
systemic manifestations,
cell death
CELL ADAPTATION:
ATROPHY:
Decrease or shrinkage in cellular size of a
cell, tissue or organ (e.g. skeletal muscle,
2nd sex organs, brain).
Atrophy can be classified as:
Physiological (thymus in early development)
Pathological (low workload, pressure, use,
blood supply, nutrition, hormonal stimulation
and nervous stimulation).
Atrophic cells exhibit:
Less ER, myofilaments and mitochondria.
Reduced O2 consumption and aa uptake.
Low prot synthesis and/or high catabolism.
(proteosomes, ubiquitin-proteosomes
pathways, autophagic vacuoles, lipofuscin)
Body response to progressive cell injury.
Cellular Adaptations
What is a disease
life, death, suspended life,
cell as a patient, terms and
definitions, cell adaptations
Cell injury and its types
cell injury, intracellular
accumulations
CELL ADAPTATION:
HYPERTROPHY:
Increase in cell size (e.g. heart, kidney) but
not fluid accumulation. It can be physiologic
or pathologic. Is caused by specific hormone
stimulation or increased functional demand.
Cardiac muscle in sigmoid valve stenosis:
A, normal (n) vs hypertrophy (h); B,n; C,h
Cell injury & its systemic
manifestations
systemic manifestations,
cell death
Body response to progressive cell injury.
Page 7
Cellular Adaptations
CELL ADAPTATION:
HYPERPLASIA:
Increase in cell # due to rise in cell division.
What is a disease
life, death, suspended life,
cell as a patient, terms and
definitions, cell adaptations
Cell injury and its types
cell injury, intracellular
accumulations
Physiological: can be compensatory (e.g.
liver) and hormonal (e.g. E2-uterine growth).
Pathological: usually an effect of excessive
hormonal or growth factor stimulation.
Secondary thickening of obstructed urinary
bladder due to hyperplasia of the prostate.
Cell injury & its systemic
manifestations
systemic manifestations,
cell death
Body response to progressive cell injury.
Cellular Adaptations
What is a disease
life, death, suspended life,
cell as a patient, terms and
definitions, cell adaptations
Cell injury and its types
cell injury, intracellular
accumulations
CELL ADAPTATION:
METAPLASIA:
Reversible replacement of a mature cell type
for a less differentiated by reprogramming of
stem cells, due to cytokines and / or growth
factors signals.
The best example is the replacement of
normal columnar ciliated epithelial cells of
the bronchial airways by stratified squamous
epithelial cells.
Cell injury & its systemic
manifestations
systemic manifestations,
cell death
Body response to progressive cell injury.
Page 8
Cellular Injury and its Types
What is a disease
life, death, suspended life,
cell as a patient, terms and
definitions, cell adaptations
Cell injury and its types
CELL INJURY:
Most diseases start with cell injury, which
occurs when the cell is unable to maintain
homeostasis, in the face of injurious stimuli
(chemicals, hypoxia, free radicals, infection,
physical/mechanical factors, immunologic
reactions, genetic and nutritional factors).
TYPES OF PROGRESSIVE CELL INJURY:
cell injury, intracellular
accumulations
Adaptation (see previous topic)
Active cell injury
Reversible cell injury
Irreversible cell injury
Necrosis
Apoptosis
Chronic cell injury
Accumulations or Infiltrations
Pathologic Calcification
Cell injury & its systemic
manifestations
systemic manifestations,
cell death
Body response to progressive cell injury.
Cellular Injury and its Types
TYPES OF PROGRESSIVE CELL INJURY AND RESPONSES
What is a disease
life, death, suspended life,
cell as a patient, terms and
definitions, cell adaptations
Cell injury and its types
cell injury, intracellular
accumulations
Types
Responses
Adaptation
Atrophy, hypertrophy, hyperplasia, metaplasia (see previous topic)
Active cell injury
Immediate response of the “entire” cell
Reversible
ATP loss, cell swelling, ribosome detachment, lysosome autophagy
Irreversible
“point of no return” when severe mito vacuolization and Ca entry occur
Necrosis
Common type of cell death with cell swelling and organelle breakdown
Apoptosis
Cell injury & its systemic
manifestations
systemic manifestations,
cell death
Chronic cell injury
Accumulation
Calcification
Cell self-destruction for elimination of unwanted cell population
Sub-cellular alterations, persistent stimuli may involve specific
organelles or cytoskeleton (e.g. phagocytosis of bacteria)
or infiltrations of water, pigments, lipids, glycogen, proteins
Dystrophic and metastatic calcification
Body response to progressive cell injury.
Page 9
TYPES OF PROGRESSIVE CELL INJURY AND RESPONSES
Types
Responses
Adaptation
Atrophy, hypertrophy, hyperplasia, metaplasia (see previous topic)
Active cell injury
Immediate response of the “entire” cell
Reversible ATP loss, cell swelling, ribosome detachment, lysosome autophagy
Irreversible “point of no return” when severe mito vacuolization and Ca entry occur
Necrosis Common type of cell death with cell swelling and organelle breakdown
Apoptosis Cell self-destruction for elimination of unwanted cell population
Chronic cell injury
Sub-cellular alterations, persistent stimuli may involve specific
organelles or cytoskeleton (e.g. phagocytosis of bacteria)
Accumulation or infiltrations of water, pigments, lipids, glycogen, proteins
Calcification Dystrophic and metastatic calcification
Cellular Injury & its Mechanisms
What is a disease
life, death, suspended life,
cell as a patient, terms and
definitions, cell adaptations
Cell injury and its types
GENERAL MECHANISMS OF CELL INJURY:
There are four mechanisms common to cell
injury regardless its etiology.
These are:
A
cell injury, intracellular
accumulations
Cell injury & its systemic
manifestations
systemic manifestations,
cell death
ATP depletion
O2 and O2-derived free radicals
Ca alterations
Membrane permeability defects
COMMON FORMS OF CELL INJURY:
B
Hypoxic injury
Free radicals and
reactive O2 species injury
Chemical injury
Body response to progressive cell injury.
Page 10
Cellular Injury & its Mechanisms
GENERAL MECHANISMS OF CELL INJURY AND DEATH:
What is a disease
life, death, suspended life,
cell as a patient, terms and
definitions, cell adaptations
Cell injury and its types
cell injury, intracellular
accumulations
Cell injury & its systemic
manifestations
systemic manifestations,
cell death
A
Theme
Comments
ATP depletion
Loss of mitochondrial ATP and decreased ATP synthesis, results include
cellular swelling, decreased protein synthesis, decreased membrane
transport and lipogenesis, all changes that contribute to loss of integrity
of the plasma membrane
O2 and O2derived free
radicals
Lack of O2 is key in progression of cell injury in ischemia; activated O2
species (free radicals, O2, H2O2, OH) cause destruction of cell
membranes and cell structure
Intracellular Ca
and loss of Ca
steady state
Normally intracellular cytosolic Ca is very low but ischemia and certain
chemicals increase it; sustained levels of Ca continue to increase with
damage to plasma membrane; Ca causes intracellular damage by
activating a number of enzymes
Defects of
membrane
permeability
An early loss of selective membrane permeability is found in all forms of
cell injury
Body response to progressive cell injury.
GENERAL MECHANISMS OF CELL INJURY AND DEATH: A
Theme
Comments
ATP depletion
Loss of mitochondrial ATP and decreased ATP synthesis, results
include cellular swelling, decreased protein synthesis, decreased
membrane transport and lipogenesis, all changes that contribute
to loss of integrity of the plasma membrane
O2 and O2derived free
radicals
Lack of O2 is key in progression of cell injury in ischemia;
activated O2 species (free radicals, O2, H2O2, OH) cause
destruction of cell membranes and cell structure
Intracellular Ca
and loss of Ca
steady state
Normally intracellular cytosolic Ca is very low but ischemia and
certain chemicals increase it; sustained levels of Ca continue to
increase with damage to plasma membrane; Ca causes
intracellular damage by activating a number of enzymes
Defects of
membrane
permeability
An early loss of selective membrane permeability is found in all
forms of cell injury
Page 11
Cellular Injury – Hypoxic Injury
What is a disease
COMMON FORMS OF CELL INJURY AND DEATH:
HYPOXIC INJURY (most common cause of cell injury)
B
life, death, suspended life,
cell as a patient, terms and
definitions, cell adaptations
Cell injury and its types
cell injury, intracellular
accumulations
Cell injury & its systemic
manifestations
systemic manifestations,
cell death
Reversible cell injury
Irreversible cell injury
Clinical manifestations
Reversible cell injury
Irreversible cell injury
Reversible cell injury
Irreversible cell injury
Clinical manifestations
Page 12
B
Cellular Injury – Hypoxic Injury
COMMON FORMS OF CELL INJURY AND DEATH:
HYPOXIC INJURY (most common cause of cell injury)
What is a disease
B
Restoration of O2 can cause additional injury
called reperfusion injury, due to free radicals
life, death, suspended life,
cell as a patient, terms and
definitions, cell adaptations
Cell injury and its types
cell injury, intracellular
accumulations
Cell injury & its systemic
manifestations
systemic manifestations,
cell death
Body response to progressive cell injury.
Cellular Injury – Free Radicals
What is a disease
COMMON FORMS OF CELL INJURY AND DEATH:
FREE RADICALS AND REACTIVE O2 SPECIES INJURY
life, death, suspended life,
cell as a patient, terms and
definitions, cell adaptations
Cell injury and its types
cell injury, intracellular
accumulations
Cell injury & its systemic
manifestations
systemic manifestations,
cell death
Body response to progressive cell injury.
Page 13
B
B
COMMON FORMS OF CELL INJURY AND DEATH:
FREE RADICALS AND REACTIVE O2 SPECIES INJURY
Cellular Injury – Free Radicals
What is a disease
life, death, suspended life,
cell as a patient, terms and
definitions, cell adaptations
Cell injury and its types
cell injury, intracellular
accumulations
Cell injury & its systemic
manifestations
systemic manifestations,
cell death
COMMON FORMS OF CELL INJURY AND DEATH:
FREE RADICALS AND REACTIVE O2 SPECIES INJURY
B
Generation of reactive O2 species and antioxidant mechanisms in biology:
Mitochondria have 4 sites of entry for electrons coming intro the electron
transport system, one for NADH and three for FADH. These paths meet at
the lipophylic ubiquinone (CoQ), at the start of the common electron path.
Ubiquinone transfer electrons in the inner membrane, ultimately enabling
their interaction with O2 and H to yield H2O, thus allowing free energy
charge and ATP synthesis. With the transport of electrons, free radicals
are generated within the mitochondria. Reactive O2 species act as
physiological modulators of some mitochondrial functions but may also
cause cell damage. O2 is converted to superoxide by oxidative enzymes
in the mitochondria ER, plasma membrane, peroxisomes and cytosol. O2
is converted to H2O2 by superoxide dismutase and further to OH dot by
the Cu/Fe Fenton reaction. H2O2 is also derived from oxidases in
peroxisomes. The 3 reactive O2 species (H2O2, OH dot and O dot) cause
free radical damage to lipids (peroxidation of the membrane), proteins (ion
pump damage) and DNA (impaired protein synthesis). The major
antioxidant enzymes include SOD, catalase and gluthation peroxidase.
Page 14
Cellular Injury – Free Radicals
B
What is a disease
life, death, suspended life,
cell as a patient, terms and
definitions, cell adaptations
Cell injury and its types
cell injury, intracellular
accumulations
Cell injury & its systemic
manifestations
systemic manifestations,
cell death
B
Page 15
Cellular Injury – Free Radicals
COMMON FORMS OF CELL INJURY AND DEATH:
FREE RADICALS AND REACTIVE O2 SPECIES INJURY
What is a disease
life, death, suspended life,
cell as a patient, terms and
definitions, cell adaptations
DISEASES AND DISORDERS LINKED
Deterioration noted in aging
Inflammatory disorders
Atherosclerosis
Iron overload
Ischemic brain injury
Cell injury and its types
cell injury, intracellular
accumulations
Cell injury & its systemic
manifestations
systemic manifestations,
cell death
Alzheimer disease
Neurotoxins
Cancer
B
TO O2 - DERIVED FREE RADICALS
Lung disorders
Asbestosis
Oxygen toxicity
Emphysema
Cardiac myopathies
Nutritional deficiencies
Chronic granulomatose disease
Radiation injury
Diabetes mellitus
Reperfusion injury
Eye disorders
Rheumathoid arthritis
Macular degeneration
Skin disorders
Cataracts
Toxic states (xenobiotics, metal)
Body response to progressive cell injury.
Cellular Injury – Chemical Injury
COMMON FORMS OF CELL INJURY AND DEATH:
CHEMICAL INJURY (and its general mechanisms)
What is a disease
life, death, suspended life,
cell as a patient, terms and
definitions, cell adaptations
Cell injury and its types
cell injury, intracellular
accumulations
B
Chemical injury begins with a biochemical interaction between
a toxic substance and the plasmalemma or organelle, which
are damaged, leading to increase permeability. The two general
mechanisms for chemical injury are:
direct toxicity
creation of reactive free radicals & lipid peroxidation
Two of many models for chemical injuries:
Cell injury & its systemic
manifestations
systemic manifestations,
cell death
Carbon tetrachloride (CCl4) is enzymatically transformed in the
liver SER into chloromethyl (CCl3) a highly toxic free radical.
Ethanol (EtOH) is also enzymatically transformed in the liver
into highly toxic free radicals.
Body response to progressive cell injury.
Page 16
Cellular Injury – Chemical Injury
COMMON FORMS OF CELL INJURY AND DEATH:
CHEMICAL INJURY (and its general mechanisms)
What is a disease
life, death, suspended life,
cell as a patient, terms and
definitions, cell adaptations
B
CCl4
Cell injury and its types
cell injury, intracellular
accumulations
Cell injury & its systemic
manifestations
EtOH
systemic manifestations,
cell death
Reversible cell injury
Irreversible cell injury
Clinical manifestations
Exposure to CCl4
CCl4
B
Smooth endoplasmic
reticulum
CCl3 + O2
Lipid radicals
Destruction of RER
membranes
Lipid peroxidation
Destruction of plasma
membrane
Decreased protein synthesis
Decreased lipoprotein
secretion
Injury to mitochondria
Increased triglyceride
content of liver cells
Decreased ATP
Increased fatty liver
Increased Ca influx to
mitochondria
Lysosomal swelling
Release of lysosomal
enzymes (hydrolases)
Increased membrane
permeability
Na, H2O, Ca influx
Cellular swelling
Massive influx of Ca)
Decreased oxidative
metabolism
Increased glycolysis
Decreased pH
Cellular digestion
(autodigestion)
Page 17
Chemical injury of liver
induced by carbon
tetrachloride
B
Ethanol
ADH
(NAD – NADH)
MEOS
(cytochrome P-450)
Cathalase
(H2O2)
Acetaldehyde
EtOH
Major pathways of alcohol
metabolism in liver by ADH
ACDH
(NAD – NADH)
Acetate
Free radicals
Acetyl - CoA
CO2 + H2O
ADH = hepatic alcohol dehydrogenase
ACDH = hepatic acetaldehyde dehydrogenase
NAD = nicotinamide adenine dinucleotide
NADH = reduced NAD
MEOS = microsomal ethanol oxidizing system
Cellular Injury - Accumulations
MANIFESTATIONS OF CELL INJURY:
What is a disease
life, death, suspended life,
cell as a patient, terms and
definitions, cell adaptations
Cell injury and its types
cell injury, intracellular
accumulations
Cell injury & its systemic
manifestations
systemic manifestations,
cell death
Include accumulation of water, lipids, carbohydrates, glycogen,
proteins, pigments, hemosiderin, bilirubin, calcium, and urate.
They “crowded” organelles & elicit harmful catabolic products.
Water accumulation (swelling) is caused by a transport failure
and is a sign of many types of cell injury. Oncosis is a type of
cell death resulting from cellular swelling.
Accumulations of organic substances are caused by their
excess synthesis and / or decrease catabolism.
Dystrophic calcification occurs only in injured or dead cells, but
metastatic ones can occur in uninjured cells of hypercalcemics.
Disturbance in urate metabolism may result in hyperuricemia
and deposition of Na urate crystals in tissue (gout).
Body response to progressive cell injury.
Page 18
Systemic Manifestations
SYSTEMIC MANIFESTATIONS OF CELL INJURY:
MANIFESTATION
CAUSE
Fever
Release of endogenous pyrogens (IL1, TNFa, PG) from from
bacteria or macrophages; acute inflammation
What is a disease
life, death, suspended life,
cell as a patient, terms and
definitions, cell adaptations
Cell injury and its types
Increase HR
Increase in oxidative metabolic processes from fever
Leukocytosis
Increase in TWC from infection (directly proportional)
Pain
Various mechanisms (bradykinins, obstruction, pressure)
Enzyme’s presence
Cell enzymes present in ECF
cell injury, intracellular
accumulations
LDH
CK
AST/SGOT
Cell injury & its systemic
manifestations
ALT/SGOT
ALP
systemic manifestations,
cell death
Release from RBC, liver, kidney, skeletal muscle
Release from skeletal muscle, brain, heart
Release from heart, liver, skeletal muscle, kidney, pancreas
Release from liver, kidney, heart
Release from liver, bone
Amylase
Release from pancreas
Aldolase
Release from skeletal muscle, heart
Body response to progressive cell injury.
SYSTEMIC MANIFESTATIONS OF CELL INJURY:
MANIFESTATION
CAUSE
Fever
Release of endogenous pyrogens (IL1, TNFa, PG) from
from bacteria or macrophages; acute inflammation
Increase HR
Increase in oxidative metabolic processes from fever
Leukocytosis
Increase in TWC from infection (directly proportional)
Pain
Various mechanisms (bradykinins, obstruction, pressure)
Enzyme’s presence
Cell enzymes present in ECF
LDH Release from RBC, liver, kidney, skeletal muscle
CK Release from skeletal muscle, brain, heart
AST/SGOT Release from heart, liver, skeletal muscle, kidney,
pancreas
ALT/SGOT Release from liver, kidney, heart
ALP Release from liver, bone
Amylase Release from pancreas
Aldolase Release from skeletal muscle, heart
Page 19
Cellular Death and Others
CELLULAR DEATH: NECROSIS AND APOPTOSIS
Cellular death is manifested as cellular dissolution, or necrosis,
What is a disease
life, death, suspended life,
cell as a patient, terms and
definitions, cell adaptations
Necrosis is the sum of the changes after local cell death and
includes the process of autolysis or cellular destruction.
There are 4 types of necrosis which occur in different tissues:
coagulative, liquefactive, caseous, and fat necroses.
Cell injury and its types
cell injury, intracellular
accumulations
Structural signs that indicate irreversible injury and progression
to necrosis are the dense clumping and disruption of genetic
material and the disruption of the cell membrane and organelles.
Cell injury & its systemic
manifestations
Apoptosis, a distinct type of sub-lethal injury, is a process of
selective cellular self-destruction that occurs in both normal and
pathologic tissue changes.
systemic manifestations,
cell death
Gangrenous necrosis, or gangrene, is tissue necrosis caused by
hypoxia and the subsequent bacterial invasion.
Body response to progressive cell injury.
Page 20