Cellular Pathology (Lec. 03) Flashcards
cells are able to maintain normal structure and function (e.g. ion balance, pH, energy metabolism) in response to normal physiologic demands
homeostasis
any stimulus or succession of stimuli of such magnitude that tends to disrupt the homeostasis of the organism
stress
as cells encounter some stresses they may make functional or structural adaptations to maintain viability/ homeostasis
cellular adaptation
What is cell injury?
Cell injury occurs if the limits of adaptive response are exceeded, or in certain instances when adaptation is not possible.
What is reversible cell injury?
Reversible cell injury is the removal of stress or injurious stimulus that results in complete restoration of structural and functional integrity.
If severe stimulus persists in a cell, what will happen?
Irreversible cell injury
It is a type of cell death characterized by severe membrane injury and enzymatic degradation; always a pathologic process
Necrosis
What is apoptosis?
A regulated form of cell death. Can be physiologic or pathologic process.
one of the most important and common causes of cell injury and cell death
hypoxia
- oxygen deficiency
- blood supply deficiency
- hypoxia
- ischemia
Hypoxia occurs with? (3)
- Deficient blood supply (Ischemia)
- Reduced oxygen-carrying capacity of the blood
- Interference with respiratory chain / oxidative phosphorylation
What are some infectious agents that can cause cell injury?
a. Viruses
b. Bacteria / rickettsiae / chlamydia
c. Fungi
d. Protozoa
e. Metazoan parasite
cell injury occurs if stimulus prolonged and/or exceeds ability to adapt
overworked cells
prolonged lack of stimulation (e.g. disuse, denervation, lack of trophic hormones) can lead to atrophy and eventually the loss of cells
underworked cells
the cumulative effects of a lifetime of cell damage (chemical, infectious, nutrition, etc) lead to a diminished capacity of aged cells / tissues to maintain homeostasis and adapt to harmful stimuli
cell aging
What are the 2 types of nutritional imbalance?
deficiency and overnutrition
combined effects of environmental factors and 2 or more mutated genes (eg neoplasia, hypertension, coronary artery disease)
multifactorial inheritance
What are the different chemical, drugs and toxins that can cause cell injury?
- Inorganic poisons
- Organic poisons
- Manufactured chemicals
- Physiologic compounds
- Plant toxins
- Animal toxins
- Bacterial toxins / Mycotoxins
What are the three types of immunologic reactions that can cause cell injury?
- Immune response
- Hypersensitivity reactions
- Autoimmune diseases
What are the four intracellular system that are particularly vulnerable to injury?
- cell membranes
- mitochondria
- protein synthesis, folding and packaging
- genetic apparatus
chemical species with a single unpaired electron in outer orbit (donate or steal electrons, extremely unstable)
free radicals
Generation of free radicals (4)
- Cellular metabolism
- Enzymatic metabolism of exogenous chemicals
- Ionizing radiation
- Divalent metals
Where are the main sites of damage of Free radicals? (3)
- Damage of membranes
- Damage of proteins
- Damage to DNA
What are the protective mechanism of the cell against free radicals?
- Storage and transport proteins
- Antioxidants
- Enzymes involved in neutralizing free radicals
What are some pathologic causes of atrophy?
- decreased workload (disuse atrophy)
- loss of innervation
- loss of hormonal (trophic) stimulation,
- reduced blood supply / hypoxia, inadequate nutrition, compression
(by tumors, etc.) - persistent cell injury
- aging (senile atrophy).
not dead or necessarily badly injured but they have a reduced functional capacity
atrophic cells
What are the two main types of reversible cell injury recognized?
Cellular swelling and fatty change
the most common and most important response to cellular injuries of all types, including mechanical, anoxic, toxic, lipid peroxidation, viral, bacterial and immune mechanisms
cellular swelling
Etiology of cellular swelling
a. injury, then
b. results to loss of ion and fluid homeostasis
As water continues to accumulate inside the cell, many vacuoles of variable sizes appear in the cytoplasm. It is called as?
hydropic or vacuolar degeneration
Other term for hydropic degeneration when severity increased especially in viral infected cells
Ballooning degeneration
- literally may imply a “sick cell”
- a reversible form of injury
- an adaptive change that may progress to cell death (necrosis)
degeneration
What are the ultrastructural changes of cellular swelling especially ischemia?
- Plasma membrane - blunting, loss of microvilli, blebbing, myelin figures appear
- ER - swelling of cisternae, detachment of ribosomes in Rough Endoplasmic Reticulum
- Mitochondria - swelling, appearance of small densities
- Nucleus - clumping of chromatin
It is the abnormal accumulation of lipids within the cell.
Fatty change
Fatty change occurs mainly in cells dependent on fat metabolism, give 1 organ.
liver
refers to the rapid death of a limited portion of an organism and is
considered to be the final stage in irreversible degeneration
necrosis
the term used for the entire process of degeneration and death of cells
necrobiosis
Gross indicators or Characteristics of Necrosis
- Loss of color or paleness of the tissue
- Loss of strength of the tissue as it softens
- A definite zone of demarcation between necrotic and viable tissue
- Location or pattern of the lesion
term used to describe the range of morphologic changes that occur
following cell death in living tissue
necrosis
What are the 7 types of Necrosis?
- Coagulation necrosis
- Liquefactive necrosis
- Caseous necrosis
- Gangrenous necrosis
- Fat necrosis
- Infarction
- Zenker’s Necrosis
a shallow area of necrosis confined to epidermis that heals without
scarring
erosion
an excavation of a surface produced by necrosis and sloughing of the
necrotic debris and implies involvement of the tissue below the surface layer
ulcer
a piece of necrotic tissue in the process of separation from viable tissue and implies a process of shedding when used with reference to a surface
slough
an area of liquefactive necrosis of the nervous tissue. Literally means
“softening”
malacia
an isolated necrotic mass
sequestrum
Gross appearance
* affected tissue is liquefied; becomes a soft to viscous fluid
- if process was initiated by inflammation, the liquid is often mostly dead
neutrophils (ie called pus)
Liquefactive necrosis
removal of organs (esp eyes, tongue, rectum) of carcass by carrion eating animals (e.g., dogs, coyotes, ravens, vultures)
postmortem scavenging
rigidity or stiffening of muscles after death due to contraction of muscle fibers as ATPs are depleted or exhausted
rigor mortis
gradual cooling of the body after death
algor mortis
gravitational pooling/settling of blood to the dependant regions (“down side”)
of the body. In this instance, you will know the position of the individual when it
was dead.
livor mortis
▪ occurs in heart and vessels
▪ rbc’s may separate from plasma (esp in animals with high fibrinogen levels, eg
horses) = “chicken fat clot”
postmortem clotting
▪ HgB released by rbc breakdown (after death) → staining tissues.
▪ especially lining of heart and blood vessels; also common in tissues of aborted
fetuses and frozen tissues.
hemoglobin imbibition
leakage of bile from gall bladder and major bile ducts which stains adjacent
tissues green to yellow
bile imbibition
term used to describe an artifactual black discoloration of tissues (similar in an
appearance to melanosis)
pseudomelanosis
refers to the enzymatic decomposition of organic material (tissue) with production of foul-smelling compounds (eg H2S, NH3,
mercaptans), especially by saprophytic / putrefactive bacteria
putrefaction (rotting)
occurs when saprophytic bacteria produce gas,
causing gaseous distention of G-I tract, organs and body cavities
postmortem emphysema
with swelling of viscera (due to postmortem emphysema) rectal prolapse, visceral dislocation, gastric rupture (horses), diaphragmatic hernia
postmortem ruptures and organ displacements
Give the other enzymes used to evaluate tissue damage. (3)
- Lactic dehydrogenase (LHD)
- Creatine phosphokinase (CPK)
- Alkaline phosphatase (AP
released from the cytoplasm of injured liver
cells (in moderate injury)
Alanine transaminase
located in mitochondria and is released in more
extensive injury. This occurs in liver, muscles
Aspartate transaminase
brown to black pigment in the airways of monkeys with lung mites
Pneumonyssus simicola
malarial pigment from excretion of catabolized hemoglobin
(large deposits in macrophages of spleen and liver)
plasmodia
liver fluke of ruminants; see black discoloration of
tissue around bile ducts due to regurgitated iron-porphyrin pigment
(“fluke puke”)
fascioloides magna
deposition of asbestos into lung, associated with mesotheliomas, and
chronic lung injury
asbestosis
deposition of silica dust in the lungs, is a special problem for miners;
causes granulomatous pneumonia
silicosis
deposition of carbon particles (esp from air pollution), into lungs /
lymph nodes
anthracosis
Give examples of exogenous pigments.
carbon, soot, dusts, silica, asbestos, tattoo pigment
microscopically elongate, needle-like crystals, often in picket fence type arrangement
cholesterol cleft
end product of nitrogen metabolism, so, any significant renal dysfunction (including dehydration) can lead to abnormal accumulations/deposits of urates
uric acid (birds and reptiles)
Give two examples of crystals.
- Calcium oxalate
- Urates and uric acid
a term that describes widespread of deposition of
calcium in tissues of individual treated with a calcium sensitizer
calciphylaxis
Deposition of calcium salts in vital tissues and is always associated with
hypercalcemia
metastatic calcification
Term sometimes used for extensive metastatic calcification
calcinosis
calcification of injured cells (no hypercalcemia or other disturbances of
calcium homeostasis).
dystrophic calcification
What are the characteristics of dystrophic calcification?
Grossly appearance is white, irregular areas, sometimes dry and gritty
True or False.
Occurrence of dystrophic calcification is most prominent when there is a good supply in the injured tissue.
True.
Gross characteristics of metastatic calcification.
often as white plaques or streaks
Occurrence of urates and uric acid (3)
birds, reptiles, humans
Gross and microscopic characteristics of urates and uric acid.
Gross - chalky white masses in tissues or frosting of crystals on serosal membranes
Microscope - variably sized clear crystals, frequently associated with macrophages
death of single cells as a result of activation of a genetically programmed
“suicide” pathway
apoptosis
Give three examples of physiologic causes of apoptosis.
- Embryonic development (sculpting of digits)
- Cells undergoing normal turnover
- Immune System such as depletion of autoreactive T cells in thymus
What are some pathologic causes of apoptosis? (5)
- DNA damage
- Misfolded proteins
- Specific infectious agents
- Specific immune response
- Pathologic atrophy of organs after duct obstruction (eg pancreas,
kidney, salivary gland)
Give the morphologic features of Apoptosis.
- Cell shrinkage
- Chromatin condensation
- Blebs formation
- Phagocytosis of cell bodies
What are the lipids that can accumulate in the intracellular space? (3)
- Triglycerides
- Inherited storage diseases
- Cholesterol accumulation
accumulation of lipids in smooth muscle cells
and macrophages in walls of arteries / arterioles
atherosclerosis
tumor like masses in skin formed by clusters of foamy macrophages; seen with inherited or acquired
hyperlipidemic states
xanthomas
name given to any substance, intracellular or extracellular, which has a homogeneous, glassy, eosinophilic appearance
hyaline
a nonspecific term for hyaline material within an arterial wall.
- the presence of plasma proteins / Ag-Ab / complement within
a damaged vascular wall causes intense eosinophilic staining
fibrinoid
a pathologic proteinaceous substance (95% amyloid fibrils) which is
resistant to proteolysis
amyloid
insoluble aggregates that result from the self-assembly of abnormally folded proteins
amyloid fibrils
a disorder of protein folding in which normally soluble proteins are deposited as abnormal, insoluble fibrils that disrupt tissue structure and function
amyloidosis
Refers to the deposition of calcium salts in soft tissues. Usually occurs following tissue necrosis.
Pathologic calcification / calcification
bright yellow-brown homogenous pigment occasionally seen at sites
of previous hemorrhage
hematoidin
end product of heme degradation (no iron); mostly from
senescent rbc’s via macrophages
bilirubin
blood and tissues produces a yellow discoloration, called jaundice or icterus.
bilirubin
when a massive accumulation of hemosiderin causes cell damage
hemochromatosis
common in sheep because of the reduced biliary
excretion of copper in this species
copper toxicity
What is the major organ involved in the regulation of copper levels?
Liver
insoluble, intracellular, brown-black pigment derived from tyrosine.
melanin
(colored substances) are those that originate in the
animal
endogenous substances
semipermeable membrane with pumps for ionic / osmotic homeostasis
plasma membrane
site for transcription of genes
nucleus
site for oxidative phosphorylation
mitochondria
Functions of Smooth ER.
a. lipid biosynthesis
b. detoxification of harmful compounds
c. sequestration of Ca 2+ ions
assist proper folding of proteins and transport across organelle
membranes
chaperones
degrade both excess proteins and incorrectly folded (misfolded)
proteins
proteasomes
provide structure and movement of cells/organelles/ granules/ surface molecules/
phagocytosis
cytoskeleton
It provides enzymatic digestion of materials in the cell
lysosomes
Give examples of microtubules.
flagella, cilia, mitotic
spindle
Function of peroxisomes
catalase and oxidase for metabolism of hydrogen peroxide (free radicals) and fatty acids
Mechanisms and biochemistry of atrophy.
a. decreased amount of substance
b. organelles removed by phagocytosis
c. cell shrinks n volume and shut down its differentiated function
organs are increased in size due to an increase in cell size without cellular proliferation
hypertrophy
etiology of hypertrophy
- response to increased workload
- a response to trophic signals
- response to certain drugs or toxins
mechanisms and biochemistry of hypertrophy
- anabolic processes exceed catabolic ones
- increase in organelles / total cellular proteins
This type of cellular adaptation has cellular enlargement due to a proportional increase in the number and size of organelles.
hypertrophy
True or false.
Cellular swelling is the same as hypertrophy.
False. Cell swelling is due to an increased intake of fluid by the cell.
increase in organ size or tissue mass caused by an increase in the number
of constituent cells
hyperplasia
Give the two features that consistently characterize irreversibility of cell injury.
- Inability to reverse mitochondrial dysfunction.
- Profound disturbances of membrane function
have a cloudy appearance or cloudy swelling
cellular swelling
may be an expression of cell injury or a stage of injury in cells that are
destined to die
fatty change
disorder of purine metabolism with hyperuricemia and deposition of urates in tissues
gout (humans)
Gross appearance of urates and uric acids (gout)
chalky white masses in tissues (called “tophi”) or “frosting” of crystals on serosal membranes.
Its origin are plants with high levels of oxalic acid, eg halogeton, rhubarb,
greasewood.
Occurs in cats and dogs due to ingestion of antifreeze.
calcium oxalate
Possible occurrence of calciphylaxis?
- primary hyperparathyroidism
- renal failure
- vitamin d toxicosis
- paraneoplastic syndrome
- may occur naturally by overfeeding mineral and vitamins
most common manifestation of cell death
coagulation necrosis
coagulative necrosis is characteristic of hypoxic / ischemic death of cells in all tissues, except for?
Brain
In coagulative necrosis, it predominates over enzymatic digestion.
protein denaturation
dissolution /fading of the nucleus
karyolysis
shrunken and densely basophilic nuclei
pyknosis
nuclear fragmentation
karyorrhexis
occurs when enzymatic digestion of necrotic cells predominates over protein
denaturation
liquefactive necrosis
seen in many bacterial infections, due to attraction of neutrophils which contain potent hydrolases which are capable of digesting dead cells
liquefactive necrosis
typical lesion seen with specific bacterial diseases, eg tuberculosis, caseous
lymphadenitis
caseous necrosis
What is the gross appearance of caseous necrosis?
grey-white and dry with friable (ie crumbly) to pasty texture; note,
caseous = cheese like
True or False.
Caseous necrotic cells do not retain cellular outline as seen with coagulation
necrosis
true
True or false.
Caseous necrotic cells do not undergo complete dissolution as seen in liquefactive necrosis.
true
Occurs when saprophytic bacteria grow in necrotic tissue.
gangrene necrosis
What is the requirement for gangrene?
necrosis (dead cells) and putrefaction (rotting)
occurs in necrotized portion of the skin with moisture loss due to evaporation and drainage and presence of saprophytic bacteria
dry gangrene
common cause of dry gangrene?
ischemia
Where are the usual location of dry gangrene?
Extremities such as the tail, ears or limbs
when the coagulative necrosis of dry gangrene is modified by the liquefactive action of invading saprophytic / putrefactive bacteria
wet gangrene
color is usually black, with gas bubbles and may have much hemorrhage and edema in and around the lesion
wet/moist gangrene
production of gas bubbles in the necrotic tissue by invading bacteria (esp. Clostridia)
gas gangrene
type of necrosis distinguished by its location within body fat stores, esp. abdominal or subcutaneous fat
fat necrosis
a form of coagulative necrosis resulting from a sudden deprivation of blood supply. Commonly occurring in areas or organs with end artery (i.e., kidney) blocked by thromboembolic lesions
infarction
a type of coagulative necrosis in striated muscles characterized by loss of striations following necrosis
Zenker’s Necrosis (Zenker’s degeneration)
Chemical composition of most common forms of amyloid?
- Protein AA
- Protein AL
- Familial Amyloid
- Endocrine amyloid
Occurences are:
- prehepatic jaundice - primarily with increased breakdown of
erythrocytes, eg hemolytic disease. - hepatic jaundice - with failure of conjugation or excretion.
- post hepatic jaundice - obstruction of bile duct flow
Bilirubin
the transition metals (copper and iron), accept or
donate free electrons during certain intracellular reactions, ie
catalyze free radical formation
divalent metals
hydrolyzes water into hydroxyl (OH) and
hydrogen (H
) free radicals
ionizing radiation
Generation of free radicals (4)
- Cellular metabolism
- Enzymatic metabolism of exogenous chemicals
- Ionizing radiation
- Divalent metals
either block the formation of free radicals or inactivate
/ scavenge them (eg: Vitamin A, E, C
antioxidants
Examples of enzymes which are involved in neutralizing free radicals?
- Glutathione peroxidase
- Superoxide dismutase
- Catalase
General considerations of cell injury
a) the cellular response to injurious stimuli is dependant on the type of injury,
its duration and its severity
b) consequences of an injurious stimulus are dependent on the type of cell
injured and its current status, ie nutritional, hormonal, metabolic, oxygen
requirement, etc.
steroid hepatopathy
hepatocytes of dogs with excess corticosteroids
A result of immunoglobulin accumulating in the cisternae of RER
Russell bodies
Seen lightly eosinophilic, amorphous, hyaline material deposited extracellularly
Amyloid
melanin is derived from
tyrosine
melanocytes are derived from
Neural crest cells
blood and stomach HCI results to
melena
dystrophic calcification does not bear much clinical significance other than
indicates previous parasitic larval migration
He said, “Once you know the normal and the artifacts, all the rest is pathology.”
Dr. T Van Winkle
Also called as Alanine Transaminase
Serum glutamic pyruvic transaminase
Also called as Aspartate transaminase
Serum glutamic oxaloacetic transaminase
hypostatic congestion
livor mortis
due to improperly buffered (acidic) formalin reacting with blood from
tissues
acid hematin
represents stored iron recovered from the hemoglobin of destroyed rbc’s
hemosiderin
one of the most crucial events in pathology and can affect any type of cell
cell death
double MINT
malformation
miscellaneous
infectious
immune
neoplastic
nutritional
trauma
toxicity
protective mechanism of cell against free radicals that can catalyze formation of reactive oxygen forms
iron and copper
chemical that damages mitochondrial cytochrome oxidase then blocks oxidative phosphorylation
cyanide
prevents citrate from being used in the citric acid cycle
fluroacetate (converted to fluorocitrate)
may be an expression of cell injury or a stage of injury in cells that are
destined to die
fatty change
soluble dye used to confirm fatty change
oil red o (stains red if lipid)
morphologic appearance of necrosis is due to
- denaturation of proteins
- enzymatic digestion of the cell
often used to describe the changes that occur in all of the cells after an animal has died
autolysis
proper term = postmortem autolysis, postmortem decomposition
dead neutrophils
pus
common in birds since heterophils don’t have the potent hydrolytic enzymes
to liquefy cells
caseous necrosis
hardening of intestine
lipomatosis
this term is applied to necrosis of surface epithelia
slough
a piece of necrotic tissue separating from viable tissue
slough
indicates selective elimination of cells
apoptosis
Adipose Tissue seen in skeletal muscles and myocardium sometimes called
muscle steatosis
familial amyloid can occur in
humans, shar pei dogs, abyssinian cats
as seen in “brown gut syndrome”
lipofuscinosis
stains black with a Von Kossa special stain
dystrophic calcification
stains positive with Perl’s Prussian blue
hemosiderin
locally precipitated bilirubin
hematoidin
