Cellular Pathology Flashcards
(101 cards)
1
Q
Plasma membrane
A
➢ phospholipid bilayer with embedded proteins / glycoproteins / glycolipids (eg
ion pumps, receptors, adhesion molecules, etc)
➢ semipermeable membrane with pumps for ionic / osmotic homeostasis
2
Q
Nucleus
A
➢ chromatin (euchromatin vs heterochromatin)
➢ nucleolus (synthesis of ribosomal RNA/subunits)
➢ transcription of genes
3
Q
Mitochondria
A
➢ inner & outer membrane, cristae
➢ intermembranous and inner matrix compartments
➢ oxidative phosphorylation (main source of ATP)
4
Q
Endoplasmic reticulum (ER), Ribosomes, & Golgi Apparatus
A
➢ RER & Golgi - synthesis & packaging of proteins for export. Membranes,
lysosomes
➢ SER - lipid biosynthesis (eg membranes, steroids)
- Detoxification of harmful compounds (via P450’s)
- Sequestration of Ca 2+ ions
5
Q
Chaperones & Proteasomes
A
➢ Chaperones assist proper folding of proteins and transport across organelle
membranes.
➢ Proteasomes degrade both excess proteins and incorrectly folded (misfolded)
proteins.
6
Q
Lysosomes
A
➢ Enzymatic digestion (acid hydrolases) of materials in the cell
➢ Primary vs secondary lysosomes; residual bodies
➢ Autophagy vs heterophagy/endocytosis
➢ Phagocytosis/phagosome; pinocytosis/pinocytic vesicle; receptor-mediated
endocytosis
7
Q
Cytoskeleton
A
➢ Structure and movement of cells/organelles/ granules/ surface molecules/
phagocytosis
8
Q
: actin in various forms – cell shape and movement
A
Microfilaments
9
Q
: polymers of tubulin – organelle movement/flagella/cilia/ mitotic
spindle
A
Microtubules
10
Q
Intermediate filaments:
A
cytokeratin, vimentin, desmin, GFAP, neurofilament
proteins
11
Q
Peroxisomes
A
➢ Enzymes (eg catalase, oxidases) – metabolism of hydrogen peroxide and fatty
acids
12
Q
– metabolism of hydrogen peroxide and fatty
acids
A
Enzymes (eg catalase, oxidases)
13
Q
CELLULAR INJURY CELL ADAPTATION AND CELL DEATH
The __________ are in constant fight for living from all kinds of aggressions
that could cause injury, and provided the operating environment is appropriate, could adapt to almost all situations. All these aggressions are called ______, and injury alters
the preceding normal steady state of the cell.
A
tissues and cells
stress
14
Q
If the injury is acute, one of two possible
things can happen to the cell:
A
- It can either survive in a damaged state and adapt to the injury (reversible
injury) or; - It can die (irreversible injury or cell death). If the injury is of a chronic nature,
the cell may be able to adapt to it, resulting in a variety of cellular changes
known as adaptations. These include atrophy, hypertrophy, hyperplasia,
intracellular accumulations, metaplasia and dysplasia, that will be described
later
15
Q
Homeostasis
A
cells are able to maintain normal structure and function (eg ion balance,
pH, energy metabolism) in response to normal physiologic demands
16
Q
Stress –
A
any stimulus or succession of stimuli of such magnitude that tend to
disrupt the homeostasis of the organism.
17
Q
Cellular adaptation
▪
A
as cells encounter some stresses (eg excessive physiologic demand or
some mild pathologic stimuli) they may make functional or structural
adaptations to maintain viability/ homeostasis.
18
Q
cells may respond to these stimuli by either ___________ or __________
their content of specific organelles.
A
increasing or decreasing
19
Q
adaptive processes:
A
atrophy, hypertrophy, hyperplasia and metaplasia
are forms of adaptation
20
Q
Cell injury
▪ if the limits of adaptive response are exceeded, or in certain instances
when adaptation is not possible (eg with severe injurious stimulus), a
sequence of events called _______ occurs.
A
cell injury
21
Q
Cell injury
A
A. Reversible cell injury
B. Irreversible cell injury / cell death
22
Q
*removal of stress / injurious stimulus results in complete restoration
of structural and functional integrity.
A
a) Reversible cell injury
23
Q
*if stimulus persists (or severe enough from the star) the cell will
suffer irreversible cell injury and death
A
b) Irreversible cell injury / cell death
24
Q
- is one of the most crucial events in pathology and can
affect any type of cell.
A
cell death
25
Two principle morphologic patterns that are indicative of cell death:
Necrosis
Apoptosis
26
– type of cell death characterized by sever membrane
injury and enzymatic degradation; always a
pathologic process.
Necrosis
27
– regulated form of cell death; can be a physiologic
or pathologic process.
Apoptosis
28
CAUSES OF CELLULAR INJURY
1. Hypoxia (Oxygen Deficiency)
2. Physical agents
3. Chemical, Drugs & toxins
4. Infectious agents
5. Immunologic Reactions
6. Genetic Abnormalities
7. Nutritional Imbalances
8. Workload Imbalances
9. Cell Aging
29
one of the most important and common causes of cell injury and cell
death.
Hypoxia (Oxygen Deficiency)
30
causes impairment of oxidative respiration, ie it interferes with
energy production.
hypoxia
31
Hypoxia (Oxygen Deficiency)
occurs with:
a) Deficient blood supply
b) Reduced oxygen-carrying capacity of the blood
c) Interference with respiratory chain / oxidative phosphorylation
32
= deficiency of blood supply from impeded
arterial flow or reduced venous drainage = hypoxia +
↓ delivery of nutrients and ↓ removal of metabolites.
ischemia
33
= localized area of ischemic necrosis.
infarction
34
Reduced oxygen-carrying capacity of the blood
due to anemia
due to Hb dysfunction
35
= reduction in numbers or volume of
erythrocytes or quantity of hemoglobin (Hb).
due to anemia
36
eg methaemoglobinemia - nitrate / nitrite poisoning,
carboxyhaemoglobinemia-carbon monoxide
poisoning
due to Hb dysfunction
37
- nitrate / nitrite poisoning,
eg methaemoglobinemia
38
-carbon monoxide
poisoning
carboxyhaemoglobinemia
39
Interference with respiratory chain / oxidative phosphorylation
-
eg, cyanide poisoning inactivates cytochrome oxidase in
mitochondria → blocks oxidative phosphorylation.
40
________ may be increased by tissue hypoxia due to
associated local vascular injury.
physical injury
41
Physical agents
a) Direct mechanical trauma
b) Temperature extremes
c) Radiation
d) Electrocution
e) Sudden changes in atmospheric pressure
42
- lacerations or crush injuries.
Direct mechanical trauma
43
- heat (thermal burn), cold (frostbite).
Temperature extremes
44
- radioactive isotope emissions or electromagnetic
radiation (eg UV light, x-rays).
Radiation
45
- pets chewing electric cords, faulty wiring in
barns, lightning strike, etc.
Electrocution
46
Sudden changes in atmospheric pressure - marine mammals
have mechanisms to mostly avoid the “______”
Sudden changes in atmospheric pressure - marine mammals
have mechanisms to mostly avoid the “bends”
47
Chemical, Drugs & toxins
a) Inorganic poisons
b) Organic poisons
c) Manufactured chemicals
d) Physiologic compounds
e) Plant toxins
f) Animal toxins
g)Bacterial toxins / Mycotoxins
48
eg lead, copper, arsenic, selenium, mercury, etc.
Inorganic poisons -
49
- eg nitrate/nitrite, oxalate, hydrocyanic acid, etc.
Organic poisons
50
eg drugs (overdose / idiosyncratic),
pesticides, herbicides, rodenticides, etc.
Manufactured chemicals -
51
Physiologic compounds
eg salt, glucose, oxygen, etc
52
Plant toxins -
eg ragwort, sweet clover, braken fern, etc.
53
Animal toxins -
eg snake or spider venom, tick toxin, etc.
54
Bacterial toxins / Mycotoxins -
eg botulinum toxin, aflatoxin, ergot, etc.
55
Infectious agents
a. Viruses
b. Bacteria / rickettsiae / chlamydia
c. Fungi
d. Protozoa
e. Metazoan parasite
56
Immunologic Reactions
a. Immune response - eg cells damaged as “innocent bystanders” in immune
/ inflammatory response.
b) Hypersensitivity (allergic) reactions - eg anaphylactic reaction to a foreign
protein or drug.
c) Autoimmune diseases - reactions to self-antigens
57
Genetic Abnormalities
a) Cytogenetic disorders / chromosomal aberrations
b) Mendelian disorders (mutant genes)
58
- one cause of congenital
anomalies.
Cytogenetic disorders / chromosomal aberrations
59
• enzyme defects, eg lysosomal storage disease.
• structural / transport protein defects - eg collagen dysplasia, cystic
fibrosis, sickle cell anemia, etc.
b) Mendelian disorders (mutant genes)
60
- combined effects of environmental factors and 2
or more mutated genes (eg neoplasia,
hypertension, coronary artery disease, etc).
Multifactorial inheritance
61
Nutritional Imbalances
a) Deficiencies - deficiencies of protein-calories (starvation), vitamins (A to E)
minerals (eg copper).
b) Overnutrition - eg excess lipids / calories → obesity, diabetes,
atherosclerosis, etc.
62
Workload Imbalances
a) Overworked cells - cell injury occurs if stimulus prolonged and/or exceeds
ability to adapt.
b) Underworked cells - prolonged lack of stimulation (eg disuse, denervation,
lack of trophic hormones) can lead to atrophy and
eventually the loss of cells.
63
the cumulative effects of a life time of cell damage (chemical, infectious,
nutrition, etc) leads to a diminished capacity of aged cells / tissues to
maintain homeostasis and adapt to harmful stimuli
Cell Aging
64
Mnemonic acronym for agents of disease = “double MINT”
Malformation (genetics, teratogens, etc)
Miscellaneous (metabolic, aging, hypoxia, etc)
Infectious (viruses, bacteria, fungi, etc)
Immune (immune mediated, hypersensitivity, autoimmune, etc)
Nutritional (protein-caloric intake, vitamins, minerals, etc)
Neoplastic (genetic, viral, chemical, radiation, etc)
Trauma (mechanical, temperature, radiation, etc)
Toxicity (inorangic, chemicals / drugs, plant toxins, etc.
65
MECHANISMS OF CELL INJURY
1. General consideration
2. Biochemical Mechanisms
3. Chemical (Toxic) Injury
66
4 intracellular systems are particularly vulnerable to injury.
• cell membranes - especially ionic / osmotic homeostasis.
• mitochondria - oxidative phosphorylation / ATP production.
• protein synthesis, folding and packaging - structural and functional
proteins.
• genetic apparatus - DNA / RNA.
67
sites are commonly damaged by a variety
of inciting causes.
Biochemical Mechanisms
▪ several molecular / biochemica
68
are chemical species with a single unpaired electron
in outer orbit (donate or steal electrons, extremely unstable);
readily react with organic or inorganic chemicals, avidly
attack/degrade membranes, proteins & nuclei acids.
free radicals
69
Generation of free radicals
1. Cellular metabolism
2. Enzymatic metabolism of exogenous chemicals
3. Ionizing radiation
4. Divalent metals
70
- small amounts produced from cell redox
reactions, eg normal oxidative phosphorylation (leakage from
mitochondria), other intracellular oxidases (eg peroxisomes), PMN’s
in inflammation, excess O2, altered metabolism in cell stress (eg
reperfusion injury)
Cellular metabolism
71
- some intermediary
metabolites of chemical / drugs are highly reactive free radicals
Enzymatic metabolism of exogenous chemicals
72
- hydrolyzes water into hydroxyl (•OH) and
hydrogen (H•
) free radicals.
Ionizing radiation
73
- the transition metals (copper and iron), accept or
donate free electrons during certain intracellular reactions, ie
catalyze free radical formation.
Divalent metals
74
Important reactants
1. superoxide anion (O2•) hydroxyl radical (•OH), hydrogen peroxide
(H2O2) and peroxynitrite (ONOO•)
2. H2O2 (not a free radical) is a frequent by-product of oxidative
metabolism that can generate hydroxyl radicals from reactions with
copper or ferrous ions (eg Fenton reaction = Fe2+ + H2O2 → •OH +
OH- + Fe3+)
3. most intracellular stored iron is in the ferric (Fe3+) state and must be
reduced to the ferrous (Fe2+) state to act in the Fenton reaction (often
reduced by O2 -.); iron & O2 -.
required for maximal cell damage
75
Main sites of damage
1. Damage of Membranes (lipid peroxidation)
• free radicals (esp •OH) are highly reactive & unstable (don’t
last long or travel far) → “steal” single electrons from the
hydrogen next to a double bond in unsaturated fatty acids in
cell membranes → form lipid peroxides (which themselves
are reactive & unstable) → autocatalytic chain reaction (selfpropagating) → can cause rapid widespread membrane /
organelle damage.
2. Damage of Proteins
• free radicals cause fragmentation and cross-linkage between
proteins → damaged structural proteins / loss of enzymatic
activity → increased degradation by proteosomes.
3. Damage to DNA
• free radicals damage nuclear & mitochondrial DNA, producing
strand breaks & DNA-protein adducts (short-term →
apoptosis; long-term → low level damage implicated in cell
aging & neoplasia).
76
Protective mechanisms of the cell
1. Storage and transport proteins:
• iron & copper can catalyze formation of reactive oxygen
forms; they are minimized by being bound to storage and
transport proteins (eg ceruloplasmin, transferrin, lactoferrin,
apoferritin/ferritin) and kept in an oxidized state.
2. Antioxidants - either block the formation of free radicals or inactivate
/ scavenge them:
• Vitamins A&E (lipid soluble, found in cell membranes),
Vitamin C (aqueous-phase antioxidant) and glutathione
(reduced form [GSH] reacts with H2O2 or •OH → oxidised
glutathione [GSSG] + H2O).
3. Enzymes which are involved in neutralizing free radicals:
• Glutathione peroxidase - a selenium-containing enzyme
which catalyzes GSH to GSSG.
- this enzyme also catalyzes the reduction of lipid
peroxides by glutathione, preventing propagation of lipid
peroxidation reactions.
• Superoxide dismutase (SOD) - catalyzes the conversion of
O2-.
to H2O2.
• Catalase - catalyzes the breaks down H2O2 to O2 + H2O.
77
Storage and transport proteins:
• iron & copper can catalyze formation of reactive oxygen
forms; they are minimized by being bound to storage and
transport proteins (eg ceruloplasmin, transferrin, lactoferrin,
apoferritin/ferritin) and kept in an oxidized state.
78
- either block the formation of free radicals or inactivate
/ scavenge them:
• Vitamins A&E (lipid soluble, found in cell membranes),
Vitamin C (aqueous-phase antioxidant) and glutathione
(reduced form [GSH] reacts with H2O2 or •OH → oxidised
glutathione [GSSG] + H2O).
Antioxidants
79
- a selenium-containing enzyme
which catalyzes GSH to GSSG.
- this enzyme also catalyzes the reduction of lipid
peroxides by glutathione, preventing propagation of lipid
peroxidation reactions.
Glutathione peroxidase
80
- catalyzes the conversion of
O2-.
to H2O2.
Superoxide dismutase (SOD)
81
- catalyzes the breaks down H2O2 to O2 + H2O
Catalase
82
Chemical (Toxic) Injury
▪ chemicals and certain drugs/toxins produce damage in one of two ways.
a.) Direct interaction
b) Conversion to reactive toxic metabolites
83
oxic metabolites usually produced by _________________
mixed function oxidase (MFO) in the SER of liver.
cytochrome P-450
84
in humans & dogs most_________ is detoxified in liver to glucuronide
and sulfate conjugates which are then excreted in the urine; only small
amounts converted to highly reactive metabolite NAPQI by P450 MFO.
acetaminophen
85
__________________ metabolized by P450 MFO enzyme system on the SER of the
hepatocyte (CCl4 + e → CCl3 • + Cl-).
______________ •
is highly reactive and causes lipid peroxidation (autocatyzing) →
see severe and rapid membrane destruction → ↓protein synthesis (30
min); ER swelling & ribosomal dissociation (2 hrs.).
Carbon Tetrachloride (CCl4) Toxicity
CCl4
CCl3
86
CELLULAR ADAPTATIONS
▪ major adaptive responses:
atrophy, hypertrophy, hyperplasia
87
Two main types of reversible cell injury are recognized →
cellular swelling and
fatty change.
88
the critical transition point to irreversible injury is not known; however,
two features consistently characterize irreversibility (ie “point of no
return” or “lethal hit”):
▪ inability to reverse mitochondrial dysfunction.
▪ profound disturbances of membrane function.
89
- refers to the rapid death of a limited portion of an organism and is
considered to be the final stage in irreversible degeneration.
Necrosis
90
- is the term used for the entire process of degeneration
and death of cells
Necrobiosis
91
Gross Indicators/Characteristics of Necrosis (Source:Dr. Camer)
- term used to describe the range of morphologic changes that occur
following cell death in living tissue.
• 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
• The location or pattern of the lesion
92
Types of Necrosis
1.Coagulation (coagulative) Necrosis
2. Liquefactive Necrosis
3. Caseous Necrosis
4. Gangrenous Necrosis
5. Fat Necrosis
6. Infarction (Ischemic Necrosis)
7. Zenker’s Necrosis (Zenker’s degeneration)
93
OTHER TERMS USED IN ASSOCIATION WITH NECROSIS
1. Erosion
2. Ulcer
3. Slough
94
– is a shallow area of necrosis confined to epidermis that heals without
scarring.
Erosion
95
– is 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
96
– is 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.
-a piece of necrotic tissue separating from viable tissue.
-this term is applied to necrosis of surface epithelia
Slough
97
Other terms used in reference to necrosis
1. Malacia
2. Sequestrum
98
– an area of liquefactive necrosis of the nervous tissue. Literally means
“softening”.
Malacia
99
– an isolated necrotic mass
-process is called sequestration
Sequestrum
100
Favorable outcome
1. organization, replacement by connective tissue with formation of a scar or
a capsule
2. petrifaction
3. ossification
4. aseptic autolysis
101
: saprogenic fusion of necrotic tissue followed by sepsis
Unfavorable outcome
