Cellular Pathology Flashcards by Hartzel Lelix

“All organ injuries start with structural or molecular alterations in cells” concept began by

Rudolf Virchow in 1800’s

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phospholipid bilayer with embedded proteins / glycoproteins / glycolipids (eg ion pumps, receptors, adhesion molecules, etc)

Plasma membrane

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semipermeable membrane with pumps for ionic / osmotic homeostasis

Plasma membrane

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➢ chromatin (euchromatin vs heterochromatin)
➢ nucleolus (synthesis of ribosomal RNA/subunits)
➢ transcription of genes

Nucleus

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➢ inner & outer membrane, cristae
➢ intermembranous and inner matrix compartments
➢ oxidative phosphorylation (main source of ATP)

Mitochondria

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synthesis & packaging of proteins for export. Membranes, lysosomes

RER & Golgi

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lipid biosynthesis (eg membranes, steroids)
Detoxification of harmful compounds (via P450’s)
Sequestration of Ca 2+ ions

SER

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➢ 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

Lysosomes

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degrade both excess proteins and incorrectly folded (misfolded) proteins.

Proteasomes

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assist proper folding of proteins and transport across organelle membranes.

Chaperones

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➢ Structure and movement of cells/organelles/ granules/ surface molecules/ phagocytosis
➢ Microfilaments: actin in various forms – cell shape and movement
➢ Microtubules: polymers of tubulin – organelle movement/flagella/cilia/ mitotic spindle
➢ Intermediate filaments: cytokeratin, vimentin, desmin, GFAP, neurofilament proteins

Cytoskeleton

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metabolism of hydrogen peroxide and fatty acids

Enzymes (eg catalase, oxidases)

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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.

Cellular adaptation

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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

cell injury

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*Two principle morphologic patterns that are indicative of cell death:

Necrosis and Apoptosis

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type of cell death characterized by sever membrane injury and enzymatic degradation; always a pathologic process.

necrosis

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regulated form of cell death; can be a physiologic or pathologic process.

apoptosis

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CAUSES OF CELLULAR INJURY:

Hypoxia (Oxygen Deficiency)
Physical agents
Chemical, Drugs & toxins
Infectious agents
Immunologic Reactions
Genetic Abnormalities
Nutritional Imbalances
Workload Imbalances

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one of the most important and common causes of cell injury and cell death.

Hypoxia (Oxygen Deficiency)

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deficiency of blood supply from impeded arterial flow or reduced venous drainage = hypoxia + ↓ delivery of nutrients and ↓ removal of metabolites.

ischemia

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localized area of ischemic necrosis.

infarction

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5 Physical agents:

a) Direct mechanical trauma
b) Temperature extremes
c) Radiation
d) Electrocution
(e) Sudden changes in atmospheric pressure

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6 Chemical, Drugs & toxins

a) Inorganic poisons
b) Organic poisons
c) Manufactured chemicals
c) Physiologic compounds
d) Plant toxins
e) Animal toxins
g) Bacterial toxins / Mycotoxins

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5 Infectious agents

a. Viruses
b. Bacteria / rickettsiae / chlamydia
c. Fungi
d. Protozoa
e. Metazoan parasite

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3 Immunologic Reactions

a. Immune response b) Hypersensitivity (allergic) reactions c) Autoimmune diseases

reactions to self-antigens

Autoimmune diseases

one cause of congenitalanomalies.

Cytogenetic disorders / chromosomal aberrations

combined effects of environmental factors and 2 or more mutated genes (eg neoplasia, hypertension, coronary artery disease, etc).

Multifactorial inheritance

2 Nutritional Imbalances

defiences and overnutrition

cell injury occurs if stimulus prolonged and/or exceeds ability to adapt.

Overworked cells

prolonged lack of stimulation (eg disuse, denervation, lack of trophic hormones) can lead to atrophy and eventually the loss of cells.

Underworked cells

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

“double MINT”

M - Malformation M - micsellaneous I - Infectious I - immune N - Nutritional N - Neoplastic T - trauma T - Toxicity

MECHANISMS OF CELL INJURY

1. General consideration 2. Biochemical Mechanisms 3. Chemical (Toxic) Injury

4 intracellular systems are particularly vulnerable to injury.

* cell membranes * mitochondria * protein synthesis, folding and packaging - * genetic apparatus

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

hydrolyzes water into hydroxyl (*OH) and hydrogen (H*) free radicals.

Ionizing radiation

the transition metals (copper and iron), accept or donate free electrons during certain intracellular reactions, ie catalyze free radical formation.

Divalent metals

Main sites of damage:

1. Damage of Membranes (lipid peroxidation) 2. Damage of Proteins 3. Damage to DNA

a selenium-containing enzyme which catalyzes GSH to GSSG.

Glutathione peroxidase

catalyzes the conversion of O2-. to H2O2.

Superoxide dismutase (SOD)

CELLULAR ADAPTATIONS:

1.Atrophy 2.Hypertophy 3.*Hyperplasia

definition: decrease in the amount of a tissue or organ after normal growth has been attained. ▪ adaptive response whereby a tissue or organ undergoes a reduction in mass (size), due to a decrease in the size and/or number of cells.

Atrophy

Atrophy Gross appearance:

tissue/organ is decreased

▪ definition: organs are increased in size due to an increase in cell size without cellular proliferation. ▪ in organs / tissues which have minimal proliferative capacity (cardiac and skeletal muscle) see only hypertrophy, whereas in tissues / organs with cells capable of division see both hypertrophy and hyperplasia.

hypertrophy

Hypertrophy Gross appearance

tissue /organ increased in size/ weight

* increase in organ size or tissue mass caused by an increase in the number of constituent cells. * hypertrophy and hyperplasia are not mutually exclusive and are often seen together in structures which can undergo division (esp reproductive and endocrine organs). [*to be discussed in

Hyperplasia

Two main types of reversible cell injury are 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

(literally may imply a “sick cell”) -a reversible form of injury -an adaptive change that may progress to cell death (necrosis).

degeneration

IRREVERSIBLE CELL INJURY:

Necrosis and Apoptosis

refers to the rapid death of a limited portion of an organism and is considered to be the final stage in irreversible degeneration.

Necrosis

is the term used for the entire process of degeneration and death of cells.

necrobiosis

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)

is the most common manifestation of cell death.

Coagulation (coagulative) Necrosis

occurs when enzymatic digestion of necrotic cells predominates over protein denaturation.

liquefactive necrosis

➢ typical lesion seen with specific bacterial diseases ➢ common in birds since heterophils don’t have the potent hydrodrolytic enzymes to liquefy cells.

Caseous necrosis

➢ definition: necrosis (usually ischemic) of extremities, eg distal limbs / digits or tips of ears. ➢ Occurs when saprophytic bacteria grow in necrotic tissue.

Gangrenous Necrosis

Two types of Gangrene:

Wet gangrene and Dry gangrene

occurs in necrotized portion of the skin with moisture loss due to evaporation and drainage and presence of saprophytic bacteria.

dry gangrene

when the coagulative necrosis of dry gangrene is modified by the liquefactive action of invading saprophytic / putrefactive bacteria.

wet 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

fat necrosis gross appearance

firm to hard, white / chalky,  gritty areas (often adjacent to normal fat).

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

Infarct

a type of coagulative necrosis in striated muscles characterized by loss of striations following necrosis.

Zenker’s Necrosis (Zenker’s degeneration)

OTHER TERMS USED IN ASSOCIATION WITH NECROSIS:

Erosion, Ulcer & Slough

is a shallow area of necrosis confined to epidermis that heals without scarring.

erosion

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

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

Other terms used in reference to necrosis:

Malacia and Sequestrum

an area of liquefactive necrosis of the nervous tissue. Literally means “softening ”.

malacia

- an isolated necrotic mass - process is called sequestration

sequestrum

▪ derived from the Greek = “falling off” ▪ death of single cells as a result of activation of a genetically programmed "suicide" pathway.

apoptosis

PIGMENTS AND OTHER TISSUE DEPOSITS:

1. Lipid Accumulation 2. Glycogen Accumulation 3. Protein Accumulation 4. Amyloid and Amyloidosis 5. Endogenous Pigments 6. Pathologic Calcification (Mineralization)

is the name given to any substance, intracellular or extracellular, which has a homogeneous, glassy, eosinophilic appearance; the substance is often protein in nature (eg’s amyloid; Ag-Ab complexes causing thickened BM’s; protein droplets in renal tubular epithelium)

hyaline

- is 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 which is resistant to proteolysis.

amyloid

a disorder of protein folding in which normally soluble proteins are deposited as abnormal, insoluble fibrils that disrupt tissue structure and function.

amyloidosis

derived from an acute phase protein called serum amyloid A (SAA) in chronic inflammation.

protein AA

derived from immunoglobulin light chains with plasma cell neoplasia.

protein AL

in humans, Shar pei dogs, Abyssinian cats.

familial amyloid

derived from polypeptide hormones or prohormones in neoplastic or degenerative conditions, eg islet amyloidosis in cats & humans with type 2 diabetes mellitus.

endocrine amyloid

chemical composition of most common forms of amyloid:

1. Protein AA 2. Protein AL 3. Familial amyloid 4. endocrine amyloid 5. other amyloids

Cellular Pathology Flashcards

(84 cards)