Pathology

ATP depletion, membrane damage, metabolic damage, genetic damage

What are the 4 mechanisms of cell injury?

cellular injury

Oxygen deficiency, physical damage, infectious agents, nutritional imbalance, genetic damage, workload imbalance, toxic damage, immune dysfunction, and aging are all causes of _______________

hypoxia

An oxygen deficiency due to decreased circulating oxygen

ischemia

An oxygen deficiency due to decreased flow of oxygen and nutrients to and from tissues

physical damage

Trauma, temperature extremes, radiation, and electricity are all forms of _______________ that can cause cellular injury

reversible

Hydropic degeneration is a form of ______________ cellular injury in which the cell swells due to water accumulation

hydropic degeneration

reversible cell injury in which the cell swells due to water accumulation resulting in an increased cell size and volume and cytoplasmic vacuolation

hypoxia (less oxidative phosphorylation so less ATP for Na/K pump)

What causes hydropic degeneration?

sodium

Hydropic degeneration starts with hypoxia to the tissue preventing oxidative phosphorylation. This means that less ATP is produced in the cell so the Na/K pump cannot move sodium out of the cell and K into the cell. The accumulation of ______ increases the osmotic pressure of the cell, causing water to follow which distends the cisternae of the organelles leading to rupture and vacuolation

irreversible

Necrosis is a form of ____________ cellular injury

necrosis

Cell death after injury by hypoxia, ischemia, or cell membrane damage

necrosis

Acute cell swelling can lead to ___________ after it passes a “point of no return”

cell membrane

Chemicals and free radicals can cause chemical injury to the _________________ resulting in necrosis of the cell

anti-oxidants

Superoxide dismutase, glutathione peroxidase, and vitamins E and C are ______________ that cells use as protective mechanisms to avoid free radical injury

ischemia-reperfusion

________________ injury follows restoration of blood supply to ischemic tissue causing the generation of Reactive Oxygen Species (ROS) following restored oxygen supply and a Ca influx due to impaired ion pumps that can lead to necrosis of tissue

pyknosis

Shrunken, dark, round spots representative of nuclear changes caused by tissue necrosis

hypereosinophilia

Cytoplasmic ___________________ is a histologic change of necrosis in which the cytoplasm becomes bright red/pink when stained with Eosin

karyorrhexis

Nuclear fragments representative of nuclear changes associated with tissue necrosis

karyolysis

A pale nucleus due to the dissolution of chromatin which is representative of nuclear changes associated with tissue necrosis

pyknosis, karyorrhexis, karyolysis

List the three nuclear changes associated with necrosis as they would progress through the necrotic process: karyorrhexis, pyknosis, karyolysis

coagulation

______________ necrosis is a morphologic change of necrosis in which the cells die but the overall structure remains

vascular

Sharp lines of demarkation and geometric shapes are indicative of lesions of ___________ origin

caseous

______________ necrosis is a morphologic change of necrosis in which the cells have a “cheesy” appearance

liquefactive

______________ necrosis is a morphologic change of necrosis which is associated with fluid changes in the necrotic tissue

gangrenous

______________ necrosis is a morphologic change of necrosis which occurs when you have ischemic necrosis where tissues meet, caused by putrification or dessication of the cells

wet

Putrification caused by bacteria leads to ______ (wet, dry) gangrene

dry

Dessication of cells leads to __________ (wet, dry) gangrene

fat

______________ necrosis is a morphologic change of necrosis in which saponification (“soap making”) of fat cells occurs due to released lytic enzymes

apoptosis

programmed cell death caused by:

1. Physiologic processes - involution after hormone withdrawal, elimination of self-reactive lymphocytes, age-related thymic involution

2. Pathologic processes - viral infections, gland involution following duct blockages, accumulation of misfolded proteins, immune-mediated

extrinsic

The ____________ pathway as a mechanism of apoptosis occurs with the binding of cell surface death receptors (TNF family receptors)

FAS

What triggers the caspase cascade that initiates apoptosis for the EXTRINSIC pathway?

intrinsic

The ____________ pathway as a mechanism of apoptosis occurs with increased mitochondrial permeability causing a release of pro-apoptotic molecules into the cytoplasm

cytochrome c

What triggers the caspase cascade that initiates apoptosis for the INTRINSIC pathway?

caspase

Both the extrinsic and intrinsic pathways of apoptosis lead to the activation of the ___________ cascade which culminates in DNA degradation and apoptosis

shrinkage, without

Morphologic features of apoptosis include:

1. Cell _______________ (swelling, shrinkage)

2. Condensed chromatin

3. Cytoplasmic buds (forms apoptotic bodies for phagocytosis)

4. ____________ (with, without) inflammation

apoptotic bodies

With the process of apoptosis, the cell shrinks and forms cytoplasmic buds off called __________________ which can be phagocytized by other cells in the body for more controlled cell death

cell shrinks with apopotosis but swells with necrosis, inflammation with necrosis but not apoptosis

What are the two primary differences between apoptosis and necrosis?

dystrophic

____________ calcification occurs in LOCALIZED areas of necrosis where calcium accumulates in the mitochondria of cells

metastatic

_____________ calcification occurs SYSTEMICALLY in normal tissue secondary to hypercalcemia due to diseases such as renal failure, Vitamin D toxicosis, elevated parathyroid hormone or parathyroid hormone related peptide, or neoplastic bone destruction

PTHrp (parathyroid hormone related peptide)

Complex that mirrors the function of parathyroid hormone to mobilize Ca which is produced by neoplastics

lymphoma, AGASACA

What two types of neoplasm produce parathyroid hormone related peptide (PTHrp) which acts like parathyroid hormone to induce primary hyperparathyroidism that can cause metastatic calcification?

cell function/viability, cellular replication

Cellular aging causes a decrease in:

1. ____________________ - progressive exposure to exogenous influences and accumulation of cellular damage, reduced oxidative phosphorylation, and reduced protein/nucleic acid synnthesis

2. ____________________ - progressive telomere shortening

intracellular accumulations

_____________________ result from dysregulated cellular metabolism such as:

1. Normal production with inadequate removal

2. Normal production but defective enzymatic removal

3. Abnormal production due to gene mutation

4. Abnormal exogenous substances being present in the cell

hepatic lipidosis

An intracellular inclusion of lipids caused by the accumulation of intracellular triglycerides due to increased supply of free fatty acids or decreased metabolism or excretion of lipoproteins which can be seen in early lactation dairy cows and obese animals causing distinct, clear, smooth walled cytoplasmic vacuoles on histology and pale tan, friable/greasy lesions grossly

glycogen

Intracellular accumulations of _____________ often occur in hepatocytes due to corticosteroids, diabetes mellitus, or glycogen storage diseases

exogenous

Carbon (such as from smoking) and tattoo ink are examples of ____________ pigments that can cause intracellular accumulations

endogenous

Melanin, lipofuscin, and hematogenous (iron based) pigments including hemosiderin are examples of ____________ pigments that can cause intracellular accumulations

inflammation

A well-organized cascade of fluid and cellular changes within vascularized tissue which is a host response to remove damaged and necrotic tissue or foreign invaders

fluid

What is the first change in the well-organized cascade of inflammation?

heat, redness, swelling, pain, loss of function

What are the five cardinal signs of inflammation?

repair, healing

Inflammation is part of the process of ________ and ___________, designed to destroy, dilute, or wall of injurious agents and initiate healing and tissue repair

protective

Fundamentally, inflammation is a ______________ response to get rid of pathogens, remove necrotic debris, and repair damage to return normal structure and function, but it can be harmful, particularly in excessive amounts

rapid, short, edema, neutrophils

Acute inflammation is characterized by:

1. ___________ (rapid, slow) development

2. ___________ (long, short) duration

3. ___________ - exudation of fluid and plasma protein

4. Emigration of leukocytes, primarily ____________

slow, long, macrophages, lymphocytes

Chronic inflammation is characterized by:

1. ___________ (rapid, slow) development

2. ___________ (long, short) duration

3. Emigration of leukocytes, primarily ____________ and _____________

4. Proliferation of blood vessels and connective tissue (fibrosis)

increased (arteriole dilation, venule dilation)

The first stage of Acute Inflammation is vascular alteration leading to ____________ blood flow

permeability

The second stage of Acute Inflammation is an increase in microvasculature ____________ of the epithelium to allow leakage of fluid and plasma proteins that induce edema and movement of leukocytes

emigration

The third stage of Acute Inflammation is the ___________ of leukocytes, primarily neutrophils, into the perivascular area

acute

Infections, trauma, physical and chemical agents, tissue necrosis, foreign bodies, and immune reactions are all potential stimuli for _______ inflammation

exudate

Inflammatory extravascular fluid with a HIGH protein concentration and HIGH cell count leading to a high specific gravity (over 1.020)

permeability

Exudate is formed when there is significant alteration in small blood vessel ____________ at the site of injury associated with vascular damage or inflammation

transudate

Clear/transparent extravascular fluid with a LOW protein concentration and LOW cell content leading to a low specific gravity (less than 1.012)

ultrafiltrate

Transudate is due to _____________ of blood such as increased hydrostatic pressure or decreased oncotic pressure due to hypoproteinemia (low plasma proteins/albumin in blood)

edema

The accumulation of excess interstitial fluid due to:

1. Increased vascular permeability (exudate)

2. Increased intravascular hydrostatic pressure (transudate)

3. Decreased intravascular osmotic pressure (transudate)

4. Decreased lymphatic drainage

hydrostatic, osmotic

Normal movement of fluid in and out of the blood vessel is controlled by a balance of ______________ pressure caused by blood pressure and colloid ___________ pressure caused by the presence of plasma proteins in the blood vessel

transudate

An increase in hydrostatic pressure due to obstruction or congestive heart failure could cause accumulation of ____________ fluid

transudate

A decrease in colloid osmotic pressure due to decreased protein synthesis from liver failure or increased protein loss from kidney disease could cause accumulation of ____________ fluid

exudate

Inflammation leading to vasodilation and increased endothelial permeability of the blood vessel allowing fluid AND protein leakage could lead to the accumulation of ___________ fluid

pus

A purulent exudate which is rich in leukocytes (mostly neutrophils) and cell debris

purulent

Adjective use of pus

arterioles

Vasodilation is the first step of inflammation, beginning in the _____________

histamine, nitrous oxide

When the arterioles dilate during the first vasodilation step of inflammation, ____________ and _____________ act as bioactive mediators to open new capillary beds by causing the smooth muscle to relax

viscosity (greater concentration of red cells = thicker = slower moving)

With increased permeability of the blood vessels, fluid pours out into the extravascular tissue, resulting in a loss of fluid in the blood vessel which increases the blood _____________ and induces blood stasis

stasis

Blood ________ created by the increased blood viscosity from the loss of fluid to extravascular tissue during inflammation allows leukocytes to marginate, in which they accumulate along the endothelium and stick to the wall for emigration

endothelial contraction

Mechanism for vascular leakage in acute inflammation mediated by histamine, bradykinins, and leukotrienes which stimulate the endothelial cells to contract, thereby increasing the interendothelial space

direct endothelial injury

Mechanism for vascular leakage in acute inflammation in which direct damage to the endothelium from burns or lytic bacteria causes necrosis and detachment, thereby increasing the microvascular permeability

leukocyte-dependent injury

Mechanism for vascular leakage in acute inflammation in which activated leukocytes secrete free radicals and proteolytic enzymes designed to kill invading pathogens, unintentionally leading to damage of the endothelial cells which increases microvascular permeability

transcytosis

Mechanism for vascular leakage in acute inflammation in which there is an increase the transport of fluid and protein through the endothelial cells from the blood vessel to the tissue

thrombosis (platelet clotting)

Unlike endothelial contraction, direct endothelial injury starts immediately and lasts until ____________ occurs or the endothelium is repaired

endothelial contraction

What mechanism for vascular leakage is rapid and short lived?

cytokines

The endothelium of blood vessels must be activated by ______________ released by macrophages stimulated by the presence of a pathogen or other phagocytized molecule to “catch” leukocytes because this does not occur in normal blood flow

selectins

The cytokines released by activated macrophages in tissue upregulate the presentation of ____________ on the surface of blood vessels which allow leukocytes to adhere transiently to the endothelium and roll until they become firmly attached

integrins

____________ on leukocytes adhere to immunoglobulin family receptors on the blood vessel endothelium surface firmly to allow transmigration into the tissue

immunoglobulin family receptors

Integrins on leukocytes adhere to ___________________ on the blood vessel endothelium surface firmly to allow transmigration into the tissue

weak (allows rolling)

Leukocytes bind with _________ (strong, weak) affinity to selectins

strong (allows transmigration)

Leukocytes bind with _________ (strong, weak) affinity to immunoglobulin family receptors

margination

The movement of leukocytes toward the endothelium of the blood vessel with blood stasis

rolling

The slow movement of leukocytes along the endothelium of blood vessels due to weak affinity binding with selectins

adhesion

The firm attachment of leukocytes to the endothelium of blood vessels due to strong affinity binding between integrins and immunoglobulin family receptors that allows transmigration into the tissue

transmigration (diapedesis)

Movement of leukocytes through the endothelium into tissue, primarily in venules

migration

Movement of leukocytes in interstitial tissue toward a chemotactic stimulus

genetic

___________ deficiencies in leukocyte adhesion are heritable deficiencies in type and amount of adhesion molecules which can inhibit leukocyte transmigration and acute inflammation

recurrent

Genetic deficiencies in leukocyte adhesion can cause a poor inflammatory response to pathogens and dead tissue, allowing ___________ infections

pseudopod

During transmigration, leukocytes insert a ___________ into the junction between endothelial cells and squeezes through

chemotaxis

The movement of leukocytes in tissue along a chemical gradient

exogenous

_____________ products from bacteria can create a chemical gradient for leukocytes to follow during chemotaxis

endogenous

Complement system components serve as ______________ products that act as a chemical gradient for leukocytes to follow during chemotaxis

C5a

What complement system component from the COMPLEMENT CASCADE serves as an endogenous product as a chemical gradient for leukocytes to follow during chemotaxis?

leukotriene B4

What complement system component from the ARACHADONIC CASCADE serves as an endogenous product as a chemical gradient for leukocytes to follow during chemotaxis?

TNF-alpha, IL-1

What two complement system CYTOKINES serves as an endogenous product as a chemical gradient for leukocytes to follow during chemotaxis?

filopodia

Leukocytes move through tissues by extending a __________ that pulls the back of the cell forward