Pathoma Flashcards - Cellular Adaptations

Questions and Answers

In what 3 ways can caspases be activated?

Intrinsic mitochondrial pathway (cytochrome c), 2. Extrinsic receptor-ligand pathway (FAS ligand), 3. Cytotoxic CD8 T cell-mediated pathway (granzyme)

What is Bcl2?

It stabilizes the mitochondrial membrane by binding to bax/bak, in order to inhibit leakage of cytochrome c into the cytosol.

What events lead to the inactivation of Bcl2? What's the consequence?

Cellular injury, DNA damage, and loss of hormonal stimulation. Inactivation of Bcl2 allows cytochrome c to leak from the inner mitochondrial matrix into the cytoplasm and activate caspases.

What is the extrinsic receptor-ligand pathway? How does CD95 play a role?

FAS ligand binds FAS death receptor (CD95) on the target cell, activating caspases. Alternatively, TNF binds the TNF receptor on the target cell, activating caspases. Signup and view all the answers

What is the cytotoxic CD8 T cell-mediated pathway?

CD8 T cells secrete perforins, which create pores in the membrane of target cells. They then secrete granzymes, which can enter through the pores and activate caspases. Signup and view all the answers

When does apoptosis occur in aberrant T cell maturation?

Negative selection in the thymus, which assesses whether or not the T cell binds too avidly to self-Ag. If it does, FAS ligand is expressed, binds FAS death receptor, apoptosis. Signup and view all the answers

What are the 2 ways a cytotoxic T cell kills cells expressing foreign Ag?

FAS-induced apoptosis and perforin pathway. Signup and view all the answers

What process is involved in physiologic free radical generation?

Oxidative phosphorylation. Signup and view all the answers

What enzyme transfers electrons to O2, the final electron acceptor?

Cytochrome c oxidase (complex IV). Signup and view all the answers

What are the free radicals produced in oxidative phosphorylation? How many accepted electrons does each radical state represent?

O2 + 1 electron = superoxide (O2-), 2 = hydrogen peroxide (H2O2), 3 = hydroxyl radical (*OH), 4 = water (H2O). Signup and view all the answers

When does pathologic generation of free radicals arise?

Ionizing radiation, inflammation, metals accumulation, drugs and chemicals, reperfusion after ischemic injury. Signup and view all the answers

How does ionizing radiation generate free radicals?

Water is hydrolyzed to hydroxyl free radical (•OH). Signup and view all the answers

An increase in stress on an organ leads to?

An increase in organ size by hypertrophy or hyperplasia. Signup and view all the answers

By what three general processes does cellular hypertrophy occur?

Gene activation, increased protein synthesis, increased production of organelles. Signup and view all the answers

By what general mechanism does hyperplasia occur?

Production of new cells from stem cells. Signup and view all the answers

Is the pregnant uterus an example of hypertrophy or hyperplasia?

True Signup and view all the answers

A permanent tissue is one that cannot make new cells (no lingering stem cells/progenitors). Permanent tissues can only grow by ______.

hypertrophy Signup and view all the answers

How does the heart respond to persistent hypertension?

Being a permanent tissue, it grows via hypertrophy. Signup and view all the answers

What concern exists with endometrial hyperplasia?

Pathologic hyperplasias increase risk for cancer. Signup and view all the answers

What are three examples of 'decreases in stress' that lead to atrophy?

Decreased hormonal stimulation, disuse, decreased nutrient/blood supply. Signup and view all the answers

What cellular changes does atrophy represent?

Decrease in size and number of cells. Signup and view all the answers

How is cell number decreased in an atrophic process?

Apoptosis. Signup and view all the answers

In what two ways is cell size reduced in atrophy?

Ubiquitin-proteosome degradation of the cytoskeleton and autophagy of cellular components. Signup and view all the answers

What is ubiquitin-proteosome degradation?

Proteins are tagged with ubiquitin and destroyed by proteosomes. Signup and view all the answers

How does autophagy occur in atrophy?

Autophagic vacuoles engulf cellular components that are no longer needed. Signup and view all the answers

What does a change in stress on an organ lead to?

Metaplasia. Signup and view all the answers

What is metaplasia?

A change in cell type, most commonly involving surface epithelium. Signup and view all the answers

Describe the metaplastic process observed in Barrett esophagus.

Change from non-keratinizing stratified squamous to non-ciliated columnar with goblet cells. Signup and view all the answers

Is metaplasia reversible?

True Signup and view all the answers

How do you treat Barrett esophagus?

Remove the stressor, such as treating acid reflux. Signup and view all the answers

Are we concerned about metaplastic processes?

True Signup and view all the answers

Does all metaplasia lead to cancer?

False Signup and view all the answers

What processes is vitamin A essential for?

Differentiation of specialized epithelial surfaces and maturation of certain immune cells. Signup and view all the answers

Describe the pathological effects of vitamin A deficiency.

Deficiency leads to metaplastic changes in specialized epithelium. Signup and view all the answers

What is myositis ossificans?

Inflammation of skeletal muscle induces metaplastic change in connective tissue to produce bone. Signup and view all the answers

What is dysplasia?

Disordered cellular growth, often referring to proliferation of precancerous cells. Signup and view all the answers

What pathologic proliferation is a precursor to cervical cancer?

Cervical intraepithelial neoplasia (CIN), which is a dysplastic process. Signup and view all the answers

What processes can precede a dysplastic process?

Longstanding pathologic hyperplasia or metaplasia. Signup and view all the answers

Is dysplasia reversible?

True Signup and view all the answers

What is aplasia? Example?

Failure of cell production during embryogenesis, e.g. unilateral renal agenesis. Signup and view all the answers

What is hypoplasia? Example?

Decrease in cell production during embryogenesis, resulting in a small organ, e.g. streak ovary in Turner syndrome. Signup and view all the answers

When does cellular injury occur?

When a stress exceeds the cell's ability to adapt. Signup and view all the answers

Which is more susceptible to ischemic injury: neurons or skeletal myocytes?

True Signup and view all the answers

How does the rapidity of a stressor affect the response of the cells?

Slowly developing ischemia leads to atrophy; acute ischemia results in injury. Signup and view all the answers

What are 5 common causes of cellular injury?

Inflammation, nutritional deficiency (or excess), hypoxia, trauma, genetic mutations. Signup and view all the answers

How does hypoxia cause cellular injury?

It hinders ATP production by limiting oxygen availability in the electron transport chain. Signup and view all the answers

What is ischemia?

Reduced blood flow through an organ. Signup and view all the answers

What 3 pathologies/pathologic states can cause ischemia?

Decreased arterial perfusion, decreased venous drainage, shock. Signup and view all the answers

What is hypoxemia?

A low partial pressure of O2 in the blood (i.e. PaO2 < 60 mm Hg). Signup and view all the answers

List 4 causes of hypoxemia.

High altitude, hypoventilation, diffusion defect, V/Q mismatch. Signup and view all the answers

What are 3 general causes of hypoxia in a tissue?

Hypoxemia, reduced carrying capacity of blood, ischemia. Signup and view all the answers

When does decreased O2 carrying capacity arise? Examples?

With hemoglobin loss or dysfunction. Examples include anemia and CO poisoning. Signup and view all the answers

How does CO poisoning reduce O2 carrying capacity?

CO binds hemoglobin more avidly than O2 does. Signup and view all the answers

What are the PaO2 and SaO2 in anemia? CO poisoning?

Anemia: both normal; CO poisoning: PaO2 normal, SaO2 decreased. Signup and view all the answers

Common exposures to CO?

Smoke from fires and exhaust from cars or gas heaters. Signup and view all the answers

What’s the classic physical finding in CO poisoning?

Cherry-red appearance of skin. Signup and view all the answers

What is methemoglobinemia?

When Fe2+ is oxidized to Fe3+, RBCs can't bind O2. Signup and view all the answers

PaO2 and SaO2 in methemoglobinemia?

PaO2 normal, SaO2 decreased. Signup and view all the answers

When does methemoglobinemia occur?

With oxidant stress and in newborns (immature Fe-reducing enzymes). Signup and view all the answers

What’s the classic finding in methemoglobinemia?

Chocolate-colored blood. Signup and view all the answers

Tx for methemoglobinemia?

Intravenous methylene blue helps reduce Fe3+ to Fe2+. Signup and view all the answers

What cellular functions does low ATP affect? Consequences?

Na-K pumps, aerobic glycolysis, leading to swelling and lactic acid buildup. Signup and view all the answers

Is cellular injury reversible? What's the hallmark of reversible injury?

True Signup and view all the answers

What histologic findings indicate reversible injury?

Loss of microvilli and membrane blebbing indicate cytosol swelling. Signup and view all the answers

What is the hallmark of irreversible cellular injury?

Membrane damage. Signup and view all the answers

What are the consequences of specific membranes in the cell being damaged?

Leakage of cytosolic enzymes and additional Ca++ entering the cell. Signup and view all the answers

What is the morphologic hallmark of cell death? How does it occur?

Loss of the nucleus by condensation, fragmentation, and dissolution. Signup and view all the answers

What are the 2 mechanisms of cell death?

Necrosis and apoptosis. Signup and view all the answers

Describe the main differences between necrosis and apoptosis.

Apoptosis is self-initiated; necrosis involves inflammation and large groups of cells. Signup and view all the answers

Describe coagulative necrosis.

Necrosis where the organ and cell structures are preserved by coagulation of proteins. Signup and view all the answers

When and where does coagulative necrosis occur?

Ischemic infarction in any organ but the brain. Signup and view all the answers

How do you recognize an organ that has undergone coagulative necrosis?

It will have maintained its shape, with an often wedge-shaped and pale infarcted area. Signup and view all the answers

When does red infarction arise? Examples?

When blood re-enters a loosely organized tissue; examples include testicular and pulmonary infarctions. Signup and view all the answers

What is liquefactive necrosis?

Necrotic tissue that becomes liquefied by enzymatic lysis of cells and proteins. Signup and view all the answers

When and where does liquefactive necrosis occur?

Any time an organ is exposed to proteolytic enzymes, in the brain, abscesses, and pancreatitis. Signup and view all the answers

When does acute inflammation arise?

It is the result of either infection or necrosis. Signup and view all the answers

What type(s) of necrosis are associated with the pancreas?

Fat and liquefactive necrosis. Signup and view all the answers

What are the types of necrosis?

Coagulative, liquefactive, gangrenous, caseous, fat, and fibrinoid. Signup and view all the answers

What is gangrenous necrosis?

Coagulative necrosis that resembles mummified tissue. Signup and view all the answers

Where does gangrenous necrosis most often occur?

It is characteristic of ischemia of the lower limb and GI tract. Signup and view all the answers

Describe caseous necrotic tissue.

Soft and friable, with a cottage cheese appearance. Signup and view all the answers

When and where does caseous necrosis occur?

It is characteristic of granulomatous inflammation due to tuberculous or fungal infection. Signup and view all the answers

What is fat necrosis?

Necrotic adipose tissue with a chalky-white appearance due to the deposition of Ca. Signup and view all the answers

When and where does fat necrosis occur?

Trauma to fat and pancreatitis-mediated damage of peripancreatic fat. Signup and view all the answers

What is dystrophic calcification?

Calcium deposition in the context of normal calcium levels. Signup and view all the answers

What does fat necrosis have to do with dystrophic calcification?

Saponification is an example; necrotic tissue acts as a nidus for calcification. Signup and view all the answers

What are the serum Ca and P levels in dystrophic calcification? Metastatic calcification?

Dystrophic: Ca and P levels are normal; metastatic: Ca and P levels are high. Signup and view all the answers

What's the differential for Ca2+ deposits in the breast?

Carcinoma in situ or fat necrosis. Signup and view all the answers

Why might a patient with fat necrosis think they have breast cancer?

The release of fatty acids can lead to a giant cell reaction, presenting as a mass. Signup and view all the answers

What is fibrinoid necrosis?

Necrotic damage to the blood vessel wall causing proteins to leak into the wall. Signup and view all the answers

How do you identify fibrinoid necrosis?

It stains bright pink. Signup and view all the answers

For what two general pathologies can fibrinoid necrosis occur?

Malignant hypertension and vasculitis. Signup and view all the answers

What is malignant hypertension?

Hypertensive emergency defined as a BP of 180/120 or greater with papilledema. Signup and view all the answers

What kind of necrosis would pre-eclampsia lead to?

Fibrinoid necrosis of the placental vessels. Signup and view all the answers

What is a free radical?

A chemical species with unpaired electrons in its outer orbit. Signup and view all the answers

What is apoptosis?

Energy dependent, genetically programmed cell death involving single cells. Signup and view all the answers

Three examples of physiologically appropriate apoptosis?

Endometrial shedding during menstruation, removal of cells during embryogenesis, CD8 T cell-mediated killing. Signup and view all the answers

Describe the morphologic changes in the apoptotic process?

The dying cell shrinks, cytoplasm becomes eosinophilic, nucleus condenses and fragments. Signup and view all the answers

What are the main enzymatic mediators of apoptosis? How do they work?

Caspases are the main mediators that execute cell death by cleaving specific substrates. Signup and view all the answers

Study Notes

Cellular Responses to Stress and Injury

An increase in stress on an organ can lead to hypertrophy or hyperplasia, resulting in increased organ size.
Cellular hypertrophy occurs through gene activation, increased protein synthesis, and increased organelle production.
Hyperplasia involves the production of new cells from stem cells.
The pregnant uterus undergoes both hypertrophy and hyperplasia for growth.

Tissue Types

Permanent tissues, such as skeletal muscle, cardiac muscle, and nerve, cannot generate new cells and only grow through hypertrophy.
The heart responds to persistent hypertension with hypertrophy, categorized into concentric (pressure overload) and eccentric (volume overload) growth.

Hyperplasia and Atrophy

Pathologic hyperplasias, like endometrial hyperplasia caused by excess estrogen, increase cancer risk, unlike benign prostatic hyperplasia (BPH).
Atrophy occurs due to decreased hormonal stimulation, disuse, or reduced nutrient supply and is characterized by cell size and number reduction through apoptosis.
Ubiquitin-proteosome degradation and autophagy are cellular processes involved in reducing cell size during atrophy.

Metaplasia

A change in stress can lead to metaplasia, defined as a transformation of one cell type into another more suitable type, often reversible.
An example is Barrett esophagus, where squamous epithelium becomes columnar due to acid exposure.
Metaplasia is concerning as it can progress to dysplasia and cancer.

Dysplasia and Cell Development

Dysplasia refers to disordered cellular growth and can precede cervical cancer (e.g., cervical intraepithelial neoplasia).
Aplasia is the failure of cell production during embryogenesis, while hypoplasia is a decreased production resulting in a smaller organ.

Cellular Injury Mechanisms

Cellular injury occurs when stress surpasses the cell's adaptive capabilities.
Neurons are more susceptible to ischemic injury than skeletal myocytes, demonstrating rapid response differences to stress.
Common causes of cellular injury include inflammation, nutritional deficiencies, hypoxia, trauma, and genetic mutations.

Hypoxia and Ischemia

Hypoxia impairs cellular function by reducing ATP production due to the lack of oxygen as the final electron acceptor.
Ischemia refers to reduced blood flow to an organ, resulting from arterial perfusion issues, venous drainage challenges, or shock states.
Hypoxemia is defined as a low arterial oxygen pressure, and can arise from various factors including high altitude and V/Q mismatch.

Cell Death Mechanisms

Cell death occurs via necrosis (a non-programmed, pathologic process) or apoptosis (a regulated, energy-dependent process).
Necrosis is associated with inflammation and affects large groups of cells, while apoptosis targets individual cells.
Various types of necrosis include coagulative, liquefactive, gangrenous, caseous, fat, and fibrinoid necrosis—each with distinct causes and appearances.

Necrosis Types

Coagulative necrosis preserves organ structure and occurs in ischemic situations, excluding the brain.
Liquefactive necrosis involves enzymatic breakdown and is often found in the brain, abscesses, and pancreatitis.
Caseous necrosis appears cheese-like and is seen in tuberculous or fungal infections.
Fat necrosis results from trauma to adipose tissue or pancreatitis, marked by calcium deposition (saponification).

Dystrophic and Metastatic Calcification

Dystrophic calcification occurs in necrotic tissue regardless of calcium blood levels, while metastatic calcification involves high calcium levels causing deposits in normal tissues.

Apoptosis Mechanism and Regulation

Apoptosis involves distinct morphological changes: shrinking cells, eosinophilic cytoplasm, and nuclear condensation and fragmentation.
Caspases are the key enzymes driving apoptosis, activated through intrinsic, extrinsic, or cytotoxic pathways.
Bcl2 inhibits apoptosis by stabilizing mitochondrial membranes; its inactivation allows for cytochrome c release, triggering caspase activation.

T Cell Maturation and Killing Mechanisms

Aberrant T cell maturation leads to apoptosis via negative selection in the thymus.
Cytotoxic T cells eliminate infected cells using FAS-induced apoptosis or perforin-mediated pathways.### FAS Ligand
FAS ligand is a cytokine belonging to the TNF (Tumor Necrosis Factor) family.

Physiologic Free Radical Generation

The process involved in physiologic free radical generation is oxidative phosphorylation.

Electron Transfer to O2

Cytochrome c oxidase (Complex IV) is the enzyme responsible for transferring electrons to O2, which acts as the final electron acceptor.
This enzyme's activity can be inhibited by cyanide and carbon monoxide (CO).

Free Radicals in Oxidative Phosphorylation

O2 accepts one electron to form superoxide (O2-).
Superoxide can accept an additional electron to become hydrogen peroxide (H2O2).
Hydrogen peroxide can accept another electron to form hydroxyl radical (*OH).
Finally, four electrons lead to the formation of water (H2O), which is not considered a free radical.

Pathologic Generation of Free Radicals

Pathologic generation of free radicals can arise in several scenarios:
- Ionizing radiation.
- Inflammation.
- Accumulation of metals.
- Exposure to drugs and chemicals.
- Reperfusion following ischemic injury.

Mechanism of Ionizing Radiation in Free Radical Generation

Ionizing radiation generates free radicals by hydrolyzing water, resulting in the formation of hydroxyl free radicals (€¢OH).

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Test your knowledge on cellular adaptations with these flashcards based on the PATHOMA resource. Cover key concepts such as hypertrophy, hyperplasia, and their mechanisms. Perfect for students preparing for exams in pathology or related fields.