Week 1: Cellular Response to Stress

Question 1

What kind of tissue is depicted here?

Answer 1

Liver/hepatocyte (normal)

Question 2

What is etiology?

Answer 2

Etiology is the cause or set of causes for a given disease. Etiology can be genetic or acquired, and most diseases have multifactorial causes.

Question 3

What is pathogenesis?

Answer 3

The mechanism of disease–cell, biochemical, or molecular events that follow the exposure of a cell to injurious stimuli

Question 4

What are morphological changes? Why do we assess them?

Answer 4

Morphologic changes are structural alterations in cells or tissues characteristic of a disease. These are assessed in order to determine clinical manifestations of a disease.

Question 5

What are the main ways cells respond to stress?

Answer 5

Cells can adapt to stress, or if the stress is overwhelming, the cell can become injured. Some injuries are mild and reversible, while others are irreversible and lead to cell death (necrosis or apoptosis)

Question 6

What are the general categories of physiologic stress and toxic stimuli that cells might encounter?

Answer 6

Increased demand

Decreased nutrients

Increased or decreased stimulation

Chronic irritation

Reduced oxygen supply (hypoxia, reduced blood supp. = ischemia)

Microbial infection

Metabolic alterations

Question 7

What are the types and definitions of cellular adaptations? Are they reversible?

Answer 7

Cell adaptations are somewhat reversible until a certain point. Reversible changes in cell size, number, type, activity or function can all occur in response to the environment. These include:

Hypertrophy = enlargement of an organ or tissue from increase in cell size

Atrophy = decrease in organ/tissue size from a decrease in cell size

Hyperplasia = enlargement of an organ caused by an increase in cell reproduction rate and, thus, cell number (i.e. in cancer)

Metaplasia = the transformation of a differentiated cell type into another differentiated cell type

Question 8

What is hypertrophy and why does it occur?

Answer 8

Increase in cell size, resulting in increased organ size, usually due to increase in synthesis

Etiology: Increased workload and/or stimulation

Mechanisms: Induction of select genes, and subsequent protein synthesis

Ex: lifting weights increases muscle cell size

Question 9

What stimuli can induce cells to behave differently?

Answer 9

Mechanical stretch (increased workload, as in muscles), agonists like (a-adrenergic hormones, angiotensin) and growth factors (i.e. IGF1)

This helps reduce the workload of a cell by increasing mechanical performance

Question 10

What organ is depicted here? What kind of tissue is mostly present? What is the difference between right and left sides?

Answer 10

This is uterine smooth muscle tissue–it has hypertrophied (R side, cell size increase) compared to its normal state (L side)

Question 11

What is hyperplasia and why does it occur? What is it’s etiology? What are it’s mechanisms?

Answer 11

Hyperplasia is an increase in the number of cells. It can occur concurrently with hypertrophy and lead to an increase in the size of an organ.

Etiology: physiologic–hormonal/compensatory, and pathologic–excessive stimulation (hormonal)

Mechanisms: Growth factors, increased receptor #, stem cell activation

Question 12

What is the difference between the left and right images shown here? What tissue is this, and what structures are shown?

Answer 12

The left side shows normal tissue, whereas the right side displays hyperplasia. This is prostate tissue showing glands and a mesenchymal framework (fibroblasts and smooth muscle cells as well).

Question 13

What is atrophy and why does it occur? When is it frequent (and normal)? What is its etiology and what are its mechanisms? What cellular changes are observed?

Answer 13

Decrease in cell size, accompanied by a decrease in organ size. Can be physiologic or pathologic. Physiologic atrophy is normal and common during development.

Etiology: Decreased workload, denervation, decreased blood supply, decreased endocrine stimulation

Mechanisms: increased protein degradation, lysosomal breakdown, ubiquitin/proteosome pathway

Cell changes include an increase in autophagic vacuoles and lipofuscin granules

Question 14

What tissue type is shown here, and what is occurring within it? How can you tell?

Answer 14

This is atrophy of the prostate gland displaying prostate cancer On the LH side, the cells lining the glands are very thin and stretched, and become filled with proteinaceous material

Question 15

What is metaplasia? What is its etiology and what are its mechanisms?

Answer 15

Metaplasia is the replacement of one differentiated cell type with another. This results from external stress, and often involves epithelial tissues. This originates at the stem cell level, and involves reprogramming.

Etiology: irritation or persistent stress

Mechanisms: reprogramming of stem cells, signaling from specific cytokines and growth factors

Question 16

What tissue type and cellular response is being shown here?

Answer 16

This is metaplasia of respiratory tract cells due to smoking, in which normal, ciliated columnar epithelium is transitioning to squamous epithelial cells, which can “deal” with smoke better. However, these cells cannot clear mucus and infections as effectively, so this is an overall detriment to the person’s health.

Question 17

What is the etiology of cell injury?

Answer 17

Hypoxia/ischemia, infection, physical/chemical injury, immunologic response, genetic, and nutritional

The type of injury depends on the cell type, and the degree to which the cell can react.

Question 18

What ae the two forms of cell death and how do they arise?

Answer 18

Necrosis - can occur due to decreased ATP or increased ROS in mitochondria, or from damage to lysosomal/plasma membranes

Apoptosis - usually occurs do to DNA mutations, which activate caspases and lead to apoptosis

Question 19

What is the difference between necrosis and apoptosis?

Answer 19

Necrosis is accidental/unregulated cell death from membrane damage and loss of ion homeostasis

Apoptosis is programmed cell death, often secondary to DNA damage

Question 20

How is necrosis identified in tissue? Why does it usually occur?

Answer 20

Cytoplasmic changes: increased eosinophils, nuclear shrinkage/distortion, and calcification in late stages

Question 21

What is pyknosis?

Answer 21

Nuclear shrinkage in necrotic cells

Question 22

What is karyolysis?

Answer 22

Fading of the color of the nucleus

Question 23

What is karyorrhexis?

Answer 23

Fragmentation of the nucleus

Question 24

What are the general patterns of necrosis?

Answer 24

Cobras Like Cats Fat and Full

Coagulative (most common)

Liquefactive

Caseous

Fat necrosis

Fibrinoid necrosis

Question 25

What is coagulative necrosis?

Answer 25

Usually due to hypoxia/ischemia. Cells become eosinophilic (pink), outlines become blurred, nucleus breaks down, neutrophils come in during late stage and remove debris. Macrophages are present to "clean up" in final stages. Kidney shown has necrosis in yellowed areas, with necrotic tissue shown in green circle

Question 26

What is liquefactive necrosis and where does it occur? What role do neutrophils play in the process?

Answer 26

Occurs in the **brain** due to ischemia and in the **kidneys**. Occurs due to enzymatic digestion of brain/kidney tissues. Neutrophils break down tissue and "liquefy" it, often producing pus. Thus, neutrophils are a sign of necrotic tissue.

Question 27

What is caseous necrosis and where does it often occur?

Answer 27

Caseous necrosis occurs in **granulomatous** **inflammation,** a coagulative necrosis in the center of a granuloma. Specialized inflammatory cells surround/**encase** necrotic dissue and attempt to destroy it. The border between necrotic (pink) and healthy tissue is shown in the lower righthand photo.

Question 28

What is fat necrosis and where does it occur?

Answer 28

Necrosis within adipose tissue, which becomes blurry when ischemia or other injury occurs. This is often due to enzymatic release from the pancreas, and subsequent breakdown of fat.

Question 29

What is fibrinoid necrosis and where does it usually occur?

Answer 29

Occurs in vessels, an example being vasculitis or the inflammation of blood vessels

Question 30

What areas is necrosis commonly seen? What kinds of necrosis is occuring?

Answer 30

ITTI: Ischemic areas - MI + stroke, coagulative and liquefactive Tumors - malignant and aggressive, coagulative Trauma - peripheral tissues and pancreatitis, fat necrosis Infection - TB, classic caseous

Question 31

What is the etiology of common forms of apoptosis in healthy, active cells?

Answer 31

Embryogenesis, hormone-dependent involution, cell deletion, elimination of lymphocytes, and cytotoxic T cell signaling to virally infected cells

Question 32

What are caspases? When and how are they activated?

Answer 32

Proteases activated in the cell, which activate enzymes that cause the nucleus of a cell to fragment. Leads to formation of apoptotic bodies. They are activated by intrinsic mitochondrial pathways (BCL2 sensors/effectors, cytochrome c from mitochondria) as well as extrinsic death receptor pathways (Fas and TNF receptor-ligand interaction)

Question 33

What morphological changes are seen in apoptosis?

Answer 33

Cell shrinkage, chromatin condensation, cytoplasmic blebs, and phagocytosis

Question 34

What are the ways things can accumulate in cells?

Answer 34

1) Inadequate removal of substance 2) Accumulation of normal endogenous substance due to defects in folding/packaging/transport/secretion 3) Failure to degrade metabolites 4) Deposition and accumulation of abnormal exogenous substances, when cells can't degrade or expel the substance

Question 35

What does excess alcohol do to liver tissue?

Answer 35

Alcohol-damaged liver tissue can take up FAs normally, but **cannot properly incorporate them into lipoproteins for export**. This is called **steatosis.**

Question 36

What kinds of pigments can accumulate in cells?

Answer 36

Endogenous: lipofuscin, melanin, hemosiderin (breakdown of RBCs, mostly iron) Exogenous: carbon (smoke), tattoo ink

Question 37

How does calcification generally occur? How do we recognize it in a stain?

Answer 37

We recognize calcified tissue as having a deep purple color (see photo). It occurs **dystrophically**, either via: Normal systemic calcium metabolism or From abnormal tissues, like tumors, which might recruit and/or secrete increased calcium levels Also occurs **metastatically** via systemic hypercalcemia in normal tissues.