PATHO ATLAS

Decreased ATP generation, Loss of cell membrane integrity, Defects in protein synthesis, Cytoskeletal damage, DNA damage

What five morphologic changes are associated with reversible and irreversible cell injury?

Increased eosinophilia, Glassy homogeneous appearance, Vacuolated and moth-eaten cytoplasm, Possible calcification of FA residues

What are the histologic features associated with irreversible cell injury (necrotic cells)?

Cellular swelling (Hydropic change or Vacuolar degeneration)

What is the reversible cell injury characterized by an increase in cell volume due to increased water content?

Impaired regulation of ionic concentration (Na+/K+-ATPase)

What is the cause of hydropic swelling?

Accumulation of Na in the cell

What intracellular event leads to increased intracellular water during hydropic swelling to maintain isosmotic conditions?

Fatty Change (Steatosis)

What is the reversible cell injury commonly seen in cells with high energy demand, such as the liver, caused by toxins, chronic hypoxia, or metabolic issues?

Toxins (alcohol, etc.), chronic hypoxia (hypoxic injury), diabetes mellitus, obesity, toxic/metabolic injury

What are common causes of Fatty Change (Steatosis)?

Distention (dilation) of endoplasmic reticulum

What is a subcellular (ultrastructural) change seen in reversible injury involving the ER?

Mitochondrial swelling

What subcellular change occurs in mitochondria during ischemia due to dissipation of membrane potential (impaired volume control)?

Plasma membrane blebbing

What change is seen in the plasma membrane during reversible cell injury?

Clumping of nuclear chromatin

What change is seen in the nucleus during reversible cell injury?

Necrosis

What type of irreversible cell injury is caused by damage to the cell membrane and loss of ion homeostasis?

Apoptosis

What type of irreversible cell injury is characterized by highly regulated programmed cell death?

Ischemia, toxin exposure, infections, trauma

Give four causes of necrosis.

Lysosomal enzymes enter cytoplasm, digest cellular contents, leakage via damaged plasma membrane into extracellular space, and inflammation

What are the characteristics of necrosis?

Severe mitochondrial damage with depletion of ATP, rupture of lysosomal and plasma membranes

What two major intracellular damages characterize necrosis?

Pathologic or physiologic

What are the two general classifications for the causes of apoptosis?

Nuclear dissolution, fragmentation of the cell without complete loss of membrane integrity, rapid removal of cellular debris

What are the characteristics of apoptosis?

Unregulated cell death

Necrosis is characterized as what kind of cell death?

Always pathologic

Necrosis is classified pathologically as what?

4-12 hours

What is the earliest histologic evidence of myocardial necrosis?

Discontinuities in plasma and organelle membranes, mitochondrial dilation with large amorphous densities, intracytoplasmic myelin figures, aggregates of fluffy material (denatured protein)

What are the ultrastructural changes associated with irreversible injury (necrosis)?

Pyknosis

What nuclear change in necrosis involves shrinkage and condensation?

Karyorrhexis

What nuclear change in necrosis involves fragmentation, often described as “nuclear dust”?

Karyolysis

What nuclear change in necrosis involves fading and lysis?

Myelin figures

What intracytoplasmic structures consisting of large, whirled, phospholipid masses are associated with dead cells/damaged membranes in irreversible injury?

Coagulative Necrosis, Liquefactive Necrosis, Gangrenous Necrosis, Caseous Necrosis, Fat Necrosis, Fibrinoid Necrosis

What are the six listed types of necrosis?

Infarction

Coagulative necrosis is often associated with what event?

Fragmentation of the cell without complete loss of membrane integrity

What feature of apoptosis prevents the contents from leaking out and causing inflammation?

No inflammation

A key difference between apoptosis and necrosis is the presence or absence of what?

Clean and organized

Apoptosis is often described as this, due to the rapid removal of cellular debris.

DNA or proteins are damaged beyond repair

Apoptosis occurs when the cell’s components are damaged to what extent?

Chromatin condensation into a dense aggregate

What is the main nuclear change seen in apoptosis?

Cytoplasmic blebs

What forms during apoptosis that detach to become apoptotic bodies?

Macrophages

What cells phagocytose apoptotic bodies?

Muscular dystrophy

What is an example of a consequence of pathologic apoptosis?

Caspase-3

What enzyme is noted to be involved in nuclear fragmentation during apoptosis?

Steatosis (Fatty liver)

What is the term for abnormal accumulations of triglycerides within parenchymal cells?

Liver

What organ is often seen with steatosis because it is the major organ involved in fat metabolism?

Toxins, protein malnutrition, diabetes mellitus, obesity, and anoxia

What are causes of abnormal accumulations of triglycerides (steatosis)?

Atherosclerosis, Xanthomas, Cholesterolosis, Niemann-Pick disease, type C

In which conditions do cholesterol and cholesterol esters accumulate in macrophages as intracellular vacuoles?

Rounded, eosinophilic droplets, vacuoles, or aggregates in the cytoplasm

How do protein accumulations appear histologically?

Reabsorption droplets in proximal renal tubules

What is an example of protein accumulation seen in renal diseases?

Carbon (coal dust)

What is a ubiquitous exogenous pigment picked up by macrophages that blackens lung tissues?

Lipofuscin (aka lipochrome or wear-and-tear pigment)

What endogenous pigment is a sign of free radical injury and lipid peroxidation, composed of polymers of lipids and phospholipids in complex with protein?

Melanin

What is the only endogenous brown-black pigment formed by the enzyme tyrosinase catalyzing oxidation of tyrosine?

Hemosiderin

What hemoglobin-derived golden yellow-to-brown, granular, crystalline pigment is a major stage form of iron when there is local or systemic excess?

Psammoma bodies

What structure associated with intracellular accumulations is noted in the brain?

Pathologic Calcifications

What category includes Dystrophic and Metastatic calcification?

Dystrophic calcification

What type of calcification occurs locally in dying tissues, despite normal serum calcium levels?

Metastatic calcification

What type of calcification occurs in normal tissues, associated with elevated serum calcium (hypercalcemia)?

Areas of necrosis

Dystrophic calcification occurs in which type of tissue area?

Gastric mucosa, kidneys, lungs, systemic arteries, pulmonary veins

Metastatic calcification occurs in the interstitial tissues of which four major locations?

Calcifications in atheromas of advanced atherosclerosis

What is an example of Dystrophic calcification relating to blood vessels?

Aging or damaged heart valves

Dystrophic calcification commonly develops in these structures.

Increased secretion of PTH, Resorption of bone tissue, Vitamin D-related disorders, Renal failure

What are the four principal causes of hypercalcemia leading to metastatic calcification?

Fine, white granules or clumps, sometimes felt as gritty deposits

How do calcium salts appear at sites of deposition in Dystrophic calcification?

Noncrystalline, amorphous deposits or hydroxyapatite crystals

How do calcium salts appear at sites of deposition in Metastatic calcification?

Nephrocalcinosis

What condition caused by metastatic calcification may lead to renal damage?

Meningiomas and Papillary thyroid carcinoma

In what two types of tumors are psammoma bodies found?

Caseous granuloma (tuberculosis)

Dystrophic calcification is noted to occur in this structure.

Hypertrophy

What cellular adaptation involves an increase in the size of cells?

Synthesis and assembly of additional intracellular structural components

What causes the increase in cell size during hypertrophy?

Increased functional demand, stimulation from hormones/growth factors

What are two general causes of physiologic hypertrophy?

Bodybuilders, pregnant uterus

What are two examples of physiologic hypertrophy?

Increased workload

What is the most common stimulus for pathologic hypertrophy, such as in the heart?

Increased protein production

What is the MAIN mechanism of cardiac hypertrophy?

Switch of contractile proteins from adult to fetal/neonatal forms

What change in contractile proteins occurs in cardiac hypertrophy?

Hyperplasia

What cellular adaptation involves an increase in the number of cells?

Tissues where cells can divide

Hyperplasia happens in what kind of tissues?

Hormonal Hyperplasia, Compensatory Hyperplasia

What are the two types of physiologic hyperplasia?

Increase functional capacity of hormone-sensitive organs

What is the purpose of Hormonal Hyperplasia?

Compensating for damage or resection

What is the purpose of Compensatory Hyperplasia?

Excessive or inappropriate actions of hormones or growth factors

What causes pathologic hyperplasia?

Endometrial Hyperplasia, Nodular Prostatic Hyperplasia, Genital or HPV Warts

What are three examples of pathologic hyperplasia?

Verruca

What is the term for HPV warts on the skin?

Condyloma Acuminata

What is the term for HPV warts on the genitals?

Metaplasia

What cellular adaptation involves a change in cell type, typically involving surface epithelium, in response to stress?

Reprogramming of stem cells

How does metaplasia occur?

Reversible

Metaplasia is considered this in theory if the driving stressor is removed.

Malignant transformation

If influences that induce metaplastic change persist, they may predispose to this outcome.

Barrett esophagus

What is a classic example of metaplasia, where the esophageal lining changes?

Nonkeratinizing squamous epithelium

What cell type normally lines the esophagus?

Nonciliated, mucin-producing columnar cells

What cell type replaces the normal lining in Barrett esophagus due to acid reflux?

Atrophy

What cellular adaptation involves tissue shrinkage?

Decreased protein synthesis, Increased protein catabolism

What two processes cause tissue shrinkage in atrophy?

Decreased workload, Ischemia, Reduced nutrition, Reduced hormone stimulation

What are four causes of atrophy?

Alzheimer’s Disease

Brain atrophy is shown as an example in the context of this disease.

Dilation, increased permeability

What are the two major changes in blood vessels during acute inflammation?

Leukocyte margination, Endothelial activation, Leukocyte rolling, Integrin activation, Stable edhesion, Transmigration

What is the order of cellular changes in acute inflammation?

Serous

What morphology of acute inflammation involves a cell-poor exudate, typical in mild injury?

Fibrinous

What morphology of acute inflammation has a "sandwich appearance" and involves replacement of normal tissue with fibrin?

Purulent

What morphology of acute inflammation is characterized by pus, often caused by bacterial infection?

Abscess

What is a localized collection of purulent inflammation with central necrosis?

Ulcer

What morphology of acute inflammation is an excavated surface due to the shedding of inflamed necrotic tissue?

Central liquefied region of necrotic leukocytes and tissue cells surrounded by a zone of preserved neutrophils

How does an abscess appear histologically?

Polymorphonuclear infiltration and vascular dilation in the margins

What is seen histologically in ulcers?

Acute inflammation

Chronic inflammation usually occurs if this process does not resolve.

Adaptive immunity

What strongly influences chronic inflammation?

Macrophages (M1), Epithelioid cells, Giant Cells

What are the three main cellular forms of macrophages found in chronic inflammation?