What is the term for the appearance of organs, tissues, and/or cells on a gross, microscopic, and ultrastructural level
What is the term for the agent or agents that initiate a chain of events, ultimately causing disease? What are the two classes?
What is the term for the mechanisms or chain of events connecting the etiology and the disease?
What is the tendency to maintain normal, internal stability despite an ever-changing environment?
What is defined as an increase in the number of cells within an organ or tissue?
What are two requirements of cells in order to become hyperplasic
-Labile (always): epidermal cels
-Stabile (only if provoked): hepatocytes
-Permanent (non-dividing): neurons
What are the two basic types of physiologic hyperplasia? Give an example of each
Hormonal hyperplasia: female breast during puberty and pregnancy
Compensatory hyperplasia: restoration of liver after resection
What usually is the cause of pathologic hyperplasia?
Excessive hormonal stimulation, or the effects of GF's on target cells
What is defined as an increase in cell size due to the synthesis of structural components rather than mere cellular swelling
Hypertrophy (does not require cell division thus any cell could theoretically undergo hypertrophy; e.g. skeletal muscle cells in body builders)
Hypertrophy of the heart can be seen in HTN, what does the heart do to combat this?
Myocardial hypertrophy can lead to reinduction of ANF gene expression by ventricular cardiac myocytes (usually only seen in atrial) which results in salt and water secretion by the kidney, thereby reducing intravascular volume and pressure, resulting in decreased hemodynamic load on the heart
What is a decrease in cell size due to loss of cellular components other than water?
(decreased in cell number is apoptosis)
(can use ubiquitin-proteasome pathway, or autophagy ((self-eating)))
Give an example of physiological atrophy.
Give an example of pathological atrophy
Involution of embryonic structures
Decreased workload, aging, inadequate nutrition
What are the four main types of cellular adaptation?
What is defined as a reversible change in which one adult cell type is replaced by another? What is an example of squamous metaplasia?
Metaplasia (metaplasia is the name for the new cell type)
Chronic exposure to cigarette smoke changes columnar respiratory epithelium to squamous
How does metaplasia result? What is an example of columnar metaplasia?
From a reprogramming of stem cells due to a change in signals e.g. cytokines, GF's, and ECM components
What are the two major types of cell death? What is the definition of each?
Necrosis: the process of cell death characterized by cellular swelling, protein denaturation, organellar breakdown, and random breakdown of nucleic acids (classic stimuli is hypoxia)
Apoptosis: the process of cell death characterized by cellular shrinkage, formation of apoptotic bodies, and ordered breakdown of nucleic acids
Questions about necrosis and apoptosis: which one....
Has disrupted plasma membrane?
Intact cellular contents?
What is a very common cause of cell injury? What is the most common reason for this?
Ischemia (decreased blood flow to an area)
What are four results of a depletion of ATP?
1. Na+/K+ pump is reduced leading to intracellular gain of water
2. Anaerobic respiration (glycolysis) is stimulated which leads to increase in glycolysis byproducts leading to decrease in intracellular pH and then clumping of nuclear chromatin
3. Ca2+ pump fails leading to increase in intracellular Ca2+ activating many damaging enzymes
4. Decreased protein synthesis and proteins begin to unfold
What are three things that can cause mitochondrial damage, and what two things do they lead to?
1. Intracellular Ca2+
2. Oxidative stress
3. Breakdown of phospholipids
A. MPT: mitochondrial permeability transition, leak in inner membrane leading to leak of proton motive force leading to necrosis
B. Leakage of cytochrome C leading to apoptosis
The entry of Ca2+ into a cell does what? Give four examples
1. Phospholipases: leading to membrane damage
2. Endonucleases: leading to genetic damage
3. Proteases: leading to protein damage
4. ATPases leading to decreased ATP stores
What are the three major effects of free radical production?
1. Lipid peroxidation of membranes
2. Oxidative modification of proteins: enhance degradation of critical enzmyes
3. Damage to DNA caused by interaction of free radicals with thymine in nuclear and mitochondrial DNA
(Antioxidants, transition metals, and enzymes can all be used to inactivate radicals)
How do reversibly damaged cells appear on a LM and TEM? Irreversibly?
LM: small, clear cytoplasmic vacuoles from ER that is pinched off
TEM: plasma membrane changes, mitochondrial changes, ER dilation, nuclear changes
Irreversible: accumulation of calcium-rich densities in mitochondrial matrix, lysosome swelling, PLASMA MEMBRANE DAMAGE (cell is now exposed to the environment)
Give three LM morphological changes that are seen in Necrosis
1. Increased eosinophilia
2. Glassy homogeneous cytoplasm
3. Nuclei showing either karyolysis, pyknosis, or karyorrhexis
What is a fading of the basophilia of the nuclear probably secondary to DNAase activity called?
What is the the shrinkage of and increased basophilia of nuclei?
What is the fragmentation of pyknotic nucleus
(These may be seen in the nuclei of necrotic cells)
Categories of necrosis:
1. The most common form, characterized by firm texture, and LM findings of loss of all cytologic details
2. Characterized by a viscous mass of liquid and due to complete digestion of cells
3. Characterized grossly by white tissue with a cheese like consistency and microscopically by coagulated cells with a disrupted architecture
4. Can be dry or wet in which each one has lost its blood supply and in wet it becomes liquefactive
5. Describes the coagulative necrosis of fat cells
6. Special form of necrosis typical of vascular immune reactions with Ag-Ab complexes deposited in walls of arteries resulting in eosinophilic appearance
1. Coagulative necrosis
2. Liquefactive necrosis
3. Caseous necrosis: seen in TB
4. Gangrenous necrosis
5. Fat necrosis
6. Fibrinoid necrosis
What is enzyme digestion of cells from a cells own enzymes? Another cells enzymes?
In non-ischemic hypoxic injury, glycolysis can continue, in ischemic hypoxic injury, glycolysis cannot continue
Reversible hypoxic injury leads to decrease in aerobic respiration, causing a decrease in ATP leading to what 6 things?
1. Inhibition of Na+ pump leading to influx of Na+ and influx of water = swelling
2. Activation of glycolysis leading to byproducts like lactic acid which reduces pH causing nuclear chromatin clumping
3. Detachment of ribosomes from RER leading to decreased protein synthesis
4. Dispersion of the cytoskeleton: loss of microvilli and formation of surface blebs
5. Formation of myelin figures
6. Swelling of mitochondria, dilation of ER
Irreversible hypoxic injury leads to what?
1. Mitochondrial vacuolization and accumulation of calcium densities
2. Loss of plasma membrane integrity
3. Lysosomal enzyme leak out leading to reduced pH
(SOME BELIEVE THAT THE FUNDAMENTAL KEY TO IRREVERSIBLE INJURY IS THE INABILITY TO REVERSE MITOCHONDRIAL DYSFUNCTION, HE HOWEVER BELIEVES THAT IT IS THE LOSS OF CELL MEMBRANE INTEGRITY DISALLOWING THE SEPARATION OF THE INTERNAL CELLULAR MILIEU AND EXTERNAL ENVIRONMENT
Reperfusion can lead to injury also, possibly due to an increase in free radicals, cytokine effects, or activation of complement pathway
What is the most common type of cell injury encountered in clinical medicine ****ANYTHING THAT SAYS MOST COMMON, IS AN EASY TEST QUESTIONS TO WRITE
(ischemia is more dangerous than non-ischemic hypoxia)
Chemicals can have a direct action on critical molecular component or organelles, or conversion to toxic metabolites as mechanisms of chemical injury
The difference in necrosis and apoptosis: in necrosis, the cell kind of just passively runs out of gas, while in apoptosis, the cell is using more energy to actively kill itself
What are three events that occur during apoptosis?
1. Proteins cleaved by caspases: cleave nuclear scaffold and cytoskeletal proteins
2. DNA breakdown
3. Expression of phosphatidyl serine on outer aspect of cell membrane allows recognition for phagocytosis
Mechanisms of apoptosis: It occurs through three phases, initiation phase, execution phase, and removal through phagocytosis. Describe the two types of initiation phases. Describe simply how the execution phase works
Extrinsic initiation phase: engagement of cell surface death receptors (e.g. Fas ligand binds Fas receptor and causes three or more Fas to aggregate which forms a binding site for FADD. After FADD binds, pro-caspase 8 binds leading to executioner caspases)
Intrinsic initiation phase: withdrawal of survival factors (e.g. growth hormones), leading to decreased expression of mitochondrial Bcl-2 anti-apoptotic genes and increased expression of pro-apoptotic genes in Bcl-2 family. This leads to increased membrane permeability leading to cytochrome c activating caspases in cytoplasm (this mitochondrial pathway is what is commonly seen with damaged DNA and misfiled proteins)
Execution stage: caspases disrupt cytoskeleton and nuclear matrix proteins
Lastly, the dead cells are removed by phagocytosis
Name two diseases in which a decrease in apoptosis is thought to play a major role? Name three diseases in which an increase in apoptosis is postulated to play a major role?
1. Malignant neoplasms
2. Autoimmune disorders (making antibodies against own body)
A. Neurodegenerative disorders
B. Ischemic injury
C. Death of virus-infected cells
What are the three types of intracellular accumulations?
1. Normal endogenous cellular constituents
2. Abnormal endogenous cellular constituents
3. Exogenous materials
What is it called when TG's and cholesterol accumulate in cells of the liver, heart, muscle, and kidney due to toxins, protein malnutrition, DM, obesity, or anoxia? What are two examples
1. Hepatic steatosis: alcohol CCl4, anoxia, starvation
2. Cardiac steatosis: during hypoxia
Cholesterol and cholesterol esters can accumulate also, this can be seen in atherosclerosis, xanthomas, inflammation with necrosis, cholesterollosis, Niemann-Pick disease
What are the two incidences in which proteins can accumulate?
1. When they exceed the catabolic ability of the cell
2. When there is a defect in protein folding
(e.g. a1-antitrypsin deficiency, in which abnormal a1-AT folds slowly, resulting in buildup of partially folded intermediates which aggregate in hepatocyte ER leading to liver damage)
(chaperones aid in folding and facilitate degradation if misfolded)
What is the most common exogenous pigment? ***MOST COMMON
What pigment is the tell tale of free radical induced injury, endogenous, and appears brown, granular, and intracytoplasmic and is often appreciated in the liver and heart of elderly or malnourished people
What is a brown black pigment derived from oxidation of tyrosine
What is the golden yellow to brown pigment formed from the breakdown of hemoglobin and represents the major storage form of iron
What is the pigment derived from Hb that does not contain iron, is found in bile, and is yellow green
(hyerbilirubinemia results in yellow discoloration of the skin (jaundice)
What is the abnormal deposition of calcium salts and smaller amounts of Fe, Mg, and other mineral salts
(grossly, calcification is evident as fine white granules or clumps that are hard)
What is the type of calcification that occurs in non-viable or dying tissue despite normal serum calcium levels and in the absence of calcium metabolism abnormalities
What is the type of calcification that occurs in living tissues and is usually associated with hypercalcemia due to abnormal calcium metabolism
(causes include increased parathyroid hormone secretion, destruction of bone tissue, vitamin D related disorders, renal failure)
What is a morphologic descriptor implying a homogeneous, glassy, eosinophilic microscopic appearance of cells or of the extracellular space (e.g. of intracellular Russell bodies, resorption droplets; extracellular = scars, walls of arteries, amyloidosis)