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Altered Cellular and Tissue Biology


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Name several common causes of cellular injury and death
Hypoxic injury (decrease O2 in tissues)
Free radicals
Chemical injury
Infectious injury
Immunological / Inflammatory injury
Injurious genetic factors
Nutritional imbalance
Temperature extremes
Changes in the atmospheric pressure
Ionizing radiation
Mechanical stress / noise
What are free radicals?
Electrically uncharged atoms with an unpaired electron. They steal or give up an electron to another causing an injurious bond which forms with carbohydrates, proteins, and lipids. They ultimately destroy plasma membrane.
Diseases implicated by free radicals.
Alzheimer's disease
Mechanisms of Injury / Effects of Free Radicals
Lipid Peroxitation, Polypeptide Fragmentation, Alterations in the DNA
Lipid Peroxitation
descruction of unsaturated fatty acids which produces peroxides which are detrimental to the plasma membrane and organelles
Polypeptide Fragmentation
Oxidative modifications of proteins causing enzyme degradation, wreaks havoc in the cell
Alterations in the DNA
Reaction with thiamine in DNA causing breaks in the DNA / malignant transformation
Name 6 reversible cellular injuries
Cellular swelling caused by the movement of extracellular water into the cells. Happens with hypoxia. Movement of water and ions into the cells is associated with metabolic failure an loss of ATP production
What happens, in terms of water and ions, if the Na+ / K+ pump fails.
Na+ in the cell increases the cells Osmotic Pressure and draws more water into the cell
the movement of water towards less water, or where there are more solutes
What happens to the cells organelles when water diffuses in?
Cisternae of the endoplasmic reticulum distend, rupture, form vacuolations. Mitochondria becomes swollen.
List the process of hydropic degeneration.
*ATP production decreases
*Na+ and water move into cell. Potassium moves out
*Osmotic pressure increaases
*More water moves into cell
*Cisternae of endoplasmic reticulum distend, rupture, and form vacoules
*Extensive vacuolation
Vacuolation represents which of the following?

a. Pigment in cells
b. Excess water in cells
c. Calcium accumulation in cells
d. Sodium in cells
e. Injury to cell
f. b, d, and e
f. b, d, and e
What parts of the patient can the nurse use assess to water accumlation in cells?
Skin, abdomen, legs, and eyes
Under what circumstances can normal substances accumulate in the cells?
Faulty mechanisms, lack of enzymes, or a disorder of cellular metabolism
What organs do lipids commonly accumulate?
Liver (most common)
Heart (2nd most common)
Neurological tissues
Gastric epithelium
Renal tubes
What part of the cell does calcium accumulates?
In the mitochondria of the eyes, heart valves, lungs, vasculature
Name the two types of calcium accumulation
Dystrophic calcification and metastic calcification
What affect does calcium accumulation have on the cells
Causes membrane damage, chromatin fragmentation, cytoskeletal dissasembly,
Causes of secondary cellular injury and death to blood vessels in the kidneys, retina and nerve tissue
Retinopathy: ischemia due to vessel changes in retina

Neuropathy: axonal degeneration of unmyelinated nerve fibers

Nephropathy: kidney disease due to microvascular changes
In Diabetes Mellitus, where does glycogen accumulate?
In the epithelial cells of the proximal tubes of the kidney, liver, beta cells of the Islet of Langerhans of the pancrease, and the heart muscle
What do neuron cells convert glucose to, and what does it interfere with?
Converto to Sorbital which interferes with nerve conduction.
Renal cells absorb glucose and store it as________?
colored substances - melanin (normal)
What is lipofuscin? Wheres is it seen? What does it indicate?
Aging pigments, seen in the liver and heart, indicating degenerative changes
What is Bilirubin? What does is represent when present in cells?
A pigment from hemoglobin that shows excessive breakdown of RBC's or liver disorder / jaundice (icterus)
What does an excess of proteins cause in cells?
*damage to organelles when released as metabolic enzymes from lysosomes
*crowd intracellular structures
Where is protein excess usually found?
*Epithelial ells of convoluted tubules of the kidneys
*B Cells of the immune system
6 Common etiology of atrophy
1. Disuse / decrease work load
2. Loss of innervation
3. Ischemia / vascular insufficiency
4. Interruption of endocrine signals
5. Persistent cell injury
6. Aging
What happens to the brain of an Alzheimer's patient as the result of atrophy?
Slender gyri (folds), Prominent sulci (grooves).
Cellular changes are the sames in ALL circumstances?
True. All exhibit:
* Decrease ER
* Less mitochondria
* Less myofilaments
* Decreased protein synthesis
* Increased protein catabolism
* Formation of Autophagic vacuoles
* Hydrolytic enzymes
Atrophy is most common in which of the following organs? Heart, brain, liver, sex organs, skeletal muscles
Heart, Brain, Skeletal muscles (the liver is less likely to atrophy)
Define hypertrophy
The increase in size of cell and organ mass accompanied by increased capacity for work. NOT new cells, just larger one.
Differentiate between physiological and pathological hypertrophy.
Physiological: cells are unable to undergo mitotic division. Increase muscle proteins in mitochondria, ER, and PM, enlarge the cell.

Pathological: increased workload due to pathological conditions. Degernation of myocardial fibers, diminished oxidative capabilities of mitochondira, and alterations in protein synthesis
Give examples of physiological hypertrophy
*Growth of uterus during pregnancy due to estrogen stimultion
*Breast enlargement due to prolactin stimulation
*Muscle enlargement due to anabolic steriods
*Increased work deman on striated skeletal muscles
What organs respond to increased work demand?
All muscles (exercise), heart, single kidney, arms & legs
Give example of pathological hypertrophy?
In the heart, hemodynamic overload, hypertension, faulty valves
Define hyperplasia
Increase in the number of cells due to increase in mitotic activity
Give example of physiological hyperplasia
Hormonal hyperplasia: breast and uterus to estrogen stimulation in breast and uterus (normal condition)

Compensatory hyperplasia: regeneration of partially removed liver
In a mature liver, what percent of liver cells undergo mitosis?
0.5 - 1.0%
In a resected liver, ____% of liver cells undergo mitosis within 12 hourse of resection due to the action of _________, __________, _______.

Polypeptide growth factors
Hepatocyte growth factors
Local stems cells
How many days does it take for the liver to fully restore itself?
7 - 14 days
What causes pathological hyperplasia?
excessive hormonal stimulation
Give an example of pathological hyperplasia
Endometrium due to ovarian estrogens causing abnormal menstrual bleeing
What makes pathological hyperplasia a clinically important change?
It is fertile ground for cancerous proliferation requiring immediate treatment
What are the most common organs where compensatory hyperplasia is seen?
*Epithelial cells (epidermal & intestinal)
*Cells of the kidney
*Bone marrow
*Fibroblasts / connective tissue cells
What cells are unable to undergo compensatory hyperplasia?
Nerve, cardiac, muscle cells, lens cells of the eye
Conversion of differentiated (mature) cell by another cell type due to persistent injury
Is metaplasia reversible or irreversible?
What is the most common change seen in metaplasia?
Columnar cells of the respiratory tract convert to stratified squamous epithelial cells. Seen in smokers.

Also seen if stones form in excretory ducts of the salivary glands, pancreas, and bile ducts
What is type of change is epithelial metaplasia? Where are cancers common?
An adaptive but undesirable changes. Cancers of liver, cervix, stomach, bladder
Alterations in size, shape and organization of cells. NOT adaptive (atypical hyperplasia) and are often found near cancer cells.
In what tissues can dysplasia most commonly seen? Give two clinical examples.
Epithelial tissues

Respiratory tract
What cellular changes are present in dysplasia?
1. Pleomorphism: variations in cell size and shape, enlarged
2. Irregular nuclei
3. Hyperchromatism of nuclei: deeply stained
4. Disorderly arrangement of internal structures
5. Increase mitotic activity: abnormal locations in epithelium
How are cellular changes graded histologically?
Low grade and High grade
At what point do dysplastic changes cease to be reversible?
When they penetrate the basement membrane on which the epithelium rests.

It is considered preinvasive neoplasm and is reverred to as "Carcinoma in Situ"
Name 6 etiologies of irreversible cell injury and death
* hypoxia
* chemical
* nutritional
* infectious and immunological
* physical
* mechanical
What factors influence the response to an injury?
Host factors, Risk factors, Genetic factors, and the Characteristics of injurious agent
What is Hypoxic injury?
Lack of oxygen tothe cells, most often due to ischemia. Interrupted blood flow to the tissues
List 4 general health disorders that cause hypoxia
* Heart & lund disease
* Red blood cell disorders: anemia, blood loss, chemo
* Blood clots
* Poisoning of intracellular oxidative enzymes
What chain of event occur in hypoxic conditions?
The lack of O2 stalls ATP production which lead to failure in the Na+/K+ and Ca++ pumps

Hydropic swelling
Extra Ca++ accumulates in cells
Further interference in ATP by mitochondria
Leads to glycolysis
End product pyruvate
Converts to lacdtic acid
Lactic acidosis lead to ____serum pH
What is a reperfusion injury?
an injury that occurs after blood supply is restored
What is the cause of the reperfusion injury?
1. Reactive O2 molecules – superoxide, peroxide, & hydroxyl radicals damage plasma membrane and chomosomes and denature proteins.
2. Inflammation following ischemia
What are the major etiologies of Irreversible Cell Injury?
Free radicals
Reactive oxygen species
What are Troponin / Troponin I and Troponin T?
Regulatory protein subunits tat are released from tropomyosin during cardiac cell injury
What are the five major types of necrosis?
Coagulative, liquefactive, caseous, fat, and gangrenous.
nuclear dissolution and lysis of chromatin due to lytic enzymes
small, dense genetic material due to shrinking of nucleus (chromatin is stained DNA and protein strands)
Describe coagulative necrosis
Typically seen in hypoxic environments (MI, infarct of spleen)
Describe liquefactive necrosis
Associated with cellular destruction and pus formation (pneumonia)
Describe caseous necrosis
A mix of coagulative necrosis and liquefactive necrosis (tuberculosis)
Describe fatty necrosis
Results from the action of lipases on fatty tissues, cellular dissolution(acute pancreatitis, breast tissue necrosis)
Describe gangrenous necrosis
Death of a tissue from sever hypoxic injury. Indicates interruption of the major arteries.
Describe the three types of gangrenous necrosis and their causes
Dry gangrene: result of coagulative necrosis. Protein denaturation and calcium accumulation, skin dry, dark, and atrophied

Wet gangrene: result of liquefactive necrosis (neurophils) common in internal ordans. Site is cold and swollen, foul odor from pus, can become systemic, leading to death

Gas gangrene: Caused by infection of injured tissue by anaerobic bacteria. Produces hydrolytic enzymes and toxins that destroy connective tissue and PM of man cells including RBC. Gas bubbles form in muscle tissues. Is very dangerous when RBC become involved/lyse
Cause of gas gangrene
bacterial infection (Clostridium bacteria) that produces gas within tissues
Define necrosis
unprogrammed death of cells/living tissues

sum of cellular changes after cell death and autodigestion
Cause of wet gangrene
bacterial infection
Cause of dry gangrene
lack of circulation in an injured or diseased rea

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