4. Altered Cellular and Tissue Biology Flashcards
Decrease or shrinkage of cell size
atrophy
Increase in size of cells
hypertrophy
Increase in the number of cells (from an increased rate of cellular division)
hyperplasia
Abnormal changes in size, shape, or organization of mature cells
dysplasia
Reversible replacement of one mature cell type by another
metaplasia
What 2 types of cellular adaptation occur in non dividing cells?
atrophy and hypertrophy
What types of body structures undergo atrophy?
skeletal muscles, heart, brain, and secondary sex organs
Physiologic vs Pathologic atrophy
- Physiologic: normal process that usually occurs in early development (ex. thymus in children) - Pathologic: due to decreased pressure, use, blood, nutrition, hormones, or stimulation (ex. disuse atrophy in skeletal muscle)
Explain the ubiquitin-proteasome pathway
proteins conjugated to ubiquitin -> degraded by proteasomes (increased activity in atrophy)
chronic malnutrition atrophy is often accompanied by what?
autophagy -> autophagic vacuoles contain cellular debris and enzymes
What types of body structures undergo hypertrophy?
striated muscle (skeletal and cardiac) and kidneys
Physiologic vs Pathologic cardiac hypertrophy
Physiologic: temporary and preserves myocardial structure (ex. endurance training, postnatal development, and pregnancy) Pathologic: includes aging, strenuous exercise, sustained workload or stress
What is is called when cardiac hypertrophy is reversed?
regression
When does renal hypertrophy mainly occur
when 1 kidney is removed and the other one has to compensate for the loss
Explain compensatory hyperplasia. Where is it significant?
adaptive and allows for some organs to regenerate (epidermal and intestinal epithelia, hepatocytes, BM cells, and fibroblasts)
Explain hormonal hyperplasia
occurs in estrogen-dependent organs in response to hormonal stimulation (uterus and breast)
Explain pathologic hyperplasia
abnormal proliferation of normal cells (usually in response to excessive hormonal stimulation or GF on those cells)
2 most common examples of pathologic hyperplasia
- hyperplasia of the endometrium (over secretion of estrogen) - BPH (due to changes in hormonal balance)
Dysplasia is also known as what?
atypical hyperplasia -> not a true adaptive change
Most common tissues to undergo dysplasia
epithelial tissue of the cervix (due to HPV) and respiratory tract
T/F: Dysplasia means the presence of cancer
False; dysplasia does NOT indicate cancer and may not progress to cancer if stimulus is removed early on
If metaplasia is not reversed, what can it advance to?
Dysplasia and possible cancerous transformations
Cellular injuries can be reversible or irreversible -> also know as what?
sublethal or lethal
Explain the general mechanisms of cellular injury (regardless of cause)
- depletion of ATP - mitochondrial damage - O2 and O2-derived free radical membrane damage - protein folding defects - DNA damage - calcium level changes
Hypoxia vs Hypoxemia
- Hypoxia: decreased O2 in tissues - Hypoxemia: decreased O2 in bloodstream (most likely to occur first)
Most common cause of hypoxia
ischemia (reduced blood supply)
What causes ischemia
narrowing of arteries (arteriosclerosis) or complete occlusion by clots (thrombosis)
Which is better tolerated - acute or progressive hypoxia? Why?
Progressive -> allows time for adaptive changes in cells
Explain what causes a cell to swell w/ hypoxic injury
decreased mitochondrial O2 -> decreased ATP -> Na/K pump failure -> increased intracellular Na -> increased intracellular H2O -> swelling
Explain what causes a decrease in protein synthesis w/ cellular hypoxic injury
increase intracellular H20 -> dilation of ER -> detachment of ribosomes
Explain what causes nuclear chromatin clumping w/ cellular hypoxic injury
decrease in O2 -> decrease in ATP -> increase anaerobic glycolysis -> decrease glycogen -> increase lactate -> decrease pH -> chromatin clumping & DNA damage
Explain changes to Na, K, and Ca during cellular hypoxic injury
- increased intracellular Na - increased extracellular K - increased intracellular Ca
Where is intracellular Ca released from?
mitochondria and smooth ER
Name 4 mechanisms for ischemia-reperfusion injury
- oxidative stress - increased intracellular Ca - inflammation - complement activation
Name 3 types of reactive oxygen species (ROS)
- hydroxyl radical (OH-) - superoxide radical (O-) - hydrogen peroxide (H2O2)
How does cell structure change after reperfusion injury?
ischemic cell = swollen reperfusion injured cell = necrotic
electrically uncharged atom or group of atoms that has an unpaired electron -> capable of injuring chemical bonds
free radical
Effect of free radicals on lipids
lipid peroxidation (destruction of polyunsaturated lipids) -> increased membrane permeability
Effect of free radicals on proteins
fragmentation of polypeptide chains -> protein misfolding -> lose ion pumps and transport proteins
Effect of free radicals on DNA
causes mutations and decreased protein synthesis
List 5 mechanisms to classify chemical injuries by
- direct damage (on-target toxicity) - exaggerated response (ex. OD) - biologic activation to toxic metabolites (includes free radicals) - hypersensitivities and other immune reactions - rare toxicities
main systems affected by lead (Pb)
nervous system and blood
Lead toxicity is a primary hazard for who?
children and during pregnancy (can cause lower IQ, learning disorders, and ADHD)
Blood lead level of intoxication
10 um/dL
carbon tetrachloride (CCl4) affects what organ
liver
Explain how CO causes hypoxic injury
has a higher affinity for hemoglobin than O2 -> carboxyhemoglobin
Sxs of CO poisoning
dizziness, weakness, N/V, headache, tinnitus, confusion, and chest pain
Primary systems affected by ethanol
brain and liver
What nutrition deficiencies are associated w/ ethanol?
Mg, B6, thiamine, and phosphorus; folic acid is a problem for chronic drinkers
Explain changes seen between acute and chronic alcoholism
- Acute: depresses the CNS (sedation, loss of coordination, delirium) - Chronic: causes structural alterations in tissue that can metabolize ethanol -> mostly liver
What is the spectrum of structural changes to the liver caused by ethanol?
fatty liver (steatosis) -> fatty w/ inflammation (steatohepatitis) -> cirrhosis
Where is mercury commonly found?
human activity and silver fillings
Active substance in marijuana
tetrahydrocannabinol (THC)
How does methamphetamine affect the CNS?
CNS stimulant (produces euphoria)
How does crack and cocaine affect the CNS?
potent CNS stimulate -> blocks reuptake of NE, dopamine, and serotonin
What is heroin closely related to and what does it do to the CNS?
- closely related to morphine, methadone, and codeine - high affinity for CNS; acts on receptors, enkephalins, and endorphins
partial and total deprivation of oxygen
partial: hypoxia total: anoxia
O2 fails to reach blood (occurs in entrapment)
suffocation
obstruction of internal airways
choking asphyxiation
compression/closure of blood vessels or air passages due to external neck pressure
strangulation
compression of the neck by body weight due to a noose -> leaves an inverted V pattern on neck
hanging
strangulation that leaves a horizontal pattern on the neck
ligature
strangulation that leaves variable external trauma and internal damage (fx of the hyoid bone)
manual
prevents delivery of O2 to tissues or blocks utilization of O2
chemical asphyxiants
Name 3 types of chemical asphyxiants
CO, cyanide, and hydrogen sulfide
alteration of O2 delivery to tissues due to inhalation of fluids (usually water)
drowning
little/no water enters the lungs due to vagal-mediated laryngospasms
dry-lung drowning
bleeding into skin or underlying tissues -> takes time to appear
contusion (bruise)
collection of blood in soft tissue that appears quickly
hematoma
superficial scrape/graze of the skin
abrasion
tear or rip in skin
laceration
extreme type of laceration where a wide area of skin is pulled away
avulsion
wound is longer than it is deep -> usually has significant external bleeding w/ little internal bleeding
incised wound
penetrating sharp-force injury deeper than it is long
stab wound
produced by items w/ sharp points but dull edges (ex. stepping on a nail)
puncture wound
heavy edged instruments that produce a combo of sharp and blunt force injuries
chopping wound
What will affect the appearance of an entrance gunshot wound?
range of the gunshot
What is seen w/ contact range entrance gunshot wound?
- searing of the edges - blowback (gaping or jagged) - muzzle imprints
What is seen w/ intermediate range entrance gunshot wound?
- tattooing/stippling: fragments of gunpowder abrade but don’t enter the skin
appearance is the same regardless of range
indeterminate range entrance wound AND exit wound
Necrosis vs Apoptosis
- Necrosis: unprogrammed death; cellular swelling -> lysis; inflammation; many cells affected - Apoptosis: programmed, organized disassembly; membrane bound shrinkage; no inflammation; one cell or small clusters
nucleus gets smaller -> DNA condenses into shrunken particles
pyknosis
fading away of nuclear envelope and nuclear material
karyolysis
nuclear fragmentation
karyorrhexis
Explain coagulative necrosis
ischemia -> decrease pH -> protein degeneration -> albumin becomes firm and opaque
Where does coagulative necrosis occur?
kidneys, heart, adrenal glands
Explain liquefaction necrosis
autolysis (hydrolytic enzymes) and heterolysis (bacterial infection) -> tissue becomes soft, liquefies, and segregates -> forms cysts
Where does liquefaction necrosis occur?
neurons and glial cells of the brain
Types of bacteria involved in liquefaction necrosis?
- Staph - Strep - E. Coli
Explain caseous necrosis?
- mycobacterium is walled off in a granuloma -> cells disintegrate but not completely digested (combo of coagulative and liquefaction) - will resemble cottage cheese (soft and granular)
Type of bacteria involved in caseous necrosis?
TB pulmonary infection (Mycobacterium tuberculosis)
Explain fat necrosis
- occurs by lipases -> break down triglycerides -> release FAs that combine w/ Ca, Mg, and Na (saponification) -> white and chalky
Where does fat necrosis occur?
breast, pancreas, and other ABD organs
Dry vs wet gangrene
- Dry: poor perfusion (coagulative necrosis) - Wet: poor perfusion + pyogenic infection (liquefactive necrosis)
Explain gas gangrene
caused by species of Clostridium -> produces hydrolytic enzymes and toxins -> destroy connective tissue and membranes -> gas bubble form in muscle cells -> death caused by shock
List 4 cellular changes characteristic of aging
- atrophy (decrease cell function) - lack of DNA repairs (possible mutations) - DNA, RNA, proteins, and membranes more susceptible to injury - compensatory hypertrophy and hyperplasia
List 2 tissue/systemic changes characteristic of aging
- progressive stiffness/rigidity - sarcopenia (loss of muscle mass/strength)
List 4 common themes of mechanisms for sarcopenia
- decrease MSK fibers and MSK protein synthesis - disregulation of anabolic hormones - cytokine production + inflammation - decrease nutrition and activity
What occurs during algor mortis?
- body temp decreases 1 degree per hour - by 24 hours -> body temp = environment
What is the main event of livor mortis and how it is physically seen?
- blood pools at the lowest point of the body (due to gravity) - purple discoloration where blood pools (line of demarcation) - can see pupils dilate and become nonreactive to light due to decreased retinal pressure (decrease muscle tension)
What is the timeframe for rigor mortis?
starts within 6 hours after death and lasts for approximately 36 hours (then body becomes flaccid)
What is the cause of rigor mortis?
acid builds up in muscles -> delete ATP -> myosin doesn’t work for relaxation -> rigid muscles (small muscles first)
What is postmortem autolysis (putrefaction)?
breakdown of tissues that occurs between 24-48 hours (all cells start necrosing)
What speeds up/slows down the process of postmortem autolysis?
- warm environment speeds it up - cold slows it down
