2 - Cell Injury

What is the manifestation of a disease?

sum of damage done by a harmful agent and the body’s response

what are the characteristics of congenital disease?

developmental, genetic mutations/abnormalities

what are the components of acquired disease?

* Inflammatory = trauma, infection, immune
* Neoplastic = tumors, cancers
* degenerative = aging
* iatrogenic = drug induced

what is a communicable disease?

infectious disease spread thru the community or hospital

what is the function of epithelial tissue?

lining, transport, secretion, and absorption

what is the function of connective tissue?

support, strength, and elasticity

what is the function of muscle tissue?

movement; skeletal, smooth, cardiac

what is the function of nervous tissue?

information synthesis, communication, and control

what is a tissue membrane?

thin layer or sheet of cells that either covers the outside of the body, lines an internal body cavity, lines a vessel, or lines a movable joint cavity

what are the functions of mucous membranes?

line the %%**digestive, respiratory, urinary**%%, and %%**reproductive tracts**%%

* coated with secretions of mucous glands

what are the functions of serous membranes?

line body cavities __**closed to the exterior of the body**__

* peritoneal
* pleural
* pericardial

what are the functions of the cutaneous membrane?

covers the body surface

what are the functions of simple squamous cells?

permits __**exchange of nutrients, wastes, and gases**__

* lines ==**blood vessels**== and ==**air sacs of lungs**==

what are the functions of simple cuboidal cells?

__**secretes and reabsorbs water**__ and __**small molecules**__

* lines ==**kidney tubules**== and ==**glands**==

what are the functions of simple columnar cells?

__**absorbs nutrients, produces mucus**__

* lines most ==**digestive organs**==

what are the functions of stratified squamous cells?

__**protects against abrasion, drying out, infection**__

* outer layer of ==**skin, mouth, vagina**==

what are the functions of stratified cuboidal cells?

__**secretes**__ __**water and ions**__

* lines ==**ducts of sweat glands**==

what are the functions of stratified columnar cells?

__**secretes mucus**__

* lines ==**epididymus, mammary glands, larynx**==

what are pseudostratified cells?

single layer that looks like multiple layers

epithelial tissue is based on __ and _____ of cell

\#of layers and type

connective tissue cells are ____ in a matrix (aka?)

dispersed ; extracellular matrix

what produces the extracellular matrix?

the connective tissue cells that are embedded within it

what is the ground substance of the extracellular matrix?

amorphous gelatinous material

* transparent
* colorless
* fills the spaces between fibers and cells

what are the components of ground substance?

glycosoaminoglycans (GAGs)

what do GAGs link together to form?

even larger molecules called %%**proteoglycans**%%

what type of cells and go in and out of connective tissue?

adipocytes, mesenchyme cells, chondrocytes, osteocytes

what are the functions of connective tissue?

helps in

* binding and supporting
* protecting
* insulating
* storing reserve fuel
* transporting substances within the body

what is cell adaptation?

@@**change in cell morphology**@@ and function in response to a stimulus

* tries to regain homeostasis

what is cell homeostasis and what does that mean for cell injury?

normal cells have a fairly **narrow range of function** or **steady state**

alteration in a cell’s functional environment, either acute or chronic, produces stress to a cell’s ability to attain or maintain homeostasis

cell injury is because of?

too much stress exceeds the cell’s adaptive capacity

Homeostasis → Adaptation → _______

INJURY

what is reversible cell injury?

occurs if the stress is __**sufficiently small in magnitude**__ or __**short enough in duration**__ that the cell is @@**able to recover homeostasis after removal of the stress**@@

what is irreversible cell injury?

if the injurious or stressful stimulus is of __**sufficient magnitude or duration**__ or if the @@**cell is unable to adapt**@@

what is pyknosis?

irreversible condensation of chromatin in the nucleus

* degeneration of the cell as the nucleus shrinks in size
* chromatin condenses to a solid mass

irreversible cell injury mainly causes damage to what?

DNA

what is karyorrhexis?

destructive fragmentation of the nucleus of a dying cell

what is karyolysis?

complete dissolution of the chromatin of a dying cell

what is acute reversible injury and its process?

impairment of ion homeostasis

* increased intracellular levels of sodium and calcium
* influx of interstitial fluid causes swelling

where does cell swelling happen?

within the cytosol and organelles

what happens when cellular swelling affects the mitochondria?

Generate less energy

* cell reverts to less efficient anaerobic glycolysis
* excessive production of lactic acid
* pH becomes acidic and slows down cell metabolism

what are blebs?

injured cell forms plasma membrane pockets that can seal off and detach from the cell surface

what happens if the rough ER is damaged?

severely injured cells

* ribosomes detach
* reduced protein synthesis

what are examples of chronic cell injury?

atrophy, hypertrophy, hyperplasia, metaplasia, and dysplasia

what is chronic cell injury

when a sublethal stress remains present over a period of time

irreversible cell injury can result in?

apoptosis or necrosis

what are the 9 causes of cellular injury?

1. hypoxia (oxygen deficiency)
2. infectious angents
3. immune reactions
4. genetic
5. nutritional
6. physical
7. mechanical
8. chemical
9. psychosocial

what is ischemia and it’s effects on the cell?

lack of blood supply

* cell membrane is preserved
* nucleus undergoes pyknosis and karyolysis (dissolution)
* organelles dissolved

what is hematologic hypoxia?

inadequate oxygenation of blood

what is hypoxic hypoxia?

obstruction of respiratory tree

* alveolar sac or obstruction in trachea
* can happen at high altitudes

what is hypoxia?

reduced availability of oxygen to the body

* loss of oxygen carrying capacity from respiratory tree; from blood
* inability to use oxygen for cellular respiration

what are some infectious agents that can cause cellular death?

bacteria, virus, mycoplasma, fungi, rickettsiae, protozoans, prions, helminths

what is tetanus toxin (TeNT) and botulinum toxin (BoNT)?

TeNT = spastic paralysis, targets inhibitory interneurons

BoNT = flaccid paralysis, targets stimulatory inerneurons

what is septic shock?

loss of plasma volume; endothelial damage (circulatory system)

* cardiovascular collapse

what can be a result of an inflammatory reaction → necrosis → ?

GANGRENE

what are the 2 mechanisms that viruses can kill cells?

1. direct cytopathic effect usually found with RNA


1. kill from within by disturbing various cellular processes or by disrupting the integrity of the nucleus
2. virally encoded proteins become inserted into the plasma membrane
3. alter the permeability of the cell membrane to ions

\
2. indirect cytopathic effect


1. integrating themselves into the cellular genome
2. encode the production of foreign proteins and get recognized by the body’s immune cells
3. immune system attack and destroy the infected cell

what is an allergic reaction?

hypersensitivity to foreign non-pathogenic antigen

* can cause kidney damage because antigen antibodies lodge themselves in glomerular filtration
* presence of high numbers of a specific antibody-E (IgE) on the surface of specialized cells

what is anaphylactic shock?

chronic presence of foreign antigen

what causes type 1 diabetes?

sensitization to endogenous antigen, autoimmune response

how does cross-reactivity relate to immune reactions?

confusion between foreign and host antigens

what are the 3 genetic alterations that lead to cellular injury or death?

1. **alterations in the structure or number of chromosomes** that induce multiple abnormalities
2. **single mutations of genes** that cause changes in the amount or functions of proteins
3. multiple gene mutations that interact with **environmental factors** to cause multifactorial disorders

what are some nutritional factors that can cause cell death?

* imbalance in essential nutrients
* deficient protein (Kwashiorkar)
* general malnutrition (Marasmus)
* abnormal levels of vitamin/minerals

what are some physical factors that can cause to cell death?

hypothermia, hyperthermia, burns (severity and surface area, adult rule of nines chart)

electrothermal, ultrasound, atmospheric pressure, radiation

what are some mechanical factors that can cause cell death?

* single high load traumatic event
* continuous/repetitive pressure/force (slow degeneration
* rupture, overstretch, compression, friction, anoxia

what are some chemical factors that contribute to cell death

* environmental pollutants
* drug induced chemical toxicity
* direct or indirect (requires metabolic transformation by liver)

what are free radicals?

a molecule with an unpaired electron in an outer valence shell

what are antioxidants?

they freely give up an electron to stabilize the oxygen atom without becoming unstable and without initiating a chain reaction

despite several causes, underlying mechanism falls into 1 of 2 categories:

1. uncontrolled free radical energy
2. hypoxic injury (converges with free radicals

what is the process of oxidation?

* normal oxygen atoms lose one of their 4 paired electrons
* the resulting unstable atom attempts to replace the missing electron by “stealing” an electron from a healthy cell
* creates another unstable atom (free radical)
* sets off a chain reaction

oxidation as a by-product of metabolism damages…?

cell membranes, proteins, and alters DNA

→ intrinsic cellular damage

how are free radicals a good thing?

* integral part of metabolism and formed continously in the body
* the body’s natural process of using oxygen and food to produce energy can create free radicals as a byproduct
* enables the body to fight inflammation, kill bacteria, and help support the immune system

mechanism of injury → hypoxia

* decreased generation of cellular ATP
* anaerobic glycolysis takes place
* reduced intracellular pH
* clumping of nuclear chromatin
* reduced intracellular protein synthesis
* damage to cytoskeleton
* increased plasma membrane permeability and membrane transport
* cellular osmolarity

what are the cellular oxidative stress damage markers?

Lipids = 4-hydroxynonenol (4HNE)

DNA = 8-Oxo-2’-deoxyguanosine (8OHdG)

Protein = 3-Nitrotyrosine (3NT)

Polysaccharides = advanced glycan end products (AGEs)

Outcome from cell injury depends on?

1. type, duration, repetition, and severity of injury
2. type, status, and adaptability of the target cell


1. some cell types sustain injury better than others
2. some tissues have a capacity to regenerate
3. underlying intracellular phenomena
4. morphologic consequences

what are 3 things than can occur from reversible injury?

1. hydropic swelling
2. cellular accumulations
3. cellular adaptations

what are the characteristics of cellular swelling?

* intracytoplasmic accumulation of water due to %%__**inability to maintain ion homeostasis**__%%
* ^^__**Malfunction of Na/K pump**__^^ results in a accumulation of Na ions
* creating an @@__**osmotic gradient for water entry**__@@

intracellular accumulations → what are some endogenous sources

1. normal intracelular substance = lipids, carbs, proteins
2. abnormal substances produced
3. pigments and particles that are unable to degrade = hemosiderin, bilirubin, calcium, heavy metals, uric acid

how do intracellular accumulations happen?

abnormal metabolism or protein folding → cannot produce proper function → lack of enzymes → substrate accumulation → indigestible material

how do lipids accumulate in the cell?

lysosomal storage disorder → increased entry of FA → inability to metabolize lipds

* fatty liver due to alcoholism

how do carbs accumulate in the cell?

a bunch of GAGs → too much substrate in the absence of enzymes → unable to turn glycogen into glucose

what is the process of sorbitol accumulation?

hydrophilic cannot pass through the cell membrane → accumulates in the cell → osmotically active attracts water inside the cell → cell swelling → adverse effects on lens and retina, kidneys, Schwann cells

what is the process of Tau accumulation neurofibrillary tangles?

attaches on the edge of proteins → repeated stress of hyperphosphorylation causes it to detach → tangles in the brain → causes alzheimers

Process of Beta-Amyloid Plaque (LOAD) → extracellular accumulations

* fragments of amyloid precursor protein
* proteins build up as Oligomers and combine with other materials to form plaque
* as Alzheimer’s disease spreads, plaques and tangles spread throughout the brain

what is hypercholesterolemia?

pathological accumulation of cholesterol in:

* **Atherosclerotic Plaques** → intima of arteries


* **Xanthoma** → under the skin

what is uric acid accumulation?

normal end product of metabolism of purine

deposition of sodium urate crystals in tissues (peripheral joints)

Tophi = small masses from deposit

what is hyperuricemia?

increase of serum uric acid

what is atrophy?

decreased cell size/reduction in number

what is pathologic atrophy?

due to loss of physiologic function

* aging, bone loss, thymus, muscle wasting, brain cell loss

what are the 4 components of cellular adaptation?

1. decreased cell growth
2. increased cell growth
3. abnormal cell differentation
4. abnormal purposeless uncontrolled cell growth

what are some general pathologic atrophies?

**Spread across the body**

starvation = emaciation, cachexia

senile = narrowing of arteries, shrinkage of brain

toxic = ex chronic wasting diseases

endocrine = hypopituitarism

what are some local pathologic atrophies?

One Area

ischemic = brain cortex

neuropathic = poliomyelites

disuse = casting, immobilization

pressure = kidneys (UTI)

physical and chemical

what is cell hypertrophy?

increase in size of the organ/tissue due to increase in size of their constituent cells (increased functional demand)

what are some adaptive and compensatory hypertrophies?

Adaptive

* urinary bladder = constant expansion
* stomach = bulemia
* left ventricle = hypertension

\
Compensatory

* removal of organ such as in a nephrectomy

what is hyperplasia?

increase in size of organ or tissue due to increase in number of its constituent cells

* capable of dividing
* maintain their differentiated structure and function

what are 2 types of hyperplasia?

physiological/hormonal

* RBC number, liver enlargement, endometrial and uterine stomach cells

\
pathological

* compensatory, hormonal, irritation

what is metaplasia?

change of one type of differentiated tissue to another type of the same class of tissue

* SAME TISSUE

what are the causes of metaplasia?

1. chronic irritation
2. chronic infection
3. deficiency of certain factors

what is epithelial metaplasia?

Squamous = columbar to squamous (cervix, prostate)

Transitional to squamous (bladder)

Pseudostratified columbar ciliated to stratified squamous (smoker’s lung)

Columnar = chronic gastric ulcer and Barret’s esophagus

what is mesenchymal metaplasia?

**Multipotent stem cells found in bone marrow**

* supporting connective tissue (osseos, cartilaginous
* fluid connective tissue (blood and lymph)

what is dysplasia?

disorganized appearance of cells due to abnormal variations in size, shape, and arrangement

* altered cell morphology and histologic organization
* considered to be preneoplasitc

what are the characteristics of dysplastic cells?

* pleomorphic = able to assume diff forms
* loss of polarity = loss of organization of proteins and lipids in membrane
* hyperchromatic nuclei = excess chromatin or nuclear staining
* presence of mitosis = cell division/replication