cells adapt to their environment to protect themselves from injury

• an adapted cell is neither normal nor injured

  • physiologic- the cell may have enhanced function

  • pathogenic- extreme adaptation to excessive functional demand

the most significant adaptive changes in cells include:

• atrophy- decrease or shrinkage in cellular size

  • e.g. thymus gland undergoes physiologyic atrophy

    • pathogenic atrophy occurs as a result of decrease in blood supply, pressure, nutrition, workload, hormonal sinulation, and nervous simulation

• hypertrophy- increase in cellular size (which leads to increased organ size)

  • increase in size is due to increased accumulation of protein in cellular components

  • caused by specific hormone simulation or increased functional demand

hyperplasia- increase in the number of cells (thus increase rate of cellular division)

• caused in response to prolonged or severe injury

• loss of cells trigger dna synthesis and mitosis

  • compensatory hyperplasia- enables an organ to regenerate

    • e.g. liver, even with removal of 70%, regeneration can be comppleted in 2 weeks

  • hormonal hyperplasia- occurs mainly in estrogen dependent organs (uterus, breast, etc)

metaplasia- the reversible replacement of one mature cell by another

• it is as if the original cells are not robust enough to withstand the new environment, and so they change into another type more suited to the new environment

  • e.g. cigarette smoke that causes the mucus secreting ciliated simple columnar respiratory epithelial cells that line the airways to be replaced by simple squamous epithelium, or a stone in the bile duct that causes the replacement of the secretory columnar epithelium with simple squamous epithelium

    • caused by reprogramming of stem cells

dysplasia- abnormal change in the size, shape, and organization of mature cell

cell cycle and possible sites of block:

• m phase → (g0 phase) [not always done, not always exited] → g1 phase → s phase → g2 phase → m phase …

  • between m and g0 there is a possible site of block leading to cell hyperplasia

  • permanently nondividing cells (neurons, normoblasts, adult myocardial cells etc) will leave the cell cycle between m and g0

  • the cells of the liver and kidney will go to g0 and can leave it if stimulated by subtotal hepatectomy, renal tubular necrosis, nephrectomy etc.

  • between s and g2 there is a possible site of block leading to cell hypertrophy

most disease begins with cell injury

• injury occurs if the cell is unable to maintain homeostasis

injured cells may be able to recover but may not (reversible vs irreversible injury)

• major disturbances and damage to the membrane or lack of atp generation due to mitochondrial dysfunction

injurious stimuli could be:

• chemical agent

• hypoxia (lack of oxygen)

• free radicals

• infectious agents

• physical and mechanical factors

• nutrition imbalance

• genetic factor

• immunological reactions

  • often its from exposure to toxic chemicals, infections, or hypoxia

hypoxic injury can result from:

• decreased amount of oxygen in the air

• loss of hemoglobin

• ischemia

  • decreased production of rbc (??? why is this here?? that’s not what ischemia is….)

  • inadequate blood supply to the area/tissue/organ

  • the most common cause of hypoxia

  • caused by arteriosclerosis and thrombosis

    • arteriosclerosis- gradual narrowing of arteries

    • thrombosis- complete blockage by blood clots

• poisoning of oxidative enzymes (cytochromes)

• diseases of CVS and/or respiratory systems

• anoxia

  • total lack of oxygen

  • caused by total sudden obstruction (ex. embolus)

  • an acute obstruction in a coronary artery can cause myocardial infarction

cellular responses to hypoxia:

• decreased oxygen leads to decrease in atp

• low atp causes the plasma membranes sodium potassium pump and sodium calcium exchange to fail

  • extracellular accumulation of Na+ and Ca2+

  • Na+ and water can enter the cell freely and lead to cellular swelling

• reperfusion injury- injury caused by restoration of oxygen

membrane injury can be caused by free radicals such as reactive oxygen species

• free radical- electrically uncharged atom or group of atoms having an unpaired electron

  • 1 unpaired electron makes the molecule unstable so to stabilize itself, it either gives or takes an electron from another molecule (such as protein, lipid, or DNA)

  • this can disrupt a chemical bond and lead to:

    • lipid peroxidation- destruction of an unsaturated fatty acid

    • alteration of proteins (ex. fragmentation of polypeptide chain)

    • alteration of DNA (ex. breakage of single strands)

• mechanisms for the inactivation of free radicals

  • some fatty acids of lipids contain double bonds

  • such bonds are venerable to be attacked by free radicals leading to lipid peroxidation

  • peroxide leads to membrane or organelle destruction

    • i have no clue what this has to do with a mechanism to inactivate a free radical…

• body can sometimes rid itself of free radicals

chemical injury:

• begins with biochemical interaction between a toxic substance and plasma membrane that leads to damage and increased permeability

  • can be caused by:

    • direct toxicity

    • reactive free radicals and lipid peroxidation

  • chemical agents that cause cellular injury:

    • lead

      • primarily hazardous to children, particularly to fetuses (the nervous system is vulnerable)

    • carbon monoxide

      • it interrupts respiration

    • ethanol (alcohol)

    • mercury

    • social or street drugs (ex. marijuana, cocaine)

unintentional or intentional injuries:

• blunt force injuries are caused by mechanical force (ex. car accidents)

  • cause tearing, shearing, or crushing of tissues

  • the most common type of injury

• some injuries caused by non sharp force:

  • contusion or hematoma- bleeding into skin or tissue

    • contusion = bruise

    • blood vessels were ruptured without breaking the skin

  • abrasion- removal of superficial layer of the skin

    • caused by friction between skin and the object that caused the injury

  • laceration- irregular tear or rip of skin or tissue

  • fracture- broken bone

• contusions and hematoma:

  • bruising → extravasated rbcs (rbcs get outside where they’re supposed to be aka the blood vessel) → phagocytosis of rbcs by macrophages → (either/or) hemosiderin or iron-free pigments

    • the color changes are due to the hemoglobin changes and the breakdown of the extravasated blood (ex. the final hemoglobin breakdown product is bilirubin which is yellow so bruises are yellow/green in their last stages)

• sharp force injuries:

  • incised wounds- a cut that is longer than it is deep

    • can be sharp or jagged

    • has sharp and distinct edges

  • stab wounds- a penetrating sharp force injury that is deeper than it is long

  • puncture wounds- a deep but relatively narrow penetrating wound

  • chopping wounds= combination of sharp and blunt force

• gunshot wounds:

  • entrance wounds- caused by the bullet entering the body

    • contact range entrance wound

    • intermediate range entrance wound

      • tattooing and stippling

        • its not talking about wounds from tattooing and stippling, its a description of things around the wound site, ‘tattooing’ is when there is unburnt particles and metal scraps embedded in the surrounding skin (also maybe when there are small burns from burning gunpowder) (might also be stippling, unsure)

    • indeterminate range entrance wound

  • exit wounds- caused by the bullet exiting the body

    • shored exit wound- caused when the skin is contact with another object when the bullet exits; produced when the outstretched skin is impaled, sandwiched, and crushed between the outgoing bullet and an unyielding object over the exit site, thus leaving an abrasion collar on the wound margin

• asphyxia injuries are caused by a failure of cells to receive or use oxygen

  • they are grouped into:

    • suffocation- can result from lack of oxygen in the air

    • strangulation- caused by compression and closure of blood vessels and air ways

    • chemical asphyxiants- prevent or block delivery of oxygen to the tissue (ex. carbon monoxide)

    • drowning

infectious injury

• pathogenic (virulence) microorganisms:

  • invade and destroy cells

  • produce toxin

  • produce damaging hypersensitivity reactions

immunologic and inflammatory injury:

• phagocytic cells cause injury to the cell

• immune and inflammatory substances such as histamine, antibodies, lymphokines, complement, and enzymes can cause cellular injury

• membrane alterations

injurious genetic factors:

• nuclear alterations

• alterations in the plasma membrane structure, shape, receptors, or transport mechanisms

• aka genetic disorders

• ex. sickle cell anemia, muscular dystrophy

injurious nutritional imbalances:

• essential nutrients are required for cells to function normally

• deficient intake (hypo-)

  • ex. hypolipidema

• excessive intake (hyper-)

  • ex. hyperlipidemia

temperature extremes:

• hypothermic injury- chilling or freezing of cells

  • slows cellular metabolic processes

• hyperthermic injury- caused by excessive heat

  • heat cramps- cramps are a result of salt and water loss (ex. during vigorous exercise)

  • heat exhaustion- in addition to fluid loss, hypotension occurs

  • heatstroke- life threatening condition caused by high humidity and high temperature

atmospheric pressure changes:

• sudden increases or decreases in atmospheric pressure

• blast injury

• decompression sickness or caisson disease (aka “the bends”)

ionizing radiation:

• any form of radiation capable of removing orbital electrons from atoms

  • xrays, gamma rays, alpha and beta particles

    • DNA is the most vulnerable target

• mechanism of damage

• effects of ionizing radiation

manifestations of cellular injury:

• cellular accumulations (infiltrations)- in addition to injury, cellular accumulations can occur as a result of normal cell function

• common accumulations consist of:

  • water- cause (s?) cellular swelling

  • lipids and carbohydrates- as a result of some metabolic disorders

  • glycogen- as a result of genetic disorders

  • proteins

• hydropic degeneration:

  • injury → hypoxia → atp production decreases → sodium and water move into the cell, potassium moves out of the cell → osmotic pressure increases → more water moves into the cell → cisternae of endoplasmic reticulum distend, rupture, and form vacuoles → extensive vacuolation → hydropic degeneration

  • the swelling from an influx of water that happens in an injured cell

  • 

• cellular accumulations (infiltrations) (ig more??):

  • pigments

    • melanin, hemoproteins, bilirubin

  • calcium- accumulate in both injured and dead tissue

    • 

  • urate- hyperuricemia can cause gout (acute or chronic arthritis)

cellular death:

• necrosis

  • sum of cellular changes after local cell death and the process of cellular autodigestion (aka self digestion)

  • irreversible injury progresses to necrosis

• processes (i think all of these go under necrosis)

  • karyolysis

    • nuclear dissolution and chromatin lysis

  • pyknosis

    • clumping of the nucleus

    • condensation (clumping) of chromatin in the nucleus

  • karyorrhexis

    • fragmentation of the nucleus

necrosis:

• the 4 major types of necrosis are:

  • coagulative necrosis- occurs primarily in kidney

    • protein denaturation

  • liquefactive necrosis- occurs in neurons and glial cells of the brain

    • hydrolytic enzymes

  • caseous necrosis

    • tuberculous pulmonary infection

    • combination of coagulative and liquefactive necrosis

  • fat necrosis

    • breast, pancreas, and other abdominal organs

    • action of lipases

apoptosis:

• programmed cellular death

• mechanisms (?)

• necrosis vs apoptosis (?)

• apoptotic signal → initiator caspase → death substrates → (either/or) disable DNA repair and cell survival proteins or condense chromosome and fragment DNA → (come back to later bc i’m confused, slide 48)

aging and altered cellular and tissue biology:

• aging vs disease (?)

• normal life span (?)

• gender differences (?)

theories of aging:

• accumulation of injurious events

• genetically controlled program

• theories

  • genetic and environmental lifestyle factors

  • alterations of cellular control mechanisms

  • degenerative extracellular changes

aging:

• cellular aging

• tissue and systemic aging

  • fraility

    • clinical fraility scale:

      • 1- very fit

        • people who are robust, active, energetic, and motivated. these people commonly exercise regularly. they are among the fittest for their age

      • 2- well

        • people who have no active disease symptoms but are less fit than category 1. often, they exercise or and very active occasionally (e.g. seasonally)

      • 3- managing well

        • people whose medical problems are well controlled, but are not regularly active beyond routine walking

      • 4- vulnerable

        • while not depending on others for daily help, often symptoms limit activities. a common complaint is being “slowed” up and/or being tired during the day

      • 5- mildly frail

        • these people often have more evident slowing, and need help in high order IADLs (finances, transportation, heavy housework, medications). typically, mild fraility progressively impairs shopping and [finished from similar chart i found: walking outside alone, meal preparation, medications, and begins to restrict light housework]

      • 6- (from a similar chart i found) moderate frailty

        • people who need help with all outside activities and with keeping house. inside, they often have problems with stairs and need help with bathing and might need minimal assistance (cuing, standby) with dressing

      • 7- severely frail

        • completely dependent for personal care, from whatever cause (physical or cognitive). even so, they seem stable and not at a high risk of dying (within 6 months)

      • 8- very severely frail

        • completely dependent, approaching the end of life. typically, they could not recover even from a minor illness

      • 9- terminally ill

        • approaching the end of life. this category applies to people with a life expectancy of less than 6 months but are not otherwise evidently frail

      • scoring frailty in people with dementia:

        • the degree of frailty corresponds to the degree of dementia. common symptoms in mild dementia include forgetting the details of a recent event, though still remembering the event itself, repeating the same question/story and social withdrawal. [finished from a similar chart i found: in moderate dementia, recent memory is very impaired, even though they seemingly can remember their past life events well. they can do personal care with prompting. in severe dementia, they cannot do personal care without help. in very severe dementia, they are often bedfast (bedbound?) . many are virtually mute]