Cellular Basis of Disease Part 2 Flashcards

1
Q

Part 6 Cellular Stress and Injury

A
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2
Q

Types of Stressors and Adaptation of Cells

  • Low stressors cause =
  • Irreversible cell injury causes =
    • Coagulative Necrosis =
    • ____ to a window after cell adapts where cell can go back to normal
  • Adaptations to persistent injury include changes in cell m____/structure (6)
A
  • change in functional demands and reversible cell injury (will change how cell functions which can potentially cause clinical manifestations)
  • coagulative necrosis
    • generic term for cell death from external causes (cell proteins and other components kind clump up)
    • Limit
  • morphology (hypertrophy, hyperplasia, atrophy, metaplasia/dysplasia, increased intracellular storage)
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3
Q

Types of Stressors and Adaptation of Cells

A
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4
Q

Mechanisms of Cell Injury

(2)

A

Hypoxic Injury

Free Radical and/or Reactive Oxygen Species Injury

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5
Q

Hypoxic Injury

(3)

A
  • Ischemia
  • Anoxia (occurs with complete blockages of blood flow and quickly precedes cell death)
  • Reperfusion Injury = secondary injury dt inflammatory response (when the blood flows back to tissues and carries inflammatory mediators and inflammation is damaging to tissue)
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6
Q

Free Radical and/or Reactive Oxygen Species Injury

(3)

  • Free radicals =
    • ​Electrons are highly __dependent (do not like being alone)
    • So if an atom loses an it leaves the other in a highly _____ state and will bump into anything to make that shell complete
    • In biological systems, most common free radical is ______
  • We have free radical forms of oxygen that are parts of normal ______ and involved in _____ responses which makes them damaging
  • Reactive oxygen species = causes injury by injurying plasma m____ through ____ ______, and damaging p____, and D___.
A

Lipid Peroxidation

Disruption of polypeptide chains

DNA damage

  • any kind of element with an unpaired electron in its outermost shell
    • ​codependent
    • reactive
    • Oxygen
  • metabolism, inflammatory
  • membrane, lipid peroxidation, proteins, DNA
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7
Q

Hypoxic Injury

  • Reduced oxygen to ______ -> drop in _____ -> inoperative _________ (accumulation of sodium __ and K ___)/inoperative ______ pumps (accumulation of Ca __ the cell)
  • Water follows sodium into cell =
    • ​Organelles ->
    • Endoplastic Reticulum ->
    • Mitochondria ->
    • Lysosome ->
  • With loss of ATP, cell also increases rate of ______ -> a product of glycolysis is _____ which is _____ -> pH _____ -> proteins ______
A
  • mitochondria -> ATP -> Na/K pumps (Na in, K out), Ca in
  • acute cellular Swelling
    • swelling
    • ribosomes on rough ER start to detach -> can’t synthesize protein
    • swelling -> can’t produce ATP -> cell death
    • swelling (stomach of cell packed with digestive enzymes) -> opens up into cell -> autodigestion of cell
  • glycolysis -> lactate, acidic -> drops -> denature
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8
Q

Hypoxic Injury Chart

A
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9
Q

Reactive Oxygen Species

  • Peroxidation of membrane lipids can have numerous effects, including:
    • increased ->
    • decreased ->
    • altered ->
    • altered ->
A
  • Peroxidation of membrane lipids
    • membrane rigidity
    • activity of membrane bound enzymes (ie sodium pumps)
    • activity of membrane receptors
    • permeability
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10
Q

Reactive Oxygen Species Notes

  • Reactive oxygen species = _____ occurring free radicals
    • ​Oxygen usually comes in the form of O2 (___polar, completely _____)
    • When oxygen is used for oxidative phos______ during _____-> frequently produces one or more of these reactive oxygen species
      • ​Red electron from chart is unpaired -> looks to steal electron from chemical bond -> which results in l_____ p______ (by stealing electrons from membrane lipids) -> membrane _____, damage enzymes and proteins, alters p_____ (AKA causes membrane, protein, DNA damage)
  • Any organism that relies on _____ metabolism will have to deal with reactive oxygen species
    • Cells have enzymes and naturally occurring ______ that neutralizes these species
  • Oxidative stress =
    • “which is why ppl claim that antioxidants help slow down cell ____”
A
  • naturally
    • ​non, satisfied
    • phosphorylation, metabolism
      • ​lipid peroxidation, rigidity, permeability
  • aerobic
    • ​antioxidants
  • stres from reactive oxygen species
    • ​aging
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11
Q

Formation of Free Radicals

  • There are things that can increase exposure
    • I_______
    • Air _____
    • S____
    • Ionizing R_____
    • ___ light from ____
  • So cellular damage is high related to _____ (beyond mere metabolism)
    • Lastly, important consequence of being exposed to reactive oxygen species = ______
A
  • Things that increase exposure
    • Inflammation (wbc arrive at area and release reactive oxygen species to attack bacteria/foreign bodies -> lots of collateral damage in tissue dt reactive O2 species
    • Pollution = release of O3 in environment -> interacts with UV light to create reactive O2 species
    • Smoking
    • Radiation
    • UV light from Sun
  • exposure
    • CANCER
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12
Q

Part 7 Morphological Adaptations to Stress and Injury

A
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13
Q

Manifestations of Cell Injury

Physiological vs. Pathological Changes

Cells adapt to chronic injury/stress in many ways

  1. Changing the morphology of tissue (3)
  2. Alterations in Cell Differentiation (2)
A
  • Atrophy, Hypertrophy, Hyperplasia
  • Metaplasia, Dysplasia
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14
Q

Morphological Changes

  • Cell number stays same, cell number increases
  • Cell number stays same but cells have gotten smaller (not shrinkage, is a proportional decrease in both cell size and content)
  • Cell number stays same cell size increases (not swelling, cell size and components both increase)
  • All three of these changes frequently result of increase or decrease in _____ deman (like smaller arm when taking off a cast)
  • Which two often happen together? why?
    • ​Example of well adpative change =
    • Example of pathological change =
A
  • Hyperplasia
  • Atrophy
  • Hypertrophy
  • functional
  • Hypertrophy and Hyperplasia, bc both result from increase in functional demand (same stimuli)
    • strength training
    • DM II - insulin resistance - pancreas cells hypertrophy and hyperplasia to overcome resistance -> does not sustain -> cell death -> less insulin over time
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15
Q

Alterations in Cell Differentiation

  • Complete derangement of cell control over tissue (never adaptive is always a consequence of cell injury) over-proliferating, less differentiated cell type
  • Normal cells that make up a tissue get replaced by less mature/less differentiated cells bc they develop more rapidly and theres a chronic injury in that area
A
  • Dysplasia
  • Metaplasia
  • Seen often in epithelial tissue
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16
Q

Atrophy

  • ______ functional demand
  • ______ nutritional support
A
  • decreased
  • decreased
  • More white space in second photo bc size of liver cells have shrunken -> ex of atrophy as a result of protein or caloric deficiency (starvation)
  • Can also have atrophy in tissue that relies on hormonal support
    • ​Reproductive tissue requires constant stimulation of reproductive hormones -> when taken away can atrophy ie) perimenopausal -> fibroid tumors
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17
Q

Hypertrophy

  • _______ functional demand
  • _______ hormonal stimulation
  • There are some cells in the body that can’t ____ and cope with increased demand through hypertrophy
  • Example: ____ : is a pathological increase in functional demand dt chronic HTN or aortic stenosis
  • Increased ______ stimulaion also common cause of inappropriate hypertrophy
A
  • Increased
  • Increased
  • can’t divide
  • LVH
  • hormonal
18
Q

Hyperplasia

  • _______ Functional Demand
  • _______ Hormonal Stimulation
  • ______ Injury/tissue repair
A
  • Increased
  • Increased
  • Chronic ​

Hyperplasia often seen with Hypertrophy bc both result from increase in functional demand/hormonal stimulation

Picture: hyperplasia of epidermal cells astcd with psoriasis (autoimmune disorder - so chronic injury from immune system is causing increase in cell number)

19
Q

Metaplasia

  • AKA Cell ______ (not for all cell types, often for epithelial tissue cells)
    • Epithelial tissue tends to form barriers (s____, __/__ tract)
      • Has ____ cells - that divide, differentiate, and replace with new lawn of epithelial tissue
      • ______ present in the differentiation steps
      • Terminal differentiated cell = most functionally ____, but ____ ability to _____
  • What is happening in the picture?
A
  • Replacement
    • Skin, GI/GU
      • stem
      • intermediates
      • most mature, loses ability to divide
  • Columnar cells originate as simple squamous -> ciliated columnar are example of terminal differentiation with functional maturity but is getting replaced by new squamous cells
20
Q

Metaplasia

  • Metaplasia: replacement of ciliated colmnar with simple squamous by can replace themselves quickly: aka more ______ activity, however ___ that functional maturity (ie. chronic injury/irritation from smoking) -> since now no silia, more vulnerable to resp infx
    • ​Therefore, metaplasia helps maintain _____ of tissue but loses ____ and creates the ______
A
  • mitotic, lacks functional maturity
    • stability, loses function -> pathology
21
Q

Metaplasia

  • ______ of ______ differentiated cell type with less differentated ___ cell
  • Caused by?

Metaplasia vs. Dysplasia is more _____ bc you can take the injury away and it can go back to ______

A
  • Replacement, terminally, stem
  • Chronic injury

adaptive, normal

22
Q

Dysplasia

  • ___adaptive con_____ of p_____ injury
    • considered “pre_______”
A
  • NONadaptive consequence of persistent injury
    • ​”precancerous” -> can develop into tumor/when found in body is usually removed to prevent progression

I don’t give a shit about anything pattern of growth - overrun/kill tissue (no regularity in cell shape

23
Q

What changes are happening in this picture?

A

Metaplasia of Tracheal Epithelium in a smoker

Replacement of ciliated columnar cells with simple squamous

24
Q

What is happening in this picture?

A

Cervical dysplasia

Normal tissue on left with all the white space - has intracellular space,dots are nuclei

Dysplasia on right - dense and crowded, nonadaptive consequence

25
Q

Other Manifestations of Cell Injury

  • A_______ (or I_______)
    • W
    • L
    • L_____accumulation in _____ cells
  • Hydropic ________
  • Sometimes cells ____ too much* from 1) cannot ____ all that extra stuff 2) digestive enzymes are ____ or immobilized 3) cell is just over_____
  • Ultimately an issue of altered _______*
A
  • Accumulations (Infiltrations)
    • Water
    • Lipid
    • Lipid, liver
  • Swelling
  • store, digest, deficient, overwhelmed*
  • digestion*
26
Q

Brain with Tay-Sachs Disease

Is an example of what?

A

Tay Sachs disease = deficiency in lipid digesting enzyme = so what you find is these vacuoles of lipid within neuronal cells that eventually interferes with cell function

27
Q

Fatty Liver Disease

Is an example of what?

Cause =

Is it reversible?

A
  • When liver cells accumulate with fat within their cytoplasm so you can see these large droplets of fat in these hepatocytes that should not be there
  • Alcohol contains ethanol which is metabolized by liver -> acetyl aldehyde is a biproduct which blocks livers ability to digest fat
    • Is reversible, stop drinking -> acetyl aldehyde will go down

Foi gras is a fatty liver disease ina goose -> consumed as a delicacy

28
Q

Part 8 Irreversible Cell Injury

A
29
Q

Pictures of?

  • Hypoxic injury/other injury that impairs cells ability to _____ water across ______
  • Top pic: band of _____ represents the dead and bloated cells
  • Bottom pic: large vacuoles of cell are ______ endoplastic reticulum
A

Acute Cellular Swelling

  • traffic, membrane
  • white
  • bloated
30
Q

Picture of?

A

Bloated mitochondria on the right

31
Q

Irreversible Cell Injury

AKA Cell ________

  • Necrosis (4)
  • Irreversible cell death = ______ cell death*
  • Necrosis = ______ death of cells*
  • General term is ______ necrosis = general tissue death as a result of cellular necrosis*
  • Depending on tissue type - necrosis can be described as?*
A

Death

  • Necrosis
    • ​Coagulative
    • Liquefactive
    • Caseous
    • Fat
  • Necrosis*
  • untimely*
  • coagulative*
  • liquefactive, casseous, fat necrosis*
32
Q

Ultrastructural features of coagulative necrosis

The intracellular gets _______ -> its intracellular contents start to c____ and c______

  • ​No longer regular shape dt disorganized ______
  • Big vacuoles of _ _, m______
  • What hapens to the nucleus?

So necrotic cell death is rely this damage to the cell being unable to maintain its in____/system

A
  • bloated, clump and coagulate
    • ​cytoskeleton
    • ER, mitochondria
    • shrunken or shriveled, or exploded and dissappeared
  • integrity
33
Q

Nuclear Changes with Necrosis

  • Pyknosis =
  • Karyorrhexis =
  • Karyolysis =
A
  • shrunken nucleus (usually first change)
  • nucleus in pieces
  • no nucleus at all
34
Q

Picture of?

  • Darker zone is the zone of?
    • Bloated and expanded = ____ white space
A

Coagulative Necrosis of Cardiac muscle tissue - soon after MI

  • zone of dead tissue
    • less
35
Q

Liquefactive Necrosis

  • When necrosis happens in tissue with?
  • Common in ______ tissue - that tissue progresses into liquefactive necrosis (tissue looks liquefied)
  • Looks like _____ space, or a ____ thats walled off with a membrane
  • Example: ______
A
  • little to no connective tissue
  • nervous
  • empty, cyst
  • Brain
36
Q

Fat Necrosis

  • Happens in tissue that is?
  • Commonly in?
  • Difference between fat necrosis with other necrosis’s
    • When the intracelular contents of the dead cell is released -> they _____ with the fatty deposits and undergo _______ -> s____ deposits in tissue (h_____)
    • Just a ______ look that the tissue takes on its morphology as a result of cell death
A
  • rich in fatty deposits (adipose tissue)
  • pancreas, breast tissue
  • Difference
    • ​react, suponification, soapy (hazinesse)
    • unique
37
Q

Casseous Necrosis

  • Happens in tissue that?
    • partially _____ bc has more connective tissue
    • “_____ _____ appearance”
  • Ofen in the ____ ____ (ie that are attacked and die from TB)
A
  • has a loose network of connective tissue (moderate amount of connective tissue)
    • ​liquefied
    • “cottage cheese”
  • Lymph Nodes
38
Q

Picture of?

A

Pulmonary Casseous Necrosis with TB

ex of a LN in the lung that has undergone casseous necrosis

39
Q

Apoptosis

  • Conditions that may trigger apoptosis:
    • _____ Infection
    • ____ damage
    • Certain kinds of m______/m______ damage
    • Cell s____ (_____ _____)
    • Induction of ______ cells
A
  • Viral
  • DNA
  • membrane/mitochondrial
  • stress (endoplastic reticulum)
  • immune
40
Q

Apoptosis Notes

Apoptosis = a _______ cell death, a set of “self-______” genes found in nucleus

  • ​is a cascade of events called the “______ pathway” aka self destruct button
  • instead of cell looking like it exploded -> the cell looks like they’ve _______ (caves in on itself)
  • Designed to be a _______ of the organism as a whole from cells that are vulnerable to become ______ cells
  • Part of process is producing proteins that ____ up ____, cell sh____, chromatin ______, nuclear ______, apoptotic ____ that are remnant of cell undergo l_____
A

programmed, “self-preserving”

  • apoptotic
  • imploded
  • protection, cancer
  • chop DNA, shrinks, condensation, collapse, bodies, lysis
41
Q

Apoptosis Notes

  • A _____ part of body function however like reactive oxygen species can be caused by _____ things (____ infetions, ___ damage, m____/m____ damage, excessive cell ____, i____ cells)
  • Excessive apoptosis eventually leads to altered tissue/organ ______
A
  • NORMAL, extraneous, viral, DNA, membrane/mitochondria, stress, immune
  • function