Cellular Basis of Disease Part 2

Question 1

Part 6 Cellular Stress and Injury

Question 2

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)

Answer 2

• 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)

Question 3

Types of Stressors and Adaptation of Cells

Answer 3

Question 4

Mechanisms of Cell Injury

(2)

Answer 4

Hypoxic Injury

Free Radical and/or Reactive Oxygen Species Injury

Question 5

Hypoxic Injury

(3)

Answer 5

• 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)

Question 6

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___.

Answer 6

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

Question 7

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 ______

Answer 7

• 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

Question 8

Hypoxic Injury Chart

Answer 8

Question 9

Reactive Oxygen Species

• Peroxidation of membrane lipids can have numerous effects, including:
  
  • increased ->
  • decreased ->
  • altered ->
  • altered ->

Answer 9

• Peroxidation of membrane lipids
  
  • membrane rigidity
  • activity of membrane bound enzymes (ie sodium pumps)
  • activity of membrane receptors
  • permeability

Question 10

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 ____”

Answer 10

• naturally
  
  • ​non, satisfied
  • phosphorylation, metabolism
    
    • ​lipid peroxidation, rigidity, permeability
• aerobic
  
  • ​antioxidants
• stres from reactive oxygen species
  
  • ​aging

Question 11

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 = ______

Answer 11

• 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

Question 12

Part 7 Morphological Adaptations to Stress and Injury

Question 13

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)

Answer 13

• Atrophy, Hypertrophy, Hyperplasia
• Metaplasia, Dysplasia

Question 14

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 =

Answer 14

• 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

Question 15

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

Answer 15

• Dysplasia
• Metaplasia
• Seen often in epithelial tissue

Question 16

Atrophy

• ______ functional demand
• ______ nutritional support

Answer 16

• 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

Question 17

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

Answer 17

• Increased
• Increased
• can’t divide
• LVH
• hormonal

Question 18

Hyperplasia

• _______ Functional Demand
• _______ Hormonal Stimulation
• ______ Injury/tissue repair

Answer 18

• 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)

Question 19

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?

Answer 19

• 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

Question 20

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 ______

Answer 20

• mitotic, lacks functional maturity
  
  • ​stability, loses function -> pathology

Question 21

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 ______

Answer 21

• Replacement, terminally, stem
• Chronic injury

adaptive, normal

Question 22

Dysplasia

• ___adaptive con_____ of p_____ injury
  
  • ​considered “pre_______”

Answer 22

• 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

Question 23

What changes are happening in this picture?

Answer 23

Metaplasia of Tracheal Epithelium in a smoker

Replacement of ciliated columnar cells with simple squamous

Question 24

What is happening in this picture?

Answer 24

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

Question 25

Other Manifestations of Cell Injury ## Footnote * 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 \_\_\_\_\_\_\_*

Answer 25

* Accumulations (Infiltrations) * Water * Lipid * Lipid, liver * Swelling * store, digest, deficient, overwhelmed* * digestion*

Question 26

Brain with Tay-Sachs Disease ## Footnote Is an example of what?

Answer 26

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

Question 27

Fatty Liver Disease ## Footnote Is an example of what? Cause = Is it reversible?

Answer 27

* 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*

Question 28

Part 8 Irreversible Cell Injury

Question 29

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

Answer 29

Acute Cellular Swelling * traffic, membrane * white * bloated

Question 30

Picture of?

Answer 30

Bloated mitochondria on the right

Question 31

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?*

Answer 31

Death ## Footnote * **Necrosis** * **​Coagulative** * **Liquefactive** * **Caseous** * **Fat** * Necrosis* * untimely* * coagulative* * liquefactive, casseous, fat necrosis*

Question 32

Ultrastructural features of coagulative necrosis ## Footnote 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

Answer 32

* bloated, clump and coagulate * ​cytoskeleton * ER, mitochondria * shrunken or shriveled, or exploded and dissappeared * integrity

Question 33

Nuclear Changes with Necrosis ## Footnote * **Pyknosis =** * **Karyorrhexis =** * **Karyolysis =**

Answer 33

* shrunken nucleus (usually first change) * nucleus in pieces * no nucleus at all

Question 34

Picture of? * Darker zone is the zone of? * Bloated and expanded = ____ white space

Answer 34

Coagulative Necrosis of Cardiac muscle tissue - soon after MI * zone of dead tissue * less

Question 35

Liquefactive Necrosis ## Footnote * 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: \_\_\_\_\_\_

Answer 35

* little to no connective tissue * nervous * empty, cyst * Brain

Question 36

Fat Necrosis ## Footnote * 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

Answer 36

* rich in fatty deposits (adipose tissue) * pancreas, breast tissue * Difference * ​react, suponification, soapy (hazinesse) * unique

Question 37

Casseous Necrosis ## Footnote * Happens in tissue that? * partially _____ bc has more connective tissue * "\_\_\_\_\_ _____ appearance" * Ofen in the ____ \_\_\_\_ (ie that are attacked and die from TB)

Answer 37

* has a loose network of connective tissue (**moderate amount of connective tissue)** * ​liquefied * "cottage cheese" * Lymph Nodes

Question 38

Picture of?

Answer 38

Pulmonary Casseous Necrosis with TB ex of a LN in the lung that has undergone casseous necrosis

Question 39

Apoptosis ## Footnote * Conditions that may trigger apoptosis: * _____ Infection * ____ damage * Certain kinds of m\_\_\_\_\_\_/m\_\_\_\_\_\_ damage * Cell s\_\_\_\_ (\_\_\_\_\_ \_\_\_\_\_) * Induction of ______ cells

Answer 39

* Viral * DNA * membrane/mitochondrial * stress (endoplastic reticulum) * immune

Question 40

Apoptosis Notes ## Footnote **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\_\_\_\_\_

Answer 40

**programmed**, "self-preserving" * apoptotic * **imploded** * **protection, cancer** * chop DNA, shrinks, condensation, collapse, bodies, lysis

Question 41

Apoptosis Notes ## Footnote * 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 \_\_\_\_\_\_

Answer 41

* NORMAL, extraneous, viral, DNA, membrane/mitochondria, stress, immune * function