Cellular Basis of Disease Part 2 Flashcards
1
Q
Part 6 Cellular Stress and Injury
A
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)
3
Q
Types of Stressors and Adaptation of Cells
A
4
Q
Mechanisms of Cell Injury
(2)
A
Hypoxic Injury
Free Radical and/or Reactive Oxygen Species Injury
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)
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
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
8
Q
Hypoxic Injury Chart
A
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
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
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
12
Q
Part 7 Morphological Adaptations to Stress and Injury
A
13
Q
Manifestations of Cell Injury
Physiological vs. Pathological Changes
Cells adapt to chronic injury/stress in many ways
- Changing the morphology of tissue (3)
- Alterations in Cell Differentiation (2)
A
- Atrophy, Hypertrophy, Hyperplasia
- Metaplasia, Dysplasia
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
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
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
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 _____
- Epithelial tissue tends to form barriers (s____, __/__ tract)
- What is happening in the picture?
A
-
Replacement
-
Skin, GI/GU
- stem
- intermediates
- most mature, loses ability to divide
-
Skin, GI/GU
- 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
