Adaptation & Injury Flashcards
What are the seven key characteristics used to describe a disease?
- etiology
- pathogenesis
- pathology
- clinical manifestations
- complications
- prognosis
- epidemiology
What is pathogenesis, and how does it differ from etiology?
Pathogenesis = MECHANISM causing disease
Differs from etiology = actual cause of the disease
What is the difference between clinical manifestations and complications?
Clinical manifestations refers to SIGNS & SYMPTOMS whereas complications refer to the SYSTEMIC, SECONDARY OR REMOTE CONSEQ
Define prognosis and provide an example of a poor prognosis.
Prognosis refers to the anticipated disease course.
Poor diagnosis = unlikely disease will resolve
Apply the characteristics of disease to a lung tumour example.
- etiology: smoking (Chem exposure)
- pathogenesis: genetic alt
- pathology: lung tumour
- clinical manifestations: breathlessness
- complications: metastasis
- prognosis: death/remission
What is the key difference between adaptation and injury?
Adaptation is a response to stress, resulting in reversible modulation of structure/function to AVOID INJURY.
Injury occurs due to direct stimulus or a failure to adapt, compromising cell function, either reversible or irreversible.
What determines whether a cell adapts or becomes injured?
Cell becomes injured when stress exceeds its adaptive capacity - can depend on type of stress, duration, intensity, type of cell etc.
Is cellular adaptation reversible? Explain.
Yes, if stimulus is removed e.g. hypertrophy reverses (atrophy) when workload decreases
What are the two main types of adaptation, and how do they differ?
- Physiological - normal cell re to stim (e.g. hormones)
- Pathological - re to disease related stim to AVOIID injury
Define hypertrophy and give an example of both physiological and pathological hypertrophy.
Hypertrophy = ↑ structural proteins/organelles → ↑ cell sz re ↑ workload → ↑ organ sz
Physio - body buidling
Path - hypertension → enlarged heart
Which types of cells undergo hypertrophy, and why?
Non-div cells e.g. skeletal myocytes
Bc cannot adapt via hyperplasia??
Define hyperplasia and explain how it differs from hypertrophy.
GF → ↑# mature + stem cells → ↑ organ sz
Hypertrophy - non div cells + same # cells but ↑ sz,
Vs hyperplasia - div cells ONLY + same sz cells, but ↑ #
dividing cells ONLY
Give an example of physiological hyperplasia and pathological hyperplasia.
Physiological - liver regen, puberty
Pathological - endometriosis, callous formation
What is atrophy, and what causes it?
↓cell sz bc↓ protein synth + ↑ degrad → ↓ struc proteins/organelles
Causes: ↓workload, ↓innervation, malnutrition, ↓ endocrine stim, chronic pressyre
Provide an example of physiological atrophy and pathological atrophy.
Physio: post-preg uterine shrinkage
Pathological: wasting diseases
Define metaplasia and explain why it occurs.
When one diff cell type replaced by another cell type that is better adapted to withstand specific stress
Give an example of metaplasia due to smoking.
Ciliated columnar epithelium → stratified squamous epithelium
How does chronic acid reflux lead to metaplasia?
Stratified squamous epithelium → gastric columnar epithelium = better adapted to withstand stress of low pH
What is hypoxia, and why is it harmful to cells?
Interferes with aerobic respiration/ATP production
Harms cellular processes + equilibrium across membranes
List four causes of hypoxia and explain each.
- Pneumonia - inadequate O2
- Haemorrhage - blood loss anemia
- CO poisoning/Fe deficiency - ↓ O2 carrying capacity
- Ischemia - ↓ blood supply
How does ischemia differ from other forms of hypoxia?
Other forms of hypoxia may have normal BF - Ischemia BF is severely reduced
Impacts both nutrient delivery + waste removal and -> damage typically more severe + rapid
What are some common chemical agents that cause cell injury?
Tobacco, alc, drugs
Glucose/salt
O2
Environ pollutants - Pb, Hg
How can oxygen itself become toxic?
ROS severely damage cellular components
How does alcohol contribute to liver disease?
- chemical causes Chem injury to cells → immune response, ROS, lipid peroxidation
- chronic immune response → fibrosis
- ROS → damage hepatocytes
- lipid peroxidation → fat accumulation in hepatocytes = steatosis
- steatosis accelerates inflamm
- fibrotic tissue replaces liver parenchyma → disrupts BF + liver fn = cirrhosis
Name five infectious agents that can cause cell injury.
- Bacteria
- Viruses
- Fungi
- Parasites
- Prions
How do prions cause disease, and why are they unique?
Prions = proteinaceous infectious particles that kill cells w/out causing inflamm response
Resistant to NA mod
Assoc w vacuolation of brain cells
What are four types of immunologic reactions that can cause injury?
- Autoimmunity
- Hypersensitivity
- Graft rejection
- Immune deficiency
What is an example of autoimmune disease that leads to cell injury?
Rheumatoid arthritis
How do genetic defects contribute to disease?
Single base mutations → fn deficiencies/protein misfolding
congenital malformations → e.g. Down syndrome
What is an example of a disease caused by a single-base mutation?
Tay-sachs disease = metab disorder → GM2 ganglioside accumulation
How can nutritional imbalances lead to disease?
Deficiency → X enough building blocks for cell fn
Excess → mechanical load, hormone dysfunction etc.
Give an example of a disease caused by nutritional deficiency.
Rickets due to vit D deficiency
What are some excessive nutritional imbalances that contribute to disease?
Excess sugar - type II diabetes, hyperglyceridemia, obesity
Excess salt - hypertension
List five types of physical injury that can damage cells.
- mechanical trauma
- thermal injury
- elec injury
- ionising radiation
- atm pressure change
Why do aging cells have a reduced ability to repair themselves?
Multi factors incl genetics + environmental conditions → progressive decline in cell fn + viability
What factors influence whether an injury is reversible or irreversible?
Injury:
- type
- duration
- intensity
Cell:
- type
- genetics
- adaptability
- state
How does the duration of an injury affect the likelihood of cell recovery?
Prolonged injury → more extensive damage → more likely that underlying structure = destroyed → irrev injury
Why do different cell types have different thresholds for irreversible injury?
- metabolic demand
- capacity for anaerobic metabolism
Skeletal muscle 2-3 hrs (anaerobic resp)
Cardiac muscle 20-30min (high E demand)
Neurons 3-5min (high E demand)
What are the key cellular structures affected during injury progression?
- ATP-dependent ion channels in PM and MC
- ER
- nucleus
- lysosomes
What are the two main types of cell death?
Necrosis & apoptosis
How can transient ischemia affect myocytes without causing irreversible damage?
Temporary non-contractility → affects heart function
What is the earliest morphological sign of reversible injury in most cells?
Cell swelling
What are the key irreversible thresholds for cell injury?
MC fn unrestorable
PMs lose struc integrity:
- lysosomal rupture → enzymatic degradation
- PM frag → cell content leakage → inflamm
- MC membrane degrades → amorphous densities in mitochondria
What are amorphous densities in mitochondria, and what do they indicate?
- irreg, e- dense granules in MC
- only visible under e- microscopy
- indicate MC Ca overload -> irrev cell injury
- assoc w necrosis
What happens to lysosomal membranes in irreversible injury, and why is this significant?
Rupture → release hydrolytic enzymes → autodigestion of cell components
How does mitochondrial membrane damage lead to necrosis?
- Disrupted membrane potential → oxidative phosphorylation stage of aer resp = fails → ↓ ATP production
- Triggers opening of MC permeability transition pores (MPTP) → pro-apoptotic proteins (e.g. cytochrome c) released → capsase activation → apoptosis initiate
NB: ATP needed for apoptosis to occur in controlled way → ATP depletion from #1 → apoptosis spirals into necrosis in #2
Why does loss of ATP lead to membrane failure?
- ATP req for ion pumps (Na/K-ATPase, Ca-ATPase) → ionic grad fail → osmo swelling
- impairs phospholipid synthesis → destab PM struc integrity
- Ca accumulation from failed ion pumps → phospholipase + protease activation → attacks membrane proteins + lipids → PM rupture
How does loss of mitochondrial function push a cell toward necrosis?
ATP depletion → unable to control apoptosis → spirals in necrosis
What is the purpose of histological staining?
Most cells = clear unless stained → enhances contrast by diff cell/tissue components → ID specific structures
What are the two main components of H&E stain?
Hematoxylin and eosin
What types of cellular structures does haematoxylin stain, and what color do they appear?
- basophilic (acidic) structures
E.g. nuclei, ribosomes, rough ER - blue/purple
What types of cellular structures does eosin stain, and what color do they appear?
Acidophillic (basic) structures e.g. cytoplasm, ECM, MC, proteins
Pink/red
What is the purpose of DAPI staining?
Why do most cells appear transparent without staining?
What color does viable myocardium appear when stained with triphenyltetrazolium chloride?
What are the main light microscope features of reversible cell injury?
How do ultrastructural changes help distinguish reversible from irreversible injury?
Why does cellular swelling occur in reversible injury?
What is fatty change, and in what type of injury does it occur?
How does chromatin clumping occur, and what does it indicate?
What is the role of ribosomal detachment in cell injury?
Why does the presence of lysosomal rupture indicate irreversible injury?
How does necrosis cause inflammation?
What are the two key thresholds that determine irreversible injury?
Why does mitochondrial membrane damage signal the point of irreversibility?
How does lysosomal enzyme leakage contribute to cell death?
What happens when the plasma membrane loses its integrity?
How does failure of the Na⁺/K⁺ pump contribute to cell swelling and death?
Why does ATP depletion result in necrosis rather than apoptosis?
What are the main causes of ATP depletion?
How does ATP depletion affect the Na⁺/K⁺ pump?
What happens when anaerobic glycolysis increases in response to ATP depletion?
How does ATP depletion affect protein synthesis?
What are the main causes of mitochondrial damage?
How does mitochondrial permeability affect ATP production?
How does cytochrome C leakage lead to apoptosis?
How do reactive oxygen species (ROS) contribute to mitochondrial damage?
Why do cells tightly regulate intracellular Ca²⁺ levels?
What are the effects of increased cytosolic Ca²⁺ on cellular enzymes?
How does Ca²⁺ affect mitochondrial permeability?
What are reactive oxygen species (ROS), and how are they generated?
How do cells normally neutralize ROS?
What are the three major types of cellular damage caused by ROS?
How does oxidative stress contribute to cell injury?
What is lipid peroxidation, and why is it damaging?
What are the three types of membranes affected by injury?
How does plasma membrane damage contribute to cell swelling?
What happens when lysosomal membranes rupture?
How does mitochondrial membrane damage lead to necrosis?
How does DNA damage contribute to apoptosis?
What role do misfolded proteins play in ER stress?
How does the unfolded protein response attempt to mitigate cell injury?
What happens when ER stress is prolonged? q
What are the key differences between necrosis and apoptosis?
How does necrosis trigger inflammation?
What is the fate of apoptotic bodies?
Why does necrosis cause widespread tissue damage, while apoptosis does not?
What are the key morphological features of necrosis under a microscope?
Why do necrotic cells appear more eosinophilic than normal cells?
What are myelin figures, and how do they form in necrotic cells?
How do the nuclear changes in necrosis progress, and what do pyknosis, karyorrhexis, and karyolysis represent?
How does the balance between coagulation and liquefaction determine the appearance of necrotic tissue?
What distinguishes coagulative necrosis from liquefactive necrosis?
Why does coagulative necrosis preserve tissue architecture, and in which organs does it commonly occur?
Why is the brain an exception to coagulative necrosis, and what type of necrosis occurs instead?
How does caseous necrosis differ from coagulative and liquefactive necrosis, and in which disease is it most commonly seen?
What is fat necrosis, and what is its role in acute pancreatitis?
What is fibrinoid necrosis, and in which pathological conditions is it observed?
What is the difference between dry and wet gangrene?
How does apoptosis differ morphologically from necrosis?
What are apoptotic bodies, and what happens to them?
What are apoptotic bodies, and what happens to them?
What are the two main pathways of apoptosis?
How does the intrinsic (mitochondrial) pathway regulate apoptosis, and what is the role of BCL2?
How does the intrinsic (mitochondrial) pathway regulate apoptosis, and what is the role of BCL2?
What triggers the extrinsic (death receptor) pathway, and how do cytotoxic T cells contribute to apoptosis?
How do caspases execute apoptosis, and what are their main functions?
What are the key differences between apoptosis and necrosis in terms of cell size, membrane integrity, nuclear changes, and inflammation?
Why is apoptosis often physiological, while necrosis is always pathological?q
How does the presence or absence of inflammation distinguish necrosis from apoptosis?
In what situations might apoptosis and necrosis coexist in the same tissue?
What is necroptosis, and how does it resemble both apoptosis and necrosis?
How does ferroptosis differ from other forms of cell death, and what is its main trigger?
What is pyroptosis, and how does it contribute to the immune response?
What are the main causes of intracellular accumulations?
How does water accumulation affect cell morphology?
What is steatosis, and how does it affect the liver?
How do macrophages contribute to cholesterol accumulation in atherosclerosis?
What are some examples of exogenous and endogenous pigments that can accumulate in cells?
How does hemosiderin accumulation occur, and what does it indicate about iron metabolism?
What role do misfolded proteins play in disease, and what are some examples of proteinopathies?
What is the difference between an injury-inducing stimulus and an stress-inducing stimulus?
How do cells attempt to maintain function in response to stress?
Why does hyperplasia only occur in cells with proliferative capacity?
What microscopic changes would you expect to see in a case of reversible cell injury?
Why does myocardial infarction cause irreversible cell injury?
How can blood tests be used to determine if a heart attack has occurred?
What is angina, and why is it considered a reversible form of injury?
How does atherosclerosis contribute to myocardial infarction?
How can an atheroma lead to a thrombus formation?
What is the key difference between the pathophysiology of angina and myocardial infarction?
Why does myocardial infarction lead to coagulative necrosis?
What are the macroscopic differences between a normal heart and a heart affected by myocardial infarction?
How does myocardial hypertrophy affect the heart’s structure?
What microscopic features are observed in myocardial infarction?
What role do neutrophils play in myocardial infarction?
How does myocardial oedema appear microscopically?
Why does coagulative necrosis occur in solid organs like the heart?
What are the macroscopic characteristics of coagulative necrosis in myocardial infarction?
How do anucleate myocardiocytes persist after necrosis, and what eventually happens to them?
