Cell Injury and Death Part 1 Flashcards
A change in stress on a cell/tissue can result in growth ____. They are reversible, functional, and structural responses to changes in physiologic states
Adaptations
The adaptive response may consist of an increase in the size of the cell, called ___, an increase in cell number, ____, a decrease in the size and metabolic activity of cells called _____, or a change in the phenotype of cells called ____.
Hypertrophy
Hyperplasia
Atrophy
Metaplasia
If adaptation is helpful for an organism, it is termed ____. If it is maladaptive, it is termed ____.
Physiologic
Pathologic
Cellular adaptations are controlled by ____ ___.
Feedback loops
____ ____ (cardiac muscle, skeletal muscle, and nerve) cannot make new cells and commonly undergo ____.
Permanent tissues
Hypertrophy
____ ____ in cells detect increased work load, activating signal transduction pathways, which activate ___ ___ that will lead to increase protein expression and induce the production of growth factors. This will ____ the workload and the cell will reach homeostasis again.
Mechanical sensors
Transcription factors
____ Hypertrophy is due to increased functional demands. Example: pregnancy. Estrogenic hormones signal and increase the smooth muscle synthesis and increases size of the uterus. Another example is bulging muscles of bodybuilders
Physiologic
An example of ____ Hypertrophy is enlargement of the heart in response to pressure overload, usually resulting from either hypertension or valvular disease. Initially, cardiac Hypertrophy improves function but overtime this adaptation often causes heart failure
Pathologic
_____ tissue is also at increased risk for development of ischemia as its metabolic demands may overstep its blood supply
Hypertrophied
Picture of cardiac Hypertrophy:
_____ involves the production of new cells from stem cells. ____ hyperplasia can progress to dysplasia and eventually cancer. A notable exception of nonPathologic hyperplasia is ___ ___ ____, which does not increase risk for prostate cancer
Hyperplasia
Pathologic
Benign prostatic hyperplasia (BPH)
An example of physiologic hyperplasia is ___ ____. Another example is the ability of ___ ___ replication in the setting of acute bleeding or premature breakdown of red blood cells. ___ ____ will halt hyperplasia after sufficient growth has occurred using feedback loops.
Liver regeneration
Bone marrow
Growth inhibitors
In Pathologic hyperplasia there is no response to ___ ___. An example is endometrial hyperplasia due to abnormal hormone induced growth
Growth inhibitors
Hyperplasia is a characteristic response to certain ___ ____ such as papillomavirus which causes skin warts. The virus makes factors that interfere with host proteins that regulate ___ ___.
Example is ___ precursor to cancer .
Viral infection
Cell proliferation
HPV
____ is not itself neoplasticism or pre-neoplastic but elevates the risk of acquiring genetic aberrations that drive cancer
Hyperplasia
____ often arises in the setting of decreases stress or decreased stimulation. Decrease in cell number occurs via ____. Decrease in cell size occurs via ___-____ degradation of the cytoskeleton and autophagy of cellular components.
Atrophy
Apoptosis
Ubiquitin-proteasome
Physiologic atrophy is most common in the ____ setting such as the notochord and thyroglossal duct. The thymus atrophies as an individual grows. The decrease in uterus size after birth is another example
Embryologic
Pathologic atrophy are commonly caused by ____ ____ (disuse atrophy), ___ of ____ (denervation atrophy), or ___ ___ supply
Decreased workload
Loss of innervation
Diminished blood
Loss of innervation is when ___ that lead to muscles are damaged and the muscles atrophy
Nerves
A gradual decrease in blood supply (___ ___) to a tissue as a result of slowly developing arterial occlusive disease results in tissue atrophy. Elderly, the brain my undergo progressive atrophy mainly because of reduced blood supply as a result of atherosclerosis, this is called ___ ____.
Chronic ischemia
Senile atrophy
Pathological atrophy can also be due to inadequate ____, loss of ___ ___, or tissue ____
Nutrition
Endocrine stimulation
Compression
____ is a cell adaptation that leads to a change in cell type. Most commonly involving a change of one type of surface ____ to another. This process is best thought of as a protective mechanism rather than a ____ change
Metaplasia
Epithelium
Premalignant
___ ____ is a classic example of Metaplasia. The normal esophagus is lined by nonkeratinizing squamous epithelium, acid reflux causes Metaplasia to non-ciliated mucus producing columnar cells (resembles intestinal epithelium)
Barrett’s esophagus
Metaplasia occurs via programming of ___ ___ which then produce the new cell type
Stem cells
The ___ gene plays a crucial role in the development of Barrett’s esophagus
Cdx-2
Barrett’s esophagus will relieve symptoms of acid reflux however if this is not treated, the patient is predisposed to a type of cancer known as _____.
Adenocarcinoma
The most common epithelial Metaplasia is actually ___ to ___ epithelium. This occurs in respiratory tract in response to chronic irritation like cigarette smoke.
Columnar
Squamous
_____ (retinoic acid) deficiency can induce squamous metaplasia in the cornea with highly deleterious effects on vision
Vitamin A
____ in the expiratory ducts of the cell salivary glands, pancreas, or bile ducts, which are normally lined by columnar epithelium may also lead to ___ ___
Stones
Squamous Metaplasia
The more rugged stratified ____ epithelium can survive when the more fragile ___ epithelium might have been destroyed
Squamous
Columnar
As the respiratory tract becomes more durable with squamous cells, the ____ secretion and protection of columnar cells are lost
Mucus
____ ____ metaplasia is the formation of cartilage, bone, or adipose cells in tissues that normally do not contain these elements
Connective tissue
Unlike most epithelial metaplasia, connective tissue metaplasia is ____ associated with increased cancer risk
Not
Bone formation within a muscle called ___ ___ occasionally occurs after intramuscular hemorrhage
Myositis ossificans
____ is disordered cell growth and most often refers to proliferation of pre-cancerous cells.
Example: cervical intraepithelial neoplasm (CIN) is a precursor to cervical cancer
Dysplasia
_____ often arises from long-standing pathologic hyperplasia or metaplasia
Dysplasia
Dysplasia is ____ in theory with alleviation of inciting stress. if stress persists dysplasia progresses to carcinoma, which is _____.
Reversible
Irreversible
____ tissue is rapidly dividing cells that lose there normal progressive maturation. This tissue takes over the area and often progresses to carcinoma
Dysplastic
_____ is failure of cell production during embryogenesis such as unilateral renal agenesis where only one kidney is formed
Aplasia
______ is decrease in cell production during embryogenesis resulting in a relatively small organ such as a streak ovary in Turner syndrome
Hypoplasia
Key concepts:
Cell ____ occurs when a stress exceeds the cells ability to adapt. It can be reversible or irreversible.
Injury
Cell death is often the result of ____ cell injury. ____ is pathologic cell death due to irreversible sell injury. ____ is programmed cell death due to a variety of factors. It may be pathologic or physiologic.
Irreversible
Necrosis
Apoptosis
Common causes of cellular injury:
Hypoxia, free, radical damage, inflammation, infection, nutritional deficiency, trauma, chemicals, or genetic mutations
_____ are highly susceptible to ischemic injury, whereas _____ ____ is relatively more resistant
Neurons
Skeletal muscle
Slowly developing ischemia results in ____ , whereas acute ischemia results in ____.
Atrophy
Injury
There are four systems that are particularly vulnerable to injury:
Membranes
Aerobic respiration
Protein synthesis
DNA and RNA synthesis
The hallmark of cell death is the ___ breaking down
Nucleus
The hallmark of reversible cell injury is cell ____ and membrane ____.
Swelling
Blebbing
_____ is low oxygen delivery to tissues. Decreased oxygen impairs ___ ____, resulting in decreased ATP production. Lack of ATP leads to cellular ___ and injury.
Hypoxia
Oxidative phosphorylation
Edema
Causes of hypoxia include:
Ischemia
Hypoxemia
Decreased O2 carrying capacity of blood
____ is decreased blood flow through an organ. It arises with decreased material perfusion (_____), decreased venous drainage ( ____ syndrome), or shock, which is generalized ____.
Ischemia
Atherosclerosis
Budd-Chiari
Hypotension
_____ refers to low oxygen in the blood. This can result from high altitude, hypoventilation, lung diffusion defect, or ventilation/perfusion mismatch, where blood bypasses oxygenated lung (___ ___) or oxygenated air cannot reach blood (___ ___).
Hypoxemia
Vascular shunt
Collapsed lung
Decreased O2 carrying capacity arises with ____ loss or dysfunction. _____ refers to decreased hemoglobin or red blood cells.
Hemoglobin
Anemia
In carbon monoxide poisoning, CO binds to ____ more avidly than oxygen
Hemoglobin
_____ is when the iron in heme is oxidized and cannot bind oxygen
Methemoglobinemia
Review of reversible and irreversible injury:
Increases cytosolic calcium:
Diagram of reaction oxygen species damage:
_____ such as glutathione and vitamins A, C, and help eliminate free radicals. Enzymes ___ ____ and ___ ___ in the mitochondria remove free radicals. Enzyme ____ in the peroxisomes also help.
Antioxidants
Superoxide dismutase
Glutathione peroxidase
Catalase
Review:
Reversible injury histology:
Reversible injury histology:
Mitochondrial swelling electron microscopy:
Key concepts review:
____ necrosis is necrotic tissue that retains structure. an injury denatures, structural proteins, and enzymes blocking ____ of the dead cells. A localized area of coagulative necrosis is called an ____.
Coagulative
Proteolysis
Infarct
____ necrosis is when necrotic tissue becomes liquefied via proteomic enzyme lysis of cells and proteins
Liquefactive
____ necrosis is soft and friable necrotic tissue with cheese like appearance. It is a combination of coagulative and liquefactive necrosis. It is a characteristic of granulomatous inflammation due to tuberculosis or fungal infection.
Caseous
____ necrosis has a chalky white appearance due to deposition of calcium. Characteristic of trauma to fat and pancreatitis mediated damage of Peripancreatic fat.
Fat
____ necrosis is damage to blood vessel walls. Leaking of proteins into vessel, wall results in a bright pink staining of the wall. Characteristic of malignant, hypertension, and immune related vasculitis.
Fibrinoid
Review of types of necrosis:
Key concepts:
Picture:
Picture of viable versus apoptotic cells
Apoptotic cells are stained with the fluorescent DNA binding dye , ____. You can see chromosome condensation and fragmentation in apoptotic cells.
Hoechst
You can also stain apoptotic cells with fluorescent _____ green dye on top of Hoechst. You can see the fragmented mitochondrial network
Mitochondrial
The functions of some proteins (like lamins) are ____ by caspase and others (like MST1 and some DNases) are ___ by caspase cleavage
Destroyed
Activated
Caspases are classified by either ____ or ___
Initiator
Effector
Intrinsic pathway of activation:
___ and ___ of the Bcl2 family promote cell death by forming an oligomeric complex in the outer mitochondrial membrane which is the basis of MOMP
Bax
Bak
BH3-only proteins are ___ and Bax and Bak are ____ of apoptosis. Pro survival proteins are ____ against apoptosis
Initiators
Effectors
Guardians
A key feature is that the initiator BH3-only and the pro survival Bcl family members are ____ ____. Together with the fact that cells express multiple members of both categories, this allows for numerous inputs to factor into the decision of whether the cell should survive or undergo apoptosis
Mutually inhibitory
Extrinsic pathway:
_____ is the complex that forms and activates caspase. ____ and ____ are modular recognition elements that DISC uses to bind constituent proteins
DISC (death inducing, signaling complex)
DDs (death domains)
DEDs (death effector domains)
The extrinsic and intrinsic pathway can be linked. ____ can be a target of the extrinsic pathway becoming activated when cleaves by caspase 8. Activated Bid inhibits the anti-apoptotic effects of ____ at the mitochondrial membrane, tilting the scales toward ___. This effect has been referred to as the ___ ___ ___.
Bid
Bcl2
Apoptosis
Mitochondrial amplification loop
FAS-FAS signaling by immune cells:
Induce (_____) an adjacent target cell to become apoptotic. Signaling back to itself to trigger apoptosis (_____)
Murder
Suicide
___ links cell proliferation, cell health, and regulated cell death pathways
p53
