| Question | Answer |
| what is a physiologic response to stimuli? | Adaptations (reversible changes to cell stress) |
| What are pathologic responses to stimuli? | 1.Injury (morphologic chanes and outcomes).
2.Death (apoptosis & necrosis).
**result from altered cell structure and function in response to cell stress (cells lose ability to withstand stress). |
| Allostasis Vs Homeostasis in terms of the cells response to stress. | Homeo: • Cells possess an innate ability to stress in such a way to work to maintain normal structure/function & viability.
Allo:cells respond to stresses by making substantive changes to structure and fnc that still allow for maintenance of viability |
| What is the ultimate endpoint of uncompensated state of injury? | Death |
| What is the goal of cell adaptation | to new conditions/demands for optimal functioning.
**reflects cells ability to alter cell cycle acitivity (G1,G2, S, and M/Proliferation). |
| 4 major kinds of Adaptive cellular responses | 1.Hyperplasia: increased number of cells.
2.Hypertrophy: increased size of cells.
3.Atrophy: decreased size of cell.
4.Metaplasia: change from one mature cell type to another. |
| When is Hyperplasia Physiologic? Pathologic? | PHYSIO:
1.Hormonal (meet functional demands).
2.Compensatory (regain functional capacity after loss of cells).
PATH:
1.Proliferation for protection. |
| examples of physiologic hormonal hyperplasia? | 1.Endometrial proliferation in response to estrogen (proliferatice phase prepares for implantation).
2.Increased cell number in mammary glands during lactaion (producing milk for infants).
3.The body's natural suturing of scars |
| What is the main cause of Hypertrophy? Where does it generally occur? | 1.Occurs Due to increased protein synthesis, not cellular swelling.
2.Generally occurs in cells that would not typically divide (e.g., muscle cells ® cardiac hypertrophy) |
| List 2 examples of adaptive responses involving both hyperplasia & Hypertrophy | 1.Gravid Uterus.
2.Mammary tissue during lactaion. |
| What is atrophy? why is substance lost? | Dec cell size resulting from Dec cellular substance. Substance is lost b/c the cell environment cannotsupport current size OR b/c functional stimuli is dimished (dec cell protein). |
| Causes of Atrophy | 1.Dec Workload (skeletal muscle, bone).
2.Loss of nerve supply (skeletal m).
3.Ischemia (brain in elderly).
4.Poor nutrition.
5.Reduced endocrine stimulation (mammary, uterus, ovaries. |
| What is Metaplasia? | Change from one mature cell type to another type due to reprogramming the gene expression of stem cells.
**Can be:
1.Epithelial tissues: squamous to columnar (Barret's esophagus) or columnar to squamous (cervix, airways).
2.Mesenchymal: muscle to bon |
| Is metaplasia a protective process? is it a reversible process? | YES to BOTH. It is protective to noxious stimuli b/c cells change from susceptible cell type to more resistant/protective type of cell. |
| 7 causes of cell injury | 1.Hypoxia (Norm BF, dec O2 delivery).
2.Physical agents/mechanical forces (Temp extremes, radiation, etc..).
3.Chemicals/Drugs (direct toxic effect).
4.Infectious agents.
5.Immunologic reactions.
6.Genetic mutations/ derangements.
7.Nutritional Imba |
| Thickening of what layer would indicate proliferative cell process indicating hyperplasia in squamous cells? | Granular cell layer as well as keratin layer. |
| Exmaples of Pathologic hyperplasia | 1.Lichen simplex.
2.Psoriasis.
3.Endometrial hyperplasia (Pre-cancerous). |
| Where is hypertrophy of cells normal? | Adipocytes. |
| Cachexia | general physical wasting. (cause of atrophy) |
| Where does cervical cancer usually occur? | At the endo/ecto cervical junction b/c there is a change in epithlium from columnar to squamous cells |
| When would you have a metaplastic change in the airway not due to stomach acid? what does this cause? | In response to cigarette smoke.
**will change from stratified columnar to stratified squamous in order to protect against cigarette smoke. This means cilia is lost in the bronchi and cough reflex will be more active. |
| What does Hypoxia cause in the tissues? How is it different from Ischemia? | CAUSES:
1.Dec BF.
2.Anemia.
3.Poor oxygenation.
**Ischemia is impaired BF which leads to dec O2 AND nutrients. |
| What organ will affected first by 1st overdose of chemicals and drugs? | LIVER b/c of the CYP450 system |
| Underlying Mechanisms of Cell Injury | Disruptions of Normal Structure/Function:
1.Disruption of Ox Phos (due to ischemia): Dec ATP.
2.disruption in removal of ROS.
3.Cell membrane integrity.
4.Ca+ Homeostasis. |
| What determines the reversibility of cell damage? | 1.Severity.
2.Duration. |
| Hypertrophy in the heart in adaptation to chronic stress and injury is due to what? | Inc mRNA. |
| What does the threshold of irreversibility on the continuum of cell injury represent? | When self function declines below the cell death risk level.
**there is greater chance of cell death than cell function. |
| Morphologic changes in Cell injury | REVERSIBLE:
1.Cell swelling (due to disruption of fluid homeostasis): Dec ATP-dependent ion pump activity.
2.Fatty change (accumulation of lipid vacuoles): seen in cells using FA metab (heart, liver).
IRREVERSIBLE:
1.Ultimately Cell death |
| What is occuring during Necrosis? | Mitochondria become swollen, membrane Does NOT maintains integrity.
**Cells are consumed by phagocytes so they dont damage other cells. |
| Ischemia-Reperfusion Injury | Some cells recover when BF is restored, but others do not, could be due to:
1.generation of ROS.
2.Some inflammatory mechanisms.
**Especially important in CNS & heart. |
| Compare and Contrast Apoptosis and Necrosis | 1.Both undergo nuclei shrinkage & fragmentation.
2.Membrane Integrity: lost w/ necrosis (leakage of cell material), blebbing with apop.
3.Area of tissue: Large w/ nec, small/isolated w/ apop.
4.No inflamm repsonse w/ apop.
5.Apop isnt ALWAYS pathologi |
| Does Apoptosis or Necrosis result from "Un-programmed" cell death? What are the 4 different types? | NECROSIS:
1.Coagulative.
2.Liquefactive.
3.Caseous.
4.Fat necrosis. |
| What type of Necrosis is most commonly seen w/ ischemia? | Coagulative (except in brain) |
| Nuclear changes seen with Coagulative Necrosis | 1.Pykonsis (nuclear shrinkage).
2.Karyolysis (nuclear dissolution).
3.Karyorrhexsis (fragmentation of pyknotic nucleus).
**Nuclei disappears in a few days, ghost cells left behind. |
| Morphology and process behind coagulative necrosis | MORPHOLOGY:
1.Cell outline & tissue architecture remain for 48 hrs.
2.Cytoplasmic changes: Shrunken, Inc eosinophilia.
3.Nuclear changes.
PROCESS:
1.Denaturation of cytosolic proteins (due to Dec pH). |
| What are the only 2 times Liquefactive necrosis occurs? | 1.Bacterial Infection.
2.CNS necrosis. |
| Morphology and process behind Liquefactive necrosis | MORPHOLOGY:
1.Tissue architecture is lost, no cell outlines (Pink blob with NO nuclei).
2.Associated with dead inflammatory cells & pus.
PROCESS:
1.Complete enzymatic digestion of dead cells (released from neutrophils). |
| Morphology of Caseous necrosis | 1.No tissue architecture remains.
2.Surrounded by granulomatous inflammation .
3.Cheesy white/yellow friable material.
**seen with TB. |
| What is the Process involving Fat Necrosis? Where all does it occur? | PROCESS: Destruction of adipocytes within fatty tissue.
Seen in:
1.Acute pancreatitis (lipases leak into fat surrounding pancrease).
2.Traumatic destruction of fat (surgical).
3.Inflamm destruction of fat.
4.Neoplastic destruction of fat. |
| Since fat necrosis is such a large-scale destruction, what can it lead to? what will be seen in tissue? | SOPONIFICATION.
**deposition of Ca+ salts in tissue (Ca is released from stores in damaged tissue). |
| Dry Vs Wet Gangrenous Necrosis | DRY: Coagulative necrosis of tissues secondary to profound ischemia (toes of diabetes pt, intestine of ischemic bowel pt).
WET:o Liquefactive necrosis from inflammatory necrosis superimposed on ischemic necrosis (usually secondary to bacterial infectio |
| 4 examples of Apoptosis as a physiologic process | 1.Involution of structures during dev (webbing).
2.Elimination of immune cells.
3.Involution following hormonal withdrawal (Endometrium).
4.Cytotoxic T-cell mediated elimination of infected/neoplastic cells. |
| Pathologic Apoptosis is seen with | 1."Insults" (such as radiation, drugs, DNA damage).
2.Viral infection.
3.Autoimmunity.
4.Neoplastic cells |
| Main Pathways of Apoptosis | STIMULUS PATHWAYS:
1.Intrinsic ("Injury" such as ROS/toxins/radiation or withdrawal of growth factors).
2.Extrensic (Death receptors or cytotoxic T cell mediated).
**COMMON PATHWAY (shared by all):
1.Execution pathway (caspase enzyme cascade) |
| What are 2 Pro-apoptotic proteins? 2 Anti-apoptotic proteins? | PRO:
1.Bax.
2.Bak.
ANTI:
1.bcl-2.
2.bcl-x |
| Mechanism behind the Itrinsic Injury stimulus pathway leading to Apoptosis | 1.Injury (from ROS, toxin, radation) causes Inc p53 tumor suppressor gene production.
2.Cell is arrested in G1 phase to repair DNA.
3.If repair is unsuccessful: Apoptosis.
4.Inc production of Bax and Bak. |
| Mechanism behind the Intrinsis withdrawal of growth factor stimulus pathway leading to apoptosis | 1.Growth factor withdrawal alters the balance of bcl family proteins.
2.Inc Bax & Bak.
3.Dec bcl-2 & bcl-x. |
| Mechanism behind the extrinsic Death receptor stimulus pathway leading to Apoptosis | 1.Death receptors (Fas & FasL) bind a ligand (TNFR1 & TNF).
2.Increases Bax & Bak. |
| Important molecule in the extrinsic cytotoxic T-cell mediated cell death stimulus pathway leading to Apoptosis | Granzyme B |
| Are the Pro-apoptosis & Anti-apoptosis noramlly in balance? What happens if they aren't? | YES.
**Disruption of this balance can participate in disease processes |
| What 2 things can occur if there is too little Apoptotic activity? | 1.Cancers: Neoplastic cells proliferate despite DNA damage (p53 has failed).
2.Autoimmunity: Failure to eliminate self-reacting lymphocytes |
| What 3 things can occur if there is too much apoptotic activity? | 1.Neurodengenerative disorders (parkinson's).
2.Ischemic injury.
3.Death of virally infected cells. |
| 2 main forms of Normal Lipid that can build up in excess causing accumulations | 1.Fatty Acid: w/in cells w/ normally very active FA metabolism (heart & liver).
2.Cholesterol: Atherosclerosis (extracelluarly), Xanthalamas (intracellularly) |
| Steatosis | Part of cell injury in the liver causing Fatty change.
**reversible process (unlike cirrhiosis) |
| Xanthelasma | Cutaneous xanthomas deposited around the eyelids and neck.
**50% associated with hypercholesterolemia due to genetic mutation. |
| Endogenous & exogenous Pigment Acculumations | EXO:
1.Carbon dust (coal, soot, smog): anthracosis.
ENDO:
1.Melanin.
2.Lipofuscin (NOT iron).
3.Hemosiderin (iron stored in cells) |
| 2 different types of pathologic calcifications | 1.Dystrophic: normal Ca levels, associated with dying/degenerating cells (seen in: calcific atheroscl, fat necrosis, psammona body).
2.Metastatic: Hypercalcemia due to Inc PTH, destruction of bone, and excess Vit D. |
| 2 major contributors to Cellular Senescence | 1.Replicative senescence (cells have limited capacity to replicate: telomeres).
2.Declining Function of proteosome (Cell loses its main method of disposing of unwated protein within the cell). |
