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Growth Adaptations, Cellular Injury, and Cell Death
Path shelf prep
40
Pathology
Graduate
03/18/2012

Additional Pathology Flashcards

 


 

Cards

Term
Homeostasis
Definition
The state an organ reaches with all of the physiological forces acting against it.
Term
What can result in Growth Adaptations?
Definition
  • increase
  • decrease
  • change in stress on an organ
Term
Hypertrophy
Definition
  • Increase in the size of cells b/c of an increase in stress on the organ
  • Involves gene activation, protein synthesis, and production of organelles.  (with an increase in the number of these things you must have an expansion of the cell size.)
  • Permanent tissus (ex cardiac muscle, skeletal muscle, and nerve), however, cannot make new cells and undergo hypertrophy only.
Term
Hyperplasia
Definition
  • New cells are produced from stem cells
  • happens in cells that are able to grow.
  • Happens with hypertrophy usually- like the uterus during pregnancy
  • Pathologic forms can progress to dysplasia and eventually cancer
  • Remember** the big exception to this is BPH, which does not increase the cancer risk!
Term
Dysplasia
Definition
Disordered Cellular growth
-Most often proliferation of precancerous cells
!)For example, cervical intraepithelial neoplasia (CIN) represents dysplasia and is a precursor to cervical cancer
-often happens with longstanding pathologic hyperplasia or metaplasia
-Is reversible w/ alleviation of inciting stress, but if the stress persists the dysplasia -->carcinoma (irreversible)
Term
Atrophy
Definition
  • Decrease in stress- Ex) decreased hormones, disuse, or decreased nutrients or blood supply
  • decrease in number and/or size of cells-->apoptosis
Term
Apoptosis
Definition
  • There is a  ubiquitin-proteasome degradation of the cytoskeleton and autophagy of cellular components
  • The intermediate filaments of the cytoskeleton are tagged with ubiquitin and destroyed by proteosomes.
  • Autophagy of cellular components involves generation of autophagic vacuoles.
  • These vacuoles fuse with lysosomes whose hydrolyctic enzymes breakdown cellular components
Term
Metaplasia
Definition
  • Changing the stress on an organ leads to a change in cell type. 
  • MC change of one type of surface to another cellular type. 
  • Squamous to columnar
  • Barrett Esophagus
  • Stem cells get reprogrammed--removable with the removal of the stressor
  • Mesenchymal or connective tissue can also undergo metaplasis
Term
Barrett Esophagus
Definition
  • non-keratinized Squamous epithelium is best for dealing with the friction of a food bolus
  • Acid reflux from stomach-->nonciliated, mucin-producing columnar cells
  • May proceed to adenocarcinoma of the esophagus
Term
Myositis Ossificans
Definition
muscle tissue changes to bone
Term
Vitamin A deficiency
Definition
  • b/c vitamin A is necc for the specialized epithelial surfaces like the conjunctiva of the eye
  • so the thin squamous lining of conjunctiva-->stratified keratinizing squamous epithelium=keratomalacia
Term
Aplasia
Definition
failure of cell production during embryogenesis

ex) unilateral renal agenesis
Term
Hypoplasia
Definition
decrease in cell production during embryogenesis--> relatively small organ. Ex streak ovary in turner syndrome
Term
Cellular injury
Definition
  • occurs when a stress exceeds the cell's ability to adapt
  • the likliehood of injury depends on the type of stress, it's severity, and the type of cell affected.
  1. Neurons are highly susceptible to ischemic injury; whereas, skeletal muscle is relatively more resistant
  2. Slowly developing ischemia (ex renal artery atherosclerosis) results in injury
  • Common causes of cellular injury include inflammation, nutritional deficiency or excess, hypoxia, trauma, and genetic mutations
Term
Hypoxia
Definition
  1. Low oxygen delivery to tissue:important cause of cellular injury
  • oxygen is the final electron acceptor in the electron transport chain of oxidative phosphorylation
  • decreased oxygen impairs oxidative phosphorylation-->decreased ATP production
  • Lack of ATP (essecntial energy source) leads to cellular injury.
  1. Common cuases of hypoxia include ischemia, hypoxemia, and decreased O2 carrying capacity of blood
Term
Ischemia
Definition
  • Decreased blood flow through an organ.  Arisses w/
  • Decreased Arterial perfusion (ex atherosclerosis)
  • Decreased venous drainage (ex Budd-Chairi syndrome)
  • Shock-- generalized hypotension resulting in poor tissue perfusion
Term
Hypoxemia
Definition
  • Low partial pressure of oxygen in the blood (PaO2 <60 mm Hg, Sa O2 <90%).  Arises with
  • High altitude--decreased barometric pressure results in decreased PaO2
  • Hypoventilation-- Increased PaCO2 results in decreased PaO2
  • Diffusion Defect-- PAO2 not able to push as much O2 into the blood due to a thicker diffusion barrier (ex interstitial pulmonary fibrosis)
  • V/Q mismatch --Blood bypasses oxygenated lung (circulation problem Ex. R-->L shunt), or oxygenated air cannot reach blood (ventilation problem, ex atelectasis)
Term
Decreased O2 carrying capacity
Definition
  • arises with Hemoglobin (HB) loss or dysfunction
  • Anemia (decrease in RBC mass)-- PaO2 normal; SaO2 normal
  • Carbon Monoxide poisoning
  • CO binds Hb more avidly than oxygen--PaO2 normal; SaO2 decreased
  • Exposures: smokefrom fires and exhaust from gars or gas heaters
  • Classic finding is cherry-read apprearance of skin
  • Classic sign of exposure is headache; significant exposure leads to coma and death
  • Methemoglobinemia
  • Iron in heme is oxidized to Fe3+ which cannot bind oxygen--Pa O2 normal; SaO2 decreased
  • Seen with oxidat stresss (ex sulfa and nitrate drugs) or in newborns
  • Classic finding is cyanosis with chocolate colored blood
  • Treatment is intravenous blue, which helps reduce Fe3+ back to Fe2+
Term
Cell Death
Definition
  • The morphologic hallmark of cell death is loss of the nucleaus, which occurs via nuclear condensation (pyknosis), fragmentation (karyorrhexis), and dissolution (karyolysis)
  • The two mechanisms of cell death are necrosis and apoptosis
Term
Cellular Injury
Definition
  • Hypoxia impairs oxidative phosphorylation resulting in decreased ATP
  • Low ATP disrupts key cellular functions including
  1. Na+-K+ pump, resulting in sodium and water buildup in the cell
  2. Ca2+ pump resulting in Ca2+ buildup in the cytosol of the cell
  3. Aerobic glycolysis, resulting in a switch to anaerobic glycolysis.  Lactic acid buildup results in low pH, which denatures proteins and precipitates DNA
  • Te initial phase of injury is reversible.  The hallmark of reversible injury is cellular swelling
  1. Cytosol swelling results in loss of microvilli and membrane blebbing
  2. Swelling of the rough ER results in dissociation of ribosomes and decreased protein synthesis
  • Eventually the damage becomes irreversible.  The hallmark of irreversible injury is membrane damage
  1. Plasma membrane damage results in
  • cytosolic enzymes leaking into the serum (ex cardiac troponin)
  • additional calcium entering into the cell
  • 2)Mitochondrial damage results in
  • loss of the ETC (inner mitochondrial membrane)
  • cytochrome c leaking into cytosol (inactivates apoptosis)
  • 3)  Lysosome membrane damage results in hydrolytic enzymes leaking into the cytosol, which, in turn, are activated by the high intracellular calcium
  • The end result= Irreversible injury
Term
Oxidative Phosphorylation
Definition
[image]
Term
Necrosis
Definition
  1. Death of large groups of cells followed by acute inflammation
  2. due to some underlying pathologic process; never physiologic
  3. Divided into several types based on gross features
Term

Coagulative necrosis

 

 

Definition

[image]

 

  1. Necrotic tissue remains firm
  2. cell shape and organ structure are preserved by coagulation of proteins, but the nucleus disapears
  3. Characteristic of ischemic infarction of any organ except the brain
  4. Area of infarcted tissue is often wedge shaped (pointing to focus of vascular occlusion) and pale
  5. Red infarction arises if blood re-enters a lossely organized tissue (ex pulmonary or testicular infarction)

 

Term

Liquefactive Necrosis

 

 

Definition

[image]

 

  • Necrotic tissue that becomes liquefied; enzymatic lysis of cells and protein results in liquefaction
  • Characteristic of
  1. Brain infarction--Proteolytic enzymes from microglial cells liquefy the brain
  2. Abcess-- Proteolytic enzymes from Neutrophils liquefy tissue
  3. Pancreatitis--Proteolytic enzymes from pancreas liquefy parenchyma
Term
Gangrenous necrosis
Definition

[image]

 

  1. Coagulative necrosis that resembles mummified tissue
  2. Characteristic of ischemia of lower limb and GI tract
  3. If superimposed infection of dead tissues occurs, then liquefactive necrosis ensues (wet gangrene)
Term
Caseous Necrosis
Definition

[image]

 

  1. Soft and friable necrotic tissue with "cottage cheese-like" appearance
  2. Combination of coagulative and liquefactive necrosis
  3. Characteristic of granulomatous inflammation due to tuberculous or fungal infection
Term

Fat necrosis

 

 

 

Definition

[image]

 

  • Necrotic adipose tissue with chalky-white appearance due to deposition of calcium
  • characteristic of trauma to fat and pancreatitis-mediated damage of peripancreatic fat
  • FAs released by trauma (ex to breast) or lipase (ex pancreatitis) join with calcium via a process called saponification

 

  1. Saponification is an example of dystrophic calcification in which calcium deposits on dead tissues.  In dystrophic calcification, the necrotic tissue acts as a nidus for calcification in the setting of normal serum calcium and phosphate
  2. Dystrophic Calcification is distinct from metastatic calcification in which high serum calcium or phosphate levels lead to calcium deposition in normal tissues (ex hyperparathyroidism leading to nephrocalcinosis).
Term

Fibrinoid Necrosis

 

Definition

[image]

 

  1. Necrotic damage to blood vessel wall
  2. Leaking of proteins (including fibrin) into vessel wall results in bright pink staining of the wall microscopically
  3. Characteristic of malignant HTN and vasculitis
Term

Apoptosis

 

 

 

 

Definition

[image]

 

  • Energy ATP dependent, geneticall programmed cell death involving single cells or small groups of cells.  Examples include

 

  1. Endometrial shedding during menstrual cycle
  2. Removal of cells during embryogenesis
  3. CD8+ T cell-mediated killing of virally infected cells

 

  • Morphology

 

  1. Dying cell shrinks, leading cytoplasm to become more eosinophilic
  2. Nucleus condenses
  3. Apoptotic bodies fall from the cell and are removed by macrophages; apoptosis is not followed by inflammation

 

  • Apoptosis is mediated by caspases that activate proteases and endonucleases

 

  1. proteases break down the cytoskeleton
  2. Endonucleases  break down DNA

 

  • Caspases  are activated by multiple pathways

 

Term
Intrinsic mitochondrial Pathway
Definition

{image:http://www.erin.utoronto.ca/~w3bio380/picts/lectures/lecture3/Apoptosis%20Pathways%201.jpg}

 

  • Cellular injury, DNA damage, or loss of hormonal stimulation leads to inactivation of Bcl2
  • Lack of Bcl2 allows cytochrome c to leak from the inner mitochondrial matrix into the cytoplasm and activate caspases
Term
Extrinsic Receptor-ligand Pathway
Definition

[image]

 

  • FAS ligand binds FAS death receptor (CD95) on the target cell, activating caspases (ex negative selection of thymocytes in thymus)
  • Tumor necrosis factor (TNF) binds TNF receptor on the target cell, activating caspases

 

Term
Cytotoxic CD8+ T cell-mediated pathway
Definition

[image]

 

  • Perforins secreted by CD8+ T cell create pores in membrane of target cell
  • Granzyme from CD8+ T cell enters pores and activates caspases
  • CD+ T-cell killing of virally infected cells is an example
Term

Free Radical Injury

 

 

 

Definition

[image]

 

  • Free Radicals are chemical species with an unpaired electron in their outer orbit
  • Physiologic generation of free radicals occurs during oxidative phosphorylation.

 

  1. Cytochrome C oxidase (complex IV) transfers electrons to oxygen
  2. Partial reduction of O2 yiels superoxide Ox, hydrogen peroxide H2O2, and hydroxyl radical OH

 

  • Pathologic generation of free radicals arises with

 

  1. Ionizing radiation- water hydrolyzed to hydroxyl free radical
  2. Inflammation-NADPH oxidase generates superoxide ions during oxygen-dependent killing by neutrophils
  3. Metals (ex copper and iron)-- Fe2+ generates hydroxyl free radicals (Fenton reaction)
  4. Drugs and chemicals- P450 system of liver metabolizes drugs (ex acetaminophen) generating free radicals

 

Free radicals cause cellular injury via peroxidation of lipids and oxidation of DNA and proteins; DNA damage is implicated in aging and oncogenesis

 

 

 

  • Elimination of free radicals occurs via multiple mechanisms

 

  1. Antioxidants (ex. glutathione and vitamins A, C, and E)
  2. Enzymes

 

  • superoxide dismutase (in mitochondria)-- Superoxide (O2)-->H2O
  • Glutathione peroxidase (in mitochondria)--GSH+free radical -->GSSH and H2O
  • Catalase (in peroxisomes)-- H2O2-->O2 and H2O
  • Metal Carrier proteins (extransferrin and ceruloplasmin)
Term

CCl4

 

Definition
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Term
Reperfusion injury
Definition
  • Return of blood to ischemic tissue results in production of O2 derived free radicals, which further damage tissue
  • Leads to a continued rise in cardiac enzymes (ex troponin) after reperfusion of infarcted myocardial tissue
Term
Amyloidosis
Definition
  • Amyloid is a misfolded protein that deposits in the extracellular space, thereby damaging tissues
  • Multiple proteins can deposit as amyloid.  Shared features include
  1. Beta-pleated sheet configuration
  2. Congo red staining and apple-green birefringence when viewed microscopically under polarized light
  3. Deposition can be systemic or localized
Term

Systemic Amyloidosis

 

Definition

[image]

 

 

  • Primary Amyloidosis is systemic deposition of AL amyloid, which is derived from immunoglobulin light chain

 

  1. Associated with plasma cell dyscrasias (ex multiple myeloma)

 

  • Secondary Amyloidosis is systemic deposition of AA amyloid, which is derived from serum amyloid-associated protein (SAA)
  • SAA is an acute phase reactant that is increased in chronic inflammatory states, malignancy, and familial Mediterranean fever (FMF)
  • FMF  is due to a dysfunction of neutrophils (AR) and occurs in persons of mediterranean origin
  • Presents with episodes of fever and acute serosal inflammation (can mimic appendicitis, arthritis, or myocardial infarction)
  • High SAA during attacks deposits as AA amyloid in tissues

 

  • Clinical findings of systemic amyloidosis include

 

  1. Nephrotic syndrome; kidney is the most common organ involved
  2. Restrictive cardiomyopathy or arrhythmia
  3. Tongue enlargement, malabsorption, and hepatosplenomegaly

 

  • Diagnosis requires tissue biopsy.  Abdominal fat pad and rectum are easily accessible biopsy
  • Damaged Organs must be transplanted.  Amyloid cannot be removed

 

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