1. Cell Injury Flashcards
Erythroid Hyperplasia is commonly seen in what characteristic group of people?
Those living in high altitudes- lower oxygen
Low oxygen stimulates this hormone that induces hyperplasia of red blood cells in bone marrow.
Erythropoietin
What is a typical feature of fat necrosis?
Saponification of fat cells derived from peripancreatic fat exposed to pancreatic enzymes.
Free fatty acids binding to Calcium forms…
soaps
What causes the increased release of free fatty acids during acute pancreatitis?
Lipase is released from pancreatic acinar cells and it hydrolyzes fats into free fatty acids and glycerol
What causes Hypocalcemia in acute pancreatitis?
calcium entry in the injured tissue leads to less calcium found in blood
Patient sypmtoms in Acute Pancreatitis
vomiting, sudden onset abdominal pain, and distention
Give one example of where squamous metaplasia occurs
Bronchial epithelium of smokers
What adaptive response is occuring when esophageal squamous epithelium is replaced by columnar epithelium as a result of chronic GERD
Glandular Metaplasia
Metastatic calcification is associated with what change in blood concentrations that wlead to various disorders.
Increased serum calcium levels that can cause calcification of renal tubules, alveolar septum and blood vessels.
Dypslasia: Examples of disturbances of uniform epithelium
- change in cell size/shape2. nuclei irregularity, enlargement, hyperchromatism3. disorderly arrangement
How do bronchial epithelium respond to smoke carcinogens?
Dysplasia
What abnormality often leads to Atrophy?
Stress as in Vascular insufficiency and chronic inflammation `
What is Anaplasia?
Lack of differentiated features in a neoplasm
What are two characteristics of Atrophy of the brain as in Alzheimer’s Disease?
- thinned gyri2. widened sulci
Hypertrophic cardiac myocytes have ______ cytoplasm and ________ nuclei than normal cells due to transcriptional regulation that increases production of more ________, ______, and __________.
More, larger, mRNA, rRNA, and protein
What are three complications often seen in the brain for intrauterine infections?
Microcephaly, hydrocephalus, and microgyri
In Dystrophic calcification, where are calcium deposits located?
Serum calcium levels are normal but calcium deposits are found in injured tissue.
What is hydropic?
characterized by swelling and taking up of fluid—used of a type of cellular degeneration
Impairment of cell volume regulationcan lead to what acute, reversible (sublethal) cell injury?
Hydropic swelling
Cellular volume regulation especially for sodium involves what cellulart structures and molecules?
- the plasma membrane2. plasma membrane sodium pump3. ATP supply
Is lipid peroxidation reversible or irreversible?
irreversible
Hydropic degeneration of CNS neurons is most likely mediated by what cellular process impairment?
Plasma membrane sodium transport(Sodium accumulates in the cell and water content increases causing cellular swelling)
Any material that exhibits a reddish homgenous appearance when stained with hematoxylin and eosin is known as
Hyaline
What is Alcholholic hyaline composed of ?
Cytoskeletal Intermediate Filaments (cytokeratins)(IF aggregrates because of hepatocyte injury seen in alcholic patients)
Alcoholic hyaline is also known as
Mallory Hyaline
Pulmonary hyaline consists of what ?
plasma proteins deposited in alveoli
Patients with alpha 1 antitrypsin deficiency often acumlate what molecule in the liver?
structurally abnormal alpha 1 antitrypsin
What molecule accumulates in neurons in the substantia nigra of patients with Parkinsons?
alpha-Synuclein
Storage of carbon particles in the lung and regional lymph nodes is known as
Anthracosis
Where are carbon particles in the lung that are accumulated by alveolar macrophages transported to?
Hilar and mediastinal lymph nodesThe indigestible material is stored indefinitely within tissue macrophages
What does the presence of toxic/fibrogenic dusts such as silica cause to develop in the lungs?
Pulmonary fibrosis
What is pneumonoconiosis?
Coal Workers’ Disease. It develops from breathing in coal, C, graphite over a long time period
Hemosiderosis represents the intracellular storage of what ion?
Iron
What development abnormalities are infants of diabetic mothers at risk for?
Anomalies of the heart and vessels Neural tube Defects
How do fetuses exposed to hyperglycemia in utero respond on a cellular level?
They develop hyperplasia of the pancreatic beta cells
How can hyperlasia of pancreatic beta cells adversely affect an infant at birth/
it may secrete insulin immediately leading to hypoglycemia
Define metaplasia
the conversionof one differentiated cell pathway to another
What imbalance would lead to the appearance of liquefactive necrosis?
the rate of dissolution of necrotic cells is faster than the rate of repair
In an acute inflammatory reaction, what cells have potent hydrolases that digest dead cells?
Polymorphonuclear leukocytes
Liquefactive necrosis in a solid tissue forms what clinical manifestation?
an abscess
Where can a caseous necrosis be found?
Necrotizing granuloma
Is there fat present in lung parenchyma?
no
In what patients can one find a fibrinoid necrosis?
patients with necrotizing vasculitis
What part of the cell is retained in a coagulative necrosis? What does this necrosis refer to?
the outline of the celllight microscopic alterations in dying cells
Describe the appearance of a caseious necrosis?
they are amorphous, coarsely granular, conatin eusinophilic debris resembling clumpy cheese
Tuberculosis classic symptoms
Caseios necrosisnon-specific symptoms: feber, loss of appetite, occasional coughing
Describe a Ghon complex clinical manifestations
parenchymal consolidationipsilateral enlargment of hilar lymmph nodesoften accompanied by pleural effusion
When stained with H and E, the cytoplasm of a necrotic cell is what color (H or E)?
Eusinophilic - pink
Degeneration of a nucleus, shrinking, and choromatin clumping is known as what process? DDescribe the nucleus stain ?
Pyknosis, basophilic
Name two steps after pyknosis in the fragmentation and dissolution of the nucleus?
Karyhorrhexis- nucleus breaks up into fragments in the cytoplasm * Hallmark of coagulative necrosis”Karyolysis- nucleus may exit cell or it may have progressive loss of staining
The humoral and cellular arms of the immune system elimnate virus -infected cells by 2 mechanisms what are theys?
- Inducing apoptosis2. Directing complement-mediated cytolysis
How does a rabies virus entering a peripheral nerve arrive at the brain and spinal cord?
they are transported by retrograde axoplasmic flow
Define dystrophy
degeneration of tissue
How does a cell respond to trophic signals or increased functional demand, as if 1 kidney loses function?
Hypertrophy (more likely than hyperplasia)
What characterizes necrosis at the cellular level?
Swelling of cell and organelle, increased plasma permeability, ATP depletion, release of macromolecules, and ultimate death
Where is Calcium normally highest (10000xs difference)? Interstitial fluid or intracellular fluid? How is this gradient maintained?
Interstitial fluid; ; plasma membrane
Massive influx of calcium into the cell would lead to what pathology?
Coagulative Necrosis
What is the most common cause of atrophy?
reduced functional demand
Can an atrophic cells resume function when restoring normal conditions?
Yes
Describe the molecular pathway of the leading form of necrosis causing death in the Western world
Coagulative Necrosis: Interruption of blood delivery to heart leads to reduced glucose and lack of Oxygen to cardiac muscles.On the molecular level, this leads to reduction of ATP synthesis in Mitochondrial electron transport and a build up of ROS. Mitochondrial damage leads to cytochrome c release into cytosol (reducing amount of cytochrome c available for ATP production) and death.
List some substances that accumulate in cells becuase they cannot be metabolized
- Endogenous substrates of an enzyme that is missing (as in a Lysosomal storage disease)2. Insoluble indogenous pigments (melanin and lipofuscin)3. Exogenous particulates (silica and carbon)
What “wear and tear” substance accumulates due to aging?
Lipofuscin. It accumulates in organs such as the brain, heart, and liver
Where is lipofuscin normally found and what does it contain?
Found in lysosomes containing peroxidation products of unsaturated fatty acids.
As a result of inadequate defenses to oxygen radicals, how would lipfuscin affect the cellular membrane?
It would continuously have lipid peroxidation of cellular membranes
What color is hemosiderin microscopically?
Yellow-brown granules of hemosiderin in cytoplasm that turn blue with the Prussian blue reaction
Excess iron is stored intracellularly mostly by …
Hemosiderin, a denatured form of ferritin that aggregrates easily
What is hereditary hemochomatosis?
Genetic abnormality of iron absorption in the small intestine. excess iron ist stored as hemosiderin mostly in the liver.
What does transferrin do?
bind serum Fe
What is bilirubiin? Does it stain with Prussian blue?
Heme catabolism product that may accumulate in liver cells but does not stain Prussian blue
Cystitis Glandularis (chronic inflammation of the bladder ) often presents with epithelium changing from transitional to glandular epithelium. What is this adaptive process called?
Metaplasia
After a liver transplantation, what can causedS reprfusion injury?
ROS
How does a hydroxyl radical interact with unsaturated fatty acids of membrane phospholipids during lipid peroxidation?
OH radicals remove a H atom from the unsaturated fatty acid and the radicals formed form a lipid peroxide radical., intiating a chain reaction. The reaction is that lipid peroxids break down into smaller molecules and membrane integrity is lost.
Apoptoti cells are visible under the light microscope as what structure?
Acidophilic (Councilman) bodies They are deeply eosinophilic structures that represent membrane-bound cellular remnants that are extruded into hepatic sunusioids.
What pattern of DNA degradation is characteristic of apoptotic cell death?
“Laddering”This results from cleavage of chromosomal DNA at nucleosomes by endonucleases. Nucleosomes are regularly space across a genome and as a result, there is a pattern of regular bands seen when DNA is fragmented and separated by electrophoresis
What cellular response process is often seen around inadequately perfused margins of infarcts in the herat, brain, and kidneys?>
Atrophy
What disease is characterized by formation of bony traveculae within striated muscle?
Myositis Ossificans
What membrane is a key regulator of apoptosis?
Mitochondrial membrane
What leaks out of mitochondrial pores when opened and ultimatelyl activates downstream caspsaes (cysteine proteases)?
Cytochrome C (which activates Apaf-1, which converts procaspase9 to caspase 9 to activate downstream capses
What do effector caspases do.
they traget proteins that mediated the changes that accompany apoptosis.
Describe 3 mechanisms that can cause hydropic swelling.
- Increasing permeability of plasma membrane to sodium2. Damaging the membrane pump 3. Interfering with synthesis of ATPCauses: Toxins, Infections, Ischemia
Differentiate between karyorrexis, karyolysis, and pyknosis.
These are all patterns of nuclear changes due to breakdown of DNA and chromatin. Pyknosis: nuclear shrinkage and basophilia, DNA condenses into a solid shrunken mass . This nucleus can unedergo fragmentation so that it becomes karyorrrhexis pattern. Karyolysis is when basophilia of chromatin fade, secondary to Dnase activity.
What physiological change occurs that causes necrosis to occur after periods of ischemia?
Decrease in intracellular pH from the build up of lactate in the cytosol from anaerobic glycolysis
An alteration of injured blood vessels which histologically stains with eosin due to the accumulation of plasma proteins is known as what pathological process?
Fibrinoid Necrosis.
What gene is associated with Hutchinson-Gilford Progeria? What protein?
Human Lamin A Gene (LMNA)is the gene for Lamins (intermediate filament proteins that form a fibrous meshwork between the nuclear envelope)
What occurs when lamin A of Progeria is defective?
It makes the DNA nucleus unstable, leading to cell injury and death.
What is the phenotype of a Porgeria patient?
Early catarcats, hair loss, atrophy of the skin, osteoporosis, atherosclerosis- premature aging in children
What will lack of trophic signals do to an organ?
Cause atrophy
What is the trophic factor for the adrenal cortex necessary to prevent atrophy?
Adrenocorticotropic Hormone (ACTH)
What is Sheehan syndrome?
Postpartum Infarction of the anterior pituitaray gland causing decreased ACTH and adrenal cortex. The infarction is often a result of postpartum hemorrhage
Metaplasia is an adaptive response to persistent injury. Is it reversible or irreversible?
Reversible
Give two examples of irreversible morphologic adaptations
Malignant Transformation ; Necrosis and scarring
What cellular histologic change is a preneoplastic lesion?
Dysplasia
Which form of dysplasia is histologically characterized by atypical squamos cells that vary in size and shape and do not undergo regular maturation as they move from the basal epidermis to the surface as a result of sun-exposed skin.
Actinic keratosis
Bone marrow hyperplasia as a result of EPO upregulation will lead to what abnormal CBC value?
Increased hematocrit
Disordered growth and maturation of tissue seen in a cervix epithelium would lead to what diagnoistic problem for a pathologist?
Distinguisihing between dysplasia and early cancer
What is the suspected cause of displasia?
mutations in a proliferating cell population. A particular mutation may confer a groth or survival advantage annd its progeny will predominate the affected cell, continue proliferation, and allow further opportunities for mutation (this can lead to neoplasia)
What metabolizes CCl4? Where?
Mixed function oxygenase system (p450) of the liver in the smooth endoplasmic reticulum
What are products of CCl4 metabolism? How does this lead to hepatotoxicity and cell death?
A chloride ion and a highly reactive trichloromethyl free radical. The radical is a potent initiator of lipid peroxidation which damages the plasma membrane and leads to cell death.
What adaptiationo chronic inury is seen in Psoriasis?
Hyperplasia (of the Epidermis keratinocytes)
What are some skymptoms o fPsoriasis?
Large, erythematous, scaly plaques, commonly on the dorsal extensor cutaneous surface. Abnormality in the microcirculation of the dermis is a possible cause of psoratic lesions.
Where is acetaminophen metabolized? What is the product?
Liver SER; reactive quinones
What substance accelerates acetaminophen metabolism?
Alcohol ( It induces increase in cytochrome p450)
What leads to the pathology seen in Alpha1 Antitrypsin deficiency?
Mutations in the gene for alpha 1 antitrypsin yield an insoluble protein that is not easily exported and subsequently accumulates in the liver cells causing cell injury and cirrhosis.
What pulmonary disorder is a complicationof alpha 1 antitrypsin deficiency?
Pulmonary emphysema
What extracellular deposits are seein in Amyloidosis?
Deposists of fibrillar proteins arranged in beta-pleated sheet.
What phenotype is seen in Werner Syndrome?
Early catarcts, skin atrophy, osteoporsis, and accelerated atherosclerosis + increased riskof cancer.
What gene and gene product is associated with Werner syndrome?
WRN gene: encodes a protein with multiple DNA-dependent enzymatic functions, including proteins with ATPase, helicase, and exonuclease activity.
What is the function of Topoisomerase?
regulate the overwinding or underwinding of DNA
What characterisitc DNA damage will lead to apoptosis activation?
Severe and unrepairable
When p53 binds to areas of DNA damage what happens?
Proteins that arrest the cell in G1 of the cell cycle are actibvated allowing time for DNArepair to proceed. It also directs DNA repair enzymes to the site of injury
Which genes ar eproapaptotic in the p53 pathway?
Bax and Bak
What antiapoptotic protein is downregulated by p53?
Bcl-2
Beta-Catenin is a membrane protein associated with what type of molecules?
cell adhesion
Selectins are cell adhesion molecules involved in the recirculation of what cells?
leukocytes
