Path Flashcards
In response to systemic hypertension, cardiac myocytes will undergo what cellular adaptation process?
Hypertrophy: can’t undergo hyperplasia because they are an established tissue.
Increase in organ size is accomplished by what 2 cell adaptation processes?
Hypertrophy, hyperplasia. Generally both are involved, like the uterus during pregnancy.
Which involves gene activation? Hypertrophy or hyperplasia?
Hypertrophy: gene activation, increased protein synthesis, and production of organelles.
Bigger cells, gotta fill it up.
HYPERPLASIA involves new cells generated from adult stem cells.
Pathologic hyperplasia (like endometriosis) can lead to _____________, and eventually neoplasia.
Dysplasia: abnormale growth of cells.
Decrease in stress on an organ will cause that organ to undergo……
Atrophy.
What is an indicative factor of atrophy in histology?
Autophagic vacuoles within the cell (stain yellow a lot of times)
A change in cell type based on new stress factors is called__________.
Metaplasia.
Metaplasia is ALWAYS _______________, and ALMOST ALWAYS_______________.
Metaplasia is always PATHOLOGIC, and almost always REVERSIBLE.
The process in which residual tissue grows after removal or loss of part of an organ is called_______________. Is this physiologic or pathologic?
Compensatory hyperplasia: physiologic.
Most forms of pathologic hyperplasia are caused by______________.
Excessive hormonal or growth factor stimulation.
Example:
There is a fine balance between estrogen and progesterone in the menstruation. Throw this off, and the endometrium may grow abnormally, causing abnormal bleeding.
Is wound healing an example of hyperplasia?
Yes. Rapidly proliferating cell population.
The degradation of cellular proteins occurs by what pathway?
Ubiquitin-proteosome
The mechanism of atrophy consist of a combination of _________________, and ______________ in cells.
Decreased protein synthesis (due to decreased metabolic activity) and increased protein degradation (via autophagy….proteosome)
Why is the metaplastic change from respiratory epithelium to squamous epithelium in the lungs bad? Doesn’t the squamous epithelium withstand the environmental stress better?
Yes, but the function of respiratory epithelium is lost. No cilia or mucous.
What else, other than smoking, can inside squamous metaplasia in the lungs?
Vitamin A deficiency. - Vitamin A is necessary for the differentiation of epithelial types.
Osteogenic metaplasia. WTF is that…>?
Bone is occasionally formed in tissues, specifically at the focal point of an injury.
What causes cell injury? (2 things)
- Direct injury
2. Stress so severe, or for such a long duration that cells can no longer adapt.
2 types of cell death?
Apoptosis/Necrosis
2 phenomena characterize irreversible cell damage. Describe them.
- Inability to correct mitochondrial damage (lack of ox phos and ATP generation)
- Extensive membrane damage
What are the 2 main morphologic correlates of REVERSIBLE CELL INJURY? What is the physiology behind that?
Cell Swelling and fatty change. (remember… they’re reversible.)
- Cell swelling due to failure of energy-dependent ion pumps in the plasma membrane. No fund/osmotic homeostasis.
- Fatty change: hypoxic damage/ toxic damage, etc…
The first manifestation of all forms of injury to cells is…….
Swelling. Can see with a light microscope or on a gross scale.
What is the histological landmark for cell swelling and fatty change?
1) Membrane: blebbing, distortion of cilia,
2) vacuoles in the cells, mostly cardiac myocytes or liver.
What color does RNA stain in H&E?
Blue. RNA is basophilic.
What are the histological characteristics of necrotic tissue?
What 3 things happen to the nuclei of necrotic cells?
Increased eosinphilia.
“moth eaten” with vacuoles.
Pyknosis - nuclear shrinkage
Karyorrhexis - pyknotic nucleaus fragments
Karyolysis - dissolution of the nucleus (no more basophilia due to RNA b-down)
Which type of necrosis can only be discovered upon histological examination?
Fiibrinoid.
Most organs (except the brain) undergo what type of necrosis (post-infarct).
Coagulative necrosis
Describe coagulative necrosis.
Tissue form remains.
Wedge shaped.
Occurs in every organ but the brain.
Microscopic: anucleate ghost cells.
If an abscess has pus in it, what do you do?
Drain the abscess and culture the pus. Pus is indicative of infection.
Gangrenous necrosis is what?
Coagulative necrosis of the extremities, esp. feet.
How does fat necrosis occur?
Acute pancreatitis. Pancreatic lipases are released into the peritoneal cavity. They liquify the membranes of fat cells, and lipase’s split the TGs into FA’s. The FA’s combine with calcium to form white chalky areas.
If an area of caseous necrosis is closed off by a distinctive inflammatory border, it is called a……
Granuloma.
What form of necrosis comes from an immune-mediated disease? Describe it.
Fibrinoid.
Only visible with light microscopy. Immune complexes are deposited on the walls of arteries, and they combine with fibrin that leaks out of the vessels
Histo: Dark pink, eosinophillic ring around the vessel.
What is the role of lymph nodes in inflammation?
Lymph flow is increased, and they help drain edema fluid, leukocytes, and cell debris from the area.
An infection of the lymph vessels, usually as a result of bacterial infection, is called what?
Lymphangitis
Inflammation of a lymph node is called….
Lymphadenitis
Pathologic inflamed lymph nodes are generally a result of what?
Hyperplasia of lymphoid follicles and increased #s of lymphs and phagocytes.
The first contraction of endothelial cells that leads to vascular permeability is due to what cytokines?
Histamine, Bradykinin, Leukotrienes
A slower, more prolonged retraction of endothelial cells caused by changed in the cytoskeleton is induced by what cytokines?
IL-1 and TNF (tumor necrosis factor)
These 2 play an important role in endothelial cell activation
Prolonged vascular permeability (>36 hours) is usually because of……
Endothelial injury
What cytokine stimulates endothelial GROWTH?
VEGF (vascular endothelial growth factor)
TNF and IL-1 upregulate selectins and adhesion molecules on endothelial cells. What do E-selectin and P-selectin (on endothelium) bind to on the Leukocyte in the post capillary venules?
Sialyl lewis X (sialylated oligosaccharides)
P-selectin, when not upregulated on the endothelial cell surface, is stored where? What causes it to be expressed?
Wiebel- Palade bodies
Histamine and Thrombin cause it to be released and expressed on endothelial surface.
Name some integrins.
LFA-1, ICAM-1, ICAM-2.
What integrin is only displayed on the surface of mature T-cells? What does it bind to on the vascular endothelium?
VLA-4 on T-cells bind VCAM-1 on endothelium for ADHESION
Diapedesis is mediated by what adhesion molecule?
PCAM-1
What 4 things cause neutrophil chemotaxis in peripheral tissues?
1- Bacterial products
2- C5a Anaphylatoxin
3- Chemokines: IL-8, IL-17
4- LTB4 (Leukotriene B4)
What cell type predominates acute infection initially? What is it replaced by?
Neutrophils/ Macrophages
What leukocyte enzyme converts O2 to O2- (oxygen –> superoxide)>
NADPH oxidase.
What enzyme converts H2O2 to HOCL (bleach) in leukocytes?
Myeloperoxidase
What are the main reactive species in an Oxidative Burst?
ROS
NO
HOCl
What is the most important lysosomal enzyme involved in bacterial killing?
Elastase.
Describe LAD (Leukocyte adhesion deficiency) Types 1 and 2.
Type 1: Defect in the CD18 subunit of integrins (LFA-1 and Mac-1 usually). Adhesion defect.
Type 2: No sialyl-Lewis X on Leukocytes. Rolling defect.
Characterized by no pus formation, increased neutrophil count in blood, and recurrent bacterial infections.
What is Chediak-Higashi syndrome?
Autosomal Recessive protein trafficking defect.
NO PHAGOLYSOSOME FORMATION
Characterized by:
- Increased pyogenic infections
- Neutropenia
- granules in leukocytes
- albinism
What is Chronic Granulomatous disease?
Lack of Oxidative killing due to a mutation in NADPH oxidase.
Engulfing of bacteria doesn’t result in O2-dependent killing mechanisms. In an attempt to control these infections, the microbes are surrounded by ACTIVATED MACROPHAGES.
A blister is an example of what kind of inflammation?
Serous inflammation- characterized by outpouring of watery, protein-poor fluid.
Fluid in a serous cavity is called __________.
Effusion
What does the term ORGANIZATION mean?
The ingrowth of fibroblasts and blood vessels.
Abscesses are …..?
Localized areas of liquefactive necrosis.
OR
The result of the multiplication of pyogenic organisms in tissue
The usual outcome of abcess formation is……
Scarring
A local defect, or excavation, of the surface of an organ or tissue that is produced by cell necrosis or sloughing of inflammatory tissues is called?
An Ulcer.
Where are complement proteins produced ?
Liver
WTF id Hageman factor? (Factor XII)
Inactive proinflammatory protein produced by the liver. Gets activated upon exposure to the endothelium or tissue collagen and breaks down BRADYKININ!
Causes pain!
Most common places for ulcers?
GI tract: anywhere from mouth to colon.
Lower extremities when vascularity is limited.
WHat are the local and systemic effects of TNF, IL-2, and IL-6?
Local: Endothelial cell activation
Systemic: Fever, metabolic abnormalities, Hypotension (shock)
Do all chemical mediators of inflammation require a receptor to function?
No. Some have direct enzymatic or toxic properties like ROS.
What cells make histamine? What are the effects?
Mast cells in periphery, circulating basophils and platelets.
Arteriolar dilation and rapidly increased vascular permeability
Where do you find serotonin and what is its function in actuate inflammation?
Stored pre-formed in platelets. It’s released when the platelets aggregate and causes VASOCONSTRICTION when clotting occurs.
What cells are the main source of Arachidonic Acid metabolites in inflammation?
Leukocytes, mast cells, endothelial cells, and platelets.
What’s the major ArA derivative made by platelets and what is its function?
TxA2. (Thromboxane A2- made from the cyclooxygenase pathway just like PGE2 and PGI2)
TxA2 = VASOCONSTRICTOR and PLATELET AGGREGATOR
________ (ArA derivative) is secreted by endothelial cells. What is its function?
PGI2 - vasoDILATOR and platelet aggregation inhibitor,
PGE2 is associated with what symptoms of inflammation? What cells make it?
Feeeeever and pain.
Mast cells.
Neutrophils produce what kind of Arachidonic acid derivatives?
Leukotrienes.
LTB4 = neutrophil chemotaxis
LTC4
LTD4
LTE4 = increased vascular permeability
Which of the COX enzymes is inducible and which is constitutively expressed?
COX-1 = constitutively expressed. homeostatic maintenance.
COX-2 = inducible in response to inflammation
What is PAF?
Platelet activating factor. Stimulates platelets,induces bronchoconstriction and is 100-1000x more potent that histamine at inducing vasodilation and vascular permeability.
It mediates and up regulates a lot of the inflammatory factors and cytokines.
What is the source of PAF?
Phospholipase A2 cleaves it from the membranes of many cells.
WHat cytokine activates the inflammasome?
IL-1
What are the 3 most important cytokines (chemokines) in acute inflammation?
TNF, IL-1, IL-6
What are the most important cytokines for chronic inflammation?
IFN-gamma and IL-12
What does Il-6 do?
Increased liver synthesis of inflammatory mediators.
