MT1 Flashcards
Decreased oxygen in the cell impairs _____ in the _____. Reduced ATP reduces the ability of the plasma membrane to maintain homeostasis. This leads to a net ___ of ___ and isosmotic ___ in ____water
- oxydative phosphorylation
- mitochondria
- gain of solute
- isosmotic gain in cytoplasmic water
An isosmotic gain in water leads to:
Dilation of ER leads to ____ of ribosomes from RER and dissociation of ____ and a decrease in _______. This can lead to increased _____
-Cell, mitochondria, and endoplasmic reticulum swelling
- Detachment
- polysomes
- protein synthesis
- lipid deposition
REDUCED oxidative phosphorylation leads to _____ glycolysis.
Increased glycolysis produces _____ and ____ that decrease _____ leading to ____ clumping
-INCREASED
- lactic acid and inorganic phosphates
- Intracellular pH
- Chromatin clumping
Does hypoglycemia (reduced substrate for ATP production) have the same patterns as hypoxia?
YES
Where do oxidative reactions take place that produce ROS
Plasma membrane, mitochondria, cytoplasm, and peroxisomes
What inactivates Superoxide?
What inactivates Hydrogen peroxide?
Hydroxyl radicals are GENERATED by?
- Inactivated spontaneously or by superoxide dismutase (SOD) to form H2O2
- Detoxified by glutathione peroxidase and catalase
- Hydrolysis of water by ionizing radiation or by transitional metals such as Fe2+ or Cu2+
3 ways ROS damages cells:
- Lipid peroxidation
- Protein cross-linking
- Reaction w/ thymidine and guanine to induce single strand DNA breaks
Antioxidant systems act to reduce the effects of ___.
Intracellular antioxidant systems include:
Extracellular antioxidant systems include:
- ROS
- SOD (superoxide dismutase), catalase, and glutathione peroxidase
- Vitamins A,C,E, iron binding proteins (transferrin, ferritin) and copper (ceruplasmin)
What is the final common pathway of cell injury?
Which degradative enzymes does it activate?
- Increased cytoplasmic Ca2+
- phospholipase, protease, endonucleases, ATPase
Which complement proteins can cause cell membrane injury?
C5-C9 membrane attack complex
In cell injury, which occurs first, biochemical alterations or morphological?
Biochemical BEFORE morphologic
REVERSIBLE cell injury.. plasma membrane injury leads to increased intracellular __ which leads to an isosmotic __ of water.
What does this make the cell look like?
- Na+ leading to GAIN of water
- Pale and swollen
What are the 2 MORPHOLOGIC forms of cell death
necrosis and apoptosis
If a cell has a glassy homogenous pink staining cytoplasm, it most likely is:
necrosed
During coagulative necrosis, the ___ is lost but the eosinophilic outline of the cell is retained prior to being removed by inflammatory response
nucleus
What kind of necrosis is when the tissue is totally digested by the release of lysosomal enzymes during the acute inflammatory response.
Often associated with:
- Liquefactive necrosis (“pus”)
- bacteria, fungal infections (abscesses/gangrene), also central nervous system
Caseous necrosis is associated with:
Tissue appearance:
- Tuberculosis
- White and “cheesy” appearance
Which necrosis give a “soap bubble” appearance?
Common in trauma to:
- Fat necrosis
- breast or pancreatitis
In morphologic apoptosis (programmed cell death), chromatin condensation is followed by ____
fragmentation
What is a Fas-ligand
“death signal” for apoptosis
For apoptosis, what is a removal of a trophic signal?
removal of hormones
- For apoptosis what does Bcl-2 and Bcl-x do?
- What do Bax and Bak do?
How do all these work?
- INHIBIT apoptosis
- STIMULATE apoptosis
-on/off switches that regulate membrane permeability of the mitochondria
What is released from the mitochondria membrane to disrupt inhibitory Bcl-2 (so it FAVORS apoptosis)
Cytochrome-C
- Caspases are considered the:
- Their substrates include:
- “executioner” of apoptosis
- matrix and transcription proteins, DNase
Besides capsases, what’s another apoptosis executioner
mitochondria release of Ca2+ that activates various enzymes
What are the 2 stimuli for necrosis?
2 stimuli for apoptosis?
- Hypoxia and toxins
- Physiologic and Pathologic
Which one effects multiple cells, necrosis or apoptosis
NECROSIS
Which causes cell swelling, necrosis or apoptosis
NECROSIS
Which mechanism of DNA destruction is ATP DEPENDENT (necrosis/apoptosis)
APOPTOSIS
Does apoptosis cause inflammation?
NO, only necrosis does
- Hypertrophy:
- Hyperplasia:
- Metaplasia:
- cell size
- cell number
- cell differentiation
What can cause cellular hypertrophy (increase in cell size)
- hormones (i.e. smooth muscle hypertrophy in pregnant uterus)– GOOD
- Overproduction of TSH due to iodine deficiency induces thyroid follicle hypertrophy (goiter) – BAD
Is a goiter (thyroid) hypertrophy, hyperplasia, or metaplasia?
HYPERTROPHY (overproduction of TSH b/c of iodine deficiency)
Exercise causes muscle ____
hypertrophy
Endometrial glandular cells during menstruation is (hypertrophy/hyperplasia/metaplasia)
HYPERPLASIA (increase in cell number)
What can hyperplasia increase the risk of?
neoplasia
Wound healing is (hypertrophy/hyperplasia/metaplasia) of connective tissue walls and epithlium
HYPERPLASIA (increase in cell number)
Callus’s on hands are (hypertrophy/hyperplasia/metaplasia) of epidermal cells
HYPERPLASIA
When an adult cell type is replaced by another adult cell type in response to chronic stress, this is called:
METAPLASIA
When normal epithelium in intestines is replaced with goblet cells and other mucosal cells this is (hypertrophy/hyperplasia/metaplasia) —SIMILAR TO BARRET’S ESOPHAGUS
METAPLASIA
If you are a chronic smoker, or have a vitamin A deficiency, your cells will adapt, this is (hypertrophy/hyperplasia/metaplasia)
METAPLASIA
What is steatosis?
What can cause it?
- Fatty liver. An abnormal accumulation of triglycerides within cells.
- Obesity, diabetes, anorexia
Where does cholesterol primarily accumulate?
Macrophages (foam cells)
Protein cellular accumulations…
a1-anti-trypsin deficiency:
Mallory bodies:
Neurofibrillary tangle in Alzheimer’s:
- impaired folding due to gene mutation
- impaired secretion due to improper folding or precipitation
- accumulations of microtubule-associated proteins and neurofilaments
What is the “wear and tear brown-yellow granular pigment”, a lipoprotein complex due to ROS peroxidation of membranes
lipofuscin
What is the black-brown pigment produced by melanocytes but accumulated in adjacent epidermal cells and macrophages
Melanin
What is Hemosiderin?
Where does its accumulation arise from?
What is hemochromatosis?
- A yellow-brown pigment that represents aggregates of ferritin micelles.
- Excess iron locally due to hemorrhage
- Genetic disease associated with cell death due to uncompensated hemosiderin accumulation
What is the yellow-brown pigment that’s the end product of heme metabolism?
Where does it accumulate?
- Bilirubin
- In hepatocytes and bile ducts due to hemolysis, obstructed bile flow, and/or hepatocellular disease
For inflammation….Heat, redness, and swelling are due to ____, while pain and loss of function are due to ______
- vascular changes
- chemical mediators and leukocytes
Neutrophils are characterized in ___ inflammation, while lymphocytes, macrophages, and plasma cells are characterized in ____
- acute inflammation (hours-days)
- chronic inflammation (days-years)
Fever is mediated by:
IL-1, TNF, and PGE2
In acute inflammation , where does vasodilation begin?
What is it mediated by?
—What does this induce?
-Vasodilation is maintained by?
- precapillary arterioles
- NO
- –Vascular smooth muscle relaxation and mast cell release of histamine
- Prostaglandins (PG_)
During acute inflammation, vascular permeability ___ which results in movement of fluid ___ the micovasculature. The blood becomes ____ concentrated and flow ___ (stasis)
- increases
- out of
- more concentrated
- flow slows
In acute inflammation, what level does movement of inflammatory cells out the vessels (diapedesis) occur at?
Post-capillary venules
In inflammation…endothelial cell CONTRACTION forms intercullular ___ due to reversible ___. This occurs (how fast)___ and lasts for ___.
Contraction is mediated by:
- intercellular gaps
- reversible contractions
- occurs rapidly
- lasts for 15-30 minutes
-Histamine and bradykinin
In inflammation…endothelial cell RETRACTION due to restructuring of _____ is mediated by ________. This takes _____ to develop and lasts for ___
- cytoskeletal proteins
- IL-1, TNF, IFN-y
- 4-6hrs
- Lasts 24 hours or more
What is the order of leukocyte extravasion?
margination, rolling, adhesion, emigration, chemotaxis (MRAEC)
Cell adhesion molecules mediate the processes involved in the movement of ____ from the blood stream into extravascular tissue
leukocytes
Leukocyte margination:
Rolling:
Adhesion:
- mechanical process due to slowing of blood
- selectins mediate a weak, transient, sticking that slows the cells forward progression
- mediated by integrins (ICAM/VCAM)
Is chemotaxis random or non-random movement of leukocytes to the site of injury
-What are the 2 potent chemotactic factors
NON-random
-PAF and LTB4
Activation of leukocytes is characterized by production of ___ and ___ from ____
leukotrienes and prostaglandins from arachidonic acid
Phagocyte attachment is mediated by ____ on targets and specific leukocyte receptors
opsonins
What is the morphologic hallmark of acute inflammation?
Neutrophils (PMNs)
What do neutrophils release for acute inflammation
ROS and lysosomal enzymes
What end up replacing neutrophils in acute inflammation within 48 hours?
What is their half life?
Monocytes (macrophages/histiocytes)
-months
Which immune cell reacts to allergic reactions and parasitic infections
eosinophils
An abscess is a localized area of:
liquefactive necrosis
Acute inflammation relies on ___ immunity while chronic relies on ____
innate
specific/adaptive
Granulomatous inflammation is linked to the delayed-type ___ hypersensitivity immune reaction
IV
Granulomatous inflammation includes epitheloid (activated) ___. They are healed by ___
- histiocytes
- fibrosis
NSAIDs inhibit release of ____ from cell membrane phospholipids
arachidonic acid
While prostaglandins generally cause vasodilation, _______ causes vasoconstriction
thromboxane A2
When is peak neovascularization during wound healing
DAY 5
Arterial thrombi have a ____ appearance with distinct lines of ___.
Venous thrombi have a ___ appearance. They often form in:
Pale/white
lines of Zahn
- red
- deep veins of legs
Sterile (non-infectious) thrombi on heart valves are called:
Nonbacterial thrombotic endocarditis (NBTE)
Fate of thrombi... Propagation: Embolization: Dissolution: Organization:
- Propagation: enlarge by additional fibrin/platelt deposition
- Embolization: entire thrombus dislodges or a piece breaks loose
- Dissolution: lysis by fibrinolytic activity
- Organization: ingrowth of fibroblasts and smooth muscle cells, leads to deposition of collagen (replacing the fibrin) and recanalization, which may reestablish some flow through the thrombus
Disseminated Intravascular Coagulation (DIC) is the widespread activation of the coagulation cascade and fibrinolytic system leading to depletion of ______ and ____ and accumulation of ____split products. This can be associated with formation of ____and risk of ____
- depletion of coagulation factors and platelets
- formation of fibrin split products
- risk of of hemorrhage
Embolism defintion:
A solid, liquid, or gas carried from one point to another in the vascular system
Thrombo-emboli that lodge in pulmonary arteries usually arise from where?
deep veins in the legs
Do small embolisms cause ischemia? Why/why not
No, cuz of double blood supply in the lungs
What is a saddle embolus?
Sudden death due to large emboli straddling the bifurcation of the pulmonary arterial trunk
Can gradual obstruction of many small pulmonary arteries by repeated embolization over time result in in pulmonary hypertension?
yes
What’s a paradoxical embolus?
embolus that arises in a systemic vein and crosses a communication from the venous side to the arterial side
Usual origin of systemic embolization?
Can they travel to any systemic artery?
Left atrium, left ventricle, or ulcerated atherosclerotic plaque.
-YES
What kind emboli is caused by fracture of large long bone?
fat emboli
Infarction definition:
Usually due to:
Less often due to:
-ischemic (restriction of blood supply to tissue –>shortage of oxygen) necrosis of an organ. (AKA an are of dead tissue resulting from failure of blood supply)
- Due to arterial obstruction
- less often because of shock or vessel twisting
Infarcts tend to be ____shaped with the wedge at the site of ______
wedge
arterial obstruction
The histologic changes of coagulation necrosis do not develop for (how long) after the infarct has occurred.
Infarction is followed by ______ that peaks at ___days. Healing occurs by ________, starting at the _____ of the infarct, followed by ____
Several hours (NOT immediately)
- acute inflammation
- 2-3 days
- granulation tissue ingrowth
- edge
- scar formation
Infarcts in the brain result in ____ necrosis and heal with formation of a ____
- liquefactive necrosis (NOT coagulative)
- cystic space
What’s more vulnerable to hypoxia…brain/heart or arm/leg
brain/heart
Shock definition
systemic hypoperfusion (decreased blood flow) of tissues
What is cardiogenic shock? hypovolemic? septic? Anaphylactic? Neurogenic?
- cardiogenic: loss of pumping capacity of the heart
- hypovolemic: blood loss
- septic: bacterial
- hypersensitivity reaction mediated by IgE
- neurogenic: loss of vascular tone (anesthesia/spinal cord injury)
During septic (bacterial shock), _____ bind to ____ on ___and ___ mediating the release of ___ and ___ .
This causes vaso____, ____tension, (increased/decreased) myocardial contractility
- PAMPS
- bind to toll-like receptors (TLRs)
- on monocytes and neutrophils
- release of IL-1 and TNF
-vasoDILATION, HYPOtension, decreased
Difference of nonprogressive and progressive stages of shock
nonprogressive: compensatory mechanisms maintain tissue perfusion
progressive: leads to reduced perfusion and hypoxic injury leading to DIC (intravascular coagulation)
