Powerpoint-Chap1 Flashcards
What are the main contributors to cellular aging
telomere shortening, environmental insults, DNA repair defects, Abnormal growth facto signaling
How is it hyposthesized that sirtuins reduce aging
insulin sensitization, decreasing free radicals and prevention of apoptosis
What to sirtuins require for action
NAD
What pharm agent induces Sirt1 activity
resveratrol
What is the first line of defense against cell injury
atrophy, hypertrophy, hyperplasia, metaplasia for ways of adaptation
inability of a cell to adapt leads to what
irreversible or reversible injury
Addition of growth factors and hormones can lead to what cell adaptations
hyperplasia and hypertrophy
decreased nutrients and stimulation can lead to what cell adaptations
atrophy
chronic irritation whether physical or chemical can lead to what cellular adaptation
metaplasia
actue transient hypoxic or injurious attacks lead to what type of cell injury
reversible. cell may swell or there are fatty changes
progressive and severe hypoxic or chemical attacks lead to what type of cell injury
irreversible
cell death by necrosis or apoptosis
metabolic alterations can lead to what type of cell response
intracellular accumulation, calcification
cumulative sublethal injury results in what type of cell response
cellular aging
having a cast causes what type of atrophy
decreased workload/disuse
what can cause denervation
disease or lack of use
what is worse, hypoxia or ischemia
ischemia
what is marasmus
really total malnutrition
breakdown fat really well still
what is cachexia
wasting away from diseases that cannot be reversed nutritionally
how does atrophy happen from endocrine system
loss of stimulation from those hormones
what is a pressure atrophy
presses on surrounding structures causing atrophy in surrounding areas
what is a common cause of pressure atrophy
decubitus ulcers
what are types of atrophy from inflammatory and immunologic processes
atrophic gastritis, celiac sprue
autoimmune!
what is atrophy senility
senile osteoporosis
aging!
What are the main mechs of atrophy
ubiquitin-proteasome protein breakdown pathway
accelerated proteolysis in catabolic conditions
What is lipofuscin
left over cell components after breakdown–> aging pigment
golden brown
what is brown atrophy
atrophy with lots of lipofuscin
What are the autophagy bodies called
residual bodies
what is kwashiorkor. signs?
moon face, swollen abdomen, thin muscles.
deficiency only in proteins.
(watered down formula)
massive edema
what occurs in cell metabolism in the casted limbs
lose proteoglycans in articular cartilage
decrease strength ligaments(atrophy)
osteopenia(loss of bone mass)
what causes fat atrophy
starvation or dissuse. replaced m with fat
when can function return after motor denervation of skel m
3-5 weeks
useless after 20-24 months
what are the cellular changes in hypertrophy
increased cytoplasm, increased ribosomes, more protein, nucleolus enlarged ( increased RNA, DNA)
what are the cellular changes in hyperplasia
nucleus enlarged but less basophilic(chromatin is dispersed)
increased DNA transcription
What are some causes of hypertrophy and hyperplasia
increased functional demands patholdy compensation excessive nutrition increased blood flow endocrine stimulation mechanical factors
bladder hypertrophy is an example of what cause of hypertrophy
mechanical
prostatic hyperplasia is an example of what cause of hyperplasia
endocrine stimulation
Hypertrophy without hyperplasia occurs where**
heart and skel m
what organs of body commonly have increased functional demands
kidney, striated m, smooth m
how does the kidney respond to increase demand
hypertrophy and hyperplasia
how does striated m respond to increased demand
endurance- increased number and volume mitochondria
resistant- hypertrophy of contractile elements and increased capillary network
how does smooth m respond to increased demand
hypertrophy and hyperplasia
VASCULAR smooth muscle polyploidy
what is polyploidy
increase number DNA content
What are the two main pathways for mycardial hypertrophy
phosphinositide3-kinase/AKT pathway
GPCRs
what is the main pathway of myocardial hypertrophy from exercise
Phosphinositide 3-Kinase/AKT pathways
what is the main pathway for pathologic myocardial hypertrophy
GPCR downstream cascade signaling increase
What are the main changes in myocardial hypertrophy
switch of contractile protein to fetal forms
early development genes re-expressed
what is the fetal form of myocardium contractile protein
alpha heavy to beta heavy chain (energy economical)
what are the early development cardiac genes
increased ANF
what does increased ANF cause
increased Na excretion in kidney
decrease intravascular volume and pressure (vasodilates)
What can cause myocardial hypertrophy
mechanical stress worload
agonists like alpha adrenergic and Angiotensin
Growth factors like IGF-1
What are permanent changes from reversible cardiac hypertrophy
increased nuclear size and the scarring remains from initial insult- decreased compliance
what causes subcellular hypertrophy
cytochrome P450 activation can break down toxins(drugs and ethanol)
what happens with increased use of drugs and toxins
hypertrophy of the ER so can detoxify more of the toxins. Products from breakdown process may be more injurious because release ROS
What are physiologic causes hyperplasia
hormonal and compensatory
what are pathologic causes hyperplasia
hormonal (gigantism)
increased functional demand
persisten cell injury
infectious agents
what type of injury is from lichen simplex chronicus
pathologic hyperplasia due to persisten cell injury
what are the main mech of hyperplasia
GF driven proliferation of mature cells
Increased output of new cells from stem cells
What happens after you remove a lobe of liver
the rest of the liver hypertrophies and hyperplasia. “compensatory”
What are the stem cells in liver
oval cells or “satellite”
if the hepatocytes in a liver cannot replicate what happens
the oval cells take over and regenerate new lineage of cells
In the menstrual cycle what occurs to cells in proliferative, secretory and menstrual phases
proliferative is hyperplasia
secretory is hypertrophy
menstrual is atrophy
what metaplasia occurs from smoking
squamous metaplasia of ciliated columnar epithelium
chronic irritation to the endocervix leads to what metaplasia
squamous metaplasia of endocervical glandular epithelium
chronix reflux esophagitis leads to what metaplasia
intestinal and gastric glandular metaplasia
what layer of epithelium undergoes the metaplasia
begins at the base where the less differentiated cells are
What vitamin is critical for regulating gene transcription
Vit A thru retinoid R
Where is the main problem caused by Vit A deficiency
eye and the production of keratinizing metaplasia of the specialized epithelium
What is the most common example of metaplasia
switch from columnar to squamous as a protective measure
What is the double edged sword of squamous metaplasia
dec cilia in bronchi inc in mucus
malignant transformation may occur
What causes periductal mastitis
keratin trapped after metaplasia
ruptures the duct resulting in inflammatory response
fistulas occur recurrently thereafter
what is a common example of glandular metaplasia
barretts esophagus
What is Barretts esophagus
at gastroesophageal junction there is gastric acid that refluxes and transitions the squamous cells into columnar with lots of goblet cells
What are the structures of the cell that change in cell injury
nuclei ER mitochondria PM other cell structures
What is oncosis
cell death with swelling (associated with necrosis)
What pathway occurs from ischemia that goes directly to irreversible injury
membrane damage
decrease ATP production ultimately leads to what if it is persistent
necrosis
If you turn off Na K pump what happens
increase intracellular Na, water follows
swelling
What is the sequence Ca after membrane dysfunction.
increase intracell Ca- activation phospholipases, digest cell
What does the mitochondrail release
cytochrome C which ultimately signals apoptosis
What do mitochondria look like when injured
megamitochondria
what commonly causes megamitochondria
alcoholic liver disease
If oxygen acceps one electron what is it
superoxide O2negative
If oxygen accepts two electrons what is it
hydrogen peroxide H2O2
if hydrogen peroxide is presence of divalent Fe2+
hydroxyl radical OHelectron
What is the fenton rxn
Fe2+ +H2O2 –> Fe3+ +OH- +OHelectron
What radical causes most damage
hydroxyl radical
what are natural mech to remove free radicals
antioxidants storage and transport proteins superoxide dismutatses Glutathione peroxidases catalase
What are our antioxidants
Vit E and A, ascorbic acid and glutathione (cytosol)
what are our storage proteins for free radicals
transferrin, ferritin, lactoferrin, ceruloplasmin
what are the superoxide dismutases that we have
manganese SOD (mitochondria
copper-zinc SOD (cytosol)
these all convert O2- to H2O2
what is the glutathione peroxidase
mitochondria converts Ohelectron to H2O2 and O2
what is clinically important of the ratio of oxidized glutathione GSSG to reduced form GSH
reflects cells ability to oxidize free radicals
What does the catalase do
peroxisomes
decompose H2O2 to H2O and O2
What do free radicals do in cytosol (ROS)
disrupt PM lipids
misfolded proteins
DNA damage
What is the hydroxyl radical from
H2O by hydrolysis
H2O2 by fenton reaction
what is the mechanism of innactivation of hydroxyl radical
conversion to H2O by glutathione peroxidase
What happens if CCl4 gets in ER
P450 oxidases act and form CCl3- which inhibits protein synthesis and inhibits apoprotein synthesis and damages PM
what can occur if apoprotein synthesis is inhibited
steatosis
What is hydropic degeneration
swollen cells with bubbles inside (vacuoles) from hypoxic injury
Why does repercussion cause injury
letting O2 back in so increase amount of ROS, also adding iron into area. everything is leaky = inflammation
what is the prime time to do recatheterization
within 20 minutes is prime time
Describe differences in PM between necrosis and apoptosis
necrosis has disrupted PM
apoptosis the PM still intact, maybe in apoptotic bodies
Is necrosis both physiologic and pathologic
strictly pathologic
what is karyolysis
no more DNA, it was all chewed up
before it would be karyorrhexis
What are morphologic features of necrosis
eosinophilia because loss ribosomes(basophilic)
eosin dye is taken up by denatured proteins
swelling of mitochondria with Ca bodies
pyknosis, karyorrhexis and karyolysis
what does early cell injury from reperfusion look like
microvilli loss and blebbing
what do cells look like after irreversible ischemic injury
swollen mitochondria with densities
disrupted cell membranes
ruptured lysosomes
dense pyknotic/fragmented nucleus
best sign for irreversible morphologic feature
PM is ruptured
What is coagulative necrosis
denaturation of protein is the primary pattern
myocardial infarct
what is caseous necrosis
distinct amorphous necrosis
mycobacterium TB
what is liquefactive necrosis
enzyme digestion is dominant
bacterial abscess, cerebral infarct
what is gangrene
necrosis with or without putrefaction
Where does fat necrosis happen
in acute pancreatitis saponification
when does fibrinoid necrosis take place
hypertension
immune complex deposition
vasculitis
where is coagulative necrosis seen
hypoxic death of cells in tissues, NOT brain
what is the morphology of coagulative necrosis
homogenous glassy eosinophilic appearance due to loss of cytoplasmic RNA(basophilic) and glycogen
Pinker than normal
what is an hemorrhagic infarct
dual blood supply with large amounts of loose CT into which hemorrhage may occur
what is a pale or anemic infarct
sudden arrest of circulatory blood flow. usually from thrombus or embolus
What type of degradation is dominant in liquefactive necrosis
enzyme digestion- completely
What is Pus
the left over from neutrophils and WBCs in the area
What can lead to abscess propagation
bacteremia
local expansion
what plane does pus travel along
fascial planes
why is affected tissue from gangrene black
deposition of iron sulfide from degraded Hb
what is dry gangrene
black brown, mummified appearance (coagulative necrosis)
what is wet gangrene
bacterial superinfection of necrotic material with liquefactive necrosis
what is gas gangrene
wet gangrene with infarction of bowel since rapid bacterial superinfection happens
diabetics have what type gangrene usually
wet
what usually causes gas gangrene
clostridium welche and Cl perfringes
what conditions can gas gangrene live in
anaerobic conditions
under microscope what does caseous necrosis look like
granular debris, fragmented coagulated cells
inflammatory granulamtous reaction
fibrinoid is what color histo
light pink
what can cause fibroid necrosis
aging, HTN or immune complex deposition in arteriolar walls
what causes pancreatic fat necrosis
large amounts of hydrolytic enzymes
phospholipase and proteases attacking adipocyte PM
How does saponification occur in pancreatic fat necrosis
pancreatic lipase hydrolyzes triglycerides
producing FFA which combine with Ca to form soaps
When does traumatic fat necrosis occur.
if occurs in breast tissue can be mistaken for?
after crushing injury
breast cancer
What are causes of pancreatitis
steroids, alcohol, trauma
what are complications of pancreatitis
pancreatic pseudocyst
fat necrosis
can be fatal
what does pancreatitis look like under microscope
adipocytes show loss of nuclei and blueish color
basophilic calcium deposits
What can we measure necrosis by in the liver?
GGT AST ALT from liver
alkaline phosphatase from biliary obstruction
how do we measure necrosis of CV system
creatine kinases, LDH and troponins from myocardial cells
how do we measure necrois in pancreas
lipase and amylase levels
how do we measure necrosis from RBC
LDH and Hb
What are cell injuries that lead to apoptosis
DNA damage, abnormal protein accumulations
what mechanisms in body trigger apoptosis
mitochondrial cytochrome C
p53 if DNA damage is unrepairable
What is the intrinsic pathway of apoptosis
mitochondrial
action of sensors and effectors of the Bcl-2 family inducing leakage of the mitochondrial proteins
What is the extrinsic pathway of apoptosis
death receptor mediated caspase activation
What are the pro-apoptotic proteins that form channels in the mitochondria
Bax and Bak
what proteins leak from mitochondrial layers
cytochrome c and other proteins that lead to caspase activation
What ligands and proteins are included in the death receoptor pathway of apoptosis
FasLigand binds tot he Fas-associated death domain which downstream activates caspase 8
What inflammatory mediator is capable of inducing apoptosis
cytokine TNF
what does TNF do to tumor blood vessels
induces thrombosis
Describe the CTL mediated apoptosis
CTL secrete perforin so that granzymes can enter and activate caspases to initiate effector phase
what protein prevents cell replication when DNA damage is detected
p53
what main type of disease is characterized by defective apoptosis
cancer
what type of diseases/injuries involve increased apoptosis
neurodegenerative diseases- misfolded proteins build up
ischemic injury
death of virus infected cells
What causes dysregulated apoptosis
unable to cope with a large number of misfolded proteins
What is the main mechanism of DNA breakdown in apoptosis
Gene activation and endonucleases
how does apoptosis and necrosis appear on a gel electrophoresis
apoptosis in laders
necrosis in large smear
What is the role of alpha1-antitrypsin
inhibits neutrophil elastase
what occurs in an alpha1-antityrpsin deficiency
accumulation of abnormally folded protein in ER
causes hepatocyte death(apoptosis)
lung disease(enzymatic digestion)
What is Reye syndrome
children with viral infection and concomitant use of aspirin results in mitochondrial injury leading to decreaed FFA oxidation
What occurs to organs in Reye syndrome
liver develops steatosis with micro vesicular pattern
What are signs of Reye syndrome
vomiting, liver failure and neurologic symptoms
What can cause accumulation of triglycerides
diabetes, starvation, ethanol, hypoxia and Reye syndrome, toxins, malnutrition CCL4
how does diabetes and starvation lead to accumulation triglycerides
increased supply of FFA
how does ethanol lead to accumulation triglycerides
increased supply of FFA
increased esterification of FFA to triglyceride
decreased oxidation of FFA
how does hypoxia and reye syndrome lead to accumulation of triglycerides
decreased oxidation of FFA
how do toxins lead to accumulation of triglycerides
decreased oxidation of FFA
reduced apoprotein availability
how does malnutrition and CCl4 lead to accumulation of triglycerides
reduced apoprotein availability
thin filaments are targets for what
toxins like mushrooms
what filament is responsible for rigor mortis
thin
what filaments are responsible for mallory alcoholic hyaline
intermediate
What protein in our bodies inactivates toxins
cytochrome p450
what induce cytochrome p450
ethanol, phenobarbital and tobacco
what surgery protects against second drug effect of cytochrome p450
partial hepatectomy
What occurs with cell injury due to alcohol
cytochrome p450 induction hydropic changes fatty changes hyaline degeneration leaving mallory bodies also causes pancreatitis
how do mallory bodies stain with H&E
eosinophilic
what is the genetic syndrome with defective dynein arms
kartagener syndrome
what happens with kartagener syndrome
primary ciliary dyskinesia leading to brochiectasis chronic sinusitis infertile males subfertile females
What other strange anomaly occurs with kartagener syndrome
situs inversus
What is steatosis
accumulations of FA and triglycerides
What occurs with intracellular accumulations of cholesterol
atherosclerosis, xanthomas, cholesterolosis and Niemann-Pick type C
what occurs wih intracellular accumulations of proteins
proteinuria, plasma cell dyscrasias, cytoskeletal proteins, abnormal proteins
what occurs with intracellular accumulations of glycogen
DM and glycogenoses
What is mallory hyaline
keratin intermendiate filaments building up
what are neurofibrillary tangles
accumulations of neurofilaments
What occurs in diabetic hepatopathy
glycogenosis (accumulation glycogen)
Lipofuscin granules accumulate in what tissue
cardiac myocyte
What is hemosiderin
breakdown of Hb, ferritin micelles
what stain is used to visualize iron in Hb
prussian blue stain
accumulation of melanin presents how on epidermis
blue nevus
What stain is used to visualize copper
rhodamine
what is anthracosis
accumulation of coal
what is it called when there is accumulation of lead and where is this seen in people
plumbism
gingival lead line
hemolytic anemia and renal tubular necrosis from toxic effects of lead
what is dystrophic calcification
in site of previous tissue damage
may end up with bony metaplasia
Where does metastatic calcifaication show up
in alkaline environment
interstitium of acid secreting organs (stomach, kidney, lung)
What other pathologies usually exist with metastatic calcification
HyperPTH
vit D excess
bone destruction
idiopathic hypercalcemia of infant, aluminum intoxication, milk alkali syndrome
