Adaptation, injury, death (lecture) Flashcards
What is Death of cells, tissues or organs in a living person?
necrosis
What is ISCHEMIA?
REVERSIBLE INJURY
due to inadequate blood supply
What is an infarction?
IRREVERSIBLE
NECROSIS
due to ischemia not relieved in time
The type of necrosis determines the Tx. Name the types and associated Tx
Liquefactive: Drainage
Caseous: Anti-fungal and –TB
Gangrenous: Amputation
Pathologic apoptosis is important in what?
- certain cancers
- chemotherapy
- radiation
- transplant rejection
- Hypoxia
- Certain viral infections
What is etiology?
cause
What is morphology?
visible manifestation
What does the term gross mean?
visible w/o a microscope
What are physiologic and morphologic changes, modulating function, bringing it to a new altered steady state of homeostasis?
adaptation
What is the general princicple of adaptation?
most vital organs have a large reserve capacity
surgical removal of 60% of the liver
in a normal person causes minimal (or transient)
hepatic impairment. What is this an example of?
adaptation
What is a general principle of adaptation wrt disease?
Disease commonly uses up
an organ’s reserve capacity
silently until it is too late.
What is an example of a disease adaptation that slowly uses up vital organs reserve capacity?
atherosclerosis gradually narrows
the lumen of critical blood vessels in the heart
until suddenly something (like severe exertion)
demands more blood flow than can be delivered
or something (like a blood clot) reduces blood
flow below the minimum needed at rest, and
then the person dies, [suddenly].
What is the irreversible enlargement of airspaces due to the destruction of the walls constituting them?
pulmonary emphysema
What is a reversible pathophysiologic and morphologic response to stress or noxious stimulus? Describe it
injury
exceeding capacity of cell, tissue, organ or person to adapt, but not enough to be lethal
Describe cells of Injured tubules:
Some cells shrunken and hypereosinophilic,
a few swollen
Describe cells of Partially necrotic tubules:
more cells swollen, some with lost nuclei, some
sloughed into lumen
The injurious reactive oxygen species (ROS) include what?
superoxide, hydrogen peroxide, hydroxyl radical and
peroxynitrite (apt chemical name ONOO-)
What happens when there is mitochondrial damage?
decrease ATP => downstream effects
increase ROS => damage to lipids, proteins, DNA
What are the results if calcium entry to a cell is affected?
increase Mt permeabilityactivation of multiple cellular enzymes
What happens if there is plasma membrane damage? lysosomal membrane damage?
plasma membrane => loss of cellular components
lysosomal membrane => enzymatic digestion of cellular components
What is the result of protein misfolding, DNA damage?
activation of pro-apoptotic proteins
If the Mt damage occurs and ATP is decreased due to decrease in oxidative phosphorylation. What are the downstream effects? (3)
- decrease in Na pump => influx of Ca, H20, Na and efflux of K = > resulting in ER and cellular swelling and loss of microvilli, Blebs
- increase in anaerobic glycolysis => decrease of glycogen and pH (clump of nuclear chromatin), increase of lactic acid which will further decrease pH
- detachment of ribosomes => decrease in protein synthesis
What 2 actions are disrupted due to increased cytosolic Ca+? What are the 3 results?
Activation of cellular enzymes => membrane damage, nuclear damage and decrease in ATP
Increase Mt permeability transition => decrease in ATP
What is the restoration of blood supply to ischemic cells?
reperfusion
Why can reperfusion be injurioius as well as restorative?
it brings oxygen that can be converted to
ROS and calcium that can increase mitochondrial
permeability and activate enzymes inappropriately
in cells already damaged
What are the results of the production of ROS?
removal of free radicals
pathologic effects (membrane damage, misfolding, mutations)
What 3 items can cause membrane damage?
- phospholipid loss
- lipid breakdown products
- cytoskeletal damage
Injured and dead cells and tissues
leak their contents into the bloodstream. How is this helpful to know?
Blood tests for these contents can be
used to diagnose tissue injury or necrosis
In doing the blood tests to diagnose tissue injury or necrosis, Name 2 enzymes that would be present. Describe them
AMYLASE = an enzyme that digests
carbohydrates, secreted by both the
pancreas (into the duodenum) and by
the salivary glands (into the saliva).
LIPASE = an enzyme that digests fats, secreted by the pancreas (into the duodenum, good) and released into the retroperitoneal peri-pancreatic fat with pancreatitis (bad).
What is an enzyme concentrated in muscle and brain composed of M and B dimers? How will you know if there is an injury?
CREATINE PHOSPHOKINASE (CPK): creatine kinase (CK)
MB fraction released into blood
with myocardial injury.
What are proteins that regulate calcium-mediated contraction of cardiac and skeletal muscle? When are they released?
troponins
released into blood with myocardial injury
What is a transaminase that catalyzes the interconversion of glutamate and alanine? When does it signify injury?
ALT
more released by liver injury than AST
What is a transaminase that catalyzes the interconversion of glutamate and aspartate? What does it signify when it is released?
AST
released by
muscle, liver and other organ injury
What is a phosphatases who transfer phosphate from donor to receptor molecules at alkaline pH? When is it released?
ALP
released by liver or bone injury, especially
with biliary obstruction or hepatic
space-occupying disease.
What is an outer cell membrane enzyme that functions to transport amino acids into cells? When is it released?
GGT
released by liver injury (especially toxic injury)
What enzyme that catalyzes the conversion of lactate to pyruvate by removing two hydrogens? When is it released?
LDH
released by injury to red
blood cells, liver, muscle or other organs
What is morphological manifestation of irreversible injury to cell, tissue or organ due to ischemia (except in brain)?
COAGULATIVE NECROSIS
ischemia is reversible for certain periods for different organs. Give in relation to brain, heart, liver
- 3 minutes in brain,
- 20 minutes in heart,
- 2 hours in liver
What are features of coagulative necrosis? What does it cause?
Preservation of ghost cell outline
** Cytoplasm**: increased pink eosinophilia
Nucleus: pyknosis (increased blue basophilia and shrinkage)
karyorrhexis (fragmentation)
karyolysis (fading away)
** Acute inflammatory response**
The renal tubules are much more susceptible to ischemic injury and necrosis than the glomeruli. Why?
the glomeruli get first dibs on the
blood supply to the kidney
What is necrosis with conversion of solid tissue to liquid? What is it due to?
LIQUEFACTIVE NECROSIS
due to severe acute infection, toxicity or (brain only) ischemia
What is localized area of liquefactive necrosis?
ABSCESS
What is localized area of liquefactive necrosis visible only microscopically?
Micro-abscess
What distinguishes gangrene from coagulative necrosis? Where is it found?
blackening and shrinkage
typically of distal extremity, but sometimes of internal organs such as gallbladder
What occurs when adipose tissue digested by pancreatic lipase, creating chalky white saponification?
fat necrosis
Apoptosis can be initiated how?
internal over time => Mt pathway
external via trauma => death receptor pathway (Fas, TNF)
What are features of apoptosis?
- Cell shrinkage
- Cytoplasmic hypereosinophilia
- Chromatin condensation and karyorrhexis (nuclear DNA clumping and fragmentation)
- Phagocytosis by macrophages
How can you identify apoptosis in skin?
shrunken cell with a halo around it, condensed pink-red
cytoplasm, irregularly clumped DNA
Describe the pathway of apoptosis
- normal nucleus recieves signal or damage
- nucleus condenses (pyknosis), cell shrink, blebs form
- nucleus fragmenting (karyorrhexis), apoptotic body forms
- professional or non-professional phagocyte engulfs apoptotic bodies
What is the difference in apoptosis and necrosis?
Apoptosis:
- single cells or small clusters
- cell membrane intact
- no inflammatory response
Necrosis:
- large groups of cells
- cell membrane disrupted
- does have an inflammatory response
Physiologic apoptosis is important in what?
- Embryogenesis
- Involution
- Ending inflammation
- Eliminating self-reactive lymphocytes
- Eliminating virally infected cells*
- Eliminating tumor cells*
* when due to host response
Name 2 ways which the production of ROS is involved removal of free radicals
- conversion of H2O2 by SOD
- decomposition to H2O by glutathione peroxidase, catalase
What can cause an excess of misfolded proteins?
- metabolic alterations decreases energy stress
- genetic mutations in proteins, chaperones
- viral infections
- chemical insults
In protein misfolding, if the cell adapts, then what happens? if cell is unable to adapt?
adaptation => decreases protein synthesis and increase production of chaperones to guide to a mature folded protein
Failure of adaptation causes apoptosis
What is the differential diagnosis of fatige?
Toxic, autoimmune, metabolic
Toxic causes
- Drugs, downers
- Anti-allergy and Anti- anxiety
- Alcoholic liver disease
Autoimmune causes
- Lupus
Metabolic Causes
Hypothyroidism
Hypoadrenalism
What are the idiopathic causes of fatigue?
What are the neoplastic causes of diseases?
Depression, Sarcoidism
Anemia due to leukemia,
What are the caues of hypoglycemia
Sepsis- systemic inflammatory response syndrome due to infection.
Insulin- Given for diabetes or secreted by a tumor.
Alcohol- several day binge of drinking without eating.
Hormone defficency- epinephrine, cortisol, glucagon, or combination.
