Lecture 1- Cell injury, cell death, cell adaptations 8/23 Flashcards
The…. is the origin of the disease, including underlying causes and modifiers. WHY a disease occurs
etiology
The… is the development of disease, from molecular/cellular changes to functional and structural abnormalities. HOW a disease occurs
pathogenesis
cell injury may be…, may result in … or lead to ….
reversible
cell adaptation
cell death
If cell injury is irreversible then it will lead to one of 2 kinds of cell death:
necrosis
apoptosis
7 causes of cell injury (patients view)
hypoxia chemicals/drugs physical injury immune response nutritional imbalance genetic abnormalities infectious agents
3 examples of hypoxic inury
cerebral infarction
myocardial infarction
renal atrophy
4 examples of infectious diseases
tuberculosis
actinomycosis
candidiasis
primary herpes
2 examples of physical injury
thermal burn
traumatic ulcer
2 examples of chemical/drug reactions
gingival hyperplasia
aspirin burn
2 examples of immunologic responses
hemodent rxn (cotton rolls) cinnamon rxn (gum)
3 examples of genetic abnormalities
downs syndrome
cancer
Ehlers-danlos (collagen defect)
2 examples of nutritional imbalance
scurvy (vit C deficiency)
diabetes
4 cellular targets
DNA
cell membranes
mitochondria
cell proteins
clinical signs and symptoms are usually …. from the molecular or biochemical changes following injury
several steps removed
cell injury results from a disruption of 1 or more cellular components that maintain…
cell viability
Injury at 1 point induces a …. of …
cascade
effects
… is common to all forms of pathology
cell inury
6 cell injury mechanisms
ATP depletion altered membrane permab. DNA/protein damage generation of ROS loss of Ca2+ homeostasis mitochondrial damage
In the hypoxic-ischemia model, impaired functionn of the plasma membrane ATP dependent Na+ pump leads to an increase in…. influx, an increase in …. influx and an increase in … efflux.
This leads to an increase in … influx which ultimately leads to…. swelling, … swelling, membrane… and loss of ….
Na+
Ca2+
K+
H2O cellular ER blebs microvilli
In the hypoxia-ischemia model, detachment of ribosomes leads to a decrease in…. which then leads to … deposition
protein synthesis
lipid
In the hypoxia-ischemia model, an increase in glycolysis leads to a decrease in… which leads to … clumping.
There is also a decrease in … stores
pH
chromatin
Generation of ROS is associated with ? (5)
Oxygen toxicity Inflammation Chemical/drugs- metabolism Radiation (UV, xray) Aging
3 types of ROS
superoxide
hydrogen peroxide
hydroxyl radicals
ROS damage cells in 3 different ways:
- lipid peroxidation
- protein cross-linking (fragmentation)
- react w/ thymidine&guanine to induce single strand DNA breaks
ROSS cause … breaks
single stranded
ROS cause more than…. different base modifications in both purines and pyrimidines– … and… being major sites
30
thymidine
guanine
ROS are controlled by enzymes such as …, … and …
and antioxidants such as vitamins …, …, and … and …. and …
and serum proteins that reduce/bind iron such as … and …
SOD
catalase
glutathione peroxidase
A C E glutathione cysteine
transferrrin, ferritin
copper (ceruloplasmin)
In calcium induced cell injury, there is an increase in cytoplasmic calcium which leads to an increase in these 4 enzymes: …
which causes?
ATPases
Endonucleases
Proteases
Phospholipases
decrease ATP, decrease phospholipids, protein damage, DNA damage
5 causes of cell membrane injury
- complement- C5-C9 MAC
- Cytotoxic T and NK cells- perforin
- Virus
- Bacterial endotoxins and exotoxins
- drugs
The degree of cell injury is determined by: (4)
- physiologic state of cell
- intensity of insult
- duration of insult
- # of exposures to insult
4 common etiologies of reversible cell injury
hypoxia
infectious agents
toxins
thermal injury
is there a single biochemical event that equates death?
no
2 morphologic forms of cell death are
necrosis
apoptosis
cell death leads to release of cellular constituents into the …
extracellular environment
example MI
5 cell proteins released hours after an acute MI
cTNT cTNI CK/CK-MB LD/LD1 Myoglobin
4 morphologic types of necrosis
coagulative
liquefactive
caseous
enzymatic
… necrosis is the most common form, the histologic signs are that the … is retained, there is a … cytoplasm and they are … cells
Coagulative
cell outline
pink
anucleated
… necrosis is associated with pus and bacterial or fungal infections
liquefactive
… necrosis is associated with a tuberculosis infection, the tissue has a white and cheesy appearance on gross examination
Caseous
… necrosis is common in trauma to the breast or in cases of pancreatitis. Adipose tissue has a chalky white-yellow gross appearance and the dead adipocytes give a “soap bubble” histologic appearance
Enzymatic (fat)
