Apoptosis/Necrosis Flashcards
A diagnosis based on case history, c/s, physical exam
Clinical diagnosis
List of diseases that could account for clinical findings/lesions
Differentials
Diagnosis based on changes in biochemistry, hematology, cytology
Clinical pathological
Diagnosis based on clonclusive evidence that confirms cause of disease. What may it require?
Eitiologic May require ancillary testing
Diagnosis based on predominant lesion or lesion pattern
Morphologic diagnosis
Diagnosis based on conclusive evidence from clinical data and observed lesions
Definitive
Causes of cell membrane injury
1) Transmembrane proteins (hijacked by microbes to enter cell)
2) Oxidative stress from free radicals
3) Loss of phospholipids through decreased synthesis/increased degradation
4) Cytoskeletal abnormalities
Consequences of cell membrane injury
1) Loss of Na pump –> cell swelling
2) Increased permeability –> Ca includx - Mitochondrial damage - Apoptosis
3) Injury to RER and ribosome dissociation —> inhibited protein synthesis
Oxidative damage is caused by (3)
1) Superoxide anion
2) Hydrogen peroxide
3) Hydroxyl radical
Endogenous source of oxidative damage
1) Enzymatic reactions: lipoxygenase, prostaglandin synthetase, lipid peroxidation…etc
2) Transition metal cations (Cu, Fe)
3) Inflammation and tissue injury –> increased free radical production
Exogenous sources of oxidative damage
Chemicals
Drugs
Toxins
Radiation
Tissue trauma
Aging
Stress
Antioxidant defense mechanisms (5)
1) Superoxide dismutase (SOD)–> catalyzes superoxide anion to hydrogen and oxygen
2) Catalase: catalyzes hydrogen peroxide to water and oxygen
3) Glutathione perioxidase (catalyzes llipid hydroperoxidases to water and oxygen)
4) Vitamin E: neutralizes effects of free radicals
5) Selenium: co-factor of glutathione peroxidase
What is White Muscle Disease caused by
Deficiency of Vit E and Selenium Muscle is oxidized, turns necrotic
Implications of oxidative stress on health
1) Inflammatory conditions result in chronic oxidative stress causing ORGAN FAILURE and ACCELERATED AGING
2) Chronic oxidative stress can also cause CARCINOGENESIS and NEOPLASTIC DISEASE
Causes of damage to mitochondria (2)
1) Oxidative stres
2) Calcium influx
Consequences of damage to mitochondria (2)
1) Reduced ATP production
2) Leakage of proapoptopic proteins Cell death/apoptosis
Causes of damage to nucleus
1) Oxidative stress: damages nuclear envelope DNA damage:
2) Reactive O2 species, reactive carbonyl species, lipid peroxidation products, alkylating agents, hydrolysis
3) Chemicals, drugs, radiation
4) Random mutations
5) DNA repair malfunction
Cells most susceptible to hypoxia
Neurons
Hepatocytes
Cardiac myocytes
Renal tubules
Pathogenesis of hypoxia
Lack of oxygen —> reduced ATP —> loss of Na/K pump function—> influx of ions (Na, Ca) and water –> cell swelling
What is first step of reversible cell injury
Hydropic degeneration
Types of cell injury
Reversible
Irreversible
Gross features of cell swelling
Organ enlargement, pallor
Increased fluid in tissues (noticeable during cutting)
Histological features of cell swelling
1) Cell enlargement
2) Cytoplasmic vacuolation
3) Cell membrane blebbing
What is ballooning degeneration? What is it associated with?
Swelling that occurs in EPIDERMIS Cytoplasm becomes clear.
Peripheral nuclei Inclusion bodies (viral)
Usually associated with viral infection
What is cytotoxic edema? Why is this area so susceptible
Swelling that occurs in CNS Susceptible to hypoxic injury due to lack of anerobic glycolysis
What are three types of irreverisible cell damage
Necrosis
Apoptosis
Post-mortem autolysis
Nuclear condensation, nucleus appears shrunken and dark
Pyknosis
Nuclear destruction
Karyolysis
Nuclear fragmentation
Karyorexis
Nuclear and cytoplasmic changes of necrosis
Pyknosis Karyorrhexis Kryolysis Cytoplasmic:
1) Eosinophilia (proteins)
2) Loss of boundaries, cell rupture
3) Loss of cell adhesions, individualization
Which type of necrosis occurs with sudden loss of blood - resulting in severe acute hypoxic injury
Coagulation necrosis
Is coagulation necrosis acute or chronic
Acute
Which type of necrosis has retention of cell outlines
Coagulation
Which type of necrosis has cytoplasmic hypereosinophilia and pyknotic or absent nuclei
Coagulation
Which type of necrosis occurs with bacterial infections
Caseation necrosis
Which type of necrosis manifests in granulomatous nodules?
Caseation necrosis
Appearance of caseation necrosis
Cottage cheese!
Which type of necrosis has an inflammatory zone
Caseation necrosis
What is histological appearance of caseation necrosis
Loss of tissue architecture
Granulomatous/pyogranulomatous inflammation and cellular debris
Where do you find liquefactive necrosis
CNS, abscesses
Is caseation necrosis acute or chronic
Chronic
What is the chronic type of liquefactive necrosis
In CNS
Where does acute liquefactive necrosis occur
Abscess
What is malacia
Cavities filled with liquid
Common in liquefactive necrosis in brain and spinal cord
Is malacia in CNS acute or chronic
ACUTE - severe cases result in death
Mild cases will heal with glial scaring (chronic lesions)
Viscous, opaque, white/yellow/green fluid is known as what
Supparative inflammation
Is supparative necrosis associated with inflammation
Yes! Hyperemic ring
You see histologically an inflammed tissue with lots of degenerative neutrophils and bacteria. What type of necrosis?
Supparative (liquefactive)
Can supparative necrosis become chronic
Yes, if body walls it off
What is a combo of coagulative and liquefactive necrosis
Moist gangrene
Which type of necrosis is associated with bacteira
Moist and gas
What type of necrosis is coagulation and mummifcation
Dry necrosis
Which type of gangrene is acute? Which is chronic
Acute: dry
Chronic: moist
What is a huge risk of moist gangrene
Fatal septicemia after tissue sloughing
You have a patient with black, shriveled tissue. What is this?
Dry gangrene
Your patient has malodorous, brown tissue that is soft. What is this
Moist gangrene
Your patient has black tissue with a hemorrahagic exudate that contains bubbles. What is this?
Gas gangrene
What type of bacteria are associated with gas gangrene
Anerobes such as Clostridium
Sequelae of necrosis
1) Inflammation - Neutrophils digest and liquify - Macrophages phagocytose
2) Healing/replacement - Regeneration - Fibrosis
3) Seuqestration - Occurs when necrotic tissue doesnt heal and is removed from body via degradation and phagocytosis (bones)
T/F cells undergo apoptosis first swell
False, they shrink
T/F inflammation is an important step in apoptosis
False! No inflammation in apoptosis, only in necrosis
Morphology of apoptosis (4)
1) Chromatin condensed
2) Cytoplasm condensed
3) Apoptotic bodies: fragmentation of cell in small membrane bound segments
4) Continue maintenace of cell membranes, to prevent inflammation
Physiological causes of apoptosis (2)
Fetal development
Leukocyte apoptosis
Causes of pathologic apoptosis
1) Hypoxia
2) Withdrawal of growth factors
3) Cell mediated immune responses
Intrinsic pathway of apoptosis
Regulated by mitochondria
1) Initiated by withdrawal of growth factors/hormones or DNA damage
2) Release of pro-apoptotic factors from mitochondria. Caspase activation —> apoptosis
Extrinsic pathway of apoptosis
Initated by death receptors/ cytotoxic T-cells
Fas/FADD signalling followed by caspase activation and apoptosis
Whats the name of the enzyme cascade in apoptosis
Capase enzyme cascade
What is autophagocytosis
Cellular house-keeping Removes and recycles damaged organelles and protein
Two types of pathological calcifications
Dystrophic - at site of injury and necrosis
Metastatic - secondary to hypercalcemia
Examples of dystrophic calcificaiton (4)
1) Necrotic myocardium/skeletal muscle (white muscle disease)
2) Granulomas
3) Calcinosis cutis (collagen degeneration and calcification) due to hydroadrenocorticism )
4) Calicnosis circumscripta : repetitive injury followed by calcification
6 causes of hypercalcemia in vet med **
1) Renal failure
2) Primary hyperparathyrodism (rare)
3) Paraneoplastic (lymphoma and anal sac adenocarcinoma produced PTH-related protein)
4) Vit D toxicosis
5) Destructive bone tumor
6) Severe granulmatous disease
What causes irreversible cell damage
Oncotic necrosis
Calcinosis cutis is an example of what
Dystrophic calcification
What type of necrosis involved anerobic bacteria
Gas gangrene
What type of necrosis involved intracellular bacteria
Caseation necrosis
What type of necrosis involves extracellular bacteria
Suppurative inflammatory necrosis
Whats this
Liquefactive necrosis (clear spaces with eosiniphilic precipitate)
Whats this
Apoptotic bodies
Whats this
Ballooning degeneration
(Clear cytoplasm; peripheral nuclear; vira inclusion bodies)
Whats this
Caseation necrosis
(inflammatory zone, granulomatous to pyogranulomatous inflammation, intracellular bacteria)
Whats this
Coagulation necrosis
(distinct line of necrotic tissue; loss of nuclei; loss of (individual cell) boundaries; hypereosinophilia)
Whats this
Whats this
Supparative necrosis
(degenerative neutrophils; bacteria)
Which is necrosis and which is apoptosis
Left - necrosis (loss of definition, hypereosinophilic)
Right - apoptosis (nuclear condensation)
Which nuclear changes are occuring
- Pyknosis
- Karyolysis
- Karyohexis
