MOD1 Flashcards
List the 7 causes of cell injury
- Hypoxia
- chemical agents
- physical agents
- nutrition
- genetics
- Immune-mediated
- Infections
List the 4 types of hypoxia and define each
- Histiocytic - the inability to use oxidative phosphorylation enzymes. Ex; cyanide and paracetamol poisoning
- Anemic - decreased O2 carrying capacity. e.g; anemia, CO poisoning
- Hypoxemic - low arterial O2. e.g; high altitudes, cardioresp. failure
- Ischemic - disturbance to blood flow, e.g; blocked blood vessel
List the 5 chemical agents and drugs
- O2 in high concentrations
- glucose and salt in hypotonic concentrations
- Trace amounts of poisons; cyanide and arsenic
- daily exposures; pollutants, asbestos
- Drugs and alcohol :)
List the 2 main consequences of immune-mediated responses
- hypersensitivity
2. autoimmune diseases
List 5 physical agents
- Mechanical trauma
- temp extremes
- extreme atmospheric pressure
- radiation
- electric shock
What is a hydropic change and what does it look like?
An accumulation of water in the cell, reversible
Swelling, dense nuclei, cytoplasm looks moth-eaten, disruption/loss of membrane
Name 4 reversible ultrastructural changes
- PM blebbing, loss of microvilli
- swelling of mitochondria and appearance of small densities
- dilation of ER and ribosome detachment
- Clumping of nuclear chromatin
4 irreversible ultrastructural changes
- Nucleus: Pyknosis, karyorrhexis and karyolysis
- Myelin figures formation; Fatty acids react with calcium
- Breakdown of PM
- Organelle degradation
4 reversible Light microscopic changes
- cell swelling
- vacuolar change
- fatty change
- surface blebs
3 irreversible microscopic changes
- Increased eosinophilia
- cytoplasm looks moth eaten
- nuclear dissolution
What are the consequences of ischemia causing low ATP and lowering the na+ pump
water, na+ and calcium influx, K+ efflux –> ER and cell swelling, loss of microvilli
What are the consequences of ischemia causing low ATP and detaching ribosomes from the ER
lower protein synthesis - more fat deposition
What are the consequences of ischemia causing low ATP and increasing anaerobic glycolysis
lower glycogen, more lactic acid, lower pH - clumps nuclear chromatin
What 4 enzymes does increased intracellular calcium activate and what are the consequences
Membrane damage:
Phospholipase - damages phospholipids
Protease - hurts cytoplasmic and PM proteins
Nuclear Damage: activation of endonuclease
lower ATP: ATPase
How does intracellular calcium affect the mitochondria
increases permeability, which lowers ATP production
What is the most dangerous free radical
Hydroxyl ion OH-
Why are free radicals present in low concentrations?
- cell signalling
2. used by phagocytes to aid degradation of pathogens
Name 5 things that increase free radical production
- chemical and radiation injury
- killing of pathogens by phagocytes
- cellular ageing
- High O2 concentrations
- Ischemia-reperfusion
What two enzymes and other factors scavenge free radicles?
Catalase and peroxidase
Vit A,C,E, glutathione and storage proteins
What do Heat shock proteins do and name 3 examples
Mend misfolded proteins and provide optimal conditions for protein folding
Chaperonins, unfoldidases and stress proteins. E.g; ubiquitin
- provide optimal conditions for protein folding
- prevent protein aggregation
- mark abnormal proteins for degradation
Name the 2 main processes of necrosis
- degradation of proteins
- enzyme digestion through lysosomes essential to the dying cell and lysosomes of leukocytes that are part of the inflammatory reaction
Characteristics of coagulative necrosis including microscopic and gross changes
- most common
- result of protein degradation
Microscopic: Ghost cells (pale, cytoplasm and cell borders unrecognizable) and neutrophils
Gross: a firm pale wedge of tissue that can become softer later
Characteristics of liquefactive necrosis including a common site
The brain, seen in infections and often involves abscess formation
- degradation of tissues by enzymes
- necrotic material often creamy yellow due to the presence of dead neutrophils
Characteristics of caseous necrosis and a common associated disease…
“Cheese-like”
Amorphous debris surrounded by histiocytes, resulting in granulomatous inflammation
TB!
Characteristics of fat necrosis and what can it mimic?
Adipocyte damage due to…
1. lipases released from damaged pancreatic tissue
2. trauma
A breast tumour as it’s seen in breast tissue
Characteristics of fibrinoid necrosis?
What would you see histologically
Associated with blood vessels and immune reactions
Fibrinoid - bright pink and amorphous fibrin and immune complexes that have leaked out of vessels
4 Aetiology’s of infarction
- thrombosis
- embolism
- compression of vessels
- twisting of blood supply
3 characteristics of a white infarct plus 3 vulnerable organs
- organs with a strong stroma
- single blood supply
- arterial insufficiency
spleen, kidney and heart
3 characteristics of a red infarct plus 3 vulnerable organs
-organs with a weak stroma - easier to hemorrhage
-dual blood supply
-arterial OR venous insufficiency:
Secondary bleeding will occur as the hemorrhage floods into the veins and surrounding tissue
Liver, lungs and intestine
What causes wet gangrene
necrosis modified by bacteria
What types of necrosis can infarction be?
Coagulative and liquefactive
What causes air gangrene
necrosis modified by air
What causes gas gangrene
necrosis modified by gas-forming/anaerobic bacteria
4 Physiological reasons for apoptosis
- Embryological - apoptosis in the webbing of the hands
- hormone-dependent involution - endometrial shedding
- in already proliferating cell populations: bottom of crypts and regulation of the immune system
- When cells have served their function, e.g; neutrophils
How does apoptosis occur?
Energy-dependent cell-mediated death, non-random internucleosomal cleavage
3 pathological reasons for apoptosis
- AIDS: HIV proteins manipulate CD4 cells to target uninfected T lymphocytes - leading to depletion of the immune system
- Autoimmune diseases: failure to apoptose host-directing antibodies
- Neoplasm
Some inducers of apoptosis
Withdrawal of growth factor and ECM, viral proteins, glucocorticoids, free radicals, ionizing radiation
Some inhibitors of apoptosis
GF, ECM, sex steroids and some viral proteins
What is the activation of caspases in apoptosis referred to?
cysteine dependent aspartate directed proteases
What is the extrinsic pathway of apoptosis modulated by
TNF DEATH RECEPTORS, activated by a ligand
What is the intrinsic pathway of apoptosis modulated by
removal of hormones and growth factors causing molecules to be released from the mitochondria, e.g; Bcl2, Bax, P53
Where do the two pathways of apoptosis converge and what does this do?
Caspase 3 which cleaves proteins, causing chromatin condensation, nuclear fragmentation and blebbing
What is the eventual fate of an apoptosed cell?
Eaten by macrophages, neighbouring cells or histiocytes
Compare and contrast apoptosis and necrosis
Pounds can never prove care and patience
P-pattern: A- single, N- contiguous group
Cell size - A - shrinks, N- swells
Nucleus - A- fragmentation into nucleosome sized fragments
PM - A- stays intact but phospholipids get fucked, N - degraded
Cellular contents - A-remain intact but released into apoptotic bodies, N - degraded
Acute inflammation: A - no, N - yes
Pathological or physiological: A - can be both, N - pathological
What can high levels of myoglobin be a sign of
Rhabdomyolysis - muscle fibres dying, presents as myoglobinuria and can progress into renal failure
What 3 things (in order of highest to lowest) would you test for in an MI
- Troponin
- Creatine Kinase
- Myoglobin
Name 3 biochemical findings in cell death and injury
K+, myoglobin, enzymes
What is the biggest irreversible point in cell damage/injury
Large intracellular calcium concentration
Name 4 mechanisms for intracellular accumulations
- deranged metabolic processes
- deficiency in critical enzymes
- dysfunctional protein transport/folding
- inability to degrade phagocytose particles
Name 5 intracellular accumulations that can occur
- pigments (exogenous and endogenous)
- water and electrolytes: hydropic swell
- proteins
- carbohydrates
- fat
Name 4 exogenous pigments
Tattoos, coal, soot, carbon
What are Mallory hyaline bodies and when would you see them?
Accumulation of damaged keratin filaments, in acute hepatitis (reversible)
Why do we need alpha 1 antitrypsin globules
What things are associated with a deficiency?
Excreted by the liver to protect organs (e.g the lungs) from neutrophil elastase which breaks down ECM and collagen.
A deficiency is associated with increased microvascular damage and permeability (edema)
What is lipofuscin
Wear and tear old age pigment, and a sign of free radicals
Comprised of lipid-containing residues of lysosomal digestion
What is hemosiderin
Iron storage complex
What is hemosiderosis?
Iron overload resulting in too much hemosiderin
What is hereditary hemochromatosis
Absorbing too much iron from the diet
Why would you get a xanthelasma
Iron in the body overloads the transferrin system so it deposits under the skin, causing a local breakdown of blood vessels and tissues
Where does bilirubin accumulate? What can this cause
In the liver, jaundice and an ichterus eye (yellow looking eye)
Name 5 causes for a pathological calcification
- Vit D overdose
- Paget’s disease: abnormal bone turnover
- Parathyroid overactivity
- Malignant tumours
- Prolonged immobilization
What causes cellular ageing
Telomerase lengthens the telomeres, as you get older telomerase activity decreases and your telomere length shortens
