Cell Death & Necrosis Flashcards
Is cell degeneration reversible or irreversible cell injury?
Reversible
Is cell necrosis reversible or irreversible cell injury?
Irreversible - too far gone
What is nearly all cell damage mediated by?
Damaged membranes or enzyme systems
What can be seen under the microscope with cell death/ degeneration?
Changes in individual cells and groups of cells
What can clinical biochemistry detect with damaged/ dead cells?
Leaked intracellular substances in body fluids - Often Enzymes
What is the underlying mechanism for cell injury?
Disruption of the Na+/K+ active membrane pump - Na+ can then move into the cell - Water follows Na+ - Cell appears to swell
What is severe cell swelling?
When the whole cell and organelles swell and are damaged - this means cellular function is impaired because the organelles no longer work as well/ at all
How can membrane damage be self- perpetuating?
- Intracellular Ca2+ from the cytoplasm and the organelles leaks out and activates phospholipases – lyse membrane phospholipids - Cytoskeleton damage - Free radical damage - Broken down membrane fragments have a detergent effect and stop other membranes from working properly
What are some of the causes for cell damage?
- Physical trauma - Hypoxia - Free radical damage - Immune reactions - Genetic Defects - Nutrition - Microbiological agents - Aging
Describe Hypoxia in terms of cell damage…
- Lack of O2 - Mediated by decreased ATP production - Caused by: – respiratory disease – Anaemia – Damage to RBCs – CO poisoning – Haemorrhage – Trauma – Cardiac Dysfunction – Constriction – Thrombosis
What are free radicals?
A single unpaired electron in an outer shell - Highly reactive - Very unstable - Autocatalytic - start off with one and it makes heaps Involved in cell injury, aging anf macrophage killing
How are free radicals formed?
- Action of radiant energy - Normal cellular reactions - Inflammation - Enzyme metabolism of certain chemicals - Reperfusion injury (hypoxic tisse gets blood flow back = lots of FRs) - Also from O2, N, C - catalysed by Fe2+
What are the most common free radicals?
Oxygen derived free radicals
What are the consequences of free radicals?
- Lipid degradation of membranes by oxidation of unsat Fatty Acids - Damage to cell proteins - Breaks in DNA strands - Damage to mitochondria Can damage cells at every level!
What are some protective mechanisms against free radicals?
- Natural decay of free radicals - Anti-oxidants - Enzymatic inactivation
What changes the morphologic appearance of cell degeneration?
- Swelling and Eosinophilia - Fatty Change
Describe cell swelling?
- Cytoplasm appears swollen, cloudy, granular or vacuolated - Reversible - Increased cell size may affect organ function
Describe Eosinophilia…
One morphological appearance of cell degeneration - Cells stain pinker - Ribosomes appear blue
Describe Fatty Change?
One morphologic appearance of cell degeneration - a.k.a. lipidosis, fatty degeneration, steatosis, fatty infiltration - Increased amounts of TAGs in cells - Normal in some tissues - Liver most often affected
Why is the liver most often affected by Fatty Change?
Because it is the main organ involved in fat metabolism - fat arrives from the diet and from adipose tissue
What is the pathogenesis of fatty liver?
- Increased energy demand by foetuses in late pregnancy combined with decreased ewe intake caused by stressors or compression of digestive organs by uterus = Negative energy balance 2. HYPOGLYCAEMIA 3. Secretion of glucocorticoids by adrenal glands + mobilisation of fat stores 4. OAA build up in blood - no ACoA due to previous hypoglycaemia 5. OAA used as substrate for ketone body formation = KETONAEMIA and KETONURIA 6. Increased deposition of TAGs into liver that can’t be oxidised = FATTY LIVER - FFA’s released from Adipose are transported to liver - re-esterified to TAGs - oxidised to ACoA - ACoA into TCA cycle to produce energy or ketone bodies
What happens to the TAGs sent to the liver in mobilisation of adipose?
- Stored as TAGs - Oxidised to Acetyl- CoA - Used to make membranes, Steroid hormones - Exported in bloodstream stuck to lipids as VLDL
How does fat accumulate in the liver?
When more is entering than being removed - Increased dietary intake of fat OR moderate body fat supplies and decreased intake - Decreased metabolism of fat in the liver OR decreased transport of liver due to decreased apoproteins
What is the underlying mechanism of fatty liver disease?
Decreased mitochondria
If there is decreased apoproteins in the liver what does this indicate?
Protein malnutrition - apoproteins are made from AAs that come from the diet
What histology preparations should be used to dissolve fat out of cells?
Frozen sections OR Special Stains (Sudan, Oil red O)
What happens to the globules of fat in chronic fatty liver?
They start to coalesce to make big clear vacuoles of fat
Describe the gross appearance of a liver affected by fatty liver…
- Pale - Friable - Greasy - Bulging - Floats
What is the definition of necrosis?
Local death of tissues within a living individual - A result of irreversible cell damage
What questions should be asked to determine the significance of the necrosis?
- Where is the necrosis? - How much necrosis? - How fast has the necrosis occurred? - What are the sequelae? (consequences)
Describe a local reaction necrosis…
- Irritant = inflammation - Accumulation of WBCs – neutrophils then macrophages - Line of demarcation
Describe system reaction necrosis…
Release of enzymes from dead cells - Increased serum levels in clinical biochemistry Acute phase response - by generalised illness e.g. cat bite abscess
How can the histological appearance of necrosis be described?
- Cytoplasm is eosinophilic - Cells tend to be shrunken - Cells have loss of distinct membrane
Why is it important to classify necrosis?
- It may suggest possible causes of necrosis - Narrows down the differential diagnoses
Describe coagulative necrosis…
- The architecture of the organ remains
- Enzymes are inactivated or delayed
- Commonly due to ischaemia
Describe Caseous necrosis…
- Loss of cellular and architectural detail of the organ - Cheesy appearance - Caused by certain bacteria… – Mycobacterium sp (TB) – Corynebacterium pseudotuberculosis
Describe Liquefactive necrosis…
- Liquid mass of necrotic tissue - No cellular or architectural detail - Mostly in CNS (known as malacia)
Describe Suppurative necrosis…
- Liquefaction with pus formation - Involves pyogenic bacteria that attract neutrophils - Enzymes are released from neutrophils, bacteria and damaged cells
What is pus?
Purulent exudate - Liquid necrotic debris + Neutrophils + Tissue fluid
Describe fat necrosis…
- Occurs by saponification
What are the sequelae of necrosis?
- Liquefaction and removal into lymphatics by macrophages - Suppuration - Sequestration (encapsulation) - Ulceration/ erosion
Describe Erosion and Ulceration sequelae…
Surfaces of skin and luminal organs - Dead cells desquamate - Erosion of part of thickness of epithelium - Ulceration of Basement membrane, exposing underlying tissue
Describe Liquefaction and removal…
- Small areas of tissue AND / OR - Large amounts of fluid, enzymes and neutrophils anr absorbed into lymphatics
Describe Sequestration…
Encapsulation without liquefaction - more common with coagulative or caseous necrosis - necrotic tissue becomes surrounded by fibrous capsule - necrotic centre is called sequestrum
Describe Abscessation…
Liquefaction + Suppurative + Encapsulation - Abscess is pus confined within a tissue - Can burst or become ‘walled off’
Describe Repair…
a.k.a Organisation Involves: - WBCs - Capillaries - Fibroblasts Results in scarring
Describe regeneration…
Dead cells replaced by new cells of the same type Occurs when: - Cells in affected tissue can multiply - Some cells survive initial damage e.g. liver
Describe Gangrene…
Ischaemic necrosis - Usually involves extremities - May be complicated by bacterial infection because dead tissue becomes accessible to bacteria and normal defense mechanisms don’t work
What are the different types of gangrene?
Dry Moist Gas
Describe Dry gangrene…
Uncomplicated ischaemic necrosis - coagulative necrosis
Describe Moist gangrene…
- Tissue with large amounts of blood and fluid - Complicated by bacterial infection - Liquefaction
Describe Gas Gangrene…
- Gas-forming bacteria - Anaerobic - Produces Exotoxins
What happens if gangrene goes untreated?
- Endogenous and bacterial toxins enter the bloodstream - Blood poisoning - Can be fatal - Debridement / amputation
Describe the appearance of gangrene..
- Dark greenish colour – poorly oxygenated blood – RBC breakdown pigments – Iron Sulphide (H2S + Fe2+) - Foul odour - Cold - Unresponsive tissue - Doesn’t bleed - Line of demarcation
What are these cells associated with?
Necrosis
What is this section stained with?
Oil red O
What is the blue in this slide?
Ribosomes
(Eosinophilia)
Is this chronic or acute fatty liver?
Chronic
- Larger vacuoles
Which tissue here is necrotic and which has suffered degeneration?
Dark pink is necrotic
Swollen cells are degenerate
Is this chronic or acute fatty liver?
Acute
What type of necrosis has this liver undergone in parts?
Coagulative necrosis
- Architecture remains
- Delayed/ inactivated enzymes
- Commonly due to ischaemia
What type of gangrene is this pig suffering from?
Dry gangrene associated with sepsis
What is wrong with this liver?
- It has fatty liver
- Pale, greasy, friable, bulging, floats in water
What type of necrosis can be seen here?
Saponification necrosis
What type of necrosis can be seen here?
Liquefactive necrosis
What is this image?
- A Bone sequestrum
- a small fragment of necrotic bone is walled off
What does this image show?
A local reaction
- Line of inflammation surrounds the central lesion
What type of necrosis is this?
- Suppurative necrosis
What type of necrosis is this?
- Caseous Necrosis
- Cheesy
- Loss of cellular and architectural detail
What type of gangrene is this?
- Ganreneous mastitis “Blue Bag”
- Sharply demarcated area of black skin
What is occurring here?
Erosion
- Sequelae of necrosis
- Basement membrane is left intact
What is occurring here?
Ulceration
- Affects basement membrane and underlying tissues
