Necrosis Flashcards
1
Q
Necrosis
A
death of a substantial number of cells within or attached to the living body
when necrosis occurs:
- further changes can take place in tissue itself (e.g. mineralization)
- surrounding unaffacted living tissue can react against necrotic tissue- To try and remove because it is no longer useful or viable. Acts as reservoir for infectious disease
2
Q
Cellular Events that Occur in Necrosis
(4)
A
- Pyknosis
- Karyorrhexis
- Karyolysis
- Cytoplasm
*These are what we are using to identify a tissue as necrotic under a microscope
- 1-3 are nuclear changes. Can use to say “this nucleus indicates some necrosis”
Diagram:
- Normal cell: Change in nucleus and nucleolus membrane is still in tact
- Clumping of Chromatin and general swelling of the cell. pyknosis. Endoplasmic reticulum is becoming somewhat swollen and distended: result of sublethal injury to the cell
- Dissolution of nuclear structureand rupture of cell membrane. Karyolysis: nucleus is now fragmenting. Mixing of enzymes within the cytoplasm mixing with the nuclear material and it will become digested and will become hard to see. The membrane will also likely rupture and expose the env’t to the cell and that is what wil then trigger an inflammatory response. Influx of inflammatory cells into the necrotic tissue
3
Q
Necrosis at a Cellular Level
A
Under Microscope:
- nucleus becomes darker by taking up hematoxylin
- cytoplasm becomes more pink due to eosinophils
4
Q
What are the main causes of necrosis?
(3)
A
- Loss of Blood Supply
- LIving agents (bacteria, viruses, fungi and parasites)
- Non-living agents (chemicals and physical injuries)
5
Q
Hypoxia
A
reduced Oxygen Supply
- COMPLETE loss of oxygen would be anoxia
6
Q
Ischaemia
(ischaemic necrosis)
A
loss of blood supply. not just oxygen
7
Q
infarction
A
sudden loss of blood supply to a portion of a tissue or organ
8
Q
Consequences of Ischaemia Depend on
A
- type of cell: parenchyma much more susceptible than stroma
- metabolic activity of tissues: more active, more susceptible
- whether or not there is a good or potential collateral blood supply (kidney vs. lung)
9
Q
How does Ischaemia occur within the tissues?
(3 ways)
A
- compression of the blood vessel from outside
- narrowing of the vessel lumen due to mural (wall) thickening
- blockage of the vessel lumen
10
Q
Thromboembolism
A
- Thrombosis: is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thrombocytes) and fibrin to form a blood clot to prevent blood loss
- Embolism: is the lodging of an embolus, a blockage-causing piece of material, inside a blood vessel. The embolus may be a blood clot (thrombus), a fat globule (fat embolism), a bubble of air or other gas (gas embolism), or foreign material
- Thromboembolism: Formation in a blood vessel of a clot (thrombus) that breaks loose and is carried by the blood stream to plug another vessel. The clot may plug a vessel in the lungs (pulmonary embolism), brain (stroke), gastrointestinal tract, kidneys, or leg
11
Q
Black Disease
A
- infectious necrotic hepatitis
- Clostridium novyi type B spores germinate in anaerobic env’t created by migration of liver flukes- Fasciola heptica
12
Q
3 Zones in the appearance of necrotic lesions
A
- central zone of Necrosis (N)
- zone of degeneration (D)
- Zone of Inflammation (I)
13
Q
3 main types of necrosis
A
- Coagulative necrosis - remains firm
- Liquefactive necrosis - becomes liquid
- Caseous necrosis - looks like “cottage cheese”
Other specific types:
- fat necrosis- hard soap-like appearance of affected body fat
- gangrene- mostly a post-necrotic change
14
Q
Pyknosis
A
- greek: dense
- normal nuclear structure is replaced by very dense, heavily staining, smaller angular mass of chromatin
- Chromatin within nucleus becomes very dense and picks up a lot of hematoxylin (blue stain). Nucleus also becomes much smaller and possibly angular in shape
- Histology: Pyknotic: shrunken,darker, and the cytoplasm is much pinker!! More eosinophilic. pH drop is attracting more of eosin stain
- normal nuclei, slightly larger/paler staining.
15
Q
Karyorrhexis
(Greek- karyon= nucleus; rexis= breaking up)
A
- nucleus has broken up into several dense pieces
- The nucleus breaks up into fragments and clumps. We can look at this.
- The cells will all be at different stages when we look. Some will be pigmented (pyknosis) or fragmented (karyohexis, etc.)
- Lots of little tiny black specs and dots if you look around this (tiny specs)–> those are bits of broken up, pyknotic nuclear material. These cells are at the process of karyorrhexis
- in any one lesion we have multiple cells at different stages of necrotic pathway. Cells that are in the various of the three stages in any one lesion
16
Q
Karyolysis
(dissolution of the nucleus)
A
- nuclear staining with haematoxylin becomes faint and only the ghost outline of the nucelus remains
- Essentially the action of DNAses and RNAses (nucelases) act within the cell and break down nucleic acid material within the nucleus.
- Nuclear membrane ruptures and all the components become cytosolic and begins to get dissolved –> ghosted appearance of nucleus.
17
Q
Cytoplasmic change
A
- sometimes stains brighter pink (more eosinophilic)
- Cytoplasm will become much more eosinophilic and become pinker due to eosinophil granules!
- pH drops and cytoplasm becomes much more acidic and this really attracts the eosinophils
19
Q
Consequences of Ischaemia
A
Consequences of ischaemia depend on:
- Type of cell in tissue - essential functioning cells (parenchyma)= ↑ susceptible than connective tissue supportive cells (stroma). Parenchymal cells (e.g. liver or lung) are going to be susceptible because if we lose blood to those there is going to be a much more consequence of necrosis than if we lose blood supply to connective tissue
- The metabolic activity of the tissue - very active organs= ↑ susceptible. E.g. the heart! Very active. If you lose blood supply.. You will have consequences quickly and severely than in another type of muscle (e.g. bowel) and liver which has a reserved capacity
- Whether or not there is a good or potential collateral blood supply
- Kidneys!! (end arteriole supply.. Arteries that supply the kidney basically stop at the glomerulus. If something blocks the renal artery, that portion of tissue will become dead or the whole kidney may even die.)
- But in the lung there are lots of collateral supplies that can open up, where if you block one of the branches of the pulmonary artery there will be others that can take over and compensate
- Brain has very little when it comes to collateral supply, depends on the species. Tends to be severe
21
Q
Compression of the Blood Vessel
(e.g. intestinal torsion)
A
Classic case that happens frequently, almost on a weekly basis. Especially equine med - basically compressing blood supply to the tissue
Venous outflow impeded first due to thin walls of veins–> Organ swell & hydrostatic pressure ↑ –>leakage of oedema fluid into tissue –> Swelling eventually impedes arterial flow –> Arterial flow stops–> Tissue undergoes ischaemic necrosis–> Intestinal blood barrier compromised –> Bacterial toxins absorbed - death or intestine friable: prone to rupture with peritonitis - toxaemia and death
- Untwisting gut without clamping ends first can –> sudden release of inflammatory mediators & toxins which can –> toxic shock- could kill animal
- Intestinal intussusception- part of intestine telescopes inside itself, usually seen in young animals (puppies) after a bout of gastroenteritis (↑ movement of gut)
- One piece of intestine that basically telescopes inside another. Usually preceded by enteritis or something that upsets the stomach, something that shouldn’t. or can be an infection preceding it.
- commonly in cats it is a linear foreign body (STRING). Can cause something the gut contracts on and makes it telescope on itself
- older animals, you can get intussusceptions from tumors, gives the gut something it can wrap around within lumen
- Compromising that blood supply to the bowel and can become a surgical emergency - Can develop peritonitis or other systemic effects
22
Q
Narrowing of the vessel lumen
A
Narrowing of the vessel lumen due to mural (wall) thickening
- These are both quite unusual in animals compared to humans because of our diets and western lifestyle
- Arteriosclerosis (“hardening of the arteries’) may occur in hypertension- cells hypertrophy to compensate for the ↑ pressure
- Increase blood pressure, the smooth muscle in wall of arteries thickens to provide resistance. Our arteries will somewhat narrow to try and increase the resistance to hypertension. Perpetual issue because you increase the blood and it thickens so then you will begin to lose blood supply to parts of the body. Don’t really see this in animals really, but great apes
- Atherosclerosis is rare in animals due to diet (occasionally occurs in dogs with hypothyroidism)
- ex: Coronary arteries of a dog that have thickened quite a bit. Are somewhat white because they are filled with this atheromatous material. This is actually from a dog with hypothyroidism. Hypothyroidism is associated with high levels of circulating cholesterol, essentially a liver effect. More likely to deposit in blood vessel walls
- Made up of cholesterol and macrophages trying to phagocytose that cholesterol in the walls of arteries. Very diet related, don’t see much in animals unless they have an underlying metabolic disease. Hypothyroid or diabetes
23
Q
Blockage of the Vessel Lumen
A
- Thrombosis- damage to endothelium of blood vessel–> formation of a thrombus (fibrin & platelets) when this occurs inside body –> physical obstruction e.g. hypertrophic cardiomyopathy in cats
- Embolism: clot that travels & becomes lodged, commonly in arcuate arteries of kidney–> infarction
- Erysipelothrix rhusiopathiae (diamond skin disease’) in pigs- bacteria lodge in dermal blood vessels
- Ergotism- caused by Ingestion of Ergot (fungus)–> ischaemia of extremities (ear tips, digits etc)
24
Q
Physical and Chemical Agents
(Non-Living Agents)
A
Physical & Chemical Agents
Physical (physical Injury or Damage to tissues): burns, cold, frostbite, X-rays, pressure, pinching or crushing of tissue
-Incorrect Burdizzo castration- vessels supplying testicular skin crushed accidently–> skin slough–> sepsis.
Chemical: Can cause damage to vessels when absorbed or they can have similar effects when metabolized
- directly caustic or corrosive in action or exert effects when absorbed & metabolised to a more toxic substance
- Oak poisoning (tannins) in leaves & particularly acorns- in horses–> acute tubular degeneration in kidney
- Horses are very sensitive to tannins. They are nephrotoxic (damaging to the kidneys)
- It will attack normally the distal tubules
- histo: You can note an obvious ghosting of nuclei. This is an effect of tannins. See in autumn because storms will blow acorns into the pasture. Horses will eat them and you find them dead the next day or very unwell
25
Q
Living Agents
A
- Black disease (infectious necrotic hepatitis) – Clostridium novyi type B spores consumed from soil/ grass when grazing enter portal system–> liver & lie dormant but germinate in anaerobic environment created by migration of liver fluke – Fasciola hepatica –> ↑Clostridium–> ↑ toxin release–> necrosis
- Pale areas are necrotic tissue
- Infection causing necrosis and inflammation in the liver
- animal ingests spores of this bacteria from the pasture
- they are in the GIT, they go through the blood as they are absorbed
- they end up in the liver and they sit in the liver fairly harmlessly throughout the animals life
- UNLESS, the animal is ALSO infected with liver fluke (f. hepatica)
–> live in bile ducts of the liver, but like to go from one bile duct to another
- after another life cycle they migrate through the liver tissue and as they migrate they damage tissue and create somewhat of an anaerobic environment which is perfect then for the clostridium spores to then germinate
- they become activated and form toxins that lead to large amount of damage to tissue (NECROSIS)
27
Q
Coagulative Necrosis
A
Coagulative necrosis-remains firm,maintains architecture
- Most common
Tissue is firmer and drier on the cut surface than normal
- the gross and the microscopic architecture of the tissue is maintained
- Gross- White areas, firmer & drier on cut surface but still
resembles the adjacent viable tissue
- Micro- cells may appear somewhat larger & outline may be lost (karyolitic), but can still recognize renal tubules, cytoplasm appears structureless & homogenous, important nuclear changes
- Causes- bacteria –> toxins (esp Clostridium spp.), infarction, and some foci of viral replication e.g. CHV-1
ex: Bovine Kidney
- Paler areas are the necrotic tissue and they have rim of red around them which is inflammation around those areas (red zone)
- but if you were to look at this in black in white you wouldn’t really notice anything different based on structure and shape. Structure is maintained which tells you that this is most likely coagulative necrosis
- that actually tells you that the most likely cause of this is either toxins produced, infarction, and some foci of viral replication (occasionally). Won’t actually be the bacteria themselves! Just the toxins they produce. Bacteria themselves will actually cause a lot of inflammation and damage the tissue structure
28
Q
Liquefactive Necrosis
A
Liquefactive necrosis-becomes liquid (different to coagulative)
- Occurs in tissues with little connective tissue- e.g. brain
- Actual bacteria themselves causing damage to the tissue and attracting neutrophils which are releasing their own enzymes. Will have a change in shape and the contour of the tissue
- Two types:
a) Malacia- CNS only (encephalo/myelo- affecting brain/ spine). (ex: leukoencephalomalacia and myelomalacia- necrosis of the spinal cord)
b) Abscesses- Anywhere in the body - Abcesses- Lots of pus produced by neutrophils! pyogenic (pus producing) organisms- bacteria –> necrosis & attract vast numbers of neutrophils–> which they kill, dying neutrophils release proteolytic enzymes which digest necrotic tissue, killing further tissue cells & other incoming neutrophils.
- Pus = dead neutrophils, tissue & organisms
- Thiamine (Vit B) deficiency (dietary/ bracken related)–> cerebrocortical necrosis (CCN) in ruminants
-classic example.
Caused by a deficiency of Vitamin B1 (thiamine) in ruminants in particular -causes liquefactive necrosis in the brain
-an example of polio- (grey matter)-encephelo (brain) malacia (necrosis specifically in the CNS)
29
Q
Caseous Necrosis
A
Caseousnecrosis–‘cheese-likenecrosis’. crumbly
- Gross- white- grey- yellowish in colour, consistency varies according to fluid content, dry & crumbling–> ‘cottage cheese’ consistency: a mixture of coagulation & liquefactive necrosis
- Caused by some specific organisms e.g. mycobacteria
- why is it not the runny pus type?
DIFFERENT CELL TYPE
- these are now macrophages
- if macrophages are the main inflammatory cell then you can begin to understand that specific organisms (i.e. mycobacteria) are the cause (TB)
Know difference between abscess and caseous necrosis
30
Q
Mycobacterium tuberculosis
A
- complete loss of the architecture,
- purplish necrotic material due to random intermixing of the nuclear and cytoplasmic components that stain with haematotoxylin and eosin
- many macrophages recruited to tissue to engulf the organism (rather than release enzymes, so appearance is less liquefied than with neutrophils)
- Macrophages fuse –> MNGCs –>↑ phagocytic capacity
- Except mycobacteria have a ↑ lipid content cell wall which resists digestion & allows replication within the macrophage & evasion of phagolysis (stain with ZN –> red magenta colour)- Colored organisms are mycobacteria, they are very small
- The organisms burst the macrophage and are engulfed by other macrophages
- Main inflammatory cells in the background are macrophages
- may have multinucleate giant cells (MNGCs) which are the individual membranes of macrophages fused together to try and increase their phagocytic capacity
- useless for mycobacterium though as they replicate WITHIN the macrophage. SO that is what they want ! They have evolved to overcome defense by macrophages.
- form large caseous necrotic tissue and then the animal may succumb to disease
- Mammary gland. Thick material = caseous lesions
31
Q
Fat Necrosis
A
Fat necrosis - hard soap-like appearance of affected body fat
- Gross areas of focal opacity, very hard consistency
- When adipocytes die, the fat is broken down into fatty acids. They combine with various salts in the body and we get the actual production of soap –> saponification-fat then becomes quite firm, white, loses previous opaque appearance
- Pathogenesis- adipocytes die –> fat broken down into fatty acids–> combine with Ca2+, Na+ and K+ ions to forms soaps (saponification) –> soaps are foreign to the body –> induce a host inflammatory response do not dissolve out in routine preparation of sections foci –> remain indefinitely and often calcify
- ex: Abnormal mesenteric fat. Problem is that it becomes like a foreign body and induces inflammation. Body tries to remove it
- Enzymatic necrosis- caused by release of pancreatic enzymes (esp lipase) from a damaged pancreas –> adjacent mesenteric fat e.g. pancreatitis-Enzyme release from the pancreas. Pancreas produces lipase. If you release lipase into the abdominal space, all that fat in the mesentery and in the omentum can undergo saponification. Get a real problem that is hard to control
- Traumatic necrosis- in the subcutaneous tissue following trauma to the area
- quite common in the brisket of recumbent animals due to the prolongedpressure on the area - If you damage fat, this happens in larger animals (cattle that are recumbent for a long time). Risk it laying on the chest and putting pressure on that fat in the cranial medial stynum or the thorax.
- Diet-related- associated with diets lacking antioxidants e.g. Vit E (rarely in cats). All fish diets. If fed only this diet, they tend to get subcutaneous fat necrosis
32
Q
Gangrene
A
** Occurs when a tissue has ALREADY died (Ex: frost bite causes tissue to die. If that tissue is not removed, bacteria can inhibit that tissue and there won’t be any blood supply to that area, cant have an inflammatory response- If frost bite is the case, need to try and amputate that region or limb)
Gangrene - mostly a post necrotic change
- Wet Gangrene (life- threatening)- *wet gangrene is more life threatening
- Primary - the agent which initially kills the tissue, further putrefies it. Particularly in dairy cattle (udders)- Over time more bacteria start to grow within that and that whole quarter of the udder will slough off-Gaping wound left that can lead to systemic effects in the animal and can rapidly die. Wet gangrene is life threatening
- Secondary - dead tissue being invaded by organisms which putrefy it
- E.g. Gangrenous mastitis in cow - Staphylococcus aureus
- Dry Gangrene (non-life threatening)- a type of mummification
- Occurs on the extremities (e.g. post septicaemic Salmonellosis in calves)- Post septicemic salmonellosis: damage to extremities causes it to become very desiccated and dried out
- Air passing over the extremity removes the fluid content of the dead
tissue–> leathery appearance
33
Q
Dystrophic Calcification
A
Dystrophic calcification- Other thing that can occur in the necrotic lesions (particularly the caseous type)
- Common in necrosis in cattle and sheep- because they often get caseous necrosis
- When cells die, calcium within the cell (particularly the mitochondria) is released & may bind with other salts in the tissue to form deposits
- Gross- calcium granules can be palpated, when sectioning, the knife grates, usually chalk-white colour.
- Grossly you may be able to feel gritty and crumbly material. If you cut into these lesions, the knife will grate a bit due to calcium in there
- Micro- dark blue colour, shattering of tissue: microtome mark, stains black with Von Kossa stain.
- When you cut through the tissue, once you hit the calcium, it somewhat shatters. Always see fragmented, bits missing. Fractured look in the tissue
- Can use von kossa stain to stain it black (sometimes looks more purple)
34
Q
Surface necrosis can be shed (sloughs)
(Sequelae to Necrosis)
A
- Erosion- Where basement membrane is still intact, just surface layer is lost- epithelium regenerates.
Lose epithelium but basement Membrane is intact
- Ulceration- Basement membrane breached, there is a host inflammatory response - tissue repairs by fibrosis
- Basement membrane is breached and exposure of underlying tissue
- Some larger necrotic areas can become “walled off”. This happens particularly in bone and you get sequestra
- causes chronic pain
- happens often with racehorses?
35
Q
Internal Necrosis repaired or contained by fibrous tissue
(sequelae to necrosis)
A
- Scarring- small foci replaced by fibrous tissue
- e.g. Ascaris suum in pig liver (‘milk spot) caused by migration of larvae in liver causing small areas of fibroses, appears as white foci
- Sequestrum- larger foci are encapsulated by fibrous tissue
- E.g. this may occur within bone due to its poor blood supply
36
Q
Appearance of Necrosis
A
- central zone of necrosis (N)- Central zone
- zone of degeneration (D)- Cells that are on the border, degenerating, not quite dead, but not happy cells either
- zone of inflammation (I)- Quite easy to see, usually darker staining as neutrophils are coming in to that lesion
38
Q
Ichaemia: Blockage of the Lumen
(thrombosis)
A
Thrombosis:
- something that is damaging the endothelium, cells lining the blood vessels sets off this pathway, get platelets, fibrin (blood protein from fibrinogen and the blood converted to fibrin) and it sets off like a “platelet plug”.
- Rather than the skins surface, this is now in the body, in a VESSEL. This is occurring during life in the animal.
- Problem is that it can now narrow the lumen and vessel and pieces can break off. This can happen even in the heart as well as it is lined with epithelium (can get this somewhat clotting within the heart).
- They can break off, launch into the systemic circulation and cause another block somewhere else.
- See this condition quite a lot in cats (Hypertrophic Cardiomyopathy -HCM)
39
Q
Valvular endocarditis
(blockage of the Lumen)- embolism
A
- Bacterial infection (endocarditis- infection of endocardium lining the heart).
- This is on the valves of the heart (in this case atrioventricular valve, tricuspid (thin walled), right side of heart).
- Bits of this endocardium can break off and lodge else where. Will travel in the blood and embolise (from one place in the animal to another) and cause problems elsewhere
40
Q
Thrombosis: Hypertrphic Cardiomyopathy
A
- Essentially a thrombosis forms in the left atrium of the heart and pieces of it can break off and travel in the aorta.
- Classic thing in cats is that the piece of thrombosis that has come from the heart. Cat will usually first present as almost paralyze din its hind legs.
- Vet will feel for a femoral pulse and there wont be any–> will bring you to immediately think there is something wrong vascularely.
- Hind limbs will be cold and lose pain sensation.
- There is a problem with the HEART that may have gone undiagnosed previously. Usually caused by the heart muscle being too big (septum) and what you get rather than normal lamina flow, you get turbulent flow and some flow back into the atrium you get damage from lesions by blood swirling around and will trigger thrombis formation is the left atrium.
- May see acute renal infarcts: If the thrombis doesn’t lodge at the iliac bofication it will lodge in one of the arcuate arteries of the kidney. Branching of the renal artery (arcuate vessels) and you will see the classic shaped infarct in the kidney. That pale portion of kidney has just loss its blood supply due to that artery supplying that portion being infarcted
- Saddle thrombosis: blocking of iliac arteries from the aorta. Will lose total blood supply to the hind legs.
41
Q
Erysipelothrix rhusiopathiae in pigs
A
Erysipelothrix rhusiopathiae
- this bacteria causing “diamond skin disease”
- causes diamond shape lesions in back
- bacteria are blocking those vessels supplying that area of skin
- If you block that area of a blood vessel, you will get necrotic bacteria lying over that
- bacteria traveling in the blood and blocking those areas
42
Q
Ergot (fungus) ingestion
A
Ergot
- ergot is the name of the fungus
- this fungus causes massive vasoconstriction
- causes essentially similar effects to frost bite to hooves, ear tips, etc.
- This toxin is causing massive vasoconstriction
- this fungus grows on wheat and can be found in wheat
44
Q
Coagulative Necrosis caused by an infection
(canine herpesvirus-1 in a neonatal puppy)
A
- Gross appearance of kidney: turkeys egg kidney
- Little areas of coagulative necrosis around cortex
- Virus infects multiple organs (kidneys, lung, liver)
- Importantly!! The gross architecture of the tissues is maintained and histologically you wouldn’t be able to tell anything is wrong in that tissue (if black and white)
- can tell really by colors
