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Healing and Repair - Pathology (view source)
Revision as of 21:17, 13 August 2009
, 21:17, 13 August 2009New page: {{review}} {{toplink |linkpage =General Pathology |linktext =General Pathology |maplink = General Pathology (Content Map) |pagetype =Pathology |sublink1=Inflammation - Pathology |subtext1...
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{{toplink
|linkpage =General Pathology
|linktext =General Pathology
|maplink = General Pathology (Content Map)
|pagetype =Pathology
|sublink1=Inflammation - Pathology
|subtext1=INFLAMMATION
}}
<br>
==Introduction==
* There are several factors on which the ability to heal and repair depends:
*# '''Species'''
*#* The ability of the species to cope with that particular inflammation .
*#* For example, peritonitis.
*#** In cattle, it is often successfully walled off at the initial injury site, preventing spread throughout the whole cavity.
*#** In the horse peritonitis is not walled off, and is generally rapidly fatal.
*# '''Age'''
*#* Repair is generally more successful in younger animals than older animals.
*#* However, in young animals the immune system may still be immature.
*#** For example, Pseudorabies virus is more often fatal in pigs under three weeks old, even in the presence of maternal antibody.
*# '''Tissue and extent of damage'''
*#* Highly specialised tissue rarely repairs successfully apart from in mild injury.
*#** If the functional reserve of the damaged tissue is exceeded, clinical signs of disease related to this insufficiency will occur.
*#* When there is substantial fibrosis in the tissue, the tissue may continue to be progressively destroyed.
*#** This is due the maturation and contraction of fibrous tissue causing further injury to the adjacent normal tissue.
*#** E.g. the [[Liver - Anatomy & Physiology|liver]] in cirrhosis, and the kidney in chronic renal disease.
==Repair==
* Repair occurs through one of two mechanisms:
** '''Regeneration'''
** '''Replacement'''
===Regeneration===
* In mammals, only epithelial and connective tissues regenerate extensively.
* The ability of tissue to regenerate depends upon whether the tissue is
** Labile
** Stable
** Permanent.
====Labile Tissues====
* Labile tissues constantly replenish their cells throughout life.
** For example skin and mucous epithelia normally desquamate their outer layer of cells during life, maintaining their overall composition by division of their basal layers.
* Other examples include [[Bone Marrow - Anatomy & Physiology|bone marrow]] and fat.
* These tissues regenerate well.
** Provided the basement membrane is not breached during the inflammatory process, the epithelium migrates to cover the surface defect.
====Stable Tissues====
* Stable tissues have a limited ability to replace themselves.
* They retain the ability to
** Replace cells that have undergone programmed cell death when the cells age and cannot continue their function.
*** For example, the liver, some endocrine glands and the renal tubular epithelium.
** Respond to greater need for their function in the body.
* Blood vessels and fibroblasts are also stable tissues.
** Have great potential to divide and proliferate.
** Are the important tissue cells in repair by replacement.
====Permanent====
* Permanent tissues have poor or no regenerative capacity.
* This group includes tissues in which the cells are highly specialised and generally have only one function, for example:
** Neuronal cell bodies in the CNS
** The retina of the eye
** The cells responsible for hearing in the ear.
* Axons in the peripheral nervous system can regenerate to a limited extent when severed.
* Cardiac muscle myofibres have very poor regenerative capacity, and undergo repair by
fibrosis or fat replacement.
===Replacement===
* Replacement is essentially endothelial and fibrous tissue proliferation to replace severely damaged tissue.
** This classical dual replacement gives rise to granulation tissue.
==Repair in the Skin==
''Back to [[Integumentary System - Pathology|Integumentary System Pathology]]
* Healing of a wound or surgical incision may be by:
** '''First intention'''
** '''Second intention'''.
===Healing by First Intention===
* Healing by first intention occurs when the incised ends remain in close apposition to each other anf bacterial contamination is minimal.
** This may be induced by suturing.
** For example, a surgical incision.
* Results in minimal scarring.
====Process====
* Initially, the incision ruptures the dermal blood vessels.
** The exuded blood forms a fibrinous clot between and above the incision.
*** The clot functions to:
***# Stem the flow of blood from the injured site.
***# Adhere the two ends together.
***# Prevent infection from entering the injured area.
* The basal layer of epithelium wthin 1mm of the wound edge begins to lose its connections with adjacent basal and overlying epithelium.
** Undergoes mitosis.
** Begins to migrate down both sides of the wound under the clot using pseudopodia.
*** As they are migrating, cells differentiate to some degree to form more superficial layers of the epithelium.
**** Gives a rather thick, if not very strong, barrier of epidermis.
*** In the area of migration, the skin is usually hypopigmented and lacks hair follicles.
* Within 2-4 days, the migrating basal layer of epithelium from either side meet together under the clot.
** It is thought that there is passage of substances, from one side to another that prevents further migration and mitosis.
** This gives reconstituion of an intact barrier to micro-organisms.
* While the epithelial changes are occuring, there is a sudden proliferation of local fibroblasts and accompanying endothelial cells in the dermis surrounding the incision.
** These grow across the narrow divide from each side and link up in the middle.
*** Takes about 12 hours to accomplish.
** In the early stages (days 4-7), their alignment may be vertical, but in later stages (7-21 days) both fibroblasts and capillaries line up horizontally across the incision.
** This dermal repair forms the major portion of strength between the two sides at this time.
*** Gains in strength over a long period of time as the collagen contracts and remodels according to the stresses imposed upon it.
====Factors Inhibiting Healing====
* Factors inhibiting proper wound healing include:
*# '''Protein deficiency'''
*#* May be absolute, as in starvation, or resolute, as in some of the endocrine deficiencies.
*#** E.g. [[Thyroid Gland - Pathology#Hypothyroidism|hypothyroidism]]
*# '''Vitamin C deficiency '''
*#* Vitamin C is essential for fibroplasia and to maintain the integrity of endothelial and epithelial cells.
*# '''Cold'''
*# '''Ageing'''
*# '''Contamination'''
*#* Infection tends not to be a complication as bacteria are generally excluded.
*#** Retained foreign material such as hair portions or suture material inadvertently left in the wound will cause infection and/or a foreign body reaction.
*# '''Movement'''
*#* Gives persistent trauma.
===Healing by Second Intention===
* Healing by second intention occurs when the gap between the ends of the incision is too wide to allow close approximation of the ends.
* This process of granulation tissue repair in a large wound is also the underlying process in the repair of:
** Infarcts and thrombi in vessels.
** Surface ulcers and diphtheresis.
** Pyogenic membrane in abscesses.
** Diffuse fibrosis ( cirrhosis ) in the [[Liver - Anatomy & Physiology|liver]].
====Process====
* In comparison to healing by first intention, there is a more massive fibroblastic and endothelial proliferation in the wound which fills and repairs the defect.
* There is also considerable surface exudation.
** The exudate is composed of fibrinous fluid and numerous inflammatory cells, mainly neutrophils and macrophages.
*** The cells are scavengers, and engulf necrotic debris and any bacteria present
*** Macrophages and their secretions are also important for the promotion of fibroplasia.
* The fibroblasts tend to align themselves roughly horizontal to the surface, but the endothelium is perpendicular to the surface.
** The upper vessels form loops near to the surface.
*** Gives the gross appearance of red granules - this is [[Chronic Inflammation - Pathology#Granulation Tissue|granulation tissue]].
* Well-formed granulation tissue tends to be fairly resistant to surface infection; however, it is rather delicated and so susceptible to trauma and subsequent introduction of infection.
** Infection is therefore a common complication in the early stages of healing.
* Once the gap has been filled with granulation tissue and is free of infection, the epithelium migrates across.
** As it migrates, the epithelium secretes collagenolytic substances.
* The epidermis is usually hypopigmented and lacks hair follicles unless they have survived in the granulation tissue.
==== Factors Inhibiting Healing====
* Several factors inhibit healing by second intention.
*# '''Movement'''
*#* Movement before sufficient strength has been attained in the bond between the edges can inhibit healing.
*# '''Infections'''
*# '''Corticosteroids'''
*#* Prevent proper collagen matrix formation.
*#* Inhibit leukocyte emigration and phagocytosis.[[Image:scar tissue.jpg|thumb|right|150px|Scar tissue (Courtesy of BioMed Archive)]]
*#* Diminish any acute inflammatory response by generally stabilising cellular membranes.
====Scarring====
* As the fibroblasts mature into fibrocytes, the collagen also matures and contracts and there may be extensive scar formation.
** There may be considerable depression of the surface in such a scar.
** The scar may interfere with movement in the area.
* The scar tends to diminish in size over a long period of time, as the underlying collagen remodels according to the stresses imposed upon the area.
==Repair in the Bones==
===Causes of Fracture===
* The causes of fracture fit into two distinct categories:
*# '''Fracture of trauma'''
*#* Breakage of normal healthy bone due to excessive stress pressure of short duration.
*# '''Pathological fracture'''
*#* Breakage of bone weakened by some underlying metabolic, inflammatory or neoplastic condition.
===Description of a Fracture===
* There are various terms to describe a fracture's appearance.
* Separation of the ends of the fracture may be '''complete''' or '''incomplete'''.
* When there is no penetration of the overlying skin, a the fracture is described as '''closed'''.
* When the sharp ends penetrate the overlying skin, the fracture is '''compound'''.
** In this scenario there is the danger of introducing infection.
*'''Comminuted''' describes a fracture where there are multiple small fragments of bone at the site of breakage.
* Where the edges of the fracture are impacted into each other, the fracture is said to be '''compressed'''.
* When one side of the fracture is depressed below the plane of the other, the term '''depressed''' is used.
** This occurs in the flat bones of the skull.
* '''Microfractures''' are fractures that are only visible on histological section as cracks in the bone.
** Grossly, there might be evidence of some haemorrhage in the area.
===Fracture Repair===
[[Image:fracture repair.jpg|thumb|right|150px|Fracture repair (Courtesy of BioMed Archive)]]
* On breakage, there is rupture of the periosteal, cortical and medullary vessels, causing:
** A blood clot in the breakage area.
*** Fibrin is the important component.
** Local necrosis of tissue supplied by these vessels.
*** This lowers the local pH.
* The fate of the blood clot depends upon its location.
** The periosteal portion is lysed and disappears;
** The medullary portion is removed by macrophages.
* The necrotic material is removed by phagocytosis.
** Necrotic [[Bone Marrow - Anatomy & Physiology|bone marrow]] is removed by [[Macrophages - WikiBlood|macrophages]].
*** This is a fairly rapid process.
** Osteoclasts remove necrotic bone.
*** This is a slow process.
* On the periosteal side, the periosteum proliferates into the clot.
** Forms a fibrous collar around the bone called the soft callus.
* The cells in the inner aspect of the soft callus, particularly those near the fracture fragments, differentiate into osteoblasts. [[Image:fracture callus.jpg|thumb|right|150px|Fracture callus (Courtesy of BioMed Archive)]]
** Grow across the divide between the two fragments, laying down coarse woven bone.
* The woven bone laid is known as the hard callus.
** This periosteal coarse bone is of utmost importance in repair.
*** It is responsible for much of the strength of the fracture repair.
** This is replaced over a period of time by mature compact bone.
*** Aligns itself according to the stresses applied to it.
* Periosteal cells that are further away from the fracture fragments differentiate into cartilage-producing cells.
** Produce a cone of cartilage between the two fragments.
*** As the local pH changes to more alkaline conditions, this cartilage undergoes calcification, with invasion by blood vessels and osteoblasts.
**** The cartilage is replaced by bone - endochondral ossification.
* On the medullary side, the endosteum proliferates and invades the clot, laying down bone.
** This bone may totally occlude the medulla and is later remodelled to reconstitute a patent lumen.
===Complications===
* There are several possible complications that may arise in the repair of bone.
# Inadequate immobilisation of the fractured ends will lead to incomplete repair by callus formation.
#* An intervening mass of fibrocartilage remains, forming a false joint.
#** In some cases the false joint can even appear to form a synovial lining.
#* If the fractured ends are sufficiently far apart, no substantial callus forms.
#** The intervening space is taken up by connective tissue organisation.
# Failure to align the fractured ends in proper apposition to one another will produce excessive callus.
#* This takes a longer time to be remodelled by the adult compact bone.
# [[Healing and Repair - Pathology#Description of a Fracture|Comminution]] delays healing due to persistent irritation.
# Infection delays healing due to the effects of the toxins on theproliferating cells.
#* May give rise to a systemic infection affecting the rest of the body.
==Repair in the Respiratory Tract==
* Severe damage to the alveolar wall results in fibrous tissue organisation of the entire alveolus.
* The appearance of inflammation in the respiratory tract varies with the route of entry of the agent.
===Airborne Agents===
* Infectious droplets tend to deposit in the anterior ventral portions of the lobes.
** I.e. in the apical, cardiac and anterior portions of the diaphragmatic lobes.
* Airborne agents produce '''bronchopneumonia'''.
** So-called because the inflammation is initiated and centred upon the airways.
* The usual appearance of bronchopneumonia in ruminants and the pig is as the name suggests.
** These species have a well developed interstitial septum between groups of lobules, and little or no connection between alveoli from different terminal bronchioles.
*** Therefore, one lobule may show extensive pneumonic changes while the adjacent lobule is free from inflammation.
** The inflammatory exudate commonly gets stuck in the lower airways.
*** Invokes an inflammatory response in the smooth muscle of the wall of the airway.
**** The wall is weakened, causing it to dilate somewhat.
*** Air trapped distal to the blockage is gradually absorbed into the bloodstream.
**** This causes increased pressure on the injured wall, dilating it further.
*** This is a progressive process and results in irreversible dilatation of the airway lumen and is called '''bronchiectasis'''.
* Bronchopneumonia in the dog and cat often tends to be more diffusely spread.
** These species have a poorly-developed interlobular septum and collateral ventilation between alveoli from different respiratory units.
** Resolution of bronchopneumonia in the dog and cat is often more or less complete.
===Blood-borne Agents===
* Blood-bourne agents tend to have a patchy distribution throughout the lung.
* Cause '''interstitial pneumonia'''.
====Circulating Toxins====
* For example, "Fog Fever" in adult cattle.
** Interstitial emphysema.
** 3-methyl indole is selectively toxic to Type 1 alveolar epithelium.
*** Derived from excess tryptophan in autumn grass.
====Micro-organisms====
* A predominantly mononuclear reaction in the alveolar wall can be caused by:
** Viruses
*** E.g. [[Paramyxoviridae#Canine Distemper Virus (CDV)|Canine Distemper]]
** Bacteria
*** E.g. [[Salmonella|''Salmonella'']]
** Protozoa
*** E.g. [[Tissue cyst-forming coccidia|Toxoplasma]]
====Parasites====
* Lungworms (''Dictyocaulus vivipara'') tend to affect the dorsocaudal areas of the diaphragmatic lobes in their invasion stage as larvae in the blood.
* Later adult stages irritate the airways and also release larvae which are inhaled deeper into the lung.
* In natural outbreaks, both types of lesions are seen.
** May be complicated by bacterial infection.
===Traumatic Implantation===
* Traumatic implantation is fairly rare.
* Initially causes a pleural inflammation, with some extension to the adjacent lung tissue.
* For example:
** Stake wounds in horses.
*** Usually fatal and cause extensive purulent, smelly inflammation.
** Purulent pleuritis in dogs and cats due to [[Actinomycetes|''Nocardia'']] from a distant wound.
*** Not uncommon in cats.
*** May take some time to develop fully after the initial wound or cause has healed.
*** Generally fatal.
*** Clinical signs only developing when the lesions have become very extensive.
==Repair in the Alimentary Tract==
===The Gut===
* The gut is quite prone to infections.
** These are generally kept at bay by the profuse gut associated lymphoid tissue and the continuous movement of ingesta.
* In mild infections, the inflammation is usually catarrhal.
** Particularly in the [[Large Intestine - Anatomy & Physiology|large intestine]] where there are numerous goblet cells.
** There is rapid repair by mucosal epithelium.
* More severe infections may damage the structure of the mucosa.
** The villi may be stunted following repair.
*** There is a reduced water absorption compounded by loss of electrolytes - '''malabsorption'''.
**** Results in diarrhoea and progressive loss of weight.
**** E.g. in [[Intestines Proliferative Enteritis - Pathology#Paratuberculosis (Johnes disease)|Johne's Disease]].
===The Liver===
* The [[Liver - Anatomy & Physiology|liver]] retains limited powers to regenerate and has considerable functional reserve.
* Acute inflammation is often due to viruses and bacteria.
** E.g. Infectious Canine Hepatitis and [[Intestines Fibrinous/Haemorrhagic Enteritis - Pathology#Salmonellosis|Salmonellosis]] in young livestock.
** The [[Liver - Anatomy & Physiology|liver]] is swollen and may display hyperaemia.
** Small pinpoint foci of necrosis may be seen through the surface.
* '''Chronic [[Liver - Anatomy & Physiology|liver]] damage results in fibrosis - cirrhosis'''.
** Generally the sequel to ingestion of a toxic substance over a long period of time.
** E.g Aspergillosis.
*** Grossly, the [[Liver - Anatomy & Physiology|liver]] shows varying fibrosis imparting a pale or greyish colour.
*** In some cases, there may be attempts at nodular regeneration of the hepatic parenchyma.
** Ragwort poisoning has a fairly similar appearance.
*** The insidious deposition of fibrous tissue eventually becomes self-perpetuating, causing further damage to remaining hepatocytes as it matures and contracts.
*** Eventually neural signs referable to loss of hepatic detoxifying function occur.
===The [[Pancreas - Anatomy & Physiology|Pancreas]]===
* The [[Pancreas - Anatomy & Physiology|pancreas]] suffers both acute and chronic disease.
* The acute form called acute pancreatic necrosis is the important type in dogs.
** The aetiology is obscure.
** The mechanism involves the release of pancreatic enzymes into the surrounding fatty connective tissue.
** Commonly affects obese females.
** Animals may either die soon after the initial painful episode, or the inflammation smoulders on, often without clinical signs, until there is little pancreatic tissue left.
** [[DM|Diabetes mellitus]] or pancreatic insufficiency are common sequelae.
* Chronic pancreatitis is seen in the cat.
** A slow disease often associated with inflammation of both the pancreatic and biliary ducts. *** Fuse before entering the [[Duodenum - Anatomy & Physiology|duodenum]] in cats.
** Grossly, there is reduction in size and sometimes quite extensive periductal fibrosis and inflammation.
==Repair in the Urinary Tract==
* The kidney has a great functional reserve.
** Only 30% of the tissue is required to function properly.
===Glomerulonephritis===
* Glomerulonephritis and glomerular deposition of amyloid may cause loss of substantial quantities of protein into the urine.
* Oedema develops in the body, generally first in the back legs, then the ventral subcutis, and perhaps in the abdominal cavity.
** This is called the Nephrotic Syndrome
* Inflammation can arise in the glomeruli, interstitial tissue and in the renal pelvis.
** In the later stages of chronic inflammation, it may be difficult to determine the initial site of the inflammation.
* In severe chronic inflammation, substantial fibrosis of repair can become self-perpetuating.
** Produces more and more damage until the whole kidney appears shrunken and distorted .
*** Called "end stage".
* Signs of uraemia develop once the functional reserve has been exceeded.
** There are also characteristic (though inconsistent) lesions present in other tissues, i.e. the remote effects.
*** Inflammation of the tongue and stomach
*** Atrial endocarditis
*** Parathyroid hyperplasia
*** Widespread calcium deposition
**** Grossly noticeable intercostal muscles from the pleural aspect.
*** Anaemia
*** Hypertrophy of the left ventricle of the heart
*** Facial loss of bone
===Pyelonephritis===
* Important in the cow and sow.
** It tends to be quite acute in the sow, and chronic in the cow.
* Arises from infection ascending the urinary tract.
* There is progressive loss of tissue.
** Starts with necrosis in the pelvic area, then the inflammation spreads up into the cortex. *P oor prognosis even with therapy.
===Cystitis===
* Bladder inflammation.
* Common in females.
* A feature of inflammation in the bladder is the considerable dilation of the submucosal vessels - vascular ectasia.
** Bracken fern poisoning initially causes vascular ectasia and inflammation, but can progress
to tumour formation in the bladder.
==Repair in the Genital Tract==
===Female===
* '''Inflammation of the uterus''' in livestock can take place at two periods:
*# At service.
*#* Mild.
*#* An '''endometritis'''.
*# At parturition.
*#* Can be very severe and life threatening.
*#* Particularly occurs in assisted parturition.
*#* Causes a '''metritis''', involving the whole wall.
* '''Pyometra'''
** Pus in the uterus.
** Occurs commonly in bitches.
** Is life threatening
* '''Mastitis'''
** Inflammation of the mammary gland.
** There are several forms of mastitis.
**# Life threatening mastitis.
**#* Occurs shortly after parturition.
**#* E.g. gangrenous mastitis due to [[Staphylococcus spp.#Staphylococcus aureus|''Staphylococcus aureus'']], and Coliform mastitis.
**# Chronic mastitis.
**#* Results in progressive destruction of the glandular tissue and replacement by fibrous tissue.
**#* E.g. [[Streptococci|''Streptococcus agalactiae'']].
** Some organisms such as [[Staphylococcus spp.#Staphylococcus aureus|''Staphylococcus aureus'']] can cause gangrenous, acute and chronic mastitis.
===Male===
* '''Prostatitis'''
** Inflammation of the prostate.
** Common in dogs.
** Causes a bag of pus in the tissue.
** Results from an ascending infection of the tract.
* '''Orchitis'''
** Inflammation of the testis.
** Rather uncommon.
** In bulls, a granulomatous inflammation occurs with [[Brucella species|''Brucella abortus'']].
==Repair in the Central Nervous System==
* '''Encephalitis'''
** Inflammation of neural tissue of the brain.
** Repairs by the proliferation of astrocytes.
*** Astrocytes are the brain's form of fibrous tissue.
*** Called '''gliosis'''.
* Perivascular lymphocytic cuffing accompanies neural damage in the brain parenchyma.
* '''Meningitis'''
** Inflammation of the meninges.
** Purulent meningitis follows haematogenous spread of infection from umbilical infections and certain septicaemias.
{{toplink
|linkpage =General Pathology
|linktext =General Pathology
|maplink = General Pathology (Content Map)
|pagetype =Pathology
|sublink1=Inflammation - Pathology
|subtext1=INFLAMMATION
}}
<br>
==Introduction==
* There are several factors on which the ability to heal and repair depends:
*# '''Species'''
*#* The ability of the species to cope with that particular inflammation .
*#* For example, peritonitis.
*#** In cattle, it is often successfully walled off at the initial injury site, preventing spread throughout the whole cavity.
*#** In the horse peritonitis is not walled off, and is generally rapidly fatal.
*# '''Age'''
*#* Repair is generally more successful in younger animals than older animals.
*#* However, in young animals the immune system may still be immature.
*#** For example, Pseudorabies virus is more often fatal in pigs under three weeks old, even in the presence of maternal antibody.
*# '''Tissue and extent of damage'''
*#* Highly specialised tissue rarely repairs successfully apart from in mild injury.
*#** If the functional reserve of the damaged tissue is exceeded, clinical signs of disease related to this insufficiency will occur.
*#* When there is substantial fibrosis in the tissue, the tissue may continue to be progressively destroyed.
*#** This is due the maturation and contraction of fibrous tissue causing further injury to the adjacent normal tissue.
*#** E.g. the [[Liver - Anatomy & Physiology|liver]] in cirrhosis, and the kidney in chronic renal disease.
==Repair==
* Repair occurs through one of two mechanisms:
** '''Regeneration'''
** '''Replacement'''
===Regeneration===
* In mammals, only epithelial and connective tissues regenerate extensively.
* The ability of tissue to regenerate depends upon whether the tissue is
** Labile
** Stable
** Permanent.
====Labile Tissues====
* Labile tissues constantly replenish their cells throughout life.
** For example skin and mucous epithelia normally desquamate their outer layer of cells during life, maintaining their overall composition by division of their basal layers.
* Other examples include [[Bone Marrow - Anatomy & Physiology|bone marrow]] and fat.
* These tissues regenerate well.
** Provided the basement membrane is not breached during the inflammatory process, the epithelium migrates to cover the surface defect.
====Stable Tissues====
* Stable tissues have a limited ability to replace themselves.
* They retain the ability to
** Replace cells that have undergone programmed cell death when the cells age and cannot continue their function.
*** For example, the liver, some endocrine glands and the renal tubular epithelium.
** Respond to greater need for their function in the body.
* Blood vessels and fibroblasts are also stable tissues.
** Have great potential to divide and proliferate.
** Are the important tissue cells in repair by replacement.
====Permanent====
* Permanent tissues have poor or no regenerative capacity.
* This group includes tissues in which the cells are highly specialised and generally have only one function, for example:
** Neuronal cell bodies in the CNS
** The retina of the eye
** The cells responsible for hearing in the ear.
* Axons in the peripheral nervous system can regenerate to a limited extent when severed.
* Cardiac muscle myofibres have very poor regenerative capacity, and undergo repair by
fibrosis or fat replacement.
===Replacement===
* Replacement is essentially endothelial and fibrous tissue proliferation to replace severely damaged tissue.
** This classical dual replacement gives rise to granulation tissue.
==Repair in the Skin==
''Back to [[Integumentary System - Pathology|Integumentary System Pathology]]
* Healing of a wound or surgical incision may be by:
** '''First intention'''
** '''Second intention'''.
===Healing by First Intention===
* Healing by first intention occurs when the incised ends remain in close apposition to each other anf bacterial contamination is minimal.
** This may be induced by suturing.
** For example, a surgical incision.
* Results in minimal scarring.
====Process====
* Initially, the incision ruptures the dermal blood vessels.
** The exuded blood forms a fibrinous clot between and above the incision.
*** The clot functions to:
***# Stem the flow of blood from the injured site.
***# Adhere the two ends together.
***# Prevent infection from entering the injured area.
* The basal layer of epithelium wthin 1mm of the wound edge begins to lose its connections with adjacent basal and overlying epithelium.
** Undergoes mitosis.
** Begins to migrate down both sides of the wound under the clot using pseudopodia.
*** As they are migrating, cells differentiate to some degree to form more superficial layers of the epithelium.
**** Gives a rather thick, if not very strong, barrier of epidermis.
*** In the area of migration, the skin is usually hypopigmented and lacks hair follicles.
* Within 2-4 days, the migrating basal layer of epithelium from either side meet together under the clot.
** It is thought that there is passage of substances, from one side to another that prevents further migration and mitosis.
** This gives reconstituion of an intact barrier to micro-organisms.
* While the epithelial changes are occuring, there is a sudden proliferation of local fibroblasts and accompanying endothelial cells in the dermis surrounding the incision.
** These grow across the narrow divide from each side and link up in the middle.
*** Takes about 12 hours to accomplish.
** In the early stages (days 4-7), their alignment may be vertical, but in later stages (7-21 days) both fibroblasts and capillaries line up horizontally across the incision.
** This dermal repair forms the major portion of strength between the two sides at this time.
*** Gains in strength over a long period of time as the collagen contracts and remodels according to the stresses imposed upon it.
====Factors Inhibiting Healing====
* Factors inhibiting proper wound healing include:
*# '''Protein deficiency'''
*#* May be absolute, as in starvation, or resolute, as in some of the endocrine deficiencies.
*#** E.g. [[Thyroid Gland - Pathology#Hypothyroidism|hypothyroidism]]
*# '''Vitamin C deficiency '''
*#* Vitamin C is essential for fibroplasia and to maintain the integrity of endothelial and epithelial cells.
*# '''Cold'''
*# '''Ageing'''
*# '''Contamination'''
*#* Infection tends not to be a complication as bacteria are generally excluded.
*#** Retained foreign material such as hair portions or suture material inadvertently left in the wound will cause infection and/or a foreign body reaction.
*# '''Movement'''
*#* Gives persistent trauma.
===Healing by Second Intention===
* Healing by second intention occurs when the gap between the ends of the incision is too wide to allow close approximation of the ends.
* This process of granulation tissue repair in a large wound is also the underlying process in the repair of:
** Infarcts and thrombi in vessels.
** Surface ulcers and diphtheresis.
** Pyogenic membrane in abscesses.
** Diffuse fibrosis ( cirrhosis ) in the [[Liver - Anatomy & Physiology|liver]].
====Process====
* In comparison to healing by first intention, there is a more massive fibroblastic and endothelial proliferation in the wound which fills and repairs the defect.
* There is also considerable surface exudation.
** The exudate is composed of fibrinous fluid and numerous inflammatory cells, mainly neutrophils and macrophages.
*** The cells are scavengers, and engulf necrotic debris and any bacteria present
*** Macrophages and their secretions are also important for the promotion of fibroplasia.
* The fibroblasts tend to align themselves roughly horizontal to the surface, but the endothelium is perpendicular to the surface.
** The upper vessels form loops near to the surface.
*** Gives the gross appearance of red granules - this is [[Chronic Inflammation - Pathology#Granulation Tissue|granulation tissue]].
* Well-formed granulation tissue tends to be fairly resistant to surface infection; however, it is rather delicated and so susceptible to trauma and subsequent introduction of infection.
** Infection is therefore a common complication in the early stages of healing.
* Once the gap has been filled with granulation tissue and is free of infection, the epithelium migrates across.
** As it migrates, the epithelium secretes collagenolytic substances.
* The epidermis is usually hypopigmented and lacks hair follicles unless they have survived in the granulation tissue.
==== Factors Inhibiting Healing====
* Several factors inhibit healing by second intention.
*# '''Movement'''
*#* Movement before sufficient strength has been attained in the bond between the edges can inhibit healing.
*# '''Infections'''
*# '''Corticosteroids'''
*#* Prevent proper collagen matrix formation.
*#* Inhibit leukocyte emigration and phagocytosis.[[Image:scar tissue.jpg|thumb|right|150px|Scar tissue (Courtesy of BioMed Archive)]]
*#* Diminish any acute inflammatory response by generally stabilising cellular membranes.
====Scarring====
* As the fibroblasts mature into fibrocytes, the collagen also matures and contracts and there may be extensive scar formation.
** There may be considerable depression of the surface in such a scar.
** The scar may interfere with movement in the area.
* The scar tends to diminish in size over a long period of time, as the underlying collagen remodels according to the stresses imposed upon the area.
==Repair in the Bones==
===Causes of Fracture===
* The causes of fracture fit into two distinct categories:
*# '''Fracture of trauma'''
*#* Breakage of normal healthy bone due to excessive stress pressure of short duration.
*# '''Pathological fracture'''
*#* Breakage of bone weakened by some underlying metabolic, inflammatory or neoplastic condition.
===Description of a Fracture===
* There are various terms to describe a fracture's appearance.
* Separation of the ends of the fracture may be '''complete''' or '''incomplete'''.
* When there is no penetration of the overlying skin, a the fracture is described as '''closed'''.
* When the sharp ends penetrate the overlying skin, the fracture is '''compound'''.
** In this scenario there is the danger of introducing infection.
*'''Comminuted''' describes a fracture where there are multiple small fragments of bone at the site of breakage.
* Where the edges of the fracture are impacted into each other, the fracture is said to be '''compressed'''.
* When one side of the fracture is depressed below the plane of the other, the term '''depressed''' is used.
** This occurs in the flat bones of the skull.
* '''Microfractures''' are fractures that are only visible on histological section as cracks in the bone.
** Grossly, there might be evidence of some haemorrhage in the area.
===Fracture Repair===
[[Image:fracture repair.jpg|thumb|right|150px|Fracture repair (Courtesy of BioMed Archive)]]
* On breakage, there is rupture of the periosteal, cortical and medullary vessels, causing:
** A blood clot in the breakage area.
*** Fibrin is the important component.
** Local necrosis of tissue supplied by these vessels.
*** This lowers the local pH.
* The fate of the blood clot depends upon its location.
** The periosteal portion is lysed and disappears;
** The medullary portion is removed by macrophages.
* The necrotic material is removed by phagocytosis.
** Necrotic [[Bone Marrow - Anatomy & Physiology|bone marrow]] is removed by [[Macrophages - WikiBlood|macrophages]].
*** This is a fairly rapid process.
** Osteoclasts remove necrotic bone.
*** This is a slow process.
* On the periosteal side, the periosteum proliferates into the clot.
** Forms a fibrous collar around the bone called the soft callus.
* The cells in the inner aspect of the soft callus, particularly those near the fracture fragments, differentiate into osteoblasts. [[Image:fracture callus.jpg|thumb|right|150px|Fracture callus (Courtesy of BioMed Archive)]]
** Grow across the divide between the two fragments, laying down coarse woven bone.
* The woven bone laid is known as the hard callus.
** This periosteal coarse bone is of utmost importance in repair.
*** It is responsible for much of the strength of the fracture repair.
** This is replaced over a period of time by mature compact bone.
*** Aligns itself according to the stresses applied to it.
* Periosteal cells that are further away from the fracture fragments differentiate into cartilage-producing cells.
** Produce a cone of cartilage between the two fragments.
*** As the local pH changes to more alkaline conditions, this cartilage undergoes calcification, with invasion by blood vessels and osteoblasts.
**** The cartilage is replaced by bone - endochondral ossification.
* On the medullary side, the endosteum proliferates and invades the clot, laying down bone.
** This bone may totally occlude the medulla and is later remodelled to reconstitute a patent lumen.
===Complications===
* There are several possible complications that may arise in the repair of bone.
# Inadequate immobilisation of the fractured ends will lead to incomplete repair by callus formation.
#* An intervening mass of fibrocartilage remains, forming a false joint.
#** In some cases the false joint can even appear to form a synovial lining.
#* If the fractured ends are sufficiently far apart, no substantial callus forms.
#** The intervening space is taken up by connective tissue organisation.
# Failure to align the fractured ends in proper apposition to one another will produce excessive callus.
#* This takes a longer time to be remodelled by the adult compact bone.
# [[Healing and Repair - Pathology#Description of a Fracture|Comminution]] delays healing due to persistent irritation.
# Infection delays healing due to the effects of the toxins on theproliferating cells.
#* May give rise to a systemic infection affecting the rest of the body.
==Repair in the Respiratory Tract==
* Severe damage to the alveolar wall results in fibrous tissue organisation of the entire alveolus.
* The appearance of inflammation in the respiratory tract varies with the route of entry of the agent.
===Airborne Agents===
* Infectious droplets tend to deposit in the anterior ventral portions of the lobes.
** I.e. in the apical, cardiac and anterior portions of the diaphragmatic lobes.
* Airborne agents produce '''bronchopneumonia'''.
** So-called because the inflammation is initiated and centred upon the airways.
* The usual appearance of bronchopneumonia in ruminants and the pig is as the name suggests.
** These species have a well developed interstitial septum between groups of lobules, and little or no connection between alveoli from different terminal bronchioles.
*** Therefore, one lobule may show extensive pneumonic changes while the adjacent lobule is free from inflammation.
** The inflammatory exudate commonly gets stuck in the lower airways.
*** Invokes an inflammatory response in the smooth muscle of the wall of the airway.
**** The wall is weakened, causing it to dilate somewhat.
*** Air trapped distal to the blockage is gradually absorbed into the bloodstream.
**** This causes increased pressure on the injured wall, dilating it further.
*** This is a progressive process and results in irreversible dilatation of the airway lumen and is called '''bronchiectasis'''.
* Bronchopneumonia in the dog and cat often tends to be more diffusely spread.
** These species have a poorly-developed interlobular septum and collateral ventilation between alveoli from different respiratory units.
** Resolution of bronchopneumonia in the dog and cat is often more or less complete.
===Blood-borne Agents===
* Blood-bourne agents tend to have a patchy distribution throughout the lung.
* Cause '''interstitial pneumonia'''.
====Circulating Toxins====
* For example, "Fog Fever" in adult cattle.
** Interstitial emphysema.
** 3-methyl indole is selectively toxic to Type 1 alveolar epithelium.
*** Derived from excess tryptophan in autumn grass.
====Micro-organisms====
* A predominantly mononuclear reaction in the alveolar wall can be caused by:
** Viruses
*** E.g. [[Paramyxoviridae#Canine Distemper Virus (CDV)|Canine Distemper]]
** Bacteria
*** E.g. [[Salmonella|''Salmonella'']]
** Protozoa
*** E.g. [[Tissue cyst-forming coccidia|Toxoplasma]]
====Parasites====
* Lungworms (''Dictyocaulus vivipara'') tend to affect the dorsocaudal areas of the diaphragmatic lobes in their invasion stage as larvae in the blood.
* Later adult stages irritate the airways and also release larvae which are inhaled deeper into the lung.
* In natural outbreaks, both types of lesions are seen.
** May be complicated by bacterial infection.
===Traumatic Implantation===
* Traumatic implantation is fairly rare.
* Initially causes a pleural inflammation, with some extension to the adjacent lung tissue.
* For example:
** Stake wounds in horses.
*** Usually fatal and cause extensive purulent, smelly inflammation.
** Purulent pleuritis in dogs and cats due to [[Actinomycetes|''Nocardia'']] from a distant wound.
*** Not uncommon in cats.
*** May take some time to develop fully after the initial wound or cause has healed.
*** Generally fatal.
*** Clinical signs only developing when the lesions have become very extensive.
==Repair in the Alimentary Tract==
===The Gut===
* The gut is quite prone to infections.
** These are generally kept at bay by the profuse gut associated lymphoid tissue and the continuous movement of ingesta.
* In mild infections, the inflammation is usually catarrhal.
** Particularly in the [[Large Intestine - Anatomy & Physiology|large intestine]] where there are numerous goblet cells.
** There is rapid repair by mucosal epithelium.
* More severe infections may damage the structure of the mucosa.
** The villi may be stunted following repair.
*** There is a reduced water absorption compounded by loss of electrolytes - '''malabsorption'''.
**** Results in diarrhoea and progressive loss of weight.
**** E.g. in [[Intestines Proliferative Enteritis - Pathology#Paratuberculosis (Johnes disease)|Johne's Disease]].
===The Liver===
* The [[Liver - Anatomy & Physiology|liver]] retains limited powers to regenerate and has considerable functional reserve.
* Acute inflammation is often due to viruses and bacteria.
** E.g. Infectious Canine Hepatitis and [[Intestines Fibrinous/Haemorrhagic Enteritis - Pathology#Salmonellosis|Salmonellosis]] in young livestock.
** The [[Liver - Anatomy & Physiology|liver]] is swollen and may display hyperaemia.
** Small pinpoint foci of necrosis may be seen through the surface.
* '''Chronic [[Liver - Anatomy & Physiology|liver]] damage results in fibrosis - cirrhosis'''.
** Generally the sequel to ingestion of a toxic substance over a long period of time.
** E.g Aspergillosis.
*** Grossly, the [[Liver - Anatomy & Physiology|liver]] shows varying fibrosis imparting a pale or greyish colour.
*** In some cases, there may be attempts at nodular regeneration of the hepatic parenchyma.
** Ragwort poisoning has a fairly similar appearance.
*** The insidious deposition of fibrous tissue eventually becomes self-perpetuating, causing further damage to remaining hepatocytes as it matures and contracts.
*** Eventually neural signs referable to loss of hepatic detoxifying function occur.
===The [[Pancreas - Anatomy & Physiology|Pancreas]]===
* The [[Pancreas - Anatomy & Physiology|pancreas]] suffers both acute and chronic disease.
* The acute form called acute pancreatic necrosis is the important type in dogs.
** The aetiology is obscure.
** The mechanism involves the release of pancreatic enzymes into the surrounding fatty connective tissue.
** Commonly affects obese females.
** Animals may either die soon after the initial painful episode, or the inflammation smoulders on, often without clinical signs, until there is little pancreatic tissue left.
** [[DM|Diabetes mellitus]] or pancreatic insufficiency are common sequelae.
* Chronic pancreatitis is seen in the cat.
** A slow disease often associated with inflammation of both the pancreatic and biliary ducts. *** Fuse before entering the [[Duodenum - Anatomy & Physiology|duodenum]] in cats.
** Grossly, there is reduction in size and sometimes quite extensive periductal fibrosis and inflammation.
==Repair in the Urinary Tract==
* The kidney has a great functional reserve.
** Only 30% of the tissue is required to function properly.
===Glomerulonephritis===
* Glomerulonephritis and glomerular deposition of amyloid may cause loss of substantial quantities of protein into the urine.
* Oedema develops in the body, generally first in the back legs, then the ventral subcutis, and perhaps in the abdominal cavity.
** This is called the Nephrotic Syndrome
* Inflammation can arise in the glomeruli, interstitial tissue and in the renal pelvis.
** In the later stages of chronic inflammation, it may be difficult to determine the initial site of the inflammation.
* In severe chronic inflammation, substantial fibrosis of repair can become self-perpetuating.
** Produces more and more damage until the whole kidney appears shrunken and distorted .
*** Called "end stage".
* Signs of uraemia develop once the functional reserve has been exceeded.
** There are also characteristic (though inconsistent) lesions present in other tissues, i.e. the remote effects.
*** Inflammation of the tongue and stomach
*** Atrial endocarditis
*** Parathyroid hyperplasia
*** Widespread calcium deposition
**** Grossly noticeable intercostal muscles from the pleural aspect.
*** Anaemia
*** Hypertrophy of the left ventricle of the heart
*** Facial loss of bone
===Pyelonephritis===
* Important in the cow and sow.
** It tends to be quite acute in the sow, and chronic in the cow.
* Arises from infection ascending the urinary tract.
* There is progressive loss of tissue.
** Starts with necrosis in the pelvic area, then the inflammation spreads up into the cortex. *P oor prognosis even with therapy.
===Cystitis===
* Bladder inflammation.
* Common in females.
* A feature of inflammation in the bladder is the considerable dilation of the submucosal vessels - vascular ectasia.
** Bracken fern poisoning initially causes vascular ectasia and inflammation, but can progress
to tumour formation in the bladder.
==Repair in the Genital Tract==
===Female===
* '''Inflammation of the uterus''' in livestock can take place at two periods:
*# At service.
*#* Mild.
*#* An '''endometritis'''.
*# At parturition.
*#* Can be very severe and life threatening.
*#* Particularly occurs in assisted parturition.
*#* Causes a '''metritis''', involving the whole wall.
* '''Pyometra'''
** Pus in the uterus.
** Occurs commonly in bitches.
** Is life threatening
* '''Mastitis'''
** Inflammation of the mammary gland.
** There are several forms of mastitis.
**# Life threatening mastitis.
**#* Occurs shortly after parturition.
**#* E.g. gangrenous mastitis due to [[Staphylococcus spp.#Staphylococcus aureus|''Staphylococcus aureus'']], and Coliform mastitis.
**# Chronic mastitis.
**#* Results in progressive destruction of the glandular tissue and replacement by fibrous tissue.
**#* E.g. [[Streptococci|''Streptococcus agalactiae'']].
** Some organisms such as [[Staphylococcus spp.#Staphylococcus aureus|''Staphylococcus aureus'']] can cause gangrenous, acute and chronic mastitis.
===Male===
* '''Prostatitis'''
** Inflammation of the prostate.
** Common in dogs.
** Causes a bag of pus in the tissue.
** Results from an ascending infection of the tract.
* '''Orchitis'''
** Inflammation of the testis.
** Rather uncommon.
** In bulls, a granulomatous inflammation occurs with [[Brucella species|''Brucella abortus'']].
==Repair in the Central Nervous System==
* '''Encephalitis'''
** Inflammation of neural tissue of the brain.
** Repairs by the proliferation of astrocytes.
*** Astrocytes are the brain's form of fibrous tissue.
*** Called '''gliosis'''.
* Perivascular lymphocytic cuffing accompanies neural damage in the brain parenchyma.
* '''Meningitis'''
** Inflammation of the meninges.
** Purulent meningitis follows haematogenous spread of infection from umbilical infections and certain septicaemias.