Healing and Repair - Pathology

Introduction

• There are several factors on which the ability to heal and repair depends:
  1. 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.
  2. 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.
  3. 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 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 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 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. Canine Distemper
  • Bacteria
    • E.g. Salmonella
  • Protozoa
    • E.g. Toxoplasma gondii

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 Category:Nocardia species 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 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 Johne's Disease.

The Liver

• The 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 Salmonellosis in young livestock.
  • The liver is swollen and may display hyperaemia.
  • Small pinpoint foci of necrosis may be seen through the surface.
• Chronic 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 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

• The 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.
  • 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 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.
• Poor 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:
  1. At service.
     • Mild.
     • An endometritis.
  2. 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.
    1. Life threatening mastitis.
       • Occurs shortly after parturition.
       • E.g. gangrenous mastitis due to Staphylococcus aureus, and Coliform mastitis.
    2. Chronic mastitis.
       • Results in progressive destruction of the glandular tissue and replacement by fibrous tissue.
       • E.g. Streptococcus agalactiae.
  • Some organisms such as 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 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.