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 Skin

Repair in the Bones

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

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

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.