Tissue Regeneration and Repair – L4

Injury to cells and tissues is followed by a series of events that control the damage and initiates the ‘Healing process’.

This process can be broadly separated into Regeneration and Repair.

Regeneration results in the complete restitution of lost or damaged structures; Definition: the proliferation of new cells and tissues to replace the lost or damaged structures. Egs.: 1) The growth of an amputated limb in amphibians. 2) In mammals, whole organs and complex tissues rarely regenerate

after injury, and the term is usually applied to processes such as liver re-growth after partial resection or necrosis, but these processes consist of

compensatory growth rather than true regeneration. *** Tissues with high proliferative capacity, such as the hematopoietic system

and the epithelia of the skin and GIT, renew themselves continuously and can regenerate after injury, as long as the stem cells of these tissues are not destroyed.

Repair Is mostly a combination of regeneration and scar formation by the

deposition of collagen. The relative contribution of regeneration and scarring in tissue repair

depends on the ability of the tissue to regenerate and the extent of the injury. (Eg.: a superficial skin wound heals through the regeneration of the surface epithelium).

Repair may restore some original structures but involves collagen deposition and scar formation.

Scar formation is the predominant healing process that occurs when the ECM is damaged by severe injury.

LIVER REGENERATION This process is not one of true regeneration, because the resection of tissue

does not cause new growth of liver but instead triggers a process of compensatory hyperplasia in the remaining parts of the organ

The human liver has a remarkable capacity to regenerate (e.g., as in after partial hepatectomy, tumor resection or for living-donor hepatic transplantation).

In humans, resection of approximately 60% of the liver in living donors results in the doubling of the liver remnant in about one month.

Mini-liver: The portions of the liver that remain after partial hepatectomy, which rapidly expand and reach the mass of the original liver.

Restoration of liver mass is achieved without the re-growth of the lobes that were resected at the operation.

In both humans and rodents, the end point of liver regeneration after partial hepatectomy is the restitution of functional mass rather than the reconstitution of the original form.

Hepatocyte proliferation in the regenerating liver is triggered by the combined actions of cytokines and polypeptide growth factors.

Individual hepatocytes replicate once or twice during regeneration and then return to quiescence.

Healing by Repair, Scar Formation and Fibrosis If tissue injury is severe or chronic, healing cannot be accomplished by

regeneration. Under these conditions, the main healing process is repair by deposition of

collagen and other ECM components, causing the formation of a scar. Repair by connective tissue deposition includes the following basic features:

• Inflammation (the initial event)• angiogenesis

• migration and proliferation of fibroblasts• scar formation

• connective tissue remodelling

CUTANEOUS WOUND HEALING Cutaneous wound healing is divided into three phases:

1) inflammation,2) proliferation, and 3) maturation.

These phases overlap, and their separation is somewhat arbitrary.

1) The initial injury causes platelet adhesion and aggregation and the clot formation on wound surface, leading to inflammation.

2) Proliferative phase there is formation of granulation tissue, proliferation and migration of connective tissue cells, and re-epithelialization of the wound surface.

3) Maturation phase involves ECM deposition, tissue remodeling, and wound contraction.

• Analgesics and NSAIDs; Opiates;• Local anaesthetics;

• Neuralgia; • Muscle relaxants

ANALGESICS Analgesics (syn. painkillers): any member of the diverse group of

drugs used to relieve pain and to achieve analgesia without blocking the conduction of other nerve impulses.

Derived from Greek ‘an’ (without), and ‘algia’ (pain). Act on the peripheral and central nervous system; Egs.: paracetamol (acetaminophen), NSAIDs such as the salicylates,

narcotic drugs such as morphine, synthetic drugs with narcotic properties such as tramadol, and various others.

Lipoxygenase inhibitors: diethylcarbamazine,

nordihydroguaiaretic acid, zileuton

OPIATES Opiates are narcotic analgesics that directly depresses the CNS. Natural opiates: derived from the dried ‘milk’ of the opium poppy; Synthetic opiates: manufactured in chemical laboratories with a similar chemical structure. Natural and synthetic opiates are collectively known as opioids. The most commonly abused opioid is heroin. Opioids attach to opioid receptors (found in the brain, spinal cord,

and GIT) and block the transmission of pain impulses to the brain. Opioids induce euphoria by affecting the brain regions that mediate

pleasure. Users generally report feeling warm, drowsy and content. Opioids

relieve stress and discomfort by creating a relaxed detachment from pain, desires, and activity. Opioids also tend to produce drowsiness, reduce heart rate, cause constipation, vasodilatation, and depress coughing and breathing reflexes.

The most common opioids are opium, codeine, morphine, fentanyl, OxyContin, and heroin.

Local Anaesthesia• Provision of pain-free state in a specific area or region.• Patient is fully awake but, doesn’t feel pain in the

anaesthetized region.• E.g., anaesthesia for removal of skin warts

General Anaesthesia• Provision of pain-free state to the entire body.• Patient loses consciousness and feels no pain.• Swallowing and gag reflexes are lost (deep anaesthesia).

SOME TYPES OF LOCAL ANAESTHESIA

Topical application• Application of the anaesthetic to skin surface / open area /

mucous membrane.• Used to de-sensitize the skin or mucous membrane to the

injection of a deeper local anaesthetic.• Can be applied with a cotton swab or sprayed on the area.

Local infiltration • Injection of local anaesthetic drug into tissues.• For dental procedures, suturing small wounds, or making an

incision into a small area (as in biopsy).

Regional anaesthesia • Injection of local anaesthetic/s around the nerves.• Anaesthetized area is usually larger than area affected by

local infiltration anaesthesia.• Egs.: Spinal anaesthesia and Conduction blocks

NEURALGIA Neuralgia is a sharp, stabbing pain that follows the path of a nerve

and is due to irritation or damage to the nerve. Causes:

– Chronic renal insufficiency, DM, HZ infection, HIV, Lyme disease, Syphilis, Porphyria

– Chemical irritation – Medications: cisplatin, paclitaxel, or vincristine

Symptoms: • Increased sensitivity of the skin along the path of the damaged nerve,

(so that any touch or pressure is felt as pain)• Weakness or complete paralysis of muscles supplied by the same

nerve

Medications:• Mainly to control the pain • OTC pain medicines (aspirin, acetaminophen, or ibuprofen)• Narcotic analgesics (hydrocodone) for short-term relief of severe pain• Antidepressants (amitriptyline, nortriptyline)• Antiseizure medications (carbamazepine, gabapentin, lamotrigine,

phenytoin, or pregabalin)• Lidocaine patch• Skin creams containing capsaicin

Muscle relaxants Are not really a separate class of drugs, but rather a group of

different drugs that each has an overall sedative effect on the body. These drugs do not act directly on the muscles; rather they act

centrally (in the brain) and are more of a total body relaxant. Are prescribed early in a course of back pain, on a short-term basis,

to relieve low back pain associated with muscle spasms. Egs.: Carisoprodol, Cyclobenzaprine, Diazepam etc…

THE END