Tissue regeneration and repair involves two main processes: regeneration and repair. Regeneration results in the complete restoration of lost or damaged structures through new cell and tissue growth. Repair is a combination of regeneration and scar formation through collagen deposition. The degree of regeneration versus scarring depends on the tissue's regenerative ability and injury severity. Liver regeneration after partial resection involves compensatory growth of the remaining tissue rather than true regeneration. Cutaneous wound healing occurs through inflammation, proliferation, and maturation phases with re-epithelialization and ECM deposition. Analgesics relieve pain through effects on peripheral and central nervous systems while local anesthetics temporarily block nerve impulses in a specific region.

1. Tissue Regeneration and
Repair – L4

2.  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.

3. 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.

4. 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.

5. 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

6. 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.

7. • Analgesics and NSAIDs; Opiates;
• Local anaesthetics;
• Neuralgia;
• Muscle relaxants

8. 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.

9. Lipoxygenase inhibitors:
diethylcarbamazine,
nordihydroguaiaretic acid,
zileuton

10. 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.

11. 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).

12. 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

13. 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

14.  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

15. 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…

16. THE END