HEALING

Definition. Replacement of damages tissue by healthy tissue. It is an attempt to restore the tissue to structural and functional normalcy.

Healing may be of 2 types

A. Regeneration.

B. Repair by granulation tissue.

A. Regeneration

Where the replacement is by proliferation of parenchymatous cells of type destroyed. This depends upon:

(1) Regenerative capacity of cells. Cells may be :

(a) Labile cells which are constantly proliferating to replace cells continuously shed off or destroyed

Epithelial cells of skin and lining surfaces.

Lymphoid and haemopoietic tissue.

(b) Stable cell. Cells mostly in resting-phase, but capable of dividing when necessary e.g.

• Liver and other parenchymatous and glandular cells.
• Connective tissue cells.
• Muscle cells have a limited capacity to divide.

(c) Permanent cell. These cells, once differentiated are not capable. of  dividing e.g.-nerve

(2) The extent of tissue loss. If  there is extensive destruction including disruption of the framework, complete.regeneration is not possible. even with labile an stable cell

B. Repair by granulation tissue

Granulation tissue is formed by proliferation of surrounding connective tissue elements. which migrate into the site to be repaired.

Granulation tissue formation  seen in :

• Wound healing.
• Organisation of exudates.
• Thrombi.
• Infarcts.
• Haematomas.

The process of repair can be best studied in clean incised wounds, where there is .no or minimal tjssue loss or the_edges or the  edges of the wound are approximated closely as in a surgical wound. This is called Primary union (healing by first intention).

1. The blood in the incised area clots and the fibrin binds the edges together.

2. During the first 24 hours, an acute  inflammation sets in to .bring protein and phagocyte rich exudates to the site.

3. The superficial part of the clot get dry and dehydrated{scab). The surface epithelium proliferates just beyond the cut edges and the cells migrate-deep to dry scab. Epithelialisation is usually complete by 24- 48 hours.

4 Granulation tissue, with actively growing fibroblasts and capillary buds invades the clot (stage of vascularisation). These fibroblasts 'posses contractile myofibrils & hence are termed as myofibroblasts'.

5. Simultaneously, demolition of the debris and clot components takes place.

6 The granulation tissue initially lays down a mucopolysacharide rich ground substance

7.Reticulin and later collagen fibrils are formed by the fibroblasts (with 5 days)

8 with progressive maturation of collagen, some of the capiliary buds develop into arterioles and venules and majority of them are obliterated (stage of devascularisation).

9. With time (weeks to months) the tensile strength of the scar increases and it shrinks.

Secondary union (excised wound-healing by secondary intention).

1. Coagulum forms and fills the gap.

2. Inflammatory reaction is seen as in primary union but is more intense, as a lot more debris has to be removed. .

3. Epithelial proliferation starts covering the surface from the periphery by proliferation beyond the edges and migration under scab.

4.Debridement starts and simultaneously granulation tissue grows into the coagulum from the sides and base of the wound. This is much more exuberant than in primary union. The surface now looks red and granular.

5. Wound contraction. This is early contraction (starts after 3 days and is complete in 2 weeks) and  must be differentiated from contraction after scar formation Wounds can contract by up to 80% of original size of that the gap to be filled is much reduced, resulting in faster healing with a smaller scar.

Wound contraction is probably caused by:

• Dehydration
• Collagen contraction.
• Granulation tissue contraction .(myofibroblasts).

The exact mechanism is not known.

6. Laying down of collagen.

7 Maturation to form a scar which later shrinks and devascularises.

Factors affecting wound healing

Wound healing is delayed by :

A. Local  factors

1. Poor blood supply.

2. Adhesion to bony surfaces (e.g. over the tibia).

3. Persistent injurious agents (infective or particulate) results in chronicity of  inflammation and ineffective healing. .

4. Constant movement (especially in fracture healing).

5. ionizing radiation (in contrast, ultraviolet rays hasten healing).

6. Neoplasia.

B. General factors

I. Nutritional deficiency, especially of.

(i) Protein

(ii) Ascorbic acid (Vitamin C).

(iii) Zinc

2. Corticoids adversely affect wound contraction and granulation tissue formation

(anabolic steroids have a favorable effect).

3. Low temperature.

4. Defects (qualitative or quantitative) in polymorphs and macrophages

.Complication of wound healing

1. Wound dehiscence

2.  Infection

3. Epidermal inclusion (implantation) cysts.

4. Keloid formation

5. Cicatrisation resulting in contract Ires and obstruction(in hollow viscera).

6. Calcification and ossification.

7. Weak scar which could be a site for incisional hernia

8. Painful scar if it involves a nerve twig.

9. Rarely neoplasia (especially in burn scars).

Immunoglobulins. (Ig)

 These are made up of polypeptide chains. Each molecule is constituted by two heavy and two light chains, linked by disulfide (S-S) bonds. The h~ chains are of 5 types, with corresponding, types or  immunoglobulin. IgG (gamma), IgM (mu µ ), IgA(alpha α), IgD(delta ), IgE(epsilon)

Each of these can have light chains of either kappa (k) or lambda type.Each chain has a constant portion (constant for the subtype) land a variable portion (antigen specific).

Enzyme digestion can split the Ig molecule into.2 Fab (antibody binding) fragments and one Fc (crystallisable, complement binding ) fragment.

Human immunodeficiency virus (HIV)
1. Part of the Retroviridae family (i.e., it is a retrovirus).
2. Basic virion structure
a. The nucleocapsid contains single stranded RNA and three enzymes: reverse transcriptase, integrase, and protease.

b. An exterior consists of two glycoproteins, gp120 and gp41, which are imbedded in the lipid bilayer. This lipid bilayer was obtained from the host cell via budding.

3. Virion characteristics

a. The HIV genome includes:

(1) gag gene—codes for core proteins.
(2) pol gene—codes for its three enzymes.
(3) env gene—codes for its two envelope glycoproteins.

b. HIV enzymes

(1) Reverse transcriptase—reverse transcription of RNA to viral DNA.
(2) Integrase—responsible for integrating viral DNA into host DNA.
(3) Protease—responsible for cleaving precursor proteins. 

4. Pathogenicity

a. HIV mainly infects CD4 lymphocytes, or helper T cells. Its envelope protein, gp120, binds specifically with CD4 surface
receptors. After entry, viral RNA is transcribed by reverse transcriptase to viral DNA and integrated into  the host DNA. New virions are synthesized and released by lysis of the host cell.

b. The predominant site of HIV replication is lymphoid tissues.
c. Although HIV mainly infects CD4 helper T cells, it can bind to any cell with a CD4 receptor, including macrophages, monocytes, lymph node dendritic cells, and a selected number of nerve cells. Macrophages are the first cells infected by HIV.

5. HIV infection versus acquired immunodeficiency syndrome (AIDS).

a. AIDS describes an HIV-infected person who has one of the following conditions:

(1) A CD4 lymphocyte count of less than 200.
(2) The person is infected with an opportunistic infection or other AIDS-defining illness, including (but not limited to) tuberculosis, recurrent pneumonia infections, or invasive cervical cancer.
b. The cause of death in an AIDS patient is most likely due to an opportunistic infection.

6. Common opportunistic infections associated with AIDS:
a. Pneumonia caused by Pneumocystis jiroveci (carinii). 
b. Tuberculosis.
c. Periodontal disease—severe gingivitis, periodontitis, ANUG, necrotizing stomatitis.
d. Candidiasis.
e. Oral hairy leukoplakia (EBV).
f. Kaposi’s sarcoma (HHV-8).
g. Recurrent VZV infections.
h. Condyloma acuminatum or verruca vulgaris (warts, HPV)—less common.
i. CMV infections.
j. Disseminated herpes simplex, herpes zoster.
k. Hodgkin’s, non-Hodgkin’s lymphoma.

7. Laboratory diagnosis of HIV

a. ELISA test—detects HIV antibodies.
False negatives do occur.

b. Western blot—detects HIV proteins.
There is a 99% accuracy rate when both the ELISA test and Western blot are used to diagnose HIV infection.
c. PCR—more sensitive; can amplify and identify the virus at an early stage.

8. Treatment
a. Inhibitors of reverse transcriptase.

(1) Nucleoside analogs
(a) Inhibit viral replication via competitive inhibition.
(b) Examples: zidovudine (AZT), didanosine, lami- vudine, stavudine.

(2) Nonnucleoside inhibitors.
(a) Act by binding directly to reverse transcriptase.
(b) Examples: nevirapine, delavirdine.
b. Protease inhibitor.
c. “Triple cocktail” therapy—often consists of two nucleoside inhibitors and a protease inhibitor.

INFLUENZA

An acute viral respiratory infection with influenza, a virus causing fever, coryza, cough, headache, malaise, and inflamed respiratory mucous membranes.

Influenza B viruses typically cause mild respiratory disease

Symptoms and Signs

mild cases:

Chills and fever up to 39 to 39.5° C

Prostration and generalized aches and pains, Headache, photophobia and retrobulbar aching

Respiratory tract symptoms may be mild at first, with scratchy sore throat, substernal burning, nonproductive cough, and sometimes coryza. Later, the lower respiratory illness becomes dominant; cough can be persistent and productive.

severe cases

sputum may be bloody. Skin is warm and flushed. Soft palate, posterior hard palate, tonsillar pillars, and posterior pharyngeal wall may be reddened, but no exudate appears. Eyes water easily, and the conjunctiva may be mildly inflamed

Encephalitis, myocarditis, and myoglobinuria are infrequent complications of influenza and, if present, usually occur during convalescence

Infections caused by N. meningiditis

1.  Bacteremia without sepsis.  Organism spreads to blood but no major reaction.

2.  Meningococcemia without meningitis.  Fever, headache, petechia, hypotension, disseminated       intravascular coagulation.  The Waterhouse-Friderichsen Syndrome is a rapid, progressive meningococcemia with shock, organ failure, adrenal necrosis, and death.

3.  Meningitis with meningococcemia.  Sudden onset fever, chills, headache, confusion, nuchal rigidity.  This occurs rapidly.

4.  Meningoencephalitis.  Patients are deeply comatose.

Diagnosis made by examining CSF.

 Staphylococcal aureus
 - cutaneous infections
    - furuncles (boils)
    - carbuncles (more complicated furuncle with multiple sinuses)
    - impetigo (often mixed with Streptococcus and has a more bullous appearance than crusted)
    - hidradenitis suppurative (abscess of apocrine glands→e.g., axilla)
    - nail bed (paronychial infection) 
    - postoperative wound or stitch abscess
    - postpartum breast abscesses 
 
toxin related skin rashes
 - infants and young children develop toxic epidermal necrolysis or Ritter's syndrome (scalded baby syndrome)→large, red areas of denuded skin and generalized bulla formation.
 - toxic shock syndrome (TSS) is due to a toxin producing strain of Staphylococcus aureus (bacteriophage induced) usually, but not exclusively in tampon wearing (hyperabsorbent type), menstruating women; 1-4 day prodrome of high fever, myalgias, arthralgias, mental confusion, diarrhea and on erythematous rash that occurs during or soon after menses; rash predominantly on hands and feet with eventual desquamation in 5-12 days.