Additional information

Table showing the differences between necrosis and apoptosis

Ischemia-reperfusion injury: It is seen in myocardial infarction and stroke after restoration of the blood supply. It is characterized by increased cell death following reperfusion of ischemic tissue, paradoxically, including cells that would have otherwise survived if blood supply was restored. It is caused due to increased free radical formation like superoxide anions from ischemic tissue and locally infiltrating inflammatory cells with subsequent free radical mediated injury. Local activation of complement by IgM in the ischemic tissue may also be a contributing factor. 3. Dissolution of cells in necrosis leads to leakage of intracellular enzymes into the circulation. It can be detected by several biochemical assays. Some enzymes can be used as a marker for tissue regeneration or enzyme induction.

*cTnT and cTnI are cardiac specific troponins

Pyknosis: Nucleus becomes condensed and more basophilic.

Karyorrhexis: Pyknotic nucleus undergoes fragmentation

Karyolysis: Breakdown of nuclear material by DNAse causes the chromatin to become much less basophilic.

Conditions where Psammoma bodies are seen: (See mnemonic below)

• P - Papillary carcinoma of thyroid
• S - Serous cystadenocarcinoma of the ovary
• A - Adenocarcinoma of lung
• M - Mesothelioma
• M - Meningioma
• O - Other benign conditions like cervical polyps, endometriosis, pregnancy etc.
• MA - SchwannoMA

Wheal and flare response: Firm stroking the skin will cause the appearance of a red line followed by a red flush and swelling, known as “triple response”. Red line is due to local vasodilation, flare or flush is due to adjoining arteriolar dilation while wheal or swelling is from the transudation of fluid from the capillaries into the interstitium.

Transudate

• Due to increased capillary hydrostatic pressure or reduced plasma oncotic pressure
• Protein poor fluid accumulates, fluid protein <3g/dl
• Specific gravity < 1.015
• Fluid LDH/ Serum LDH < 0.6
• LDH lesser than ⅔ rd of serum LDH level
• Fluid LDH less than 200 U/litre
• Lack of or scant cells
• Seen in heart failure, cirrhosis, hypoalbuminemia, nephrotic syndrome, hypothyroidism

Exudate

• Due to increased vascular permeability from inflammation of any cause, endothelial damage by toxins causing loss of protein rich plasma from the vasculature
• Protein rich fluid accumulates, fluid protein >3g/dl
• Specific gravity > 1.015
• Fluid LDH/ Serum LDH > 0.6
• LDH greater than ⅔ rd of serum LDH level
• Fluid LDH more than 200 U/litre
• Inflammatory cells present like neutrophils, lymphocytes
• Pneumonia, Pulmonary embolism, malignancies, sepsis, pleural effusions, empyema, tuberculosis, rheumatoid arthritis, pancreatitis, post cardiac surgery, drug induced.

Acute phase reactants: These are proteins that are released into the plasma in response to inflammation. They are synthesized in the liver and macrophages. They help regulate and limit the extent of inflammation. Most common ones are alpha 1 antitrypsin, plasminogen activator inhibitor, factor VIII, von Willebrand factor, CRP or C reactive protein, haptoglobin, ceruloplasmin, serum amyloid A, heat shock proteins etc. Their levels are elevated during an inflammatory response

Types of neutrophil granules**

Leukocyte adhesion deficiency (LAD): It is a group of autosomal recessive, immunodeficiency syndromes characterized by inability of leukocytes to adhere to endothelium and transmigrate into tissues in response to an injury or infection. Laboratory workup shows leukocytosis. LAD I, II and III are the main syndromes in this group.

LAD I is caused due to mutations in the ITGB2 gene that codes for beta 2 subunit of beta 2 integrins, also called CD 11a:CD 18. It presents with delayed wound healing, delayed separation of the umbilical cord , absence of pus formation, recurrent bacterial and fungal infections especially of the skin and mucosal surfaces, periodontitis and gingivitis.

LAD type II, also called congenital disorder of glycosylation type IIc, is less severe than type I and occurs due to defect in neutrophil binding to endothelial selectins, hence interfering with rolling. Mutations of the SLC35C1 gene are present. There is a deficiency in the expression of cell surface fucosylated glycan structures including the H and Lewis blood group antigens and Sialyl Lewis X epitope (CD 15), resulting from a defect in the synthesis of GDP-fucose from GDP-mannose. Bombay blood type (hh) is seen in patients affected by LAD II. Patients present with recurrent bacterial infections like otitis media, pneumonia, periodontitis, cellulitis, hypotonia, mental retardation, growth retardation and short stature.

In LAD III, the genetic defect in LAD III is a mutation in the gene for Kindlin 3 or less commonly, CalDAGGEF1, proteins essential for the activation of integrins. It affects the ability of leukocytes and platelets to bind to the endothelium. Patients present with recurrent bacterial and fungal infections with bleeding tendencies due to associated Glanzmann thrombasthenia. Purpura, post-surgical bleeding, epistaxis and easy bruising are the other clinical features.

16. Types of acute inflammation

Types of acute inflammation

• Purulent: Pus formation; Seen in infections with pus forming microbes e.g. Abscess with S.aureus

• Fibrinous: Leak of plasma with plasma proteins, protein rich exudate causing causes fibrin deposition in cavities e.g. Fibrinous pericarditis

• Serous: Thin, watery exudate e.g. burn blisters

• Pseudomembranous: Characterised by pseudomembrane formation composed of necrotic tissue e.g. C.difficile colitis

Complications of wound healing

• Infection
• Deficient scar formation
• Pigmentation, rust colored from hemosiderin
• Epidermal implantation cyst from trapped epithelial cells in the wound
• Wound dehiscence
• Incisional hernia
• Excessive wound contraction e.g. Dupuytren’s contracture, Peyronie’s contracture
• Keloids and hypertrophic scars*
• Neoplasia e.g. Marjolin’s ulcer** following burns

Both keloids and hypertrophic scars are due to excessive collagen formation by fibroblasts and look similar histologically. However, hypertrophic scar is confined to the wound margins while a keloid outgrows the original wound. Both are abundant in type III collagen. Reticular dermis has to be injured to cause keloids or hypertrophic scars. Broad, haphazardly arranged dense collagen bundles are seen in keloids while dense collagen bundles oriented parallel to the epidermal surface are seen in hypertrophic scars.