NEET MDS Synopsis
PHAGOCYTOSIS AND INTRACELLULAR KILLING
General Microbiology
PHAGOCYTOSIS AND INTRACELLULAR KILLING
A. Phagocytic cells
1. Neutrophiles/Polymorphonuclear cells
PMNs are motile phagocytic cells that have lobed nuclei. They can be identified by their characteristic nucleus or by an antigen present on the cell surface called CD66. They contain two kinds of granules the contents of which are involved in the antimicrobial properties of these cells.
The second type of granule found in more mature PMNs is the secondary or specific granule. These contain lysozyme, NADPH oxidase components, which are involved in the generation of toxic oxygen products, and characteristically lactoferrin, an iron chelating protein and B12-binding protein.
2. Monocytes/Macrophages
Macrophages are phagocytic cells . They can be identified morphologically or by the presence of the CD14 cell surface marker.
B. Response of phagocytes to infection
Circulating PMNs and monocytes respond to danger (SOS) signals generated at the site of an infection. SOS signals include N-formyl-methionine containing peptides released by bacteria, clotting system peptides, complement products and cytokines released from tissue macrophages that have encountered bacteria in tissue.
Some of the SOS signals stimulate endothelial cells near the site of the infection to express cell adhesion molecules such as ICAM-1 and selectins which bind to components on the surface of phagocytic cells and cause the phagocytes to adhere to the endothelium.
Vasodilators produced at the site of infection cause the junctions between endothelial cells to loosen and the phagocytes then cross the endothelial barrier by “squeezing” between the endothelial cells in a process called diapedesis.
Once in the tissue spaces some of the SOS signals attract phagocytes to the infection site by chemotaxis (movement toward an increasing chemical gradient). The SOS signals also activate the phagocytes, which results in increased phagocytosis and intracellular killing of the invading organisms.
C. Initiation of Phagocytosis
Phagocytic cells have a variety of receptors on their cell membranes through which infectious agents bind to the cells. These include:
1. Fc receptors – Bacteria with IgG antibody on their surface have the Fc region exposed and this part of the Ig molecule can bind to the receptor on phagocytes. Binding to the Fc receptor requires prior interaction of the antibody with an antigen. Binding of IgG-coated bacteria to Fc receptors results in enhanced phagocytosis and activation of the metabolic activity of phagocytes (respiratory burst).
2. Complement receptors – Phagocytic cells have a receptor for the 3rd component of complement, C3b. Binding of C3b-coated bacteria to this receptor also results in enhanced phagocytosis and stimulation of the respiratory burst.
3. Scavenger receptors – Scavenger receptors bind a wide variety of polyanions on bacterial surfaces resulting in phagocytosis of bacteria.
4. Toll-like receptors – Phagocytes have a variety of Toll-like receptors (Pattern Recognition Receptors or PRRs) which recognize broad molecular patterns called PAMPs (pathogen associated molecular patterns) on infectious agents. Binding of infectious agents via Toll-like receptors results in phagocytosis and the release of inflammatory cytokines (IL-1, TNF-alpha and IL-6) by the phagocytes.
D. Phagocytosis
The pseudopods eventually surround the bacterium and engulf it, and the bacterium is enclosed in a phagosome. During phagocytosis the granules or lysosomes of the phagocyte fuse with the phagosome and empty their contents. The result is a bacterium engulfed in a phagolysosome which contains the contents of the granules or lysosomes.
E. Respiratory burst and intracellular killing
During phagocytosis there is an increase in glucose and oxygen consumption which is referred to as the respiratory burst. The consequence of the respiratory burst is that a number of oxygen-containing compounds are produced which kill the bacteria being phagocytosed. This is referred to as oxygen-dependent intracellular killing. In addition, bacteria can be killed by pre-formed substances released from granules or lysosomes when they fuse with the phagosome. This is referred to as oxygen-independent intracellular killing.
1. Oxygen-dependent myeloperoxidase-independent intracellular killing
During phagocytosis glucose is metabolized via the pentose monophosphate shunt and NADPH is formed. Cytochrome B which was part of the specific granule combines with the plasma membrane NADPH oxidase and activates it. The activated NADPH oxidase uses oxygen to oxidize the NADPH. The result is the production of superoxide anion. Some of the superoxide anion is converted to H2O2 and singlet oxygen by superoxide dismutase. In addition, superoxide anion can react with H2O2 resulting in the formation of hydroxyl radical and more singlet oxygen. The result of all of these reactions is the production of the toxic oxygen compounds superoxide anion (O2-), H2O2, singlet oxygen (1O2) and hydroxyl radical (OH•).
2. Oxygen-dependent myeloperoxidase-dependent intracellular killing
As the azurophilic granules fuse with the phagosome, myeloperoxidase is released into the phagolysosome. Myeloperoxidase utilizes H2O2 and halide ions (usually Cl-) to produce hypochlorite, a highly toxic substance. Some of the hypochlorite can spontaneously break down to yield singlet oxygen. The result of these reactions is the production of toxic hypochlorite (OCl-) and singlet oxygen (1O2).
3. Detoxification reactions
PMNs and macrophages have means to protect themselves from the toxic oxygen intermediates. These reactions involve the dismutation of superoxide anion to hydrogen peroxide by superoxide dismutase and the conversion of hydrogen peroxide to water by catalase.
4. Oxygen-independent intracellular killing
In addition to the oxygen-dependent mechanisms of killing there are also oxygen–independent killing mechanisms in phagocytes: cationic proteins (cathepsin) released into the phagolysosome can damage bacterial membranes; lysozyme breaks down bacterial cell walls; lactoferrin chelates iron, which deprives bacteria of this required nutrient; hydrolytic enzymes break down bacterial proteins. Thus, even patients who have defects in the oxygen-dependent killing pathways are able to kill bacteria. However, since the oxygen-dependent mechanisms are much more efficient in killing, patients with defects in these pathways are more susceptible and get more serious infections.
Dental trauma types in endodontics
EndodonticsIn endodontics, dental trauma often results in the luxation of teeth, which
is the displacement of a tooth from its normal position in the alveolus (the
bone socket that holds the tooth). There are several types of luxation injuries,
each with different endodontic implications. Here are the main types of dental
luxation:
1. Concussion: A tooth is injured but not displaced from its socket. The
periodontal ligament (PDL) is compressed and may experience hemorrhage. The
tooth is usually not loose and does not require repositioning. However, it can
be tender to percussion and may exhibit some mobility. The pulp may remain
vital, but it can become inflamed or necrotic due to the trauma.
2. Subluxation: The tooth is partially displaced but remains in the socket. It
shows increased mobility in all directions but can be repositioned with minimal
resistance. The PDL is stretched and may be damaged, leading to pulpal and
periodontal issues. Endodontic treatment is often not necessary unless symptoms
of pulp damage arise.
3. Lateral luxation: The tooth is displaced in a horizontal direction and may be
pushed towards the adjacent teeth. The PDL is stretched and possibly torn. The
tooth may be pushed out of alignment or into an incorrect position in the arch.
Prompt repositioning and splinting are crucial. The pulp can be injured, and the
likelihood of endodontic treatment may increase.
4. Intrusion: The tooth is pushed into the alveolar bone, either partially or
completely. This can cause significant damage to the PDL and the surrounding
bone tissue. The tooth may appear shorter than its neighbors. The pulp is often
traumatized and can die if not treated quickly. Endodontic treatment is usually
required after repositioning and stabilization.
5. Extrusion: The tooth is partially displaced out of its socket. The PDL is
stretched and sometimes torn. The tooth appears longer than its neighbors. The
pulp is frequently exposed, which increases the risk of infection and necrosis.
Repositioning and endodontic treatment are typically necessary.
6. Avulsion: The tooth is completely knocked out of its socket. The PDL is
completely severed, and the tooth may have associated soft tissue injuries. Time
is of the essence in these cases. If the tooth can be replanted within 30
minutes and properly managed, the chances of saving the pulp are higher.
Endodontic treatment is usually needed, with the possibility of a root canal or
revascularization.
7. Inverse luxation: This is a rare type of luxation where the tooth is
displaced upwards into the alveolar bone. The tooth is pushed into the bone,
which can cause severe damage to the PDL and surrounding tissues. Endodontic
treatment is often necessary.
8. Dystopia: Although not a true luxation, it's worth mentioning that a tooth
can be displaced during eruption. This can cause the tooth to emerge in an
abnormal position. Endodontic treatment may be necessary if the tooth does not
respond to orthodontic treatment or if the displacement causes pain or
infection.
The endodontic management of luxated teeth varies depending on the severity of
the injury and the condition of the pulp. Treatments can range from simple
monitoring to root canal therapy, apicoectomy, or even tooth extraction in
severe cases. The goal is always to preserve the tooth and prevent further
complications.
Nasogastric Tube (Ryles Tube)
Oral and Maxillofacial SurgeryNasogastric Tube (Ryles Tube)
A nasogastric tube (NG tube), commonly referred to as a Ryles
tube, is a medical device used for various purposes, primarily
involving the stomach. It is a long, hollow tube made of polyvinyl chloride
(PVC) with one blunt end and multiple openings along its length. The tube is
designed to be inserted through the nostril, down the esophagus, and into the
stomach.
Description and Insertion
Structure: The NG tube has a blunt end that is inserted
into the nostril, and it features multiple openings to allow for the passage
of fluids and air. The open end of the tube is used for feeding or drainage.
Insertion Technique:
The tube is gently passed through one of the nostrils and advanced
through the nasopharynx and into the esophagus.
Care is taken to ensure that the tube follows the natural curvature
of the nasal passages and esophagus.
Once the tube is in place, its position must be confirmed before any
feeds or medications are administered.
Position Confirmation:
To check the position of the tube, air is pushed into the tube using
a syringe.
The presence of air in the stomach is confirmed by auscultation with
a stethoscope, listening for the characteristic "whoosh" sound of air
entering the stomach.
Only after confirming that the tube is correctly positioned in the
stomach should feeding or medication administration begin.
Securing the Tube: The tube is fixed to the nose using
sticking plaster or adhesive tape to prevent displacement.
Uses of Nasogastric Tube
Nutritional Support:
Enteral Feeding: The primary use of a nasogastric
tube is to provide nutritional support to patients who are unable to
take oral feeds due to various reasons, such as:
Neurological conditions (e.g., stroke, coma)
Surgical procedures affecting the gastrointestinal tract
Severe dysphagia (difficulty swallowing)
Gastric Lavage:
Postoperative Care: NG tubes can be used for
gastric lavage to flush out blood, fluids, or other contents from the
stomach after surgery. This is particularly important in cases where
there is a risk of aspiration or when the stomach needs to be emptied.
Poisoning: In cases of poisoning or overdose,
gastric lavage may be performed using an NG tube to remove toxic
substances from the stomach. This procedure should be done promptly and
under medical supervision.
Decompression:
Relieving Distension: The NG tube can also be used
to decompress the stomach in cases of bowel obstruction or ileus,
allowing for the removal of excess gas and fluid.
Medication Administration:
The tube can be used to administer medications directly into the
stomach for patients who cannot take oral medications.
Considerations and Complications
Patient Comfort: Insertion of the NG tube can be
uncomfortable for patients, and proper technique should be used to minimize
discomfort.
Complications: Potential complications include:
Nasal and esophageal irritation or injury
Misplacement of the tube into the lungs, leading to aspiration
Sinusitis or nasal ulceration with prolonged use
Gastrointestinal complications, such as gastric erosion or
ulceration
Chloramphenicol
Pharmacology
Chloramphenicol
derived from the bacterium Streptomyces venezuelae
Chloramphenicol is effective against a wide variety of microorganisms, but due to serious side-effects (e.g., damage to the bone marrow, including aplastic anemia) in humans, it is usually reserved for the treatment of serious and life-threatening infections (e.g., typhoid fever). It is used in treatment of cholera, as it destroys the
vibrios and decreases the diarrhoea. It is effective against tetracycline-resistant vibrios.It is also used in eye drops or ointment to treat bacterial conjunctivitis.
Mechanism and Resistance Chloramphenicol stops bacterial growth by binding to the bacterial ribosome (blocking peptidyl transferase) and inhibiting protein synthesis.
Chloramphenicol irreversibly binds to a receptor site on the 50S subunit of the bacterial ribosome, inhibiting peptidyl transferase. This inhibition consequently results in the prevention of amino acid transfer to growing peptide chains, ultimately leading to inhibition of protein formation.
Spectrum of activity: Broad-spectrum
Effect on bacteria: Bacteriostatic
Root Canal Sealers
Endodontics
Root canal sealers are materials used in endodontics to fill the space between
the root canal filling material (usually gutta-percha) and the walls of the root
canal system. Their primary purpose is to provide a fluid-tight seal, preventing
the ingress of bacteria and fluids, and to enhance the overall success of root
canal treatment. Here’s a detailed overview of root canal sealers, including
their types, properties, and clinical considerations.
Types of Root Canal Sealers
Zinc Oxide Eugenol (ZOE) Sealers
Composition: Zinc oxide powder mixed with eugenol (oil of
cloves).
Properties:
Good sealing ability.
Antimicrobial properties.
Sedative effect on the pulp.
Uses: Commonly used in conjunction with gutta-percha for
permanent root canal fillings. However, it can be difficult to remove if
retreatment is necessary.
Resin-Based Sealers
Composition: Composed of resins, fillers, and solvents.
Properties:
Excellent adhesion to dentin and gutta-percha.
Good sealing ability and low solubility.
Aesthetic properties (some are tooth-colored).
Uses: Suitable for various types of root canal systems,
especially in cases requiring high bond strength and sealing ability.
Calcium Hydroxide Sealers
Composition: Calcium hydroxide mixed with a vehicle (such as
glycol or water).
Properties:
Biocompatible and promotes healing.
Antimicrobial properties.
Can stimulate the formation of reparative dentin.
Uses: Often used in cases where a temporary seal is needed or
in apexification procedures.
Glass Ionomer Sealers
Composition: Glass ionomer cement (GIC) materials.
Properties:
Good adhesion to dentin.
Fluoride release, which can help in preventing secondary caries.
Biocompatible.
Uses: Used in conjunction with gutta-percha, particularly in
cases where fluoride release is beneficial.
Bioceramic Sealers
Composition: Made from calcium silicate and other bioceramic
materials.
Properties:
Excellent sealing ability and biocompatibility.
Hydrophilic, allowing for moisture absorption and expansion to fill
voids.
Promotes healing and tissue regeneration.
Uses: Increasingly popular for permanent root canal fillings
due to their favorable properties.
Properties of Ideal Root Canal Sealers
An ideal root canal sealer should possess the following properties:
Biocompatibility: Should not cause adverse reactions in periapical
tissues.
Sealing Ability: Must provide a tight seal to prevent bacterial
leakage.
Adhesion: Should bond well to both dentin and gutta-percha.
Flowability: Should be able to flow into irregularities and fill
voids.
Radiopacity: Should be visible on radiographs for easy
identification.
Ease of Removal: Should allow for easy retreatment if necessary.
Antimicrobial Properties: Should inhibit bacterial growth.
Clinical Considerations
Selection of Sealer: The choice of sealer depends on the clinical
situation, the type of tooth being treated, and the specific properties
required for the case.
Application Technique: Proper application techniques are crucial
for achieving an effective seal. This includes ensuring that the root canal
is adequately cleaned and shaped before sealer application.
Retreatment: Some sealers, like ZOE, can be challenging to remove
during retreatment, while others, like bioceramic sealers, may offer better
retrievability.
Setting Time: The setting time of the sealer should be considered,
especially in cases where immediate restoration is planned.
Conclusion
Root canal sealers play a vital role in the success of endodontic treatment by
providing a seal that prevents bacterial contamination and promotes healing.
Understanding the different types of sealers, their properties, and their
clinical applications is essential for dental professionals to ensure effective
and successful root canal therapy.
Reaction of Acrylic Resins
Dental Materials
Reaction
PMMA powder makes mixture viscous for manipulation before curing. Chemical accelerators cause decomposition of benzoyl peroxide into free radicals that initiate polymerization of monomer
New PMMA is formed into a matrix that surrounds PMMA powder. Linear shrinkage of 5% to 7% during setting. but dimensions of appliances are not critical
HAEMORRHAGIC DISORDERS
General Pathology
HAEMORRHAGIC DISORDERS
Normal homeostasis depends on
-Capillary integrity and tissue support.
- Platelets; number and function
(a) For integrity of capillary endothelium and platelet plug by adhesion and aggregation
(b) Vasoactive substances for vasoconstriction
(c) Platelet factor for coagulation.
(d) clot retraction.
- Fibrinolytic system(mainly Plasmin) : which keeps the coagulation system in check.
Coagulation disorders
These may be factors :
Deficiency .of factors
Genetic.
Vitamin K deficiency.
Liver disease.
Secondary to disseminated intravascular coagulation.or defibrinatian
Overactive fibrinolytic system.
Inhibitors of the factors (immune, acquired).
Anticoagulant therapy as in myocardial infarction.
Haemophilia. Genetic disease transmitted as X linked recessive trait. Common in Europe. Defect in fcatorVII Haemophilia A .or in fact .or IX-Haemaphilia B (rarer).
Features:
May manifest in infancy or later.
Severity depends on degree of deficiency.
Persistant wound bleeding.
Easy Bruising with Hematoma formation
Nose bleed , arthrosis, abdominal pain with fever and leukocytosis
Prognosis is good with prevention of trauma and-transfusion of Fresh blood or fTesh plasma except for danger of developing immune inhibitors.
Von Willebrand's disease. Capillary fragility and decreased factor VIII (due to deficient stimulatory factor). It is transmitted in an autosomal dominant manner both. Sexes affected equally
Vitamin K Deficiency. Vitamin K is needed for synthesis of factor II,VII,IX and X.
Deficiency maybe due to:
Obstructive jaundice.
Steatorrhoea.
Gut sterilisation by antibiotics.
Liver disease results in :
Deficient synthesis of factor I II, V, Vll, IX and X Incseased fibrinolysis (as liver is the site of detoxification of activators ).
Defibrination syndrome. occurs when factors are depleted due to disseminated .intravascular coagulation (DIC). It is initiated by endothelial damage or tissue factor entering the circulation.
Causes
Obstetric accidents, especially amniotic fluid embolism. Septicaemia. .
Hypersensitivity reactions.
Disseminated malignancy.
Snake bite.
Vascular defects : (Non thrombocytopenic purpura).
Acquired :
Simple purpura a seen in women. It is probably endocrinal
Senile parpura in old people due to reduced tissue support to vessels
Allergic or toxic damage to endothelium due to Infections like Typhoid Septicemia
Col!agen diseases.
Scurvy
Uraemia damage to endothelium (platelet defects).
Drugs like aspirin. tranquillisers, Streptomvcin pencillin etc.
Henoc schonlien purpura Widespeard vasculitis due to hypersensitivity to bacteria or foodstuff
It manifests as :
Pulrpurric rashes.
Arthralgia.
Abdominal pain.
Nephritis and haematuria.
Hereditary :
(a) Haemhoragic telangieclasia. Spider like tortous vessels which bleed easily. There are disseminated lesions in skin, mucosa and viscera.
(b) Hereditary capillary fragilily similar to the vascular component of von Willbrand’s disease
.(c) Ehler Danlos Syndrome which is a connective tissue defect with skin, vascular and joint manifestations.
Platelet defects
These may be :
(I) Qualitative thromboasthenia and thrombocytopathy.
(2) Thrombocytopenia :Reduction in number.
(a) Primary or idiopathic thrombocytopenic purpura.
(b) Secondary to :
(i) Drugs especially sedormid
(ii) Leukaemias
(iii) Aplastic-anaemia.
Idiopathic thrombocytopenic purpura (ITP). Commoner in young females.
Manifests as :
Acute self limiting type.
Chronic recurring type.
Features:
(i) Spontaneous bleeding and easy bruisability
(ii)Skin (petechiae), mucus membrane (epistaxis) lesions and sometimes visceral lesions involving any organ.
Thrombocytopenia with abnormal forms of platelets.
Marrow shows increased megakaryocytes with immature forms, vacuolation, and lack of platelet budding.
Pathogenesis:
hypersensitivity to infective agent in acute type.
Plasma thrombocytopenic factor ( Antibody in nature) in chronic type
Biological Functions are Extremely Sensitive to pH
PhysiologyBiological Functions are Extremely Sensitive to pH
H+ and OH- ions get special attention because they are very reactive
Substance which donates H+ ions to solution = acid
Substance which donates OH- ions to solution = base
Because we deal with H ions over a very wide range of concentration, physiologists have devised a logarithmic unit, pH, to deal with it
pH = - log [H+]
[H+] is the H ion concentration in moles/liter
Because of the way it is defined a high pH indicates low H ion and a low pH indicates high H ion- it takes a while to get used to the strange definition
Also because of the way it is defined, a change of 1 pH unit means a 10X change in the concentration of H ions
If pH changes by 2 units the H+ concentration changes by 10 X 10 = 100 times
Human blood pH is 7.4
Blood pH above 7.4 = alkalosis
Blood pH below 7.4 = acidosis
Body must get rid of ~15 moles of potential acid/day (mostly CO2)
CO2 reacts with water to form carbonic acid (H2CO3)
Done mostly by lungs & kidney
In neutralization H+ and OH- react to form water
If the pH changes charges on molecules also change, especially charges on proteins
This changes the reactivity of proteins such as enzymes
Large pH changes occur as food passes through the intestines.