NEET MDS Synopsis
Biosynthesis Of Pyrimidine and Purines Nucleotides
Biochemistry
Purines synthesis and metabolism
Purines are biologically synthesized as nucleotides and in particular as ribotides, i.e. bases attached to ribose 5-phosphate. Both adenine and guanine are derived from the nucleotide inosine monophosphate (IMP), which is the first compound in the pathway to have a completely formed purine ring system
The major site of purine synthesis is in the liver. Synthesis of the purine nucleotides begins with PRPP and leads to the first fully formed nucleotide, inosine 5'-monophosphate (IMP). This pathway is diagrammed below. The purine base without the attached ribose moiety is hypoxanthine.
Biosynthesis of purine and pyrimidine nucleotides requires carbon dioxide and the amide nitrogen of glutamine. Both use an amino acid nucleus – glycine in purine biosynthesis and aspartate in pyrimidine biosynthesis. Both use PRPP as the source of ribose 1-phosphate.
The end product of purine catabolism in man is uric acid.
Biosynthesis Of Pyrimidine Nucleotides
CO2 reacts with N of glutamine to form carbamoyl phosphate, which fuses with aspartate to form carbamoyl aspartate.
Carbamoyl aspartate on ring closure forms the first pyrimidine ring named OROTATE.
Orotate combines with PRPP to form OMP which is the first pyrimidine nucleotide.
OMP forms UMP which can be converted to CMP or dTMP
Celecoxib
Pharmacology
Celecoxib
is a highly selective COX-2 inhibitor and primarily inhibits this isoform of cyclooxygenase, whereas traditional NSAIDs inhibit both COX-1 and COX-2. Celecoxib is approximately 10-20 times more selective for COX-2 inhibition over COX-1.
Being a sulphonamide can cause skin rash & hypersensitivity rxn., occasional oedema& HT.
Indication
Osteoarthritis ( 100‐200mg BID ) , rheumatoid arthritis, dysmenorrhea, acute gouty attacks, acute musculoskeletal pain.
Pleural effusion
General Pathology
Pleural effusion is a medical condition where fluid accumulates in the pleural cavity which surrounds the lungs, making it hard to breathe.
Four main types of fluids can accumulate in the pleural space:
Serous fluid (hydrothorax)
Blood (hemothorax)
Lipid (chylothorax)
Pus (pyothorax or empyema)
Causes:
Pleural effusion can result from reasons such as:
Cancer, including lung cancer or breast cancer
Infection such as pneumonia or tuberculosis
Autoimmune disease such as lupus erythematosus
Heart failure
Bleeding, often due to chest trauma (hemothorax)
Low oncotic pressure of the blood plasma
lymphatic obstruction
Accidental infusion of fluids
Congestive heart failure, bacterial pneumonia and lung cancer constitute the vast majority of causes in the developed countries, although tuberculosis is a common cause in the developing world.
Diagnosis:
Gram stain and culture - identifies bacterial infections
Cell count and differential - differentiates exudative from transudative effusions
Cytology - identifies cancer cells, may also identify some infective organisms
Chemical composition including protein, lactate dehydrogenase, amylase, pH and glucose - differentiates exudative from transudative effusions
Other tests as suggested by the clinical situation - lipids, fungal culture, viral culture, specific immunoglobulins
Effects and Toxic Actions on Organ Systems
Pharmacology
Effects and Toxic Actions on Organ Systems
1. Local anesthetics (dose dependent) interfere with transmission in any excitable tissue (e.g. CNS and CVS).
2. CNS effects
a. Central neurons very sensitive.
b. Excitatory-dizziness, visual and auditory disturbances, apprehension, disorientation and muscle twitching more common with ester type agents.
c. Depression manifested as slurred speech, drowsiness and unconsciousness more common with amide type agents (e.g. lidocaine).
d. Higher concentrations of local anesthetic may eventually produce tonic-clonic[grand mal] convulsions.
e. Very large doses may produce respiratory depression which can be fatal. Artificial respiration may be life-saving.
3.CVS effects
a. Local anesthetics have direct action on the myocardium and peripheral vasculature by closing the sodium channel, thereby limiting the inward flux of sodium ions.
b. Myocardium usually depressed both in rate and force of contraction. Depression of ectopic pacemakers useful in treating cardiac arrhythmias.
c. Concentrations employed clinically usually cause vasodilation in area of injection.
d. Vasoconstrictors such as epinephrine may counteract these effects on myocardium and vasculature.
4. Local Tissue Responses
a. Occasionally focal necrosis in skeletal muscle at injection site, decreased cell motility and delayed wound healing.
b. Tissue hypoxia may be produced by action of excessive amounts of vasoconstrictors.
Indication, Contraindication of SCC
PedodonticsIndications for Stainless Steel Crowns in Pediatric Dentistry
Extensive Tooth Decay:
Stainless steel crowns (SSCs) are primarily indicated for teeth with
significant decay that cannot be effectively treated with fillings. They
provide full coverage, preventing further decay and preserving the tooth's
structure.
Developmental Defects:
SSCs are beneficial for teeth affected by developmental conditions such as
enamel dysplasia or dentinogenesis imperfecta, which make them more
susceptible to decay.
Post-Pulp Therapy:
After procedures like pulpotomy or pulpectomy, SSCs are often used to
protect the treated tooth, ensuring its functionality and longevity.
High Caries Risk:
For patients who are highly susceptible to caries, SSCs serve as preventive
restorations, helping to protect at-risk tooth surfaces from future decay.
Uncooperative Patients:
In cases where children may be uncooperative during dental procedures, SSCs
offer a quicker and less invasive solution compared to more complex
treatments.
Fractured Teeth:
SSCs are also indicated for restoring fractured primary molars, which are
crucial for a child's chewing ability and overall nutrition.
Special Needs Patients:
Children with special needs who may struggle with maintaining oral hygiene
can benefit significantly from the durability and protection offered by
SSCs.
Contraindications for Stainless Steel Crowns
Allergy to Nickel:
Some patients may have an allergy or sensitivity to nickel, which is
a component of stainless steel. In such cases, alternative materials
should be considered.
Severe Tooth Mobility:
If the tooth is severely mobile due to periodontal disease or other
factors, placing a stainless steel crown may not be appropriate, as it
may not provide adequate retention.
Inadequate Tooth Structure:
If there is insufficient tooth structure remaining to support the
crown, it may not be feasible to place an SSC. This is particularly
relevant in cases of extensive decay or fracture.
Active Dental Infection:
If there is an active infection or abscess associated with the
tooth, it is generally advisable to treat the infection before placing a
crown.
Patient Non-Compliance:
In cases where the patient is unlikely to cooperate with the
treatment or follow-up care, the use of SSCs may not be ideal.
Aesthetic Concerns:
In anterior teeth, where aesthetics are a primary concern, parents
or patients may prefer more esthetic options (e.g., composite crowns or
porcelain crowns) over stainless steel crowns.
Severe Malocclusion:
In cases of significant malocclusion, the placement of SSCs may not
be appropriate if they could interfere with the occlusion or lead to
further dental issues.
Presence of Extensive Caries in Adjacent Teeth:
If adjacent teeth are also severely decayed, it may be more
beneficial to address those issues first rather than placing a crown on
a single tooth.
Innervation of the Pharynx
AnatomyInnervation of the Pharynx
The motor and most of the sensory supply of the pharynx is derived from the pharyngeal plexus of nerves on the surface of the pharynx.
The plexus is formed by pharyngeal branches of the vagus (CN X) and glossopharyngeal (CN IX) nerves, and by sympathetic branches for the superior cervical ganglion.
The motor fibres in the pharyngeal plexus are derived from the cranial root of accessory nerve (CN XI), and are carried by the vagus nerve to all muscles of the pharynx and soft palate.
The exceptions are stylopharyngeus (supplied by CN IX) and the tensor veli palatini (supplied by CN V3).
Rhythmicity
Physiology
1.Rhythmicity ( Chronotropism ) : means the ability of heart to beat regularly ( due to repetitive and stable depolarization and repolarization ) . Rhythmicity of heart is a myogenic in origin , because cardiac muscles are automatically excited muscles and does not depend on the nervous stimulus to initiate excitation and then contraction . The role of nerves is limited to the regulation of the heart rate and not to initiate the beat.
There are many evidences that approve the myogenic and not neurogenic origin of the rhythmicity of cardiac muscle . For example :
- transplanted heart continues to beat regularly without any nerve supply.
- Embryologically the heart starts to beat before reaching any nerves to them.
- Some drugs that paralyze the nerves ( such as cocaine ) do not stop the heart in given doses.
Spontaneous rhythmicity of the cardiac muscle due to the existence of excitatory - conductive system , which is composed of self- exciting non-contractile cardiac muscle cells . The SA node of the mentioned system excites in a rate , that is the most rapid among the other components of the system ( 110 beats /minute ) , which makes it the controller or ( the pacemaker ) of the cardiac rhythm of the entire heart.
Mechanism , responsible for self- excitation in the SA node and the excitatory conductive system is due to the following properties of the cell membrane of theses cells :
1- Non-gated sodium channels
2- Decreased permeability to potassium
3- existence of slow and fast calcium channels.
These properties enable the cations ( sodium through the none-gated sodium voltage channels , calcium through calcium slow channels) to enter the cell and depolarize the cell membrane without need for external stimulus.
The resting membrane potential of non-contractile cardiac cell is -55 - -60 millivolts ( less than that of excitable nerve cells (-70) ) .
The threshold is also less negative than that of nerve cells ( -40 millivolts ).
The decreased permeability to potassium from its side decrease the eflux of potassium during the repolarization phase of the pacemaker potential . All of these factors give the pacemaker potential its characteristic shape
Repeating of the pacemaker potential between the action potentials of contractile muscle cells is the cause of spontaneous rhythmicity of cardiac muscle cells.
Factors , affecting the rhythmicity of the cardiac muscle :
I. Factors that increase the rate ( positive chronotropic factors) :
1. sympathetic stimulation : as its neurotransmitter norepinephrine increases the membrane permeability to sodium and calcium.
2. moderate warming : moderate warming increases temperature by 10 beats for each 1 Fahrenheit degree increase in body temperature, this due to decrease in permeability to potassium ions in pacemaker membrane by moderate increase in temperature.
3. Catecholaminic drugs have positive chronotropic effect.
4. Thyroid hormones : have positive chronotropic effect , due to the fact that these drugs increase the sensitivity of adrenergic receptors to adrenaline and noreadrenaline .
5. mild hypoxia.
6. mild alkalemia : mild alkalemia decreases the negativity of the resting potential.
7. hypocalcemia.
8. mild hypokalemia
II. Factors that decrease rhythmicity ( negative chronotropic):
1.Vagal stimulation : the basal level of vagal stimulation inhibits the sinus rhythm and decrease it from 110-75 beats/ minute. This effect due to increasing the permeability of the cardiac muscle cell to potassium , which causes rapid potassium eflux , which increases the negativity inside the cardiac cells (hyperpolarization ).
2. moderate cooling
3. severe warming : due to cardiac damage , as a result of intercellular protein denaturation. Excessive cooling on the other hand decrease metabolism and stops rhythmicity.
4. Cholenergic drugs ( such as methacholine , pilocarpine..etc) have negative chronotropic effect.
5. Digitalis : these drugs causes hyperpolarization . This effect is similar to that of vagal stimulation.
6. Hypercapnia ( excessive CO2 production )
7. Acidemia.
8. hyper- and hyponatremia .
9. hyperkalemia
10. hypercalcemia
11. Typhoid or diphteria toxins.
Internal Muscles of the Pharynx
AnatomyInternal Muscles of the Pharynx
The internal, chiefly longitudinal muscular layer, consists of 3 muscles: stylopharyngeus, palatopharyngeus, and salpingopharyngeus.
They all elevate the larynx and pharynx during swallowing and speaking.
The Stylopharyngeus Muscle
This is a long, thin, conical muscles that descends inferiorly between the external and internal carotid arteries.
It enters the wall of the pharynx between the superior and middle constrictor muscles.
Origin: styloid process of temporal bone.
Insertion: posterior and superior borders of thyroid cartilage with palatopharyngeus muscle.
Innervation: glossopharyngeal nerve (CN IX).
It elevates the pharynx and larynx and expands the sides of the pharynx, thereby aiding in pulling the pharyngeal wall over a bolus of food.
The Palatopharyngeus Muscle
This is a thin muscle and the overlying mucosa form the palatopharyngeal arch.
The Salpingopharyngeus Muscle
This is a slender muscle that descends in the lateral wall of the pharynx.
The over lying mucous membrane forms the salpingopharyngeal fold.
Origin: cartilaginous part of the auditory tube.
Insertion: blends with palatopharyngeus muscle.
Innervation: through the pharyngeal plexus.
It elevates the pharynx and larynx and opens the pharyngeal orifice of the auditory tube during swallowing.