NEET MDS Synopsis
Ampholytes, Polyampholytes, pI and Zwitterion
Biochemistry
Ampholytes, Polyampholytes, pI and Zwitterion
Many substances in nature contain both acidic and basic groups as well as many different types of these groups in the same molecule. (e.g. proteins). These are called ampholytes (one acidic and one basic group) or polyampholytes (many acidic and basic groups). Proteins contains many different amino acids some of which contain ionizable side groups, both acidic and basic. Therefore, a useful term for dealing with the titration of ampholytes and polyampholytes (e.g. proteins) is the isoelectric point, pI. This is described as the pH at which the effective net charge on a molecule is zero.
For the case of a simple ampholyte like the amino acid glycine the pI, when calculated from the Henderson-Hasselbalch equation, is shown to be the average of the pK for the a-COOH group and the pK for the a-NH2 group:
pI = [pKa-(COOH) + pKa-(NH3+)]/2
For more complex molecules such as polyampholytes the pI is the average of the pKa values that represent the boundaries of the zwitterionic form of the molecule. The pI value, like that of pK, is very informative as to the nature of different molecules. A molecule with a low pI would contain a predominance of acidic groups, whereas a high pI indicates predominance of basic groups.
Hyperparathyroidism
General Pathology
Hyperparathyroidism
Hyperparathyroidism is defined as an elevated secretion of PTH, of which there are three main types:
1. Primary—hypersecretion of PTH by adenoma or hyperplasia of the gland.
2. Secondary—physiological increase in PTH secretions in response to hypocalcaemia of any cause.
3. Tertiary—supervention of an autonomous hypersecreting adenoma in long-standing secondary hyperparathyroidism.
Primary hyperparathyroidism
This is the most common of the parathyroid disorders, with a prevalence of about 1 per 800
It is an important cause of hypercalcaemia.
More than 90% of patients are over 50 years of age and the condition affects females more than males by nearly 3 : 1.
Aetiology
Adenoma 75% -> Orange−brown, well-encapsulated tumour of various size but seldom > 1 cm diameter Tumours are usually solitary, affecting only one of the parathyroids, the others often showing atrophy; they are deep seated and rarely palpable.
Primary hyperplasia 20% -> Diffuse enlargement of all the parathyroid glands
Parathyroid carcinoma 5% -> Usually resembles adenoma but is poorly encapsulated and invasive locally.
Effects of hyperparathyroidism
The clinical effects are the result of hypercalcaemia and bone resorption.
Effects of hypercalcaemia:
- Renal stones due to hypercalcuria.
- Excessive calcification of blood vessels.
- Corneal calcification.
- General muscle weakness and tiredness.
- Exacerbation of hypertension and potential shortening of the QT interval.
- Thirst and polyuria (may be dehydrated due to impaired concentrating ability of kidney).
- Anorexia and constipation
Effects of bone resorption:
- Osteitis fibrosa—increased bone resorption with fibrous replacement in the lacunae.
- ‘Brown tumours’—haemorrhagic and cystic tumour-like areas in the bone, containing large masses of giant osteoclastic cells.
- Osteitis fibrosa cystica (von Recklinghausen disease of bone)—multiple brown tumours combined with osteitis fibrosa.
- Changes may present clinically as bone pain, fracture or deformity.
about 50% of patients with biochemical evidence of primary hyperparathyroidism are asymptomatic.
Investigations are:
- Biochemical—increased PTH and Ca2+ , and decreased PO43- .
- Radiological—90% normal; 10% show evidence of bone resorption, particularly phalangeal erosions.
Management is by rehydration, medical reduction in plasma calcium using bisphosphonates and eventual surgical removal of abnormal parathyroid glands.
Secondary hyperparathyroidism
This is compensatory hyperplasia of the parathyroid glands, occurring in response to diseases of chronic low serum calcium or increased serum phosphate.
Its causes are:
- Chronic renal failure and some renal tubular disorders (most common cause).
- Steatorrhoea and other malabsorption syndromes.
- Osteomalacia and rickets.
- Pregnancy and lactation.
Morphological changes of the parathyroid glands are:
- Hyperplastic enlargement of all parathyroid glands, but to a lesser degree than in primary hyperplasia.
- Increase in ‘water clear’ cells and chief cells of the parathyroid glands, with loss of stromal fat cells.
Clinical manifestations—symptoms of bone resorption are dominant.
Renal osteodystrophy
Skeletal abnormalities, arising as a result of raised PTH secondary to chronic renal disease, are known as renal osteodystrophy.
Pathogenesis
renal Disease + ↓ vit. D activation , ↓ Ca 2+ reabsorption → ↓ serum Ca 2+ → ↑ PTH → ↓ bone absorption
Abnormalities vary widely according to the nature of the renal lesion, its duration and the age of the patient, but include:
- Osteitis fibrosa .
- Rickets or osteomalacia due to reduced activation of vitamin D.
- Osteosclerosis—increased radiodensity of certain bones, particularly the parts of vertebrae adjacent to the intervertebral discs.
The investigations are both biochemical (raised PTH and normal or lowered Ca 2+ ) and radiological (bone changes).
Management is by treatment of the underlying disease and oral calcium supplements to correct hypocalcaemia.
Tertiary hyperparathyroidism
This condition, resulting from chronic overstimulation of the parathyroid glands in renal failure, causes one or more of the glands to become an autonomous hypersecreting adenoma with resultant hypercalcaemia.
Middle-Third Facial Fractures
Oral and Maxillofacial SurgeryCharacteristics of Middle-Third Facial Fractures
Middle-third facial fractures, often referred to as "midfacial fractures,"
involve the central portion of the face, including the nasal bones, maxilla, and
zygomatic arch. These fractures can result from various types of trauma, such as
motor vehicle accidents, falls, or physical assaults. The following points
highlight the key features and clinical implications of middle-third facial
fractures:
1. Oedema of the Middle Third of the Face
Rapid Development: Oedema (swelling) in the middle third
of the face develops quickly after the injury, leading to a characteristic
"balloon" appearance. This swelling is due to the accumulation of fluid in
the soft tissues of the face.
Absence of Deep Cervical Fascia: The unique anatomical
structure of the middle third of the face contributes to this swelling. The
absence of deep cervical fascia in this region allows for the rapid spread
of fluid, resulting in pronounced oedema.
Clinical Presentation: In the early stages following
injury, patients with middle-third fractures often present with similar
facial appearances due to the characteristic swelling. This can make
diagnosis based solely on visual inspection challenging.
2. Lengthening of the Face
Displacement of the Middle Third: The downward and
backward displacement of the middle third of the facial skeleton can lead to
an increase in the overall length of the face. This displacement forces the
mandible to open, which can result in a change in occlusion, particularly in
the molar region.
Gagging of Occlusion: The altered position of the
mandible can lead to a malocclusion, where the upper and lower teeth do not
align properly. This can cause discomfort and difficulty in chewing or
speaking.
Delayed Recognition of Lengthening: The true increase in
facial length may not be fully appreciated until the initial oedema
subsides. As the swelling decreases, the changes in facial structure become
more apparent.
3. Nasal Obstruction
Blood Clots in the Nares: Following a middle-third
fracture, the nares (nostrils) may become obstructed by blood clots, leading
to nasal congestion. This can significantly impact the patient's ability to
breathe through the nose.
Mouth Breathing: Due to the obstruction, patients are
often forced to breathe through their mouths, which can lead to additional
complications, such as dry mouth and increased risk of respiratory
infections.
Conductivity
Physiology
Conductivity :
Means ability of cardiac muscle to propagate electrical impulses through the entire heart ( from one part of the heart to another) by the excitatory -conductive system of the heart.
Excitatory conductive system of the heart involves:
1. Sinoatrial node ( SA node) : Here the initial impulses start and then conducted to the atria through the anterior inter-atrial pathway ( to the left atrium) , to the atrial muscle mass through the gap junction, and to the Atrioventricular node ( AV node ) through anterior, middle , and posterior inter-nodal pathways.
The average conductive velocity in the atria is 1m/s.
2- AV node : The electrical impulses can not be conducted directly from the atria to the ventricles , because of the fibrous skeleton , which is an electrical isolator , located between the atria and ventricles. So the only conductive way is the AV node . But there is a delay in the conduction occurs in the AV node .
This delay is due to:
- the smaller size of the nodal fiber.
- The less negative resting membrane potential
- fewer gap junctions.
There are three sites for delay:
- In the transitional fibers , that connect inter-nodal pathways with the AV node ( 0.03 ) .
- AV node itself ( 0.09 s) .
- In the penetrating portion of Bundle of Hiss ( 0.04 s) .
This delay actually allows atria to empty blood in ventricles during the cardiac cycle before the beginning of ventricular contraction , as it prevents the ventricles from the pathological high atrial rhythm.
The average velocity of conduction in the AV node is 0.02-0.05 m/s
3- Bundle of Hiss : A continuous with the AV node that passes to the ventricles through the inter-ventricular septum. It is subdivided into : Right and left bundle. The left bundle is also subdivided into two branches: anterior and posterior branches .
4- Purkinje`s fibers: large fibers with velocity of conduction 1.5-4 m/s.
the high velocity of these fibers is due to the abundant gap junctions , and to their nature as very large fibers as well.
The conduction from AV node is a one-way conduction . This prevents the re-entry of cardiac impulses from the ventricles to the atria.
Lastly: The conduction through the ventricular fibers has a velocity of 0.3-0.5 m/s.
Factors , affecting conductivity ( dromotropism) :
I. Positive dromotropic factors :
1. Sympathetic stimulation : it accelerates conduction and decrease AV delay .
2. Mild warming
3. mild hyperkalemia
4. mild ischemia
5. alkalosis
II. Negative dromotropic factors :
1. Parasympathetic stimulation
2. severe warming
3. cooling
4. Severe hyperkalemia
5. hypokalemia
6. Severe ischemia
7. acidosis
8. digitalis drugs.
MANDIBULAR FIRST MOLAR
Dental Anatomy
MANDIBULAR FIRST MOLAR
It is the first permanent tooth to erupt.
Facial Surface:- The lower first permanent molar has the widest mesiodistal diameter of all of the molar teeth. Three cusps cusps separated by developmental grooves make on the occlusal outline The mesiobuccal cusp is usually the widest of the cusps. The mesiobuccal cusp is generally considered the largest of the five cusps. The distal root is usually less curved than the mesial root.
Lingual: Three cusps make up the occlusal profile in this view: the mesiolingual, the distolingual, and the distal cusp which is somewhat lower in profile. The mesiobuccal cusp is usually the widest and highest of the three. A short lingual developmental groove separates the two lingual cusps
Proximal: The distinctive height of curvature seen in the cervical third of the buccal surface is called the cervical ridge. The mesial surface may be flat or concave in its cervical third . It is highly convex in its middle and occlusal thirds. The occlusal profile is marked by the mesiobuccal cusp, mesiolingual cusp, and the mesial marginal ridge that connects them. The mesial root is the broadest buccolingually of any of the lower molar roots. The distal surface of the crown is narrower buccolingually than the mesial surface. Three cusps are seen from the distal aspect: the distobuccal cusp, the distal cusp, and the distolingual cusp.
Occlusal There are five cusps. Of them, the mesiobuccal cusp is the largest, the distal cusp is the smallest. The two buccal grooves and the single lingual groove form the "Y" patern distinctive for this tooth
Roots :-The tooth has two roots, a mesial and a distal.
Contact Points; The mesial contact is centered buccolingually just below the marginal ridge. The distal contact is centered over the distal root, but is buccal to the center point of the distal marginal ridge.
Roots: Lower molars have mesial and distal roots. In the first, molar, the mesial root is the largest. It has a distal curvature. The distal root has little curvature and projects distally.
The Protein Buffer Systems
Biochemistry
The Protein Buffer Systems
The protein buffers are very important in the plasma and the intracellular fluids but their concentration is very low in cerebrospinal fluid, lymph and interstitial fluids.
The proteins exist as anions serving as conjugate bases (Pr − ) at the blood pH 7.4 and form conjugate acids (HPr) accepting H+ . They have the capacity to buffer some H2CO3 in the blood.
Lupus erythematosus
General Pathology
Lupus erythematosus
- chronic discoid lupus is primarily limited to the skin, while SLE can involve the skin and other systems.
- pathogenesis: light and other external agents plus deposition of DNA (planted antigen) and immune complexes in the basement membrane.
Histology:
- basal cells along the dermal-epidermal junction and hair shafts (reason for alopecia) are vacuolated (liquefactive degeneration)
- thickening of lamina densa as a reaction to injury.
- immunofluorescent studies reveal a band of immunofluorescence (band test) in involved skin of chronic discoid lupus or involved/uninvolved skin of SLE.
- lymphocytic infiltrate at the dermal-epidermal junction and papillary dermis.
FUNGAL INFECTION- Aspergillosis
General Pathology
FUNGAL INFECTION
Aspergillosis
Opportunistic infections caused by Aspergillus sp and inhaled as mold conidia, leading to hyphal growth and invasion of blood vessels, hemorrhagic necrosis, infarction, and potential dissemination to other sites in susceptible patients.
Symptoms and Signs: Noninvasive or, rarely, minimally locally invasive colonization of preexisting cavitary pulmonary lesions also may occur in the form of fungus ball (aspergilloma) formation or chronic progressive aspergillosis.
Primary superficial invasive aspergillosis is uncommon but may occur in burns, beneath occlusive dressings, after corneal trauma (keratitis), or in the sinuses, nose, or ear canal.
Invasive pulmonary aspergillosis usually extends rapidly, causing progressive, ultimately fatal respiratory failure unless treated promptly and aggressively. A. fumigatus is the most common causative species.
Extrapulmonary disseminated aspergillosis may involve the liver, kidneys, brain, or other tissues and is usually fatal. Primary invasive aspergillosis may also begin as an invasive sinusitis, usually caused by A. flavus, presenting as fever with rhinitis and headache