NEET MDS Synopsis
DIABETES MELLITUS
General Pathology
DIABETES MELLITUS
a group of metabolic disorders sharing the common underlying characteristic of hyperglycemia.
Diabetes is an important disease because
1. It is common (affects 7% of the population).
2. It increases the risk of atherosclerotic coronary artery and cerebrovascular diseases.
3. It is a leading cause of
a. Chronic renal failure
b. Adult-onset blindness
c. Non traumatic lower extremity amputations (due to gangrene)
Classification
Diabetes is divided into two broad classes:
1. Type1 diabetes (10%): characterized by an absolute deficiency of insulin secretion caused by pancreatic βcell destruction, usually as a result of an autoimmune attack.
2. Type2 diabetes (80%): caused by a combination of peripheral resistance to insulin action and an inadequate secretion of insulin from the pancreatic β cells in response to elevated blood glucose levels.
The long-term complications in kidneys, eyes, nerves, and blood vessels are the same in both types.
Pathogenesis
Type 1 diabetes is an autoimmune disease and as in all such diseases, genetic susceptibility and environmental influences play important roles in the pathogenesis. The islet destruction is caused primarily by T lymphocytes reacting against immunologic epitopes on the insulin hormone located within β-cell; this results in a reduction of β-cell mass. The reactive T cells include CD4+ T cells of the TH1 subset, which cause tissue injury by activating macrophages, and CD8+ cytotoxic T lymphocytes; these directly kill β cells and also secrete cytokines that activate further macrophages. The islets show cellular necrosis and lymphocytic infiltration (insulitis). Autoantibodies against a variety of β-cell antigens, including insulin are also detected in the blood and may also contribute to islet damage.
Type 2 Diabetes Mellitus: the pathogenesis remains unsettled. Environmental influences, such as inactive life style and dietary habits that eventuates in obesity, clearly have a role. Nevertheless, genetic factors are even more important than in type 1 diabetes. Among first-degree relatives with type 2 diabetes the risk of developing the disease is 20% to 40%, as compared with 5% in the general population.
The two metabolic defects that characterize type 2 diabetes are 1. A decreased ability of peripheral tissues to respond to insulin (insulin resistance) and 2. β-cell dysfunction manifested as inadequate insulin secretion in the face of hyperglycemia. In most cases, insulin resistance is the primary event and is followed by increasing degrees of β-cell dysfunction.
Morphology of Diabetes and Its Late Complications
The important morphologic changes are related to the many late systemic complications of diabetes and thus are likely to be found in arteries (macrovascular disease), basement membranes of small vessels (microangiopathy), kidneys (diabetic nephropathy), retina (retinopathy), and nerves (neuropathy). These changes are seen in both type 1 and type 2 diabetes.
The changes are divided into pancreatic & extrapancreatic
A. Pancreatic changes are inconstant and are more commonly associated with type 1 than with type 2 diabetes.
One or more of the following alterations may be present.
1. Reduction in the number and size of islets
2. Leukocytic infiltration of the islets (insulitis) principally byT lymphocytes.
3. Amyloid replacement of islets; which is seen in advanced stages
B. Extrapancreatic changes
1. Diabetic macrovascular disease is reflected as accelerated atherosclerosis affecting the aorta and other large and medium-sized arteries including the coronaries. Myocardial infarction is the most common cause of death in diabetics. Gangrene of the lower limbs due to advanced vascular disease, is about 100 times more common in diabetics than in the general population.
2. Hyaline arteriolosclerosis
is the vascular lesion associated with hypertension. It is both more prevalent and more severe in diabetics than in nondiabetics, but it is not specific for diabetes and may be seen in elderly nondiabetics without hypertension.
3. Diabetic microangiopathy
is one of the most consistent morphologic features of diabetes, which reflected morphologically as diffuse thickening of basement membranes. The thickening is most evident in the capillaries of the retina, renal glomeruli, and peripheral nerves. The thickened capillary basement membranes are associated with leakiness to plasma proteins. The microangiopathy underlies the development of diabetic nephropathy, retinopathy, and some forms of neuropathy.
4. Diabetic Nephropathy: renal failure is second only to myocardial infarction as a cause of death from diabetes.
Three lesions encountered are:
1. Glomerular lesions
2. Renal vascular lesions, principally arteriolosclerosis; and
3. Pyelonephritis, including necrotizing papillitis.
Glomerular lesions: these include
a. diffuse glomerular capillary basement membrane thickening
b. diffuse glomerular sclerosis : diffuse increase in mesangial matrix; always associated with the above.
c. nodular glomerulosclerosis (Kimmelstiel-Wilson lesion) refers to a rounded deposits of a laminated matrix situated in the periphery of the glomerulus
Pyelonephritis: both acute and chronic pyelonephritis are more common & more severe
Ocular Complications of Diabetes: Visual impairment up to total blindness may occur in long-standing diabetes. The ocular involvement may take the form of
a. retinopathy
b. cataract formation
c. glaucoma
In both forms of long-standing diabetes, cardiovascular events such as myocardial infarction, renal vascular insufficiency, and cerebrovascular accidents are the most common causes of mortality. Diabetic nephropathy is a leading cause of end-stage renal disease. By 20 years after diagnosis, more than 75% of type 1 diabetics and about 20% of type 2 diabetics with overt renal disease will develop end-stage renal disease, requiring dialysis or renal transplantation.
Diabetics are plagued by an enhanced susceptibility to infections of the skin, as well as to tuberculosis,
pneumonia, and pyelonephritis. Such infections cause the deaths of about 5% of diabetics.
Early Childhood Caries (ECC) Classification
Conservative DentistryEarly Childhood Caries (ECC) Classification
Early Childhood Caries (ECC) is a significant public health concern
characterized by the presence of carious lesions in young children. It is
classified into three types based on severity, affected teeth, and underlying
causes. Understanding these classifications helps in diagnosing, preventing, and
managing ECC effectively.
Type I ECC (Mild to Moderate)
A. Characteristics
Affected Teeth: Carious lesions primarily involve the
molars and incisors.
Age Group: Typically observed in children aged 2
to 5 years.
B. Causes
Dietary Factors: The primary cause is usually a
combination of cariogenic semisolid or solid foods, such as sugary snacks
and beverages.
Oral Hygiene: Lack of proper oral hygiene practices
contributes significantly to the development of caries.
Progression: As the cariogenic challenge persists, the
number of affected teeth tends to increase.
C. Clinical Implications
Management: Emphasis on improving oral hygiene
practices and dietary modifications can help control and reverse early
carious lesions.
Type II ECC (Moderate to Severe)
A. Characteristics
Affected Teeth: Labio-lingual carious lesions primarily
affect the maxillary incisors, with or without molar caries, depending on
the child's age.
Age Group: Typically seen soon after the first tooth
erupts.
B. Causes
Feeding Practices: Common causes include inappropriate
use of feeding bottles, at-will breastfeeding, or a combination of both.
Oral Hygiene: Poor oral hygiene practices exacerbate
the condition.
Progression: If not controlled, Type II ECC can
progress to more advanced stages of caries.
C. Clinical Implications
Intervention: Early intervention is crucial, including
education on proper feeding practices and oral hygiene to prevent further
carious development.
Type III ECC (Severe)
A. Characteristics
Affected Teeth: Carious lesions involve almost all
teeth, including the mandibular incisors.
Age Group: Usually observed in children aged 3
to 5 years.
B. Causes
Multifactorial: The etiology is a combination of
various factors, including poor oral hygiene, dietary habits, and possibly
socio-economic factors.
Rampant Nature: This type of ECC is rampant and can
affect immune tooth surfaces, leading to extensive decay.
C. Clinical Implications
Management: Requires comprehensive dental treatment,
including restorative procedures and possibly extractions. Education on
preventive measures and regular dental visits are essential to manage and
prevent recurrence.
Routes of Drug Administration
Pharmacology
Routes of Drug Administration
Intravenous
No barriers to absorption since drug is put directly into the blood.
There is a very rapid onset for drugs administered intravenously. This can be advantagous in emergency situations, but can also be very dangerous.
This route offers a great deal of control in respect to drug levels in the blood.
Irritant drugs can be administer by the IV route without risking tissue injury.
IV drug administration is expensive, inconvenient and more difficult than administration by other routes.
Other disadvantages include the risk of fluid overload, infection, and embolism. Some drug formulations are completely unsafe for use intravenously.
Intramuscular:
Only the capillary wall separates the drug from the blood, so there is not a significant barrier to the drug's absorption.
The rate of absorption varies with the drug's solubility and the blood flow at the site of injection.
The IM route is uncomfortable and inconvenient for the patient, and if administered improperly, can lead to tissue or nerve damage.
Subcutaneous
Same characteristics as the IM route.
Oral
Two barriers to cross: epithelial cells and capillary wall. To cross the epithelium, drugs have to pass through the cells.
Highly variable drug absorption influenced by many factors: pH, drug solubility and stability, food intake, other drugs, etc.
Easy, convenient, and inexpensive. Safer than parenteral injection, so that oral administration is generally the preferred route.
Some drugs would be inactivated by this route
Inappropriate route for some patients.
May have some GI discomfort, nausea and vomiting.
Types of oral meds = tablets, enteric-coated, sustained-release, etc.
Topical, Inhalational agents, Suppositories
Comparison of Fatty acid synthesis and b-oxidation pathways
Biochemistry
b Oxidation Pathway
Fatty Acid Synthesis
pathway location
mitochondrial matrix
cytosol
acyl carriers (thiols)
Coenzyme-A
phosphopantetheine (ACP) & cysteine
electron acceptors/donor
FAD & NAD+
NADPH
hydroxyl intermediate
L
D
2-C product/donor
acetyl-CoA
malonyl-CoA (& acetyl-CoA)
Gypsum Products
Dental Materials
Gypsum Products
Characteristics
Plaster
Stone
Diestone
Chemical Name
Beta-Calcium Sulfate hemihydrate
Alpha-Calcium sulfate hemihydrate
Alpha-Calcium sulfate hemihydrate
Formula
CaSO4 – ½ H2O
CaSO4 – ½ H2O
CaSO4 – ½ H2O
Uses
Plaster Models ,Impression Plasters
Cast Stone, Investment
Improved Stone, diestone
Water(W)
Reaction Water
Extra Water
Total water
Powder (P)
W/P Ratio
18ml
32ml
50ml
100g
0.50
18ml
12ml
30ml
100g
0.30
18ml
6ml
24ml
100g
0.24
Fifth Generation:
Pharmacology
Fifth Generation:
These are extended spectrum antibiotics.
Ceftaroline, Ceftobiprole
Tooth eruption Theories
Dental Anatomy
Tooth eruption Theories
Tooth eruption occurs when the teeth enter the mouth and become visible. Although researchers agree that tooth eruption is a complex process, there is little agreement on the identity of the mechanism that controls eruption. Some commonly held theories that have been disproven over time include: (1) the tooth is pushed upward into the mouth by the growth of the tooth's root, (2) the tooth is pushed upward by the growth of the bone around the tooth, (3) the tooth is pushed upward by vascular pressure, and (4) the tooth is pushed upward by the cushioned hammock. The cushioned hammock theory, first proposed by Harry Sicher, was taught widely from the 1930s to the 1950s. This theory postulated that a ligament below a tooth, which Sicher observed on under a microscope on a histologic slide, was responsible for eruption. Later, the "ligament" Sicher observed was determined to be merely an artifact created in the process of preparing the slide.
The most widely held current theory is that while several forces might be involved in eruption, the periodontal ligaments provide the main impetus for the process. Theorists hypothesize that the periodontal ligaments promote eruption through the shrinking and cross-linking of their collagen fibers and the contraction of their fibroblasts.
Although tooth eruption occurs at different times for different people, a general eruption timeline exists. Typically, humans have 20 primary (baby) teeth and 32 permanent teeth. Tooth eruption has three stages. The first, known as deciduous dentition stage, occurs when only primary teeth are visible. Once the first permanent tooth erupts into the mouth, the teeth are in the mixed (or transitional) dentition. After the last primary tooth falls out of the mouth—a process known as exfoliation—the teeth are in the permanent dentition.
Primary dentition starts on the arrival of the mandibular central incisors, usually at eight months, and lasts until the first permanent molars appear in the mouth, usually at six years. The primary teeth typically erupt in the following order: (1) central incisor, (2) lateral incisor, (3) first molar, (4) canine, and (5) second molar. As a general rule, four teeth erupt for every six months of life, mandibular teeth erupt before maxillary teeth, and teeth erupt sooner in females than males. During primary dentition, the tooth buds of permanent teeth develop below the primary teeth, close to the palate or tongue.
Mixed dentition starts when the first permanent molar appears in the mouth, usually at six years, and lasts until the last primary tooth is lost, usually at eleven or twelve years. Permanent teeth in the maxilla erupt in a different order from permanent teeth on the mandible. Maxillary teeth erupt in the following order: (1) first molar (2) central incisor, (3) lateral incisor, (4) first premolar, (5) second premolar, (6) canine, (7) second molar, and (8) third molar. Mandibular teeth erupt in the following order: (1) first molar (2) central incisor, (3) lateral incisor, (4) canine, (5) first premolar, (6) second premolar, (7) second molar, and (8) third molar. Since there are no premolars in the primary dentition, the primary molars are replaced by permanent premolars. If any primary teeth are lost before permanent teeth are ready to replace them, some posterior teeth may drift forward and cause space to be lost in the mouth. This may cause crowding and/or misplacement once the permanent teeth erupt, which is usually referred to as malocclusion. Orthodontics may be required in such circumstances for an individual to achieve a straight set of teeth.
The permanent dentition begins when the last primary tooth is lost, usually at 11 to 12 years, and lasts for the rest of a person's life or until all of the teeth are lost (edentulism). During this stage, third molars (also called "wisdom teeth") are frequently extracted because of decay, pain or impactions. The main reasons for tooth loss are decay or periodontal disease.
Refractory Material
Conservative DentistryRefractory materials are essential in the field of dentistry, particularly in
the branch of conservative dentistry and prosthodontics, for the fabrication of
various restorations and appliances. These materials are characterized by their
ability to withstand high temperatures without undergoing significant
deformation or chemical change. This is crucial for the longevity and stability
of the dental work. The primary function of refractory materials is to provide a
precise and durable mold or pattern for the casting of metal restorations, such
as crowns, bridges, and inlays/onlays.
Refractory materials include:
- Plaster of Paris: The most commonly used refractory material
in dentistry, plaster is composed of calcium sulfate hemihydrate. It is mixed
with water to form a paste that is used to make study models and casts. It has a
relatively low expansion coefficient and is easy to manipulate, making it
suitable for various applications.
- Dental stone: A more precise alternative to plaster, dental
stone is a type of gypsum product that offers higher strength and less
dimensional change. It is commonly used for master models and die fabrication
due to its excellent surface detail reproduction.
- Investment materials: Used in the casting process of fabricating indirect
restorations, investment materials are refractory and encapsulate the wax
pattern to create a mold. They can withstand the high temperatures required for
metal casting without distortion.
- Zirconia: A newer refractory material gaining popularity,
zirconia is a ceramic that is used for the fabrication of all-ceramic crowns and
bridges. It is extremely durable and has a high resistance to wear and fracture.
- Refractory die materials: These are used in the production of
metal-ceramic restorations. They are capable of withstanding the high
temperatures involved in the ceramic firing process and provide a reliable
foundation for the ceramic layers.
The selection of a refractory material is based on factors such as the intended
use, the required accuracy, and the specific properties needed for the final
restoration. The material must have a low thermal expansion coefficient to
minimize the thermal stress during the casting process and maintain the
integrity of the final product. Additionally, the material should be able to
reproduce the fine details of the oral anatomy and have good physical and
mechanical properties to ensure stability and longevity.
Refractory materials are typically used in the following procedures:
- Impression taking: Refractory materials are used to make models from the
patient's impressions.
- Casting of metal restorations: A refractory mold is created from the model to
cast the metal framework.
- Ceramic firing: Refractory die materials hold the ceramic in place while it is
fired at high temperatures.
- Temporary restorations: Some refractory materials can be used to produce
temporary restorations that are highly accurate and durable.
Refractory materials are critical for achieving the correct fit and function of
dental restorations, as well as ensuring patient satisfaction with the
aesthetics and comfort of the final product.