NEET MDS Synopsis
Multiple Endocrine Neoplasia Syndromes
General Pathology
Multiple Endocrine Neoplasia Syndromes (MEN)
The MEN syndromes are a group of inherited diseases resulting in proliferative lesions (hyperplasias, adenomas, and carcinomas) of multiple endocrine organs. Even in one organ, the tumors are often multifocal. These tumors are usually more aggressive and recur in a higher proportion of cases than similar but sporadic endocrine tumors.
Multiple Endocrine Neoplasia Type 1 (MEN1) is inherited in an autosomal dominant pattern. The gene (MEN1) is a tumor suppressor gene; thus, inactivation of both alleles of the gene is believed to be the basis of tumorigenesis. Organs commonly involved include the parathyroid, pancreas, and pituitary (the 3 Ps). Parathyroid hyperplasia is the most consistent feature of MEN-1 but endocrine tumors of the pancreas are the leading cause of death because such tumors are usually aggressive and present with metastatic disease.
Zollinger-Ellison syndrome, associated with gastrinomas, and hypoglycemia, related to insulinomas, are common endocrine manifestations. Prolactin-secreting macroadenoma is the most frequent pituitary tumor in MEN-1 patients.
Multiple Endocrine Neoplasia Type 2 (MEN2)
MEN type 2 is actually two distinct groups of disorders that are unified by the occurrence of activating mutations of the RET protooncogene. Both are inherited in an autosomal dominant pattern.
MEN 2A
Organs commonly involved include:
Medullary carcinoma of the thyroid develops in virtually all cases, and the tumors usually occur in the first 2 decades of life. The tumors are commonly multifocal, and foci of C-cell hyperplasia can be found in the adjacent thyroid. Adrenal pheochromocytomas develop in 50% of patients; fortunately, no more than 10% are malignant. Parathyroid gland hyperplasia with primary hyperparathyroidism occurs in a third of patients.
Multiple Endocrine Neoplasia, Type 2B
Organs commonly involved include the thyroid and adrenal medulla. The spectrum of thyroid and adrenal medullary disease is similar to that in MEN-2A. However, unlike MEN-2A, patients with MEN-2B:
1. Do not develop primary hyperparathyroidism
2. Develop extraendocrine manifestations: ganglioneuromas of mucosal sites (gastrointestinal tract, lips, tongue) and marfanoid habitus
Nephron
Physiology
The nephron of the kidney is involved in the regulation of water and soluble substances in blood.
A Nephron
A nephron is the basic structural and functional unit of the kidneys that regulates water and soluble substances in the blood by filtering the blood, reabsorbing what is needed, and excreting the rest as urine.
Its function is vital for homeostasis of blood volume, blood pressure, and plasma osmolarity.
It is regulated by the neuroendocrine system by hormones such as antidiuretic hormone, aldosterone, and parathyroid hormone.
The Glomerulus
The glomerulus is a capillary tuft that receives its blood supply from an afferent arteriole of the renal circulation. Here, fluid and solutes are filtered out of the blood and into the space made by Bowman's capsule.
A group of specialized cells known as juxtaglomerular apparatus (JGA) are located around the afferent arteriole where it enters the renal corpuscle. The JGA secretes an enzyme called renin, due to a variety of stimuli, and it is involved in the process of blood volume homeostasis.
The Bowman's capsule surrounds the glomerulus. It is composed of visceral (simple squamous epithelial cells; inner) and parietal (simple squamous epithelial cells; outer) layers.
Red blood cells and large proteins, such as serum albumins, cannot pass through the glomerulus under normal circumstances. However, in some injuries they may be able to pass through and can cause blood and protein content to enter the urine, which is a sign of problems in the kidney.
Proximal Convoluted Tubule
The proximal tubule is the first site of water reabsorption into the bloodstream, and the site where the majority of water and salt reabsorption takes place. Water reabsorption in the proximal convoluted tubule occurs due to both passive diffusion across the basolateral membrane, and active transport from Na+/K+/ATPase pumps that actively transports sodium across the basolateral membrane.
Water and glucose follow sodium through the basolateral membrane via an osmotic gradient, in a process called co-transport. Approximately 2/3rds of water in the nephron and 100% of the glucose in the nephron are reabsorbed by cotransport in the proximal convoluted tubule.
Fluid leaving this tubule generally is unchanged due to the equivalent water and ion reabsorption, with an osmolarity (ion concentration) of 300 mOSm/L, which is the same osmolarity as normal plasma.
The Loop of Henle
The loop of Henle is a U-shaped tube that consists of a descending limb and ascending limb. It transfers fluid from the proximal to the distal tubule. The descending limb is highly permeable to water but completely impermeable to ions, causing a large amount of water to be reabsorbed, which increases fluid osmolarity to about 1200 mOSm/L. In contrast, the ascending limb of Henle's loop is impermeable to water but highly permeable to ions, which causes a large drop in the osmolarity of fluid passing through the loop, from 1200 mOSM/L to 100 mOSm/L.
Distal Convoluted Tubule and Collecting Duct
The distal convoluted tubule and collecting duct is the final site of reabsorption in the nephron. Unlike the other components of the nephron, its permeability to water is variable depending on a hormone stimulus to enable the complex regulation of blood osmolarity, volume, pressure, and pH.
Normally, it is impermeable to water and permeable to ions, driving the osmolarity of fluid even lower. However, anti-diuretic hormone (secreted from the pituitary gland as a part of homeostasis) will act on the distal convoluted tubule to increase the permeability of the tubule to water to increase water reabsorption. This example results in increased blood volume and increased blood pressure. Many other hormones will induce other important changes in the distal convoluted tubule that fulfill the other homeostatic functions of the kidney.
The collecting duct is similar in function to the distal convoluted tubule and generally responds the same way to the same hormone stimuli. It is, however, different in terms of histology. The osmolarity of fluid through the distal tubule and collecting duct is highly variable depending on hormone stimulus. After passage through the collecting duct, the fluid is brought into the ureter, where it leaves the kidney as urine.
Blood Pressure
Physiology
Blood Pressure
Blood moves through the arteries, arterioles, and capillaries because of the force created by the contraction of the ventricles.
Blood pressure in the arteries.
The surge of blood that occurs at each contraction is transmitted through the elastic walls of the entire arterial system where it can be detected as the pulse. Even during the brief interval when the heart is relaxed — called diastole — there is still pressure in the arteries. When the heart contracts — called systole — the pressure increases.
Blood pressure is expressed as two numbers, e.g., 120/80.
Blood pressure in the capillaries
The pressure of arterial blood is largely dissipated when the blood enters the capillaries. Capillaries are tiny vessels with a diameter just about that of a red blood cell (7.5 µm). Although the diameter of a single capillary is quite small, the number of capillaries supplied by a single arteriole is so great that the total cross-sectional area available for the flow of blood is increased. Therefore, the pressure of the blood as it enters the capillaries decreases.
Blood pressure in the veins
When blood leaves the capillaries and enters the venules and veins, little pressure remains to force it along. Blood in the veins below the heart is helped back up to the heart by the muscle pump. This is simply the squeezing effect of contracting muscles on the veins running through them. One-way flow to the heart is achieved by valves within the veins
Exchanges Between Blood and Cells
With rare exceptions, our blood does not come into direct contact with the cells it nourishes. As blood enters the capillaries surrounding a tissue space, a large fraction of it is filtered into the tissue space. It is this interstitial or extracellular fluid (ECF) that brings to cells all of their requirements and takes away their products. The number and distribution of capillaries is such that probably no cell is ever farther away than 50 µm from a capillary.
When blood enters the arteriole end of a capillary, it is still under pressure produced by the contraction of the ventricle. As a result of this pressure, a substantial amount of water and some plasma proteins filter through the walls of the capillaries into the tissue space.
Thus fluid, called interstitial fluid, is simply blood plasma minus most of the proteins. (It has the same composition and is formed in the same way as the nephric filtrate in kidneys.)
Interstitial fluid bathes the cells in the tissue space and substances in it can enter the cells by diffusion or active transport. Substances, like carbon dioxide, can diffuse out of cells and into the interstitial fluid.
Near the venous end of a capillary, the blood pressure is greatly reduced .Here another force comes into play. Although the composition of interstitial fluid is similar to that of blood plasma, it contains a smaller concentration of proteins than plasma and thus a somewhat greater concentration of water. This difference sets up an osmotic pressure. Although the osmotic pressure is small, it is greater than the blood pressure at the venous end of the capillary. Consequently, the fluid reenters the capillary here.
Control of the Capillary Beds
An adult human has been estimated to have some 60,000 miles of capillaries with a total surface area of some 800–1000 m2. The total volume of this system is roughly 5 liters, the same as the total volume of blood. However, if the heart and major vessels are to be kept filled, all the capillaries cannot be filled at once. So a continual redirection of blood from organ to organ takes place in response to the changing needs of the body. During vigorous exercise, for example, capillary beds in the skeletal muscles open at the expense of those in the viscera. The reverse occurs after a heavy meal.
The walls of arterioles are encased in smooth muscle. Constriction of arterioles decreases blood flow into the capillary beds they supply while dilation has the opposite effect. In time of danger or other stress, for example, the arterioles supplying the skeletal muscles will be dilated while the bore of those supplying the digestive organs will decrease. These actions are carried out by
the autonomic nervous system.
local controls in the capillary beds
Neurophysiology - Local Anesthetics
Anaesthesia
1. Refractory periods: absolute (neuron cannot fire) and relative (can fire with greater than normal depolarization)
2. Specific receptor theory: local anesthetics bind inside Na channel, block entry of Na
3. Membrane expansion theory: anesthetics work by disrupting lipid bilayer around ion channel
4. Mechanism of action for local anesthetics: local must be in uncharged form to cross lipid bilayer of axon
a. Locals made as salts (usually mixed with HCl). [Uncharged form] depends on pH of tissue, pKa of local-found by Henderson-Hasselbach equation- pH = pKa + log ( [RN] / [RNH+] )
b. Once inside axon, only charged form will bind to Na channel.
c. At physiologic pH, enough base exists outside nerve so anesthetic rapidly diffuses into axon. Rate-limiting step is how much uncharged local is present outside neuron.
d. So, starts with 100 molecules of local, 25 of which are uncharged and 75 charged. The 25 uncharged enter the neuron, leaving 0 on outside so the remaining 75 re-equilibrate to produce more uncharged which enters neuron . Inside neuron the reverse happens as converted to ionic form then rapidly binds channel.
5. Inflammatory effects: ® an acidic environment, less of local can be converted to uncharged form (less enters).
6. Pharmakokinetics: pool of local outside neuron depleted as local diffuses into adjacent muscles, tissues, enters blood vessels. Since locals are water soluble, they go throughout body (even cross BBB and placenta)
7. Autonomic nervous system: sympathetic and parasympathetic divisions. Both secrete pre-ganglionic acetylcholine. Postganglionic NT is acetylcholine for parasympathetic, norepinephrine for sympathetic (also secrete E, dopamine, and seratonin, all are catecholamines).
a. Sympathetic catecholamines affect receptors (local anesthetics affect a1-mediated actions which cause vasoconstriction) ® fight or flight responses (pupil & bronchiole dilation, HR, BP, blood glucose; ¯ GI)
b. Catecholamines inactivated by reuptake, diffusion, or metabolized by monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT) then metabolites excreted in urine.
c. When choosing sympathomimetic drug, consider receptor subtype in tissue and choose drug that affects it.
Bleeding Disorders
PhysiologyBleeding Disorders
A deficiency of a clotting factor can lead to uncontrolled bleeding.
The deficiency may arise because
not enough of the factor is produced or
a mutant version of the factor fails to perform properly.
Examples:
von Willebrand disease (the most common)
hemophilia A for factor 8 deficiency
hemophilia B for factor 9 deficiency.
hemophilia C for factor 11 deficiency
In some cases of von Willebrand disease, either a deficient level or a mutant version of the factor eliminates its protective effect on factor 8. The resulting low level of factor 8 mimics hemophilia A.
Gingiva
Dental Anatomy
Gingiva
The connection between the gingiva and the tooth is called the dentogingival junction. This junction has three epithelial types: gingival, sulcular, and junctional epithelium. These three types form from a mass of epithelial cells known as the epithelial cuff between the tooth and the mouth.
Much about gingival formation is not fully understood, but it is known that hemidesmosomes form between the gingival epithelium and the tooth and are responsible for the primary epithelial attachment. Hemidesmosomes provide anchorage between cells through small filament-like structures provided by the remnants of ameloblasts. Once this occurs, junctional epithelium forms from reduced enamel epithelium, one of the products of the enamel organ, and divides rapidly. This results in the perpetually increasing size of the junctional epithelial layer and the isolation of the remenants of ameloblasts from any source of nutrition. As the ameloblasts degenerate, a gingival sulcus is created.
Pit and Fissure Sealants
PedodonticsPit and Fissure Sealants
Pit and fissure sealants are preventive dental materials used to protect
occlusal surfaces of teeth from caries by sealing the grooves and pits that are
difficult to clean. According to Mitchell and Gordon (1990), sealants can be
classified based on several criteria, including polymerization methods, resin
systems, filler content, and color.
Classification of Pit and Fissure Sealants
1. Polymerization Methods
Sealants can be differentiated based on how they harden or polymerize:
a) Self-Activation (Mixing Two Components)
These sealants harden through a chemical reaction that occurs when
two components are mixed together. This method does not require any
external light source.
b) Light Activation
Sealants that require a light source to initiate the polymerization
process can be further categorized into generations:
First Generation: Ultraviolet Light
Utilizes UV light for curing, which can be less common due
to safety concerns.
Second Generation: Self-Cure
These sealants harden through a chemical reaction without
the need for light, similar to self-activating sealants.
Third Generation: Visible Light
Cured using visible light, which is more user-friendly and
safer than UV light.
Fourth Generation: Fluoride-Releasing
These sealants not only provide a physical barrier but also
release fluoride, which can help in remineralizing enamel and
providing additional protection against caries.
2. Resin System
The type of resin used in sealants can also classify them:
BIS-GMA (Bisphenol A Glycidyl Methacrylate)
A commonly used resin that provides good mechanical properties and
adhesion.
Urethane Acrylate
Offers enhanced flexibility and durability, making it suitable for
areas subject to stress.
3. Filled and Unfilled
Sealants can be categorized based on the presence of fillers:
Filled Sealants
Contain added particles that enhance strength and wear resistance.
They may provide better wear characteristics but can be more viscous and
difficult to apply.
Unfilled Sealants
Typically have a smoother flow and are easier to apply, but may not
be as durable as filled sealants.
4. Clear or Tinted
The color of the sealant can also influence its application:
Clear Sealants
Have better flow characteristics, allowing for easier penetration
into pits and fissures. They are less visible, which can be a
disadvantage in monitoring during follow-up visits.
Tinted Sealants
Easier for both patients and dentists to see, facilitating
monitoring and assessment during recalls. However, they may have
slightly different flow characteristics compared to clear sealants.
Application Process
Sealants are applied in a viscous liquid state that enters the
micropores of the tooth surface, which have been enlarged through acid
conditioning.
Once applied, the resin hardens due to either a self-hardening catalyst
or the application of a light source.
The extensions of the hardened resin that penetrate and fill the
micropores are referred to as "tags," which help in retaining the sealant on
the tooth surface.
Structural Divisions of the nervous system
PhysiologyStructural Divisions of the nervous system:
1) Central Nervous System (CNS) - the brain and spinal cord.
2) Peripheral Nervous System (PNS) - the nerves, ganglia, receptors, etc