NEET MDS Lessons
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.
The thyroid gland is a double-lobed structure located in the neck. Embedded in its rear surface are the four parathyroid glands.
The Thyroid Gland
The thyroid gland synthesizes and secretes:
- thyroxine (T4) and
- calcitonin
T4 and T3
Thyroxine (T4 ) is a derivative of the amino acid tyrosine with four atoms of iodine. In the liver, one atom of iodine is removed from T4 converting it into triiodothyronine (T3). T3 is the active hormone. It has many effects on the body. Among the most prominent of these are:
- an increase in metabolic rate
- an increase in the rate and strength of the heart beat.
The thyroid cells responsible for the synthesis of T4 take up circulating iodine from the blood. This action, as well as the synthesis of the hormones, is stimulated by the binding of TSH to transmembrane receptors at the cell surface.
Diseases of the thyroid
1. hypothyroid diseases; caused by inadequate production of T3
- cretinism: hypothyroidism in infancy and childhood leads to stunted growth and intelligence. Can be corrected by giving thyroxine if started early enough.
- myxedema: hypothyroidism in adults leads to lowered metabolic rate and vigor. Corrected by giving thyroxine.
- goiter: enlargement of the thyroid gland. Can be caused by:
- inadequate iodine in the diet with resulting low levels of T4 and T3;
- an autoimmune attack against components of the thyroid gland (called Hashimoto's thyroiditis).
2. hyperthyroid diseases; caused by excessive secretion of thyroid hormones
Graves´ disease. Autoantibodies against the TSH receptor bind to the receptor mimicking the effect of TSH binding. Result: excessive production of thyroid hormones. Graves´ disease is an example of an autoimmune disease.
Osteoporosis. High levels of thyroid hormones suppress the production of TSH through the negative-feedback mechanism mentioned above. The resulting low level of TSH causes an increase in the numbers of bone-reabsorbing osteoclasts resulting in osteoporosis.
Calcitonin
Calcitonin is a polypeptide of 32 amino acids. The thyroid cells in which it is synthesized have receptors that bind calcium ions (Ca2+) circulating in the blood. These cells monitor the level of circulating Ca2+. A rise in its level stimulates the cells to release calcitonin.
- bone cells respond by removing Ca2+ from the blood and storing it in the bone
- kidney cells respond by increasing the excretion of Ca2+
Both types of cells have surface receptors for calcitonin.
Because it promotes the transfer of Ca2+ to bones, calcitonin has been examined as a possible treatment for osteoporosis
Membrane Structure & Function
Cell Membranes
- Cell membranes are phospholipid bilayers (2 layers)
- Bilayer forms a barrier to passage of molecules in an out of cell
- Phospholipids = glycerol + 2 fatty acids + polar molecule (i.e., choline) + phosphate
- Cholesterol (another lipid) stabilizes cell membranes
- the hydrophobic tails of the phospholipids (fatty acids) are together in the center of the bilayer. This keeps them out of the water
Membranes Also Contain Proteins
- Proteins that penetrate the membrane have hydrophobic sections ~25 amino acids long
- Hydrophobic = doesn't like water = likes lipids
- Membrane proteins have many functions:
- receptors for hormones
- pumps for transporting materials across the membrane
- ion channels
- adhesion molecules for holding cells to extracellular matrix
cell recognition antigens
Lipids:
- about 40% of the dry mass of a typical cell
- composed largely of carbon & hydrogen
- generally insoluble in water
- involved mainly with long-term energy storage; other functions are as structural components (as in the case of phospholipids that are the major building block in cell membranes) and as "messengers" (hormones) that play roles in communications within and between cells
- Subclasses include:
- Triglycerides - consist of one glycerol molecule + 3 fatty acids (e.g., stearic acid in the diagram below). Fatty acids typically consist of chains of 16 or 18 carbons (plus lots of hydrogens).
- phospholipids - Composed of 2 fatty acids, glycerol, phosphate and polar groups , phosphate group (-PO4) substitutes for one fatty acid & these lipids are an important component of cell membranes
steroids - have 4 rings- cholesterol, some hormones, found in membranes include testosterone, estrogen, & cholesterol
AdenosineTriphosphate (ATP)
- Animal cells cannot directly use most forms of energy
- Most cellular processes require energy stored in the bonds of a molecule, adenosine triphosphate (ATP)
- ATP is referred to as the energy currency of the cell
It is a nucleotide, formed from:
- the base adenine (the structure with 2 rings),
- the 5 carbon sugar deoxyribose (one ring)
- 3 phosphates
Energy is stored in the bonds between the phosphates and is released when the bonds are broken
Respiration involves several components:
Ventilation - the exchange of respiratory gases (O2 and CO2) between the atmosphere and the lungs. This involves gas pressures and muscle contractions.
External respiration - the exchange of gases between the lungs and the blood. This involves partial pressures of gases, diffusion, and the chemical reactions involved in transport of O2and CO2.
Internal respiration - the exchange of gases between the blood and the systemic tissues. This involves the same processes as external respiration.
Cellular respiration - the includes the metabolic pathways which utilize oxygen and produce carbon dioxide, which will not be included in this unit.
Ventilation is composed of two parts: inspiration and expiration. Each of these can be described as being either quiet, the process at rest, or forced, the process when active such as when exercising.
Quiet inspiration:
The diaphragm contracts, this causes an increase in volume of the thorax and the lungs, which causes a decrease in pressure of the thorax and lungs, which causes air to enter the lungs, moving down its pressure gradient. Air moves into the lungs to fill the partial vacuum created by the increase in volume.
Forced inspiration:
Other muscles aid in the increase in thoracic and lung volumes.
The scalenes - pull up on the first and second ribs.
The sternocleidomastoid muscles pull up on the clavicle and sternum.
The pectoralis minor pulls forward on the ribs.
The external intercostals are especially important because they spread the ribs apart, thus increasing thoracic volume. It's these muscles whose contraction produces the "costal breathing" during rapid respirations.
Quiet expiration:
The diaphragm relaxes. The elasticity of the muscle tissue and of the lung stroma causes recoil which returns the lungs to their volume before inspiration. The reduced volume causes the pressure in the lungs to increase thus causing air to leave the lungs due to the pressure gradient.
Forced Expiration:
The following muscles aid in reducing the volume of the thorax and lungs:
The internal intercostals - these compress the ribs together
The abdominus rectus and abdominal obliques: internal obliques, external obliques- these muscles push the diaphragm up by compressing the abdomen.
Respiratory output is determined by the minute volume, calculated by multiplying the respiratory rate time the tidal volume.
Minute Volume = Rate (breaths per minute) X Tidal Volume (ml/breath)
Rate of respiration at rest varies from about 12 to 15 . Tidal volume averages 500 ml Assuming a rate of 12 breaths per minute and a tidal volume of 500, the restful minute volume is 6000 ml. Rates can, with strenuous exercise, increase to 30 to 40 and volumes can increase to around half the vital capacity.
Not all of this air ventilates the alveoli, even under maximal conditions. The conducting zone volume is about 150 ml and of each breath this amount does not extend into the respiratory zone. The Alveolar Ventilation Rate, AVR, is the volume per minute ventilating the alveoli and is calculated by multiplying the rate times the (tidal volume-less the conducting zone volume).
AVR = Rate X (Tidal Volume - 150 ml)
For a calculation using the same restful rate and volume as above this yields 4200 ml.
Since each breath sacrifices 150 ml to the conducting zone, more alveolar ventilation occurs when the volume is increased rather than the rate.
During inspiration the pressure inside the lungs (the intrapulmonary pressure) decreases to -1 to -3 mmHg compared to the atmosphere. The variation is related to the forcefulness and depth of inspiration. During expiration the intrapulmonary pressure increases to +1 to +3 mmHg compared to the atmosphere. The pressure oscillates around zero or atmospheric pressure.
The intrapleural pressure is always negative compared to the atmosphere. This is necessary in order to exert a pulling action on the lungs. The pressure varies from about -4 mmHg at the end of expiration, to -8 mmHg and the end of inspiration.
The tendency of the lungs to expand, called compliance or distensibility, is due to the pulling action exerted by the pleural membranes. Expansion is also facilitated by the action of surfactant in preventing the collapse of the alveoli.
The opposite tendency is called elasticity or recoil, and is the process by which the lungs return to their original or resting volume. Recoil is due to the elastic stroma of the lungs and the series elastic elements of the respiratory muscles, particularly the diaphragm.
Functions
Manufacture - blood proteins - albumen, clotting proteins , urea - nitrogenous waste from amino acid metabolism , bile - excretory for the bile pigments, emulsification of fats by bile salts
Storage - glycogen , iron - as hemosiderin and ferritin , fat soluble vitamins A, D, E, K
Detoxification -alcohol , drugs and medicines , environmental toxins
Protein metabolism -
- transamination - removing the amine from one amino acid and using it to produce a different amino acid. The body can produce all but the essential amino acids; these must be included in the diet.
- deamination - removal of the amine group in order to catabolize the remaining keto acid. The amine group enters the blood as urea which is excreted through the kidneys.
Glycemic Regulation - the management of blood glucose.
- glycogenesis - the conversion of glucose into glycogen.
- glycogenolysis - the breakdown of glycogen into glucose.
gluconeogenesis - the manufacture of glucose from non carbohydrate sources, mostly protein