NEET MDS Lessons
Physiology
Typical Concentration Gradients and Membrane Potentials in Excitable Cells
The Na Pump is Particularly Important in the Kidney and Brain
- All cells have Na pumps in their membranes, but some cells have more than others
- Over-all Na pump activity may account for a third of your resting energy expenditure!
- In the kidney the Na pump activity is very high because it is used to regulate body salt and water concentrations
- Kidneys use enormous amounts of energy: 0.5% of body weight, but use 7% of the oxygen supply
- Pump activity is also high in the brain because Na and K gradients are essential for nerves
- The brain is another high energy organ; it is 2% of body weight, but uses 18% of the oxygen supply
In the Resting State Potassium Controls the Membrane Potential of Most Cells
- Resting cells have more open K channels than other types
- More K+ passes through membrane than other ions- therefore K+ controls the potential
- Blood K+ must be closely controlled because small changes will produce large changes in the membrane potentials of cells
- Raising K will make the membrane potential less negative (depolarization)
- High blood K+ can cause the heart to stop beating (it goes into permanent contraction)
During an Action Potential Na Channels Open, and Na Controls the Membrane Potential
- Whichever ion has the most open channels controls the membrane potential
- Excitable cells have Na channels that open when stimulated
- When large numbers of these channels open Na controls the membrane potential
Nucleic Acids:
- Two major types: DNA
- RNA (including mRNA, tRNA, & rRNA)
- Both types have code which specifies the sequence of amino acids in proteins
- DNA = archival copy of genetic code, kept in nucleus, protected
- RNA = working copy of code, used to translate a specific gene into a protein, goes into cytoplasm & to ribosomes, rapidly broken down
- Nucleic acids are made of 5 nucleotide bases, sugars and phosphate groups
- The bases make up the genetic code ; the phosphate and sugar make up the backbone
- RNA is a molecule with a single strand
- DNA is a double strand (a double helix) held together by hydrogen bonds between the bases
- A = T; C= G because:
- A must always hydrogen bond to T
- A = T; C= G because:
C must always hydrogen bond to G
Hemostasis - the stopping of the blood. Triggered by a ruptured vessel wall it occurs in several steps:
1) vascular spasm - most vessels will constrict strongly when their walls are damaged. This accounts for individuals not bleeding to death even when limbs are crushed. It also can help to enhance blood clotting in less severe injuries.
2) platelet plug - platelets become sticky when they contact collagen, a protein in the basement membrane of the endothelium exposed when the vessel wall is ruptured. As they stick together they can form a plug which will stem the flow of blood in minor vessels.
3) Formation of the Blood Clot:
A) release of platelet factors - as platelets stick together and to the vascular wall some are ruptured releasing chemicals such as thromboxane, PF3, ADP and other substances. These become prothrombin activators. Thromboxane also makes the platelets even stickier, and increases the vascular constriction. These reactions are self perpetuating and become a cascade which represents a positive feedback mechanism.
B) prothrombin activators : prothrombin (already in the blood) is split into smaller products including thrombin, an active protease.
C) thrombin splits soluble fibrinogen, already present in the plasma, into monomers which then polymerize to produce insoluble fibrin threads. The fibrin threads weave the platelets and other cells together to form the actual clot. This occurs within four to six minutes when the injury is severe and up to 15 minutes when it is not. After 15 minutes the clot begins to retract as the fibrin threads contract, pulling the broken edges of the injury together and smoothing the surface of the clot causing the chemical processes to cease. Eventually the clot will dissolve due to enzymes such as plasmin also present in the blood.
The extrinsic pathway: when tissues are damaged the damaged cells release substances called tissue thromboplastin which also acts as a prothrombin activator. This enhances and speeds coagulation when tissue damage is involved.
Anti-thrombin III - this factor helps to prevent clotting when no trigger is present by removing any thrombin present. Its function is magnified many times when heparin is present. Therefore heparin is used clinically as a short-term anticoagulant.
Vitamin K - stimulates the production of clotting factors including prothrombin and fibrinogen in the liver. This vitamin is normally produced by bacteria in the colon. Coumarin (or coumadin) competes with Vitamin K in the liver and is used clinically for long-term suppression of clotting.
Several factors important to clotting are known to be absent in forms of hemophilia. These factors are produced by specific genes which are mutated in the deficient forms. The factors are VIII, IX, and XI.
Calcium is necessary for blood clotting and its removal from the blood by complexing with citrate will prevent the blood from clotting during storage
Serum Proteins
Proteins make up 6–8% of the blood. They are about equally divided between serum albumin and a great variety of serum globulins.
After blood is withdrawn from a vein and allowed to clot, the clot slowly shrinks. As it does so, a clear fluid called serum is squeezed out. Thus:
Serum is blood plasma without fibrinogen and other clotting factors.
The serum proteins can be separated by electrophoresis.
- The most prominent of these and the one that moves closest to the positive electrode is serum albumin.
- Serum albumin
- is made in the liver
- binds many small molecules for transport through the blood
- helps maintain the osmotic pressure of the blood
- The other proteins are the various serum globulins.
- alpha globulins (e.g., the proteins that transport thyroxine and retinol [vitamin A])
- beta globulins (e.g., the iron-transporting protein transferrin)
- gamma globulins.
- Gamma globulins are the least negatively-charged serum proteins. (They are so weakly charged, in fact, that some are swept in the flow of buffer back toward the negative electrode.)
- Most antibodies are gamma globulins.
- Therefore gamma globulins become more abundant following infections or immunizations.
Exchange of gases takes place in Lungs
- A person with an average ventilation rate of 7.5 L/min will breathe in and out 10,800 liters of gas each day
- From this gas the person will take in about 420 liters of oxygen (19 moles/day) and will give out about 340 liters of carbon dioxide (15 moles/day)
- The ratio of CO2 expired/O2 inspired is called the respiratory quotient (RQ)
- RQ = CO2 out/O2 in = 340/420 = 0.81
- In cellular respiration of glucose CO2 out = O2 in; RQ = 1
- The overall RQ is less than 1 because our diet is a mixture of carbohydrates and fat; the RQ for metabolizing fat is only 0.7
- All of the exchange of gas takes place in the lungs
- The lungs also give off large amounts of heat and water vapor
Tubular secretion:
Involves transfer of substances from peritubular capillaries into the tubular lumen. It involves transepithelial transport in a direction opposite to that of tubular absorption.
Renal tubules can selectively add some substances that have not been filtered to the substances that already have been filtered via tubular secretion.
Tubular secretion mostly function to eliminate foreign organic ions, hydrogen ions ( as a contribution to acid base balance ), potassium ions ( as a contribution to maintaining optimal plasma K+ level to assure normal proceeding of neural and muscular functions), and urea.
Here we will focus on K+ secretion and will later discuss H+ secretion in acid base balance, while urea secretion will be discussed in water balance.
K+ is filtered in glomerular capillaries and then reabsorbed in proximal convoluted tubules as well as in thick ascending limb of loop of Henley ( Na-2Cl-K symporter)
K+ secretion takes place in collecting tubules (distal nephron) . There are two types of cells in distal nephron:
- Principal cells that reabsorb sodium and secrete K+ .
- Intercalated cells that reabsorb K+ in exchange with H+.
Mechanism of secretion of K+ in principal cells : Two steps
- K+ enters tubular cells by Na/K ATPase on the basolateral membrane.
- K+ leaves the tubular cells via K+ channels in apical membrane.
Aldosterone is a necessary regulatory factor.
If there is increased level of K+ in plasma,excessive K+ is secreted , some of which is reabsorbed back to the plasma in exchange with H+ via the intercalated cells.
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.