Colour vision Physiology | Special senses

This video is about colour perception and the theories

1. Young Helmholtz theory of colour vision

2. Colour opponent theory (opponent-process theory) of colour vision

Buffers | Dissociation constant | Henderson Hasselbalch equation | Phys...

Strong acids and bases dissociate almost completely in an aqueous solution into respective ions and hence add H+ ion and hydroxyl ions into solution causing a change in pH. 

  Buffer is any substance which binds H+ ions reversibly and prevents the change in pH in case there is addition of acids or bases into a solution. Weak acids which do not completely ionise when dissolved in water behave as buffers. Fundamentally the weak acid acts as proton donor and its conjugate base acts as a proton acceptor. 

 Now when can be a buffer most effective and how one buffer differs from other buffers ? 

 A buffer will be most effective for handling changes in pH on either side when the proton acceptor and the proton donor are in equal concentrations. . This depends on the dissociation characteristics of any acid i.e its tendency to release hydrogen ions into a solution. The dissociation characteristic of the acids is studied using equilibrium constant or dissociation constant.  Dissociation constant  is equal to the dissociated ions i.e H+ ions and its conjugate base divided by the concentration of the undissociated acid in the solution. This dissociation constant can be expressed as negative logarithm. Its called pKa. Since its negative logarithm, pKa will be larger for weaker acids. 

 But how this dissociation constants helps us in understanding the characteristics of the buffer and when they are most effective  ? 

 That is better understood  with Henderson Hasselbach equation such that we are solving dissocitaion constant equation for H+. 

 pKa + log [A-] / [HA] = pH 

 Buffer is most effective for handling changes in pH on either side when the proton acceptor and the proton donor are in equal concentrations. When they are in equal concentration, pKa = pH. So  at a pH which is equal to pKa of the buffer, the dissociation is such that the concentrations of proton donor and proton acceptor are equal..so at this pH…the buffer is most effective in either directions…

Physiological buffers

 HCO3- buffer system: 

 pKa of this buffer is 6.i, so at pH 6.1 this buffer will exist equally in dissociated and undissociated form and will be most effective on both sides. But our body pH is 7.38 - 7.42 so that means at this pH which is higher than pKa , it will exist more in dissociated form. Well that’s good for us since bicarbonate ions will be available to bind to acids. 

Phosphate buffer. 

Its dissociation constant is 6.86. It also stays mostly in dissociated form and is more effective for capturing acids. 

Ammonia buffer

 pKa of ammonia buffer  is 9.25….…this ammonia buffer system mostly exists as undissociated form i.e as ammonium ion…so actually it will not be able to bind with much hydrogen ions..so actually its a very poor buffer per se…however…the production of ammonium ion by the metabolism of glutamine also produces one bicarbonate which is added back into the blood…also in medullary inerstitium…this ammonium buffer exists in equilibrium with ammonia and ammonia diffuses from their into the collecting duct..where it binds with secreted hydrogen ions…..Not only that, it is one buffer whose production is regulated by kidneys….i.e its production increases in acidosis.

Carbonmonoxide diffusing capacity of lung | Respiratory physiology

The rate of diffusion of a gas across any membrane is given by Fick’s law which states that the diffusion rate is directly proportional to partial pressure gradient for the gas, directly proportional to the area of the membrane, inversely proportional to membrane thickness, and directly proportional to solubility of the gas and inversely proportional to square root of its molecular weight. If we combine the properties of lung and properties of gases together.. we call it diffusing capacity of lungs for that gas. Physiologically for the uptake of the gases from the alveoli, 2 things should happen: 1. The gases should cross the respiratory membrane 2. They should cross the plasma, enter into RBC and react with Hb (diffusion capacity of blood) When we determine diffusion capacity of lungs using a gas, the obtained value represents both the diffusion capacity of membrane and the diffusion capacity of blood so basically DL represents the entire diffusion distance which needs to be covered by a gas physiologically. Thats why its also known as transfer factor. Measurement of carbonmonoxide diffusion capacity This diffusion capacity is measured using a gas whose rate of diffusion is diffusion limited i.e carbonmonoxide in this case. To measure diffusion capacity of lungs for CO, we need to know rate of diffusion of gas and its partial pressure gradient. For this, single breath technique is used. In this the person first exhales maximally and then inhales maximally a dilute mixture of carbonmonoxide containing approximately 0.3% of CO which is diluted with helium, holds the breath for 10 sec to allow for diffusion of gas and then exhales. Then by determining the difference between the amount of gas inhaled and amount of gas exhaled, and the lung volume by helium dilution method, we can know the amount of gas which has diffused and also the alveolar partial pressure of carbonmonoxide. Partial prssure of carbonmonoxide in blood is zero. We then put those values in the formula and get the diffusion capacity or transfer factor.. Diffusion capacity of lungs for carbonmonoxide measured by this method comes to 25 ml/min/mmHg partial pressure difference. This value increases 2-3 times in exercise due to capillary recruitment and capillary distension. Decrease in CO diffusion capacity of lungs 1. Thickening of respiratory membrane as in pulmonary fibrosis, 2. Decrease in cross-sectional area of respiratory membrane as in emphysema…. 3. Since it also depends on diffusion capacity of blood i.e on blood volume and hemoglobin.. so if these are less..then also diffusion capacity will be less.

Diffusion of gases through respiratory membrane | Diffusion vs perfusion...

The partial pressure of oxygen in alveoli (pAO2) is approximately100 mmHg while that in veins (pvO2) is  40 mmHg . Partial pressure of carbondioxide in alveoli is 40 mmHg.while in venous blood (pvCO2) is 45 mmHg. As gases diffuse from area of their higher to lower partial pressure, oxygen diffuses from alveoli to blood which carries venous blood from right side of heart to lungs while carbon dioxide diffuses from blood to alveoli. 

 For the gases to cross the alveoli and enter into the blood and vice versa, the gases should cross the respiratory membrane. This respiratory membrane has  layers which  from the alveolar side to the side of blood are: 

1. the layer of fluid lining the alveoli

2. alveolar epithelium 

3. alveolar basement membrane 

4. Interstitium 

5. capillary basement membrane 

6. capillary endothelium 

The factors which affect rate of diffusion of gases across any membrane is given by Fick’s law which states that rate of diffusion is directly proportional to the area of the membrane, partial pressure gradient and inversely proportional to membrane thickness. Then it is also  directly proportional to their solubility in the medium and inversely related to the square root of their molecular weight. In Fick’s law the two factors of the gas i.e  its the molecular weight of oxygen and solubility together form the diffusion coefficient of the gas. The molecular weight of oxygen is less but its blood solubility is much lesser than carbondioxide.. because of this carbondioxide diffuses 20 times faster than oxygen. 

For this particular membrane, the rate at which different gases will cross is expressed by diffusion capacity of the lungs for a given gas. Normally diffusion capacity of lungs for oxygen is 25 ml/min/mm Hg. That means 25 ml of oxygen will cross this membrane in 1 min for every each mmHg partial pressure difference. Obviously diffusion capacity will be much larger for carbondioxide. Oxygen takes 0.3 sec to equilibrate. In normal conditions,  0.3 sec is enough for partial pressure of oxygen to equilibrate and become 100 mmHg and thus Hb gets fully occupied with oxygen..because a column of blood remains at a spot for about 0.8 sec.   Since circulation doesn’t move, more diffusion does not occur. So basically, circulation is the limiting factor for the diffusion of oxygen. So we call this as diffusion of oxygen being perfusion limited. 

Now what happens when heart rate increases  If we consider maximum achievable heart rate as 200, duration cardiac cycle at this heart rate will be (60/200) = 0.33 sec. So, even with this heart rate, the time is sufficient for the oxygen to cross the membrane. 

 Now consider a situation in which respiratory membrane thickens, 

As Fick’s law states that rate of diffusion is inversely proportional to the thickness of the membrane, so obviously the rate of diffusion of gases will be affected. With increase in the thickness, diffusion time for oxygen will increase say upto 0.5 or even 0.6 sec. This time is adequate for rest, since till 0.8 sec a column of blood is available. But during activity, when heart rate becomes faster and duration of cardiac cycle decreases, then there will not be adequate time for oxygen to equilibrate and hence it will cause hypoxia. So in this case, perfusion is not the limitation, rather the rate of diffusion becomes the limiting factor. This is known as diffusion limited. 

 Since rate of diffusion carbondioxide is faster, its diffusion will not be limited. So even with increased respiratory membrane thickness, carbondioxide could be expelled from the body. That is the reason that even in severe cases of thickening of respiratory membrane like in pulmonary fibrosis hypoxia occurs but carbondioxide retention does not occur.

Pathophysiology of diabetes mellitus | Endocrine physiology

 Diabetes mellitus occurs due to deficiency of insulin function which may occur due to 

1. decreased insulin release or 

 2.  insulin resistance. 

 In diabetes, storage and utilisation of glucose decreases in fed state leading to increase in blood glucose concentration after food i.epost-prandial hyperglycemia. Due to continuing glycogenolysis and gluconeogenesis, glucose concentration in  blood rises in between meals too i. e fasting hyperglycemia 

Due to excess blood glucose concentration, the glucose filtered through nephron is also high. This exceeds the capacity of nephrons of absorbing glucose i.e transport maximum is reached, above which the nephrons are not able to reabsorb further glucose and hence glucose starts appearing in urine i.e glucosuria occurs. The presence of glucose in nephron acts as anosmotic pull for water preventing the reabsorption of water also from the nephron. So water loss also increases causing increase in the volume of urine i.e polyuria. Due to increase in water loss from the body, and hyperosmolarity of blood due to increased blood glucose concentration, water moves out of cells. This when happens in osmoreceptors…thirst centres are activated causing increase in the intake of water i.e polydipsia.

 Hyperphagia:  When insulin is deficient, the satiety centre neurons are not able to utilise glucose and become inactive. Thus they do not inhibit feeding centre.   Since feeding centre is not inhibited, the person feels hungry and eats often i.e polyphagia occurs. 

In insulin deficiency  lipolysis starts in adipose tissue causingrelease of  free fatty acids in circulation, proteolysis also starts. So with  increased lipolysis and proteolysis , there is weight loss.  The free fatty acids enter liver and undergo beta oxidation leading ultimately to formation of acetyl COA. In diabetes, most of the acetyl coA is channeled away from Krebs cycle and is utilised for production of ketone bodies (ketosis). When rate of productions of ketone bodies is too high which occurs when insulin levels are very low or virtually absent as seen in type 1 diabetes mellitus,  ketone bodies decrease blood pH (ketocacidosis) . 

Since blood pH decreases, body starts compensatory mechanisms for excretion of excess acids by increasing respiratory rate and depth. This is known as Kussmaul’s breathing or air hunger, Some ketone bodies i.e acetone is also excreted by breath causing fruity smell of breath. Ketoacidosis is always accompanied by dehydration. This leads to activation of renin-angiotension-aldosterone system. Thus causing hyperaldsteronism causing potassium loss from the body. 

 In type 2 DM, ketocacidosis is not that common, since insulin receptor defect starts slowly, i.e some actions of insulin are preserved so lipolysis and proteolysis are not that severe. Since lipolysis is not severe, formation of ketone bodies is also not excessive.  In contrast, another problem may occur in type 2 diabetes i.e hyperglycemia hyperosmolar state. In this also, there is hyperglycemia, causing high serum osmolarity ,  also causing glucosuria and poyluria and hence depletion of watre. However, ketoacidosis is not present. 

Functionsof insulin: https://youtu.be/JjUaj6v2vqI 

Insulin signal transduction pathways | Endocrine physiology

Insulin signal transduction pathways | Endocrine physiology 

There are 2 fundamental signal transducing pathways by which insulin acts: 

1. Phosphotidylinositol-3 kinase or PI3-Kinase pathway 

2. Ras-MAP kinase pathway. 

Insulin acts by binding to its receptors which are present on the cell membrane of its target cell. Insulin receptors are enzyme linked receptors which have inherent tyrosine kinase enzyme activity. 

The insulin receptors are present as tetramers i.e they have 4 polypeptides or subunits which assemble to form the receptor. Two of these subunits are alpha subunits while the other two are beta subunits. Alpha subunits project outside the membrane i.e form the extracellular part of the receptor which has the binding site for insulin. The beta subunits traverse through the membrane  and protrude into the cytoplasm and has  intrinsic tyrosine kinase activity i  When insulin is not bound to the receptors, the tyrosine kinase is inactive. 

When the insulin binds to its receptors, the tyrosine kinase activity of beta subunits activates which then cross-phosphorylate tyrosine residues of each other. This receptor then binds to insulin receptor substrates.  Once that happens this insulin receptor substrate becomes a docking site for other kinases and adaptor proteins. 

 1. PI3-Kinase pathway: 

 Phosphotidylinositol-3 kinase  phosphorylates  phosphatidylinositol 4-5 biphosphate. For this, initially it binds to IRS. This brings it close to its substrate which is present on the membrane and also activates it by phosphorylation. Then, it phosphorylates, PIP2 forming phosphotidyinositol 3,4,5 triphosphate.  Now this triphosphate also acts as a docking site for 2 other kinases i.e  phosphoinositide dependent kinase 1 and Protein kinase B. Now  PDK-1 phosphorylates  protein kinase B or AKT thus activating it. 

It is this protein kinase B which now dissociates and moves into the cytoplasm which then causes insertion of GLUT 4 receptors on the membrane, activates glycogen synthase for conversion of glucose to glycogen, inactivates glycogen phosphorylase for preventing glycogenolysis and hence causes varied effects on metabolism. 

 2. RAS-MAPK pathway 

 Monomeric G-proteins (Ras) have the ability to bind GDP and GTP. In inactive state , they are bound to GDP while when active they bind to GTP just like our trimeric G proteins. For activating it,  insulin receptor substrate binds with another adaptor protein GRB2 which in turn binds and activates a Guanine exchange factor protein SOS  which replaces Ras GDP with GTP causing its activation. The activation of Ras inturn leads to activation of kinase cascade including Raf, MEK and then ultimately leading to the activation of MAPKinase.  After activation, MAP kinase translocates into the nucleus and phosphorylates many transcription factors that regulate expression of important cell-cycle and differentiation-specific proteins. So that’s how insulin has effects on cell proliferation, growth and differentiation. 

 In summary, insulin acts by 2 signal transduction pathways: PI3-Kinase pathway responsible for its metabolic actions and some survival actions also and Ras MAP kinase pathway responsible for its effects on cell proliferation, growth and differentiation.

Diuretics: Mechanism of action, uses | Renal Physiology | Pharmacology

Diuretics are substances which increase the flow rate of urine. Most of the classes of diuretics work by increasing both the solute as well as water loss.

 1. Carbonic anhydrase inhibitors: They inhibit the carbonic anhydrase enzyme present in epithelial cells lining the proximal convultae tubule. Thus, they decrease the reabsorptionof sodium as well as that of bicarbonate. Due to this, there is decrease in pH causing metabolic acidosis. They ae used mianly to block carbonic anhydrase enzyme in eyes especially in open angle glaucoma and in high altitude sickness where they prevent the development of metabolic alkalosis.

 2. Loop diuretics: Loop diuretics inhibit sodium potassium 2cl- transporter. This interefers with both the concentration as well as dilution of urine. They are very effective diuretics since they interfere with absorptiono f approximatelu 25% of sodium reabsorptionin nephron.

 3. Thiazide diuretics: These diuretics act on distal convulated tubule where they block sodium chloride symporter. They mainly interfere with dilutionof urine and not with concentrationo f urine. They are moderately effective diuretics which interfere with 5-10% of reabsorption of filtered sodium.

 4. Potassium sparing diuretics: They act on late distal tubule and collecting ducts. They act by inhibiting either epithelial sodium channels or mineralocorticoid receptors. They are not very effective diuretics as such but when combined with other diuretics, they help in preventing the development of hypokalmeic alkalosis.

 5. Osmotic diuretics. Osmotic diuretics interfere mainly with reabsorption of water and not of solutes.Osmotic diuretics, are filtered from the glomerulus but are not absorbed and tend to remain in the tubular fluid. Hence,in descending limb of loop of henle which is permeable to water, they prevent the movement of water out from tubular lumen since they exert on osmotic pull on water.