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.


 

Biosynthesis of thyroid hormones

Thyroid hormones are iodinated tyrosine which is an amino acid.   Synthesis of thyroid hormones occurs in multiple steps 

 1. Synthesis of thyroglobulin: Thyroglobulin is synthesised by follicular epithelial cells just like any other protein synthesis by cells and is secreted into the colloid by exocytosis. So this protein is stored in the colloid. 

 2. Trapping and transport of iodide: Iodine is present in circulation as iodide ion. This iodide is taken up into the cytoplasm by NaI- symporter which is a secondary active transporter present on the basolateral membrane of thyrocytes. This Iodide then enters into the colloid via the apical membrane through the Cl-/I- exchanger which is also known as ‘pendrin’ 

 3. Organification: So now we got both iodide and thyroglobulin in the colloid. However, the iodide cannot react with tyrosine residues. For that it should be oxidised to iodine. So this process of oxidation of iodide to iodine and iodination of the tyrosine residues of the thyroglobulin is known as organification.  This occurs in presence of the enzyme thyroid peroxidase present on the apical membrane of thyrocytes.  Many tyrosine residues of thyroglobulin are iodinate either at single site forming monoiodotyrosines i.e MIT or two sites forming diiodotyrosines i.e DIT. 

 4. Coupling reaction: MIT and DIT are not thyroid hormones. It is the coupling or combination of these iodinated tyrosines which produces thyroid hormones. One MIT and one DIT couple to form triiodothyronine i.e. T3 and 2 DITS couple to form Tetraiodothyronine i.e T4 or thyroxine in presence of enzyme thyroid peroxidase. This is known as coupling reaction. 

So basically, thyroid hormones form within the thyroglobulin molecule.

When the gland is stimulated by Thyroid stimulating hormone, all these steps of synthesis of thyroid hormones i.e  synthesis of thyroglobulin, uptake of iodide, organification and coupling reaction are stimulated. 

Also, the follicular cells start taking up the stored iodinated thyroglobulin from the colloid by endocytosis. Intracellularly lysosomes fuse with the phagocytosed thyroglobulin and cleave T3 and T4 from thyroglobulin by proteases which are then released from the basolateral side and enter into the circulation. The separated amino acids are reused to produce thyroglobulin. The MIT and DIT which are not coupled are acted upon by the enzyme ‘deiodinase’ which as its name suggests detaches the iodine from the tyrosine both of which are recycled. 

 

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G-protein coupled receptors

G protein coupled receptors have an extracellular binding site to which the hormone binds and an intracellular cytoplasmic tail region to which G-proteins may bind.  

G proteins act as a switch and functionally couple the receptor to their target enzymes or ion channels. Switch means there is an inactive state when the hormone is not bound to the receptor and when the hormone binds, there is activation. G-proteins or heterotrimeric GTP binding proteins is a set of 3 proteins, G alpha, G beta and G- gamma which are present as an inactive complex bound to membrane just near the hormone receptor.   

The alpha subunit of G proteins is bound to GDP in inactive state.When the hormone binds to its receptor, receptor interacts with the G proteins and GDP bound to alpha subunit is replaced by GTP, which is now said to be in active state. This replacement of GDP with GTP causes alpha subunit to dissociate from beta and gamma subunits and move and associate with some other proteins causing  either opening/closing of ion channels or they affect the activity of enzymes like adenyl cyclase and phospholipase C. 

G proteins which stimulate adenyl cyclase activity are known as G stimulatory proteins i.e Galpha s. while that which inhibits their activity ate known as inhibitory G proteins i.e Galphai. The G proteins which affect the activity of phospholipase C are known as G q proteins. The effect of the hormone on the cell depends on the type of the receptor it binds for e.g. same hormone in one cell may have a receptor which is linked to stimulatory G proteins while in other cells it may have a receptor which is linked to inhibitory G proteins. By the change in the activity of these enzymes, second messenger systems or we can say signalling pathways are activated. 

 Adenylcyclase-cAMP pathway 

When adenyl cyclase enzyme is activated, it causes the conversion of ATP to cAMP. cAMP in turn cause the activation of cAMP dependent protein kinase A which causes phosphorylation of some proteins/enzymes in the cell. Now these proteins may be involved in biological reactions or these phosphorylated protein inturn activate or inhibit other proteins which are involved in cellular reactions. So ultimately this process affects the function of the cells. In addition,PKA can also increase/decrease the transcription of some genes.Close to these genes, is present a region known as cAMP-responsive element (CRE) region of DNA.  A subunit of PKA moves to the nucleus and phosphorylates another protein, the cAMP-responsive element binding protein (i,e CREB protein) which then binds to CRE and alters transcription of the genes where CRE is present. The set of proteins activated by cAMP varies in different cells. So adenyl cyclase activation  in different cells leads to different actions. However if same adenyl cyclase is activated by different ligands in the same cell, it leads to same actions. So in this pathway, cAMP acts as a second messenger.

Phospholipase C-IP3-DAG-Calmodulin pathway 

 When phospholipase C is activated by Gq proteins, it causes breakdown of the membrane phospholipid phosphatidylinositol 4,5 bi or di phosphate (PIP2) into IP3, i.e inositol triphosphate and Diacyl glycerol (DAG). Ip3 acts on IP3 receptor (IP3R) present on endoplasmic reticulum. This IP3R is itself a ligand gated calcium channel. When IP3 binds, it opens up causing release of calcium ions from ER into the cytososl. The calcium ions in turn bind with calmodulin causing activation/inhibition of calmodulin dependent protein kinases.  

DAG activates protein kinase C which then phosphorylates other proteins just as we saw for adenyl cyclase dependent kinases. So in this case IP3, DAG and calcium are second messengers.

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Weber Fechner and Steven's Power law

The concept of Just Noticeable Difference was given by Weber where he explained that we will be able to perceive the difference in intensity of the stimulus depending on the original strength of the stimulus. For higher strengths of stimulus, a greater chnage in intensity of stimulus is required is required to notice the difference in intensities. 

Fechner took this concept and tried to explain the percieved intensity of stimulus vis a vis the strength of stimulus. But Fechner law was applicable to only very high and very low intensities of stimulus. Later this was modified by Steven who gave Power law to explain the percieved intensity of stimulus.


Watch the video for details....

Classification of sensory receptors

Afferent neurons transmit action potential from the periphery to the central nervous system. These afferent neurons have sensory receptors at their peripheral endings. Receptors as the term indicates receive information or we can say characteristics of a stimulus from the surroundings. 

The stimuli are of various types depending on the type of energy change for e.g. there can be either mechanical stimulus , chemical stimulus or thermal stimulus etc. Body has receptors for detecting different types of energies. But once the receptors detect the stimulus, it has to be transmitted to the CNS as action potential, so receptors convert the stimulus energy into electrical signals. This is known as signal transduction.  

Sensory Receptors can be classified in 3 ways

1. Based on their location: exteroceptors, interoceptors and proprioceptors

2. Based on modality of stimulus they detect: mechanoreceptors, chemoreceptors, thermoreceptors, nociceptors, and electromagnetic receptors . 

3. Based on rate of adaptation: Slowly adapting receptors and fast adapting receptors.

In skin , their are various mechanoreceptors. However, they are located in various layers of skin e.g. Merke;'s disks are located superficially in dermis and detect superficial texture of the object while Ruffini ending is deeper in dermis and detects pressure. 

Also there are Meissner’s corpuscle versus Pacinian corpuscles. Both these receptors adapt very fast. Thus, they detect vibration sense. But, meissner’s corpuscle respond to slow vibration while pacinican corpuscle respond to fast vibration because pacinian corpuscle adapt very very fast. And pacinican corpuscles are located deep so they respond to deep pressure vibration while Meissner’s has to be superficial like a flutter on the skin. Also, meissner’s corpuscles detect the sensation from a small superficial area while Pacinian corpuscle respond to a stimulus even when it is present in a little larger area. This is known as receptive field of the receptor.

Starling's forces and physiological basis of edema

Starling's forces

1. Capillary hydrostatic pressure

2. Capillary oncotic pressure

3. Interstitial fluid hydrostatic pressure

4. Interstitial fluid oncotic pressure

Forces at arterial end of capillary

Starling's Forces promoting filtration: 

1. Hydrostatic capillary pressure: 32 mmHg 

2. Interstitial oncotic pressure: 8 mmHg (due to proteins)

3. Interstitial hydrostatic pressure: -3 mmHg (Some fluid is also present in interstitial space. However, due to pulling by the tissues, a negative hydrostatic pressure is generated in interstitial space. So, it promotes filtration)

Total =  43 mmHg (by adding all forces)

Forces opposing filtration

2. Oncotic capillary pressure: 28 mmHg

Net driving force at arterial end of capillaries = Forces promoting filtration - Forces oppsong filtration

                               =  43-28 = 15 mmHg

Since it is a positive force, it drives water movement out of the capillaries.

Starling's Forces at venous end of capillary: 

Starling's Forces promoting filtration: 

1. Hydrostatic capillary pressure: 10 mmHg   (hydrostatic pressure decreased due to the movement of water outside the capillaries at the arterial end

2. Interstitial oncotic pressure: 8 mmHg (due to proteins)

3. Interstitial hydrostatic pressure: -3 mmHg 

Total =  21 mmHg (by adding all forces)

Forces opposing filtration

1. Oncotic capillary pressure: 28 mmHg

Net driving force at arterial end of capillaries = Forces promoting filtration - Forces oppsong filtration

                               =  21-28 = -7 mmHg

Since it is a negative force that means it draws in water into the capillaries. So there is the inward pull of water at the venous end. 

That means water which is filtered at the arterial end is reabsorbed at the venous end. 

But at arterial end, the net outward force was 15 mmHg and at the venous end, the net inward force was 7 mmHg so some fluid remains in the interstitial space. Lymphatics carry that excess fluid from the interstitial space. 

Now when can fluid accumulate inside interstitial space? That extra fluid accumulation in interstitial space is known as EDEMA. 

 So when can oedema occur? 

1. Increased hydrostatic pressure occurs in the case of hypertension or excess fluid accumulation. ( heart failure or iatrogenic) 

2. Decreased oncotic pressure that is due to decreased protein concentration. 

It may happen due to:

Malnutrition: Decreased protein intake 

Malabsorption: Decreased protein absorption

Liver disease: Decreased synthesis of proteins

Kidney disease: Increased loss of proteins

3. Increased capillary permeability can occur in case of local injury.

4. Blocked lymphatics can occur in case of filariasis, metastasis of cancerous cells to lymph nodes 

Edema is of 2 types

1. Transudate: This means that it is the water that is being accumulated inside the interstitial space. 

2. Exudate: along with water, there is a movement of proteins also from the capillary.  So exudate is water plus proteins. It occurs when there is increased permeability of capillaries causing movement of proteins also out of the capillaries.