Showing posts with label Physiology. Show all posts
Showing posts with label Physiology. Show all posts

Monday, February 11, 2013

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May-Thurner syndrome

As seen in the diagram above, the left common iliac vein is predisposed to be compressed by the right common iliac artery. This can lead to stasis and eventually causing thrombosis. Another effect is that the pulsatile nature of the artery over the vein leads to turbulence in the blood flow, thereby favouring thrombosis. 
Because of this anatomical predisposition, most Deep Vein Thrombosis (DVT) seen during pregnancy occur in the left iliac vein system. All the classic investigations done for cases of DVT should be performed here also.

Friday, September 28, 2012

Platelets / Thrombocytes

Platelets are also called as thrombocytes.
Size: they are very small discs with diameter varying from 1 to 4 micrometers.
The normal concentration of platelets in the blood is between 150,000 and 450,000 per microliter.

They are formed in the bone marrow from megakaryocytes. The latter are extremely large cells in the marrow and they fragment into the minute platelets either in the bone marrow or soon after entering the blood.

The platelet has a half-life in the blood of 8 to 12 days. Then it is eliminated from the circulation mainly by the tissue macrophage system. More than one half of the platelets are removed by macrophages in the spleen, where the blood passes through a latticework of tight trabeculae.

Platelets do not have nuclei and cannot reproduce. Yet, they have many functional characteristics of whole cells.
1) Actin and myosin molecules are present in their cytoplasm. They are contractile proteins similar to those found in muscle cells and still another contractile protein, thrombosthenin that can cause the platelets to contract.
2) There are also residuals of both the endoplasmic reticulum and the Golgi apparatus that synthesize various enzymes and especially store large quantities of calcium ions.
3) Mitochondria and enzyme systems can produce ATP and ADP.
4) There are also enzyme systems that synthesize prostaglandins. These cause many vascular and other local tissue reactions.

The cell membrane of the platelets is also important. On its surface is a coat of glycoproteins that repulses adherence to normal endothelium and yet causes adherence to injured areas of the vessel wall, especially to injured endothelial cells and even more so to any exposed collagen from deep within the vessel wall. In addition, the platelet membrane contains large amounts of phospholipids that activate multiple stages in the blood-clotting process.

Mechanism of the Platelet Plug:
1) When platelets come in contact with a damaged vascular surface, especially with collagen fibers in the vascular wall, the platelets immediately change their own characteristics drastically. They begin to swell and assume irregular forms with numerous irradiating pseudopods protruding from their surfaces.
2) Their contractile proteins contract forcefully and cause the release of granules that contain multiple active factors.
3) They also become sticky so that they adhere to collagen in the tissues and to a protein called von Willebrand factor that leaks into the traumatized tissue from the plasma.
4) They secrete large quantities of ADP and their enzymes form thromboxane A2. The ADP and thromboxane in turn act on nearby platelets, activate them and increase their stickiness. This causes more platelets to adhere to the original activated platelets.
The above steps form a platelet plug which is usually loose and can only successfully block blood loss from small vascular openings.
The platelet-plugging mechanism is extremely important for closing minute ruptures in very small blood vessels that occur many thousands of times daily. Indeed, multiple small holes through the endothelial cells themselves are often closed by platelets actually fusing with the endothelial cells to form additional endothelial cell membrane. A person who has few blood platelets develops each day literally thousands of small hemorrhagic areas under the skin and throughout the internal tissues, but this does not occur in the normal person.

Thursday, January 12, 2012

Homeostasis - negative feedback loop

A rise of some factor e.g. X of the internal environment is detected by the sensor. This information is relayed to the integrating center that causes the effector to produce a change in the opposite direction. The initial deviation is thus reversed, thus completing the negative feedback loop.

The same holds true if the factor X is decreased. The integrating center detects a change from the set point and causes necessary effects to bring it back to normal. Below is a diagram that shows negative feedback loops maintain a state of dynamic consistency within the internal environment. 

One such example is regulation of body temperature as explained in the link that follows. Regulation of body temperature

Sunday, December 25, 2011

Regulation of body temperature

The thermostat for body temperature is located in the hypothalamus. When the body temperature falls below normal, the posterior hypothalamic sympathetic centre directs via nerve impulses the blood vessels of the skin to constrict. This conserves heat. 
Sympathetic stimulation also causes piloerection i.e. hair to stand erect and trap a layer of air that act as an insulator. However, this does not play a great role in humans.
If body temperature falls even lower, the regulatory centre sends nerve impulses to the skeletal muscles, and shivering occurs. Shivering generates heat, and gradually body temperature rises to 37°C. Metabolic systems are also activated to produce more heat. When the temperature rises to normal, the regulatory centre is inactivated.

When the body temperature is higher than normal, the regulatory centre directs the blood vessels of the skin to dilate.This allows more blood to flow near the surface of the body, where heat can be lost to the environment. Full vasodilation can increase the rate of heat transfer to the skin to up to eightfold. In addition, the nervous system activates the sweat glands, and the evaporation of sweat helps lower body temperature. Shivering and chemical thermogenesis is strongly inhibited. Gradually, body temperature decreases to 37°C.

Thursday, December 22, 2011



Erythropoiesis refers to the formation of erythrocytes. Tissue oxygenation is the most essential regulator for this continuous process. Thus conditions like anemia, high altitudes, pulmonary disorders or heart failure cause tissue hypoxia.

As a result of this, erythropoietin (EPO) is released from kidneys. It is glycoprotein in nature and 90% of it is produced in the kidneys. The remaining 10% is produced in the liver. This is why in cases where the kidneys have been removed or damaged by diseases, anemia results.

The hypoxic sensor is believed to be the high oxygen-consuming renal tubular cells. If the hypoxic blood is unable to deliver enough oxygen from the peritubular capillaries, then the renal tubular epithelial cells are thought to release the erythropoietin. There may also be a non renal sensor because at times localised hypoxia elsewhere in the body can also lead to erythropoietin secretion.

The effect of EPO is that it stimulates the production of proerythroblasts from hematopoietic stem cells in the bone marrow. Once these proerythroblasts are formed, EPO increases their speed of maturation to finally yield more new red blood cells.

Genesis of RBCs is a link showing the various stages of maturation of an RBC.

Wednesday, October 26, 2011


Effect of sleep on work

Sleep is an integral part of our lives. An average adult should sleep around 7-8 hours per day. Sleep is important to maintain metabolic-caloric balance, thermal regulation and even immune competence.

Sleep is also essential for learning and memory consolidation as well as increasing one's concentration. An advice to students will be to sleep well after studying. Your learning sessions will not show any improved performance until you have a slow wave or slow wave plus REM sleep. Slow wave sleep refers to a deep sleep while REM sleep refers to the period in sleep whereby there is a characteristic movement of the eyeballs during the sleep.

Medical interns and residents are known to burn the midnight oil. But unfortunately for them, working for more than 24 continual hours make them around 40% more prone to make medical errors. Residents are twice more likely to have attentional failure i.e. they forget what they are actually doing. Studies  have shown that 1 in 5 residents believe that they made a fatigue-related mistake and 1 in 20 of the cases eventually led to the death of the patient.

Wednesday, August 10, 2011

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Insulin - action on peripheral cells

Insulin binds to receptor on target sites. These sites have an intrinsic tyrosine kinase activity that lead to receptor autophosphorylation and recruitment of intracellular signalling molecules. The latter result in widespread metabolic and mitogenic effects of insulin as shown in the diagram above.

Another effect is the activation of phosphatidylinositol 3 kinase that fastens the translocation of GLUT-4 containing vesicles to the cell surface. This is important to allow uptake of glucose by skeletal and fat cells.
When insulin action ceases, the transporter-containing patches of membrane are endocytosed and the vesicles are ready for the next exposure to insulin.

On the other hand, in the liver, this is not the mechanism of glucose uptake. Instead, it induces glucokinase, and this increases the phosphorylation of glucose, so that the intracellular free glucose concentration stays low, facilitating the entry of glucose into the cell by diffusion.

Insulin-sensitive tissues like muscles also contain a population of GLUT 4 vesicles that move into the cell membrane in response to exercise, a process that occurs independent of the action of insulin. This is why exercise lowers blood sugar.

Tuesday, August 9, 2011

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Insulin secretion - local regulation

The diagram shows a beta cell of the islet of pancreas and will explain how local factors regulate secretion of insulin from it.
Glucose enters the cell via the GLUT-2 transporter. Inside the cell there is metabolism with the generation of ATP. This causes the ATP-sensitive K+ channel to close, as shown in A.
Closure of this channel leads to cell membrane depolarization. This in turn allows calcium ions to enter the cell via another calcium channel, shown in B. Increased intracellular calcium activates calcium dependent phospholipid protein kinase. This leads to exocytosis of insulin granules.

Sunday, July 3, 2011

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Hypokalemia - ECG changes

The ECG changes in hypokalemia is mainly due to a delayed ventricular repolarisation. The changes normally do not correlate well with the plasma concentration.Early changes include flattening or inversion of the T wave, a prominent U wave, ST-segment depression k/a thumbprint-like ST depression, and a prolonged QU interval but the QT interval will be normal.

Severe K+ depletion may result in a prolonged PR interval, decreased voltage and widening of the QRS complex, and an increased risk of ventricular arrhythmias, especially in patients with myocardial ischemia or left ventricular hypertrophy. The QT interval may be normal or lengthened.

Wednesday, June 29, 2011


ECG waves, their meaning and normal duration.

1) P wave - atrial depolarisation, < 120 ms
2) PR segment - end of P wave till beginning of QRS complex i.e. time taken between atrial and ventricular activation.
3) PR interval - onset of P wave till onset of QRS complex, 120-200 ms
4) QRS complex - ventricular depolarisation, <110 ms
5) T wave - ventricular repolarisation
6) U wave - repolarisation of Purkinje fibres
7) QT interval - beginning of QRS complex till end of T wave

Cardiac action potential

The action potential of a cardiac muscle fiber can be broken down into several phases:
0- depolarization,
1- initial rapid repolarization,
2- plateau phase,
3- late rapid repolarization,
4- baseline.

Many persons find it hard to understand why the curve is as such. I'll try to give a simple explanation in phases. The diagram shows the action potential and below it is what happens to the different ions. By convention, influx is shown by downward deflection while efflux by upward deflection. If positive ions get inside the curve will show an increase and it will show a decrease if ions get out.

Phase 0
Unlike in skeletal muscles where there is only the fast sodium channels, in cardiac muscles there are both fast sodium channels and slow calcium-sodium channels. Both open simultaneously. Phase 0 is due to the rapid opening of the voltage gated sodium channels that leads to a massive influx of sodium ions that cause the initial rapid depolarisation. The slower calcium-sodium channels are slower to open.

Phase 1
The fast sodium channels close. The voltage gated potassium channels open. So, there is a sudden efflux of potassium ions to the outside causing the initial rapid repolarisation.

Phase 2
The fast sodium channels are already closed. The potassium channels are fully open but the slow calcium-sodium channels are also fully open. So there are sodium and calcium getting into the cell while potassum is going out of the cell. Positive charges getting in and out at the same time, thus the charge inside the cell remains more or less constant leading to the plateau phase.

Phase 3
The calcium-sodium channels are now closed and only the potassium channels are open. So, only potassium is going out of the cell making the cell more negative. This phase is called as the late rapid repolarisation.

Phase 4
The potassium channels take some time to close. While closing they continue to allow some potassium ions to move out leading to a slower repolarisation until the baseline is reached and the voltage causes the potassium channels to close completely.
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cardiac muscles properties - morphology

Cardiac muscle is striated same as a typical skeletal muscle. The muscle fibrils are surrounded by numerous and elongated mitochondria since the heart needs energy supply continously. The muscle fibres branch and interdigitate. They lie parallel to one another but at the end of each muscle fibres there are extensive folds of the cell membrane that are called as intercalated disks/discs.

The intercalated discs act as gap junctions that is very permeable and allow almost free diffusion of ions. They always occur at the Z lines i.e. the dark middle section of the light (I) band of the muscle. They provide a strong union between fibers, maintaining cell-to-cell cohesion, so that the pull of one contractile cell can be transmitted along its axis to the next.

The heart muscle thus acts as a syncytium. i.e. a multinucleated mass. Therefore when one of the cells is excited, the action potential spreads from cell to cell through the latticework interconnections fast and the syncytium as a whole contracts.

The heart is divided into the atrial and ventricular syncytium separated by the fibrous annulus at the A-V juntion. The action potential has to travel through the specialised conducting system that pierces the fibrous tissue. This division of the heart into 2 functional syncytiums allow the atria to contract a short time before the ventricles, which is important for the effectiveness of the heart as a pump.

The T system in cardiac muscle is located at the Z lines rather than at the A–I junction, where it is located in mammalian skeletal muscle. The T system of transverse tubules, which is continuous with the sarcolemma of the muscle fiber, forms a grid perforated by the individual muscle fibrils. It provides a path for the rapid transmission of the action potential from the cell membrane to all the fibrils in the muscle. The sarcoplasmic reticulum is an important store of Ca2+ and also participates in muscle metabolism.
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Conducting system of the heart - SAN, AVN, Bundle of His, Purkinje fibres

The conducting system of the heart consists of:
1) Sino-Atrial Node (SAN),
2) Internodal tract,
3) Atrio-Ventricular Node (AVN),
4) Bundle of His or A-V Bundle,
5) Right and left Bundle branches,
6) Fascicles and 
7) Purkinje fibres.

In the human heart, the SA node is located at the junction of the superior vena cava with the right atrium. 

The AV node is located in the right posterior portion of the interatrial septum. 

There are three bundles of atrial fibers that contain Purkinje-type fibers and connect the SA node to the AV node: 
a) the anterior internodal tract of Bachman, 
b) the middle internodal tract of Wenckebach, and 
c) the posterior internodal tract of Thorel. 
Conduction also occurs through atrial myocytes, but it is more rapid in these bundles. 

The AV node is continuous with the bundle of His, which gives off a left bundle branch at the top of the interventricular septum and continues as the right bundle branch. 
The left bundle branch divides into an anterior fascicle and a posterior fascicle. 
The branches and fascicles run subendocardially down either side of the septum and come into contact with the Purkinje system, whose fibers spread to all parts of the ventricular myocardium.

Thursday, May 19, 2011

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Red blood cell formation

Under certain specific stimuli, pluripotent stem cells form CFU-E i.e Colony Forming Units - Erythrocytes. These cause production of cells that are the first to belong to the RBC series, proerythroblast. The next generation is called basophilic erythroblast because it stains with basic dyes. 

As the genesis continues, hemoglobin concentration increases while the nucleus condenses to a very small size. The remnant of the nucleus is either absorbed or extruded out of the cell. Endoplasmic reticulum is also absorbed. The cell is now called a reticulocyte

The reticulocyte has some basophilic remnants of Golgi apparatus, mitochondria and other organelles. During this reticulocyte stage, the cells pass from the bone marrow into the blood capillaries by diapedesis i.e squeezing through the pores of the capillary membrane.

The remaining basophilic material in the reticulocyte normally disappears within 1 to 2 days, and the
cell is then a mature erythrocyte.

Thursday, April 28, 2011


Knee reflex / Knee jerk

Tapping the patellar tendon elicits the knee jerk (L 2,3,4), a stretch reflex of the quadriceps femoris muscle, because the tap on the tendon stretches the muscle. A similar contraction is observed if the quadriceps is stretched manually. When a skeletal muscle with an intact nerve supply is stretched suddenly, it contracts. This response is called the stretch reflex. It is a type of monosynaptic reflex.

The knee jerk reflex is an example of a deep tendon reflex (DTR) in a neurological exam and is graded on the following scale:
0 (absent),
1+ (hypoactive),
2+ (brisk, normal),
3+ (hyperactive without clonus),
4+ (hyperactive with mild clonus), and
5+ (hyperactive with sustained clonus).

Absence of the knee jerk can signify an abnormality anywhere within the reflex arc, including the muscle spindle, the Ia afferent nerve fibers, or the motor neurons to the quadriceps muscle. In general the afferent loop is much more critical for reflex function than the efferent loop, so that unless the muscle is almost paralysed, loss of reflexes suggests a sensory nerve or root lesion rather than a motor nerve lesion.
The most common cause is a peripheral neuropathy from such things as diabetes, alcoholism, and toxins.

Increased tendon reflex activity suggests increased excitability of the anterior horn cells in the spinal segment of the stretched muscle due to loss of descending inhibition with a UMN or corticospinal tract lesion. Brisk reflexes alone, however, are not necessarily pathological and usually result from anxiety.

In hypothyroidism both the contraction and the relaxation phases of the tendon reflex may be prolonged, resulting in 'hung-up' reflexes.
In cerebellar ataxia the reflexes may be 'pendular': there are oscillatory limb movements after the initial reflex associated with 'loose' tone.