Glucose

Hi, in today's post we'll be discussing part of the next topic in our Veterinary Biochemistry unit, that is carbohydrates, which consists of six individual parts. Today we'll talk about the first part which is an introduction to carbohydrates and glucose. I'll define some key words and explain the glycosidic bond. I'll also discuss homoeostatic glucose concentrations and glucose transporters.

Carbohydrates

First of all, carbohydrates are molecules that consist of carbon, hydrogen, oxygen and sometimes nitrogen. They also contain hydroxide groups and aldehyde and ketone groups. They are also called saccharides or sugars. Carbohydrates are important because they are the precursors for many important substances such as: lipids, non-essential amino acids, RNA and DNA. They are also important in the release of energy from ATP. There are several types of carbohydrates, including:

• Monosaccharides: these are the simplest carbohydrates and cannot be hydrolysed into simpler forms. eg fructose.
•  Disaccharides: these are two monosaccharides linked by a glycosidic bond. eg sucrose
• Polysaccharides: these are many monosaccharides linked by glycosidic bonds. eg. cellulose

The Glycosidic Bond

Glycosidic bonds are formed by the -OH group of an anomeric carbon and a second carbon. The linkages are either α or β depending on the anomeric isomer. The diagram below shows what an anomeric isomer looks like.

An Anomeric Isomer

The only difference between the two molecules is whether or not the -OH group lies above or below the plane of the molecule. If the bond is below the plane, it is a α glycosidic bond. It will be a β glycosidic bond if the bond lies above the plane of the molecule. Enzymes are highly specific for each type of glycosidic bond.

Homeostatic Glucose Concentrations

The concentration of glucose in blood plasma is tightly controlled. Normal plasma glucose levels in monogastric animals (those with one stomach chamber, eg humans and pigs) are between 4 and 5 mM. In ruminants (an animal with a rumen eg. cattle and sheep) normal plasma glucose levels lie between 3 and 4 mM. The difference between monogastrics and ruminants is due to the fact that in ruminants, glucose is fermented and the animal absorbs volatile fatty acids where as in monogastrics glucose is absorbed. Hypoglycaemia occurs when the blood glucose levels fall below half of the normal blood glucose values. Hyperglycaemia occurs when the blood glucose levels are higher than 10mM for extended periods of time.

Glucose Transporters (GLUT)

GLUT proteins allow the facilitated passive diffusion of glucose into cells. ie they help cells absorb glucose. All cells contain GLUT proteins but they may vary in their kinetic properties. There are 4 key GLUT proteins:

• GLUT1: found in erythrocytes, the brain, placenta and kidney. They have a Km of 1mM and are not responsive to insulin
• GLUT2: found in the liver, beta cells of the pancreas and the kidney. They have a Km of 10-20 mM and aren't insulin responsive
• GLUT3: found in the brain and many other tissues, they have a Km of less than 1mM and are also not responsive to insulin
• GLUT4: found in the muscles, heart and adipose tissue. They have a Km of 5mM and are responsive to Insulin.

Glucose Dependence of Tissues

Erythrocytes (red blood cells) require GLUT1 transporters to receive their glucose. They have no mitochondria and so they rely on glucose for their energy, which is generated via glycolysis. They are unable to use fats or amino acids as an energy source because they require a mitochondria. 

The brain and nervous tissue use GLUT1 and GLUT3 transporters to receive their energy. They are entirely glucose dependent and require aerobic metabolism. 

Type II muscle (white muscle) use GLUT4 transporters to receive their glucose. This type of muscle receives a limited oxygen supply and have few mitochondria. During anaerobic metabolism, they get glucose from glycogen stores. 

The liver uses GLUT2 transporters to receive its glucose. The liver is central to glucose homeostasis and act as a glucose sink. The metabolism that occurs in the liver is not glucose dependent.

And that's it :) If you have any questions please feel free to ask :)


  

Neorohormonal Control of Blood Pressure and Volume

In this post we'll be talking about how tha autonomic nervous system can control blood pressure. I'll also discuss the arterial and atrial baroreceptor reflexes.

The short term regulaiton of blood pressure involves the heart and blood vessels regulating cardiac output and total peripheral resistance. The long term regulation of blood pressure involves the kidneys which regulate blood volume.

The Arterial Baroreceptor Reflex

The arterial baroreceptor reflex  consists of several components:

• Detectors: these are arterial baroreceptors which are located in the walls of the carotid sinus and aortic arch. They contain nerve endings which are sensitive to stretch (distension) of the arterial wall by pressure. These baroreceptors monitor the pressure of every systolic ejection. 
• Integrator: this is the neural control of cardiovascular function. The parasympathetic nervous system regulates heart rate while the sympathetic nervous system predominates during exercise. The sympathetic nervous system increases heart rate and contractility of cardiac muslce. This leads to an increase in cardiac output.
• Effectors: in most tissues, all blood vessels except capilaries and precapillary sphincters are innervated by the sympathetic nervous system. With skeletal muscle as the exception, sympatheitc stimulation of small arteries generally increases resistance and decreases flow. The sympathetic stimulation of veins causes the volume of the vessels to decrease. This increases venous return to the heart.

If arterial baroreceptors detect a decrease in Mean Arterial Pressure they decrease the level of  parasympathetic activity. This leads to an increase in the frequency of action poteintial firing, which leads to an increase in heart rate. The baroreceptors may also cause an increase in sympathetic nervous system activity. This may increase contractility which leads to an increase in stroke volume. It may also cause an increase in venomotor tone, decreasing compliance and increasing venous pressure. This leads to an increase in end diastolic volume and an increase in stroke volume. An increase in sympathetic activity may increase vasocontriction which may increase total peripheral resistance. An increase in heart rate, stroke volume and total peripheral resistance will result in an increase in mean arterial pressure.The arterial baroreceptor reflex is essential for the normal moment-to-moment stability of mean arterial pressure but has little effect on the long term level of blood pressure. 

The Atrial Baroreceptor Reflex

The atrial baroreceptor reflex has atrial volume receptors which are stretch receptors in the walls of the atria. They detect the volume of blood in each atria which indirectly monitors total blood volume. The atrial baroreceptor reflex has the same integrators and effectors as the arterial baroreceptor reflex.

The atrial volume receptors decrease in activity in response to a decrease in blood volume. This detected by the central nervous system. This may affect the hypothalamus which may cause the animal to feel thirsty, this leads to an increased water intake. The central nervous system may also communicate with the pituitary which could cause an increased amount of antidiuretic hormone to be released, this leads to a decrease in urine production. The sympathetic nervous system may also be affected causing the kidney to release more renin which decreases the excretion of Na+. In addition, the sympathetic and parasympathetic nervous systems could be stimulated causing a similar response that was seen in the arterial baroreceptor reflex. The increase in water intake and the decrease in sodium excretion and urine flow act to minimise the effects of a decrease in blood volume and pressure.

Glycolysis

Hello :) In this post we'll be discussing glycolysis. I'll outline the glycolytic pathway and list where in the cell they occur. I'll also discuss some of the major enzymes involved in glycolysis and how they can regulate this pathway.

Glycolysis

The main function of glycolysis is the catabolism (break down) of carbohydrates as glucose to produce energy in the form of ATP. Glycolysis occurs in the cytosol of all cells and may occur in the presence or absence of oxygen. In this unit we have been told to not focus on remembering the specifics of this pathway, instead we have been told to know the outline of the pathway as follows:

• Glucose, which is a 6 carbon molecule, is broken down into two 3 carbon molecules. This process involves the consumption of 2ATP molecules per molecule of glucose and is known as the investment phase.
• The two 3 carbon molecules are gradually converted to pyruvate. This involves the production of 4 ATP molecules and is known as the pay-off phase.
• In an aerobic environment, pyruvate is fed into the Tricarboxylic Acid Cycle (TCA cycle). Under anaerobic conditions pyruvate is converted to lactate which releases NAD+. This is because glycolysis is NAD+ dependent and so NAD+ needs to be recycled. 

The Regulation of Glycolysis

When we talk about enzymes, it is helpful to understand some terminology as there are different types of enzymes. A Kinase (eg.protein kinase) is any enzyme that adds a phosphate to a molecule using ATP as the phosphate donor. A phosphorylase (eg. glycogen phosphorylase) is any enzyme which adds a phosphate to a molecule using inorganic phosphate (Pi) as the phosphate donor. A Phosphatase (eg. protein phosphatase) is any enzyme that removes a phosphate from  a molecule as inorganic phosphate.

Glycolysis is regulated mainly by three different enzymes which each catalyse a particular reaction in the pathway:

1. Hexokinase: this catalyses the conversion of Glucose to Glucose-6-Phosphate which also requires the input of 1 ATP molecule which is converted to ADP. This makes glucose impermeable to the cell membrane so that it can't leak out of the cell.
2. Phosphofructokinase: this is the most important rate regulator, it catalyses the conversion of Fructose-6-Phosphate to Fructose-1,6-Bisphosphate which requires the conversion of ATP to ADP. This enzyme is inhibited by an increase in ATP, citrate and hydrogen ions. It is stimulated by Fructose-2,6-bisphosphate and AMP. 
3. Pyruvate Kinase: this inhibits the conversion of Phosphoenolpyruvate to Pyruvate which also requires the conversion of ADP to ATP. This enzyme is inhibited allosterically by ATP and alanine and covalently by glucagon. This makes sense because glucagon is released when blood glucose levels are low and its actions try to increase blood glucose leves - glucagon acts to conserve glucose. By inhibiting pyruvate kinase, glycolysis is inhibited and glucose is spared. Pyruvate Kinase is stimulated allosterically by Fructose-1,6-bisphosphate.

Pyruvate Dehydrogenase

As I mentioned earlier, under aerobic conditions the product of glycolysis (pyruvate) is fed into the TCA cycle. During this cycle, pyruvate is converted to Acetyl Coenzyme A (Acetyl CoA) and this reaction is catalysed by Pyruvate Dehydrogenase. Pyruvate Dehydrogenase needs to be regulated because pyruvate is gluconeogenic. This means that it can be used to make glucose during starvation and thus it needs to be conserved. Pyruvate Dehydrogenase is inhibited by its reaction products - Acetyl CoA and NADH. β-oxidation (which is involved in the breakdown of fats) produces these two products, high levels of these products are found during starvation.

Pyruvate Dehydrogenase (PDH) may also be regulated by covalent modulation:

•  PDH can be phosphorylated by PDH kinase which inhibits the enzyme. 
• This is reaction is stimulated by NADH, Acetyl CoA, and ATP
• This reaction is inhibited by Calcium, pyruvate and dichloroacetate.
• PDH can be dephosphorylated by PDH Phosphatase which will activate the enzyme.
• This reaction is stimulated by insulin, calcium ions and magnesium ions. This occurs when the animal is well fed and can afford to use up some pyruvate. Calcium levels may increase due to muscle contraction during exercise, this makes sense because the animal would need extra glucose which can be obtained through the gluconeogenesis of pyruvate.

That's it for this post, if you have any questions please feel free to ask :)

Local Control of Blood Flow

In this post we will be discussing the importance of arteriolar radius in the distribution of blood flow in the systemic circulation. I'll also explain the major mechanisms which regulate arteriolar radius.

Arteriolar Radius and the Distribution of Blood Flow

If you can remember from this post, you'll know that flow is determined by:

Flow = change in pressure / Resistance

Where the change in pressure is known as perfusion pressure.

All the organs in the systemic circulation are exposed to the same perfusion pressure, so the only way to alter blood flow to individual organs is to change the resistance. Arteriolar resistance is regulated intrinsically and extrinsically which allows the cardiac output between different organs to be changed according to need.

Intrinsic Regulation

The intrinsic regulation of blood flow dominates in critical tissues such as the brain, coronary circulation and working skeletal muscle.   

Active Hyperaemia

This is when blood flow is matched to metabolic rate and it is mediated by chemical changes in the tissue. As tissue metabolism increases, the concentration of vasodilators (CO2, K+ and other metabolic products) increases and the concentration of oxygen decreases. This results in vasodilation which reduces arteriolar resistance and increases blood flow. It also causes the reduction in the tone of precapillary sphincters which cause more capillaries to open. This decreases the diffusion distance and increases the total area of the capillaries. The increase in surface area, the increase in blood flow and the decrease in diffusion distance causes the amount of oxygen to increase and the vasodilators to be washed out of the tissue.

Reactive Hyperaemia: 

Reactive hyperaemia is the increase in blood flow in response to a period of inadequate blood flow. The chemical signals used are similar to what is used in active hyperaemia. During a period of reduced blood flow there is reduced O2 delivery and CO2 removal to and from cells. This causes extracellular O2 concentrations to decreases while the CO2 concentration increases, metabolites also build up. These conditions cause vasodilation which increases blood flow. The duration of reactive hyperaemia is directly proportional to the duration of vascular occlusion. 


Autoregulation:

This is the maintenance of blood flow despite changes in perfusion pressure. For example, between arterial pressures of about 70-170 mmHg blood flow increases by 30% although arterial pressure increases by 150%.  There are two possible mechainisms:

• Myogenic: an increase in perfusion pressure causes the arteriolar smooth muscle to stretch. The smooth muscle responds by contacting which increases resistance and decreases flow.
• Metabolic: An increase in blood pressure causes an increase in flow. This increases the amount of oxygen delivered to the tissues and causes the washout of vasodilators. This results in the contriction of the arterioles which increases resistance and decreases flow.  

Extrinsic Regulation

The parasympathetic nervous system has minimal influence on vascular smooth muscle, instead the sympathetic nerves play a major role. Sympathetic postganglionic neurons release noradrenaline which bind to α-adrenergic receptors on smooth muscle cells. This causes vasoconstriction.

There are 3 main hormones which are involved in the regulation of arteriolar radius:

• Adrenaline: this is released from cells in the adrenal medulla in response to sympathetic activity. In the skeletal muscle, β2 receptors respond to the adrenaline and cause vasodilation. In the GI (gastrointestinal) tract, α receptors respond to adrenaline by causing vasoconstriction.
• Antidiuretic hormone: this is synthesised in the hypothalamus and is secreted when hyperosmolaltiy and blood volume depletion occurs. The activation of V1 receptors causes arteriolar vasoconstriction and the activation of V2 receptors increases renal water reabsorption.
• Angiostensin II: Angiostensinogen is formed in the liver, this is converted to angiostensin I by renin. Angiostensis I is converted to angiostensin II by a converting enzyme present in endothelial cells. It has three major actions:

1. Renal Na+ (and hence water) retention. This is mediated by aldosterone
2. constriction of systemic arterioles
3. Regulation of glomerular filtration rate. 

So overall, extrinsic methods of regulation maintain stable arterial pressure, coordinating the circulatory system as a whole. Intrinsic mechanisms give individual organs the blood supply that it needs.
 
That's it for this post, see you next time :) 

Mechanisms of Hormone Action

In this post I'll explain how steroid hormones, the adenylate cyclase mechanism, and how tyrosine kinase receptors work to cause a cell to produce certain proteins.

There are two broad classes of hormones, steroid hormones and peptide hormones. Steroid hormones are derived from cholesterol and so are lipid soluble. This allows them to diffuse through the cell membrane to bind to intracellular receptors resulting in changes in DNA transcription. Peptide hormones are composed primarily of amino acids which are not lipid soluble, thus they are unable to easily pass through the cell membrane. Instead, peptide hormones interact with membrane receptors and are coupled to signal transduction systems. Peptide hormones provide a fast mechanism of action while steroid hormones are slower.

Steroid Hormones 

Examples of steroid hormones include the sex hormones, glucocorticoids and mineralocorticoids. They are hydrophobic and so they require a carrier protein to travel in the blood plasma.

Mechanism of Action:

All steroid hormones have the same mechanism of action which is outlined as follows.The hormone diffuses through the cell membrane and binds to a cytoplasmic receptor (some travel to the nucleus to bind to the receptor). The hormone then enters the nucleus and he hormone-receptor complex binds to hormone response elements on the DNA. The hormone-receptor complex may stimulate or inhibit the transcription of a particular gene. If the complex stimulates transcription, the binding of the hormone-receptor complex activates the gene and mRNA is transcribed and moved to the cytoplasm where protein translation takes place. Because of all the steps involved the response is relatively slow. 

Peptide Hormones

Peptide hormones are hydrophillic and so can be transported in the blood stream easily. Examples of peptide hormones include: Growth Hormone, Prolactin and Oxytocin. Because peptide hormones cannot easily diffuse through the cell membrane they have to use a mechanism of action called the G-Protein mode of action. The binding of the hormone to a receptor located on the cell surface activates a G-protein which initiates the production of a "second messenger". The most common "second messengers" are cyclic AMP (cAMP), inositol triphosphate (IP3) and diacylglycerol (DAG). The second messenger initiates a series of intracellular events such as: the phosphorylation and activation of enzymes; or the release of Ca2+ stores within the cytoplasm.

The cAMP/Adenylate Cyclase Pathway

the pathway begins when the hormone binds to the receptor. Several steps then occur:

1. The G-protein is activated causing it to exchange its bound GDP for GTP
2. Activated G-proteins bind to adenylate cyclase
3. Activated adenylate cyclase produces cAMP
4. cAMP activates Protein Kinase A
5. Protein Kinase A phosphorylates other proteins: this switches them on or off and causes a cascade of cellular events.

This process is shown in the video below.

An example of a hormone which uses this method of action is adrenaline. 

Tyrosine Kinase Associated Receptors

These types of receptors do not require G-proteins or enzymes to transfer the signal from the hormone because the receptors are themselves enzymes. When no hormone is bound the receptor exists as a monomer. The binding of a hormone causes the receptor to dimerise which initiates intracellular signalling. The receptor phosphorylates tyrosine residues on itself causing it to become active. The activated receptor then phosphorylates tyrosine residues on other proteins in the cytoplasm. Eventually the receptor is switched off by tyrosine phosphatases. 

And that's all for this post, if you have any questions please feel free to ask :)

 

Capillaries, Fluid Exchange and the Lymphatic System

Hi, in this post we'll be talking about the different types of capillaries and how substances can diffuse through capillary walls. I'll also talk about the role of the lymphatic in returning fluid to the circulatory system as well as venous pressure. 

Types of Capillaries

Capillaries are blood vessels that allow the rapid exchange of substances, there are 3 types of capillaries:

1. Continuous Capillaries: the endothelial cell wraps around the lumen and is sealed by tight junctions. This type of capillary can be found in places such as the muscles and lungs.
2. Fenestrated capillaries: the endothelial cells have windows for increased permeability. They can be found in areas such as the endocrine glands and intestinal tract. 
3. Discontinuous Capillaries: these have large gaps between endothelial cells to allow the passage of proteins. They can be found in places such as the bone marrow and spleen. 

This website has some nice diagrams which show what each of these look like. 


Control of Flow Through Capillary Beds

Not all capillaries carry blood at all times. Arterioles (which precede capillaries) alternate between constriction and dilation to periodically reduce or stop blood flow to capillary beds. This is under the control of local factors and the autonomic nervous system. Metarterioles have isolated rings of smooth muscle and act as shunts which directly connect arterioles to venules. When the metarterioles are open blood bypasses the capillary beds and when closed blood flows through the capillary beds. There are also precapillary sphincters which reduce flow to individual capillaries. They are under the control of only local factors such as carbon dioxide.   

Factors Affecting Diffusion Across Capillaries 

Water soluble substances are able to pass through the water-filled pores located between the endothelial cells. Lipid-soluble substances diffuse across the endothelial cells while some proteins cross via a process called transcytosis. There are several factors which affect the rate at which substances diffuse into capillaries:

1. concentration difference
2. area available for diffusion
3. diffusion distance: the distance from the tissue cell to the nearest capillary
4. diffusion coefficient: which increases with an increase in temperature.

These are all based on Fick's Law and are physiologically adjustable.

Bulk Flow  

Bulk flow refers to the movement of water and solutes along pressure gradients. Across the capillary, it is the movement of protein free plasma where filtration (movement out of capillary) and absorption (movement into the capillary) are possible. The purpose of bulk flow is to distribute the extracellular fluid. Bulk flow is driven by hydrostatic and osmotic pressures (known as Starling forces). Hydrostatic pressures are forces due to the fluid pressing on the vessel walls and the pressure in the interstitial tissue. Water moves from high hydrostatic pressure to low hydrostatic pressure. Osmotic pressure is the pressure exerted by the movement of water down its concentration gradient. Water moves from areas of low osmotic pressure to areas of high osmotic pressure. There are four Starling forces which act on capillaries:

1. Capillary hydrostatic pressure: the mean functional capillary pressure (17.3 mmHg)(filtration)
2. Interstitial hydrostatic pressure: the interstitial free fluid hydrostatic pressure. (-3 mmHg)(filtration)
3. Plasma colloid osmotic pressure: the capillary pressure associated with proteins in blood.(28 mmHg)(absorption)
4. Interstitial colloid osmotic pressure:the interstitial tissue pressure associated with proteins. (8 mmHg)(filtration)

The total amount of force tending to move fluid out the capillary is 28.3mmHg while the amount of force tending to move fluid into the capillary is 28.0 mmHg. Thus there is a net movement of blood into the interstitial fluid. The lymphatic system picks up this fluid and returns it to the circulatory system.

 The Lymphatic System

As mentioned earlier, the capillaries experience a net filtration of 0.3 mmHg. This may not seem like much, however, in an adult human this amounts to 2mL/min being lost from the blood stream. This adds up to 3 L/day of fluid lost from the circulatory system. This fluid is returned to the circulation via the lymphatics. 

Central Venous Pressure

Central venous pressure is the pressure in the large veins of the thoracic cavity that lead into the right atrium. Several factors affect central venous pressure including:

• The activity of the muscle pump
• the activity of the respiratory pump
• The activity in the sympathetic nerves: an increase in activity leads to an increase in venomotor tone (the degree of tension in the muscle coat of a vein which determines its shape) which leads to a decrease in compliance of the veins.
• Blood volume 

An increase in all of these will lead to an increase in venous pressure. An in crease in venous pressure results in increased driving force for venous return which leads to an increase in preload. This results in an increase in end diastolic volume which increases the stroke volume and cardiac output. This causes an increase in the amount of blood flow into the systemic circuit. 




And that's all for this post, see you next time :)
      

Systemic and Pulmonary Circulations, Mean Arterial Pressure and the Measurement of Blood Pressure.

In this post, we'll be talking about systemic and pulmonary circulations, mean arterial pressure and the measurement of blood pressure. I'll explain the difference between serial and parallel blood flow, the anatomy of blood vessels, and how arterioles work to vary vascular resistance. I'll also discuss mean arterial pressure and how it is calculated. In addition, I'll talk about how blood pressure can be measured in a clinical setting as well as how various factors can influence blood pressure.

Series and Parallel Flow

The heart is effectively two pumps working is series, this forms the pulmonary and systemic circuits. Many of the smaller, more branching pathways of the systemic circuit are arranged in parallel. For blood vessels arranged in series, the total resistance is the sum of the individual resistances (known as a relative resistance) of each blood vessel. The blood vessel which has the highest relative resistance has the greatest effect on total resistance when it is changed. In the body, the arterioles have the highest relative resistance and so have the greatest influence on total resistance. This website has a helpful explanation of series blood flow.

A parallel arrangement of vessels results in less resistance, this is due to how the total resistance for a parallel arrangement is calculated. This website shows how it is done and provides a good explanation of the concept. 

Structure of Blood Vessels

• Arteries: these have a relatively wide diameter (~4mm) and thick walls (~1mm), they are muscular and highly elastic.
• Arterioles: these have an average diameter of 0.03mm and a wall thickness of 0.006mm, they are muscular and well innervated. This means that their diameter can be altered which will have a great effect on total resistance in the body.
• Capillaries: these are the smallest blood vessels which are thin walled and highly permeable.
• Venules: they have an average diameter of 0.02 mm and a wall thickness of 0.001mm, they are thin walled and have some smooth muscle. 
• Veins: these are relatively large blood vessels (diameter: ~5mm) that are thin walled (~0.5mm in thickness), fairly muscular and highly distensible.

Because the capillaries have the smallest diameter, one would expect that they would produce the most resistance. However, this is not the case as capillaries are usually arranged in parallel which results in lower resistance. Instead, the arterioles produce the most resistance due to their small diameter, and the fact that they carry freshly oxygenated blood from the heart. Venules do not create much resistance because their perfusion pressure is low, this follows the equation:

Flow = the change in pressure / Resistance

Where the change in pressure is termed the perfusion pressure.  

Total Peripheral Resistance 

Total Peripheral Resistance (TPR) = (mean aortic pressure - vena caval pressure)/cardiac output.

However, for a dog at rest, the vena caval pressure is close to zero and the equation can be arranged to:

Mean aortic pressure = Cardiac Output x Total peripheral resistance

Mean Arterial Pressure

Now, the mean arterial pressure (MAP) is the average pressure within an artery over a complete cycle of one heartbeat. It is calculated according to the equation:

Mean arterial blood pressure = CO x TPR

Where CO is the cardiac output and TPR is the total peripheral resistance.

Arterial pressures are pulsatile, so systolic and diastolic pressures exist. The MAP is not simply the average of the systolic (SP) and diastolic pressures (DP). This is because for most of the cardiac cycle, the pressure in the distal arteries is closer to the diastolic pressure and reaches peak pressure only briefly, the pressure waveforms in arteries are not symmetric, so the MAP is slightly above the diastolic pressure. The rule for calculating MAP is:

MAP= (SP + 2 x DP)/3
or
MAP = DP + 1/3 Pulse Pressure

Pulmonary and Systemic Circuits:

The pulmonary circuit is a low pressure, low resistance circulation. Pulmonary resistance is much lower (<10%) than the systemic circuit. When an animal exercises, the pulmonary resistance decreases to allow an increased flow without a large increase in the pressure of the pulmonary artery.

The pulmonary blood vessels are highly compliant and thus gravity has an effect on pulmonary blood flow. Gravity increases the pressure in the more ventral blood vessels of the lungs. This increase in pressure distends the vessels, decreasing the resistance and increasing flow. This can cause an imbalance between the alveolar blood flow and ventilation as blood flow tends to be excessive in the more ventral areas of the lung. This is called a ventilation-perfusion mismatch and is particularly a problem in large animals.

Blood Pressure

Blood pressure can be measured directly and indirectly in animals. With direct measurement, a thin tube is placed in an artery to allow blood to flow through a sterile fluid filled system which is connected to an electronic monitor. This allows blood pressure to be measured beat by beat. With indirect measurement a sensor is placed on the animals artery in the paw and a blood pressure cuff is placed above the sensor. The sensor amplifies the sound of the blood moving through the artery and allows the veterinarian to determine the systolic and diastolic pressures using the blood pressure cuff.   

Factors Affecting Pulse Pressure

• increased stroke volume increases cardiac output, pulse pressure and mean arterial pressure.
• decreased HR increases the time for the blood to run into the systemic circulation, increasing pulse pressure but decreasing cardiac output (because CO=HR x SV) and mean arterial pressure. 
• With increased stroke volume and decreased heart rate, cardiac output and mean arterial pressure remain unchanged put the pulse pressure increases. This occurs with aerobic conditioning.

That's it for this post :) If you have any questions please feel free to ask in the comments section below. 

 

 

Endocrinology

The next topic in our Veterinary Biochemistry unit deals with endocrinology - the study of the structure and function of the endocrine glands and the hormones they produce. In this post I'll define the terms endocrine, paracrine, autocrine and hormone. I'll also discuss the hormones produced by the anterior lobe of the pituitary gland and the adrenal glands and I'll describe the actions of posterior pituitary hormones. In addition, I''ll talk about the thyroid hormones, blood glucose regulation and melatonin.

Major Glands of the Endocrine System

Firstly, there are some terms which we need to know. A hormone is any substance that carries a signal to generate some sort of alteration at the cellular level. Hormones are secreted into body fluids (ie. blood), they bind to specific receptors in or on the target cells. Hormones work to initiate changes in cellular activity and the primary function of the endocrine system is to maintain homeostasis. Hormones are degraded by enzymes in the target cell, liver or kidneys. 

In autocrine signalling the cell which produces the signal is the same as which responds to the signal. This is the least common form of signalling by cells. In paracrine signalling one cell "talks" nearby cells by releasing a chemical, eg. the release of a neurotransmitter. In endocrine signalling, the most important type, hormones are secreted into the blood and carried by blood and tissue fluids to the cells they act upon.

Hormones Produced by the Pituitary Gland

The anterior lobe of the pituitary gland releases the following:

• Growth Hormone (GH): causes the growth of the cell to which the hormone is bound. GH also causes the growth of tissues, the uptake of amino acids into tissues, stimulates protein synthesis, conserves plasma glucose and opposes the effects of insulin and increases the synthesis of glucose and its release into the blood
• Thyroid Stimulating Hormone (TSH): promotes the production of thyroid hormones, regulates metabolic rates and body temperatures and releases calcitonin.
• when not enough thyroid hormones are produces, hypothyroidism results. Symptoms include a reduced metabolism, cold intolerance, slow heart rate, weight gain and lethargy
• when too much thyroid hormones are produced hyperthyroidism may result. Symptoms include: increased metabolism, nervousness and anxiety, insomnia and fatigue, as well as protrusion of the eyeballs.
• Leutinising Hormone (LH): stimulates the gonads. In males the production of testosterone and sperm development is promoted. In females estrogen production and egg development are promoted, and ovulation is stimulated. 
• Follicle Stimulating Hormone (FSH): works with LH to stimulate the gonads
• Adrenocorticotrophic Hormone (ACTH): acts on the adrenal gland and triggers the production of adrenaline and noradrenaline.
• Prolactin (PRL)

Posterior pituitary hormones include:

• Oxytocin: which initiates labour and causes milk ejection
• Antidiuretic Hormone (ADH): its key role is to maintain fluid homeostasis. It stimulates the kidney to conserve body water by reducing the output of urine. 

Hormones Produced by the Adrenal Glands: 

The adrenal medulla (the inside of the adrenal gland) secretes adrenaline and noradrenaline which increase heart rate, and increase the amount of glucose released from the liver to prepare the body for a "fight or flight" situation. 

The adrenal cortex (the outside of the adrenal gland) secretes:

• Mineralocorticoids:  this includes aldosterone and regulates electrolyte balance.
• Glucocorticoids: which includes cortisol and helps regulate glucose metabolism.
• Sex Steroids: which supplement the sex steroid secretion by the gonads.    

 Glucose Regulation

When the amount of glucose in the blood becomes too high, the beta cells, located in the Islets of Langerhan in the pancreas, secrete insulin. Insulin removes glucose from the blood by causing the liver to make glycogen, prevent gluconeogenesis and increase the glucose transport to cells. 

When the amount of glucose in the blood becomes too low, the alpha cells, located in the Islets of Langerhans in the pancreas secrete glucagon. Glucagon works on the liver to increase the amount of glucose in the blood via gycogenolysis and gluconeogenesis. 

Melatonin 

The pineal gland secretes melatonin which determines circadian rhythms. Melatonin decreases the time it takes to fall asleep by decreasing motor activity and inducing fatigue. Melatonin is inhibited by light and is associated with jet lag and "winter depression".


That's it for this post, if you have any questions please feel free to ask in the comments section below :)

The Heart As a Pump, Heart Sounds and Cardiac Output

Hello :) In this post we'll be discussing how the heart acts as a pump, how the sounds of the heart are produced as well as how cardiac output is regulated.

Diagram of the Heart
source:http://commons.wikimedia.org/wiki/File%3ADiagram_of_the_human_heart_(cropped).svg
please see this website if you'd like to use this diagram.

The heart is really two pumps which work in series and the heart pumps in pulmonary and systemic circulations. Pulmonary circulation is the part of the circulatory system which transports deoxygenated blood from the right side of the heart to the lungs and returns oxygenated blood to the left side of the heart. The systemic circuit is the part of the circulatory system which pumps oxygenated blood from the left ventricle to to the tissues in the body and returns deoxygenated blood to the right atrium of the heart. When we talk about ventricular contraction, it is termed systole. While ventricular relaxation is referred to as diastole.  

Pressure in the heart chambers vary between different stages of the cardiac cycle. Blood flow is driven by the changes in pressure. The normal direction of blood flow is from the atria to the ventricles, then from the ventricles to the arteries. Valves in the heart ensure that the blood only flows in the correct direction, they open and close in response to pressure gradients.

The Cardiac Cycle and Pressure Changes

Ventricular Diastole

When the ventricles relax (diastole) no ventricular filling will occur until the pressure inside the ventricles is less than the atrial pressures and the AV (atrioventricular) valves open. When the pressure inside the ventricles is less than the pressure inside the atria, the ventricles fill with blood. This period of rapid ventricular filling is followed by a phase of reduced ventricular filling (known as diastisis). Diastisis persists until atrial contraction occurs. 


Ventricular Systole:

Firstly, isovolumetric ventricular contraction occurs. This is when the ventricular pressure increases but the volume remains unchanged. This increase in the ventricular pressure closes the AV valves. However, the semilunar (aortic and pulmonary) valves remain closed because the ventricular pressures are less than the aortic or pulmonary artery pressure. The ventricles eject blood when the ventricular pressure exceeds the aortic or pulmonary pressure pressure causing the semilunar valves to open. This leads to the rapid ejection of blood into the aorta or pulmonary artery. This is followed a reduction in the amount of blood ejected as the ventricular pressures begin to decline. Ventricular pressures continue to decrease which closes the semilunar valves and causes the end of systole.


Heart Sounds

There are four sounds that may be heard when the heart beats:

1. A low frequency "lub" (S1). This sound is associated with turbulence as the AV valves close. 
2. A high frequency "dup" (S2). This is associated with turbulence as the semilunar valves close. 
3.  A short, low frequency sound. This is not heard in most normal animals and is associated with turbulence as the ventricles fill.
4. A sound similar to S1. This is associated with turbulence as the atria contract.

Regulation of Cardiac Output

 There are some important terms that you'll need to become familiar with. End diastolic volume (EDV) is the volume of blood in each ventricle at the end of diastole. End systolic volume (ESV) i the volume of blood in each ventricle at the end of systole. Stroke volume is the EDV minus the ESV. For a large dog this is usually around 30 mL. Ejection fraction is the fraction of blood ejected during systole. It is calculated by dividing the strove volume (SV) by the EDV (SV/EDV). For a resting dog this is typically 50%.


Cardiac output (CO) is the total amount of blood pumped by each ventricle (L/min). 

CO = SV x HR 

Where HR is heart rate. Cardiac output can be affected by many factors, this can be summarised in the flow chart below:

Cardiac output increases only if HR increases, SV increases or both increase. Stroke Volume will increase with an increase in EDV (which can occur through increased ventricular filling) or with a decrease in ESV (which can occur through more complete ventricular emptying).  

End Diastolic Volume (EDV) is determined by:

• ventricular preload: this is the end diastolic ventricular pressure which equals the atrial pressure and the vena caval pressure.
• ventricular compliance: this is the ease with which ventricular walls stretch to accommodate diastolic filling. A non compliant ventricle increases the amount of ventricular preload required to increase the EDV. 
• diastolic filling time: this is the length of time available for ventricular filling during diastole. This is determined mainly by heart rate. As the HR increases, the ventricles have a shorter time in which to relax and fill with blood, reducing the stroke volume.

End Systolic Volume (ESV) is determined by:

• ventricular contractility: contractility refers to the ventricle's pumping ability. An increased contractility decreases the ESV because the ventricles empty more completely. A decrease in cardiac contractility is the hallmark of cardiac failure. The sympathetic nervous system can increase the heart rate and contractility. The parasympathetic nervous system can decrease the heart rate and contractility.
• systolic duration: an increase in the activity of the sympathetic NS (such as during exercise) decreases the duration of ventricular systole. This helps to preserve the diastolic filling time which will help to preserve the cardiac output
• ventricular after load: this is the pressure against which the ventricle must pump to eject blood, this is equal to the pressure in the arteries. A substantial increase on the arterial blood pressure impairs the ejection of blood by the ventricles.  

That's it for this post, see you next time :)

Protein Synthesis and Transport

Hi, in this post we'll be discussing protein synthesis and protein transport. I'll be discussing the basics of protein synthesis and how translation works. I'll also outline the post-translational modifications that occur to a protein after it has been synthesised as well as explain protein targeting.

Protein Synthesis

Protein synthesis refers to the creation of a protein from a mRNA template copied from DNA. Proteins are synthesised outside the nucleus on ribosomes. Protein synthesis starts with transcription (see previous post) which takes place in the nucleus, where RNA polymerase reads a DNA strand and synthesises a single strand of mRNA (messenger RNA) from a gene. This strand of mRNA migrates through nuclear pores to ribosomes located in the cytoplasm. 

A group of 3 consecutive nucleotides on a mRNA is termed a codon, eg. UAG. Some codons tell the ribosome where to start making the protein, these are called start codons (AUG). Some codons such as UAG, UAA, and UGA tell the ribosome where to stop adding amino acids to the polypeptide, these are termed stop codons. Codons also code for different amino acids, eg. GUU codes for Valine. When the mRNA molecule travels to the ribosomes, the ribosomes attach to the mRNA and read the codons. Transfer RNA molecules then bring the corresponding amino acid to the ribosome where it binds to other amino acids to form a polypeptide.

Transfer RNA has a three nucleotide sequence known as an anticodon which is complimentary to the codon for that particular amino acid. Aminoacyl-tRNA synthetase catalyses the attachment between each tRNA and its corresonding amino acid. There are 20 aminoacyl-tRNA synthetases, approximately 50 different tRNA molecules and 61 codons. If each codon can pair with only a unique anticodon, then 61 tRNAs would be needed. However, there are less than 61 tRNAs in the cell, so how are all the codons read?

The Wobble Hypothesis, proposed by Francis Crick in 1966, can explain this. Some codons code for the same amino acid, for example CGU and CGC both code for arginine but both pair with the same tRNA, how? A weak interaction between the third base in the codon of the mRNA (termed the wobble base) allows one anticodon to associate with several different codons. Some tRNA molecules have ionosine (I) as the wobble base which can pair with U, C or A. This means that fewer types of tRNA molecules are needed.


Translation

Translation involves three steps: initiation, elongation and termination.

Initiation: 

To begin translation, a large and small ribosomal subunit along with the initiating tRNA assemble onto the mRNA. The start signal for translation is the codon AUG which codes for methionine. The first AUG at the 5' end of the mRNA is not necessarily the start site for translation. Instead, the start codon is always preceded by a sequence specifying the AUG as the start site. Eukaryotes have specific sequences (A/GCCA/GCCAUGA/G) which base pair with a complimentary sequence near the 3' terminus of the ribosomal subunit. This positions the ribosome correctly on the mRNA molecule. Once this has occurred, elongation begins.

Elongation: 

An initiator tRNA is placed at the P site (the site where the growing protein will be) of the ribosome causing elongation to proceed. The next tRNA molecule comes in and binds to the A site (the place where the incoming tRNA will attach itself) which is next to the initiator tRNA at the P site. After this occurs, the ribosome shifts so that the tRNA is now in the P site and a new tRNA binds to the A site. Here, a peptide bond is formed between the two amino acids. The first tRNA is now released and the ribosome shifts again so that the tRNA carrying the two amino acids is now in the P site, and a new tRNA can bind to the A site. This repeats until the ribosome reaches a stop codon. 

Termination 

Translation ends when a stop codon and release factor are encountered, causing ribosomal subunits to dissociate.  

This whole process is explained well in the video below:

Post Translational Modification

Cells contain many different specialised compartments. In addition, a protein must be maintained in a translocation-competent state, that is it must not misfold or aggregate. The protein needs to be directed to its proper membrane or compartment. A particular type of protein, called chaperones, act to ensure that newly synthesised proteins remain unfolded and are delivered to their correct location. But how does a protein know where it is supposed to go?

The answer lies in the structure of the protein. Newly synthesised proteins contain specific signal sequences which are short regions of the protein that act as targeting signals to direct the protein to its correct location. The signal sequence is like the proteins "address".

Some proteins need to travel across the nuclear membrane. If the protein is small enough it can simply pass through the nuclear pores. However, if the protein is quite large it will require active transport and contain a nuclear localisation sequence (NLS). Nuclear import receptors bind to the NLS and carry the protein into the nucleus. 

 Proteins may also need to move across membranes in places such as the peroxisome, mitochondria or endoplasmic reticulum (ER). This requires energy in the form of ATP and an aqueous channel through the membrane. Transmembrane transport can be post translational, such as when travelling through the mitochondria and peroxisomes, or co translational, such as when travelling to the ER.

The ER performs two important functions for protein targeting:

1. N-linked glycosylation: this is the attachment of sugars to particular asparagine residues in proteins. The sugars act as recognition signals and are important for cellular recognition of proteins and protein folding.
2. Peptide folding: Chaperones in the cytoplasm and the lumen of the ER work together to give the polypeptide chain several opportunities to fold.

In addition, proteins may be modified after translation by:

• cleavage by proteolytic enzyme to convert the protein to a functional form
• acetylation
• phosphorylation
• ubiquitination

Proteins may be transferred from the rough ER to the Golgi complex to other areas of the cell. The ER acts as the gateway for protein transport into all the other membrane bound organelles of the secretory pathway of the cell. Proteins are transported through this pathway in small carriers called vesicles. But how do the vesicles know where to go? 

Vesicles from a donor organelle have proteins attached to the vesicles known as v-snares. The target organelle has t-snares. V-snares and t-snares have specific partners so the vesicle must have the correct v-snare to fuse with a specific organelle. The t-snares on each organelle act as "address labels" to ensure that the vesicles go to the right place.

Some proteins may be destined for the lysosome - a specialised compartment which acts as a degradative organelle. Lysosomes contain enzymes which break down proteins. A specific sugar acts as a sorting signal to target proteins to the lysosome.


That's it for this post, if you have any questions or feed back please leave a comment below.  

Electrocardiograms

Hi :) This post will deal with topic four of our Veterinary Physiology 1 unit, that is the Cardiovascular System. In this post I'll be discussing how an electrocardiogram records the electrical activity of the heart. 

The Spread Of Depolarisation of the Heart

This occurs in a series of 8 steps:

1. Depolarisation initiated at SA node
2. Depolarisation spreads through atria
3. AV nodal delay (~0.1sec)
4. Depolarisation travels down bundle of His and bundle branches
5. Depolarisation spreads through septum
6. Depolarisation spreads through bulk of ventricles (inside-out)
7. Depolarisation completed at base of left ventricle
8. Repolarisation spreads through ventricles (outside-in)

The Electrocardiogram (ECG)
The ECG records the depolarisation and repolarisation from electrodes in specific locations on the skin surface. It is the most frequently used clinical tool for the assessment of cardiac electrical dysfunction. 

Before we start talking about how ECGs work, you need to know about dipoles. A dipole occurs when a positive and negative charge is separated by a short distance. When the heart is at rest, no dipole is created. However, when the heart is stimulated the muscle fibres depolarise as the charge travels from one end of the muscle fibre to the other, this creates a dipole. When the fibre is fully depolarised no dipole is created because the charge is the same across the whole fibre. When the fibre repolarises, we get a dipole again because one part of the fibre becomes negative with respect to the other part of the fibre - different charges are separated by a small distance. 

Now, when we consider the whole heart working in the body, multiple adjacent muscle fibres are activated together. The activation of each fibre creates a dipole oriented in the direction of the activation. This produces what's known as an activation front in which the sum of all the dipoles can be represented as a single dipole. The overall strength and direction of the dipole is represented as a vector. The electrical field created in and around the heart varies at different points during the cardiac cycle. This electrical field passes through various structures until it reaches the skin where it can be detected by electrodes placed at specific sites.

Depolarisation which travels towards the positive recording electrode will give a positive (upwards) deflection on the ECG and vice versa. The larger the mass of heart muscle involved, the bigger the deflection on the ECG recording will be. If there is no movement of depolarisation or repolarisation the ECG trace will return to zero. 

Parts of an ECG trace:

An ECG Trace

I am going to refer to the diagram above which shows the various parts of an ECG trace and relate them to the steps of depolarisation of the heart mentioned earlier.


Initiation (Step 1):



In this step the SA node depolarises, however, the mass of tissue is too small to cause a deflection on the ECG. This refers to the horizontal section of the trace, just before the PR interval.


Atrial Depolarisation (Step 2): P wave

Depolarisation spreads through the atria from right to left, producing a positive charge on the positive recording electrode, resulting in a positive deflection. When the atria is full polarised, the trace returns to zero (baseline). This refers to the first bump in the trace shown above. 

AV Nodal Delay (Step 3 and 4):PR Segment


The electrical impulse travels rapidly through the bundle of His and enters the bundle branches. The mass of depolarised tissue is too small to cause a deflection on the ECG


Early Ventricular Depolarisation (step 5): Q Wave:


Depolarisation spreads from left to right through the septum. This produces a small negative charge on the recording electrode which causes a negative deflection on the ECG.


Ventricular Depolarisation (Step 6): R Wave


Left and right bundle branches conduct APs (Action Potentials) to ventricular apex. From there, Purkinje fibres carry APs up the interior walls of both ventricles. Depolarisation spreads through the bulk of the ventricular muscle from inside to outside. This produces a positive charge on the positive electrode which leads to a positive deflection on the ECG. Because the ventricles have a high mass a large deflection is produced. 

It is important to note that although a mean vector directed towards the apex of the heart is generated in small animals, in large animals the vector is generated towards the base of the heart. This causes a negative deflection to be seen in horse and other ungulates. 


Late Ventricular Depolarisation (step 7): S Wave


The last part of the ventricles to depolarise is the base of the left ventricle. This produces a negative charge on the positive electrode creating a small deflection on the ECG. Because this is a small mass of tissue a small deflection is made. After the S wave, the ECG returns to baseline and stays there for some time. This is because all cells throughout both ventricles are uniformly at the plateau of their AP and so no dipoles exist.


Ventricular Repolarisation (Step 8):T Wave

The repolarisation occurs from sites that were most recently depolarised to sites that were the first to be depolarised (from inside to outside). This causes a positive charge on the positive electrode which leads to a positive deflection on the ECG. A large mass of tissue is involved but the repolarisation is asynchronous so only a small deflection is produced.  


The Six Lead ECG


In veterinary medicine, a 6 lead ECG is used. Electrodes are placed on the left forelimb, right forelimb and left hindlimb. This makes a triangle around the animal's heart. The voltage in the left forelimb compared to the right forelimb is called lead I. The voltage between the left hindlimb compared to the right forelimb is called lead II. The voltage of the left hindlimb compared to the left forelimb is called lead III. These are known as standard limb leads and provide three different "angles" for viewing the depolarisation and repolarisation of the heart. 

Three additional "views" are provided by the augmented unipolar limb leads (aVr, aVl and aVf). aVr measures the voltage from the right forelimb electrode compared with the average voltage from the other two electrodes. aVl and aVf measure the voltages from the left forelimb and left hindlimb electrodes compared with the average voltage from the other two electrodes.  


That's it for this post, see you next time :)

Transcription and Disease

In this post I will be discussing how promoters, enhancers, transcription factors and RNA polymerase interact to transcribe DNA into RNA. I'll also be discussing a disease caused by either a defective transcription factor or a defective promoter. 

Transcription:

Transcription is the process in which the genetic information on DNA is transferred to a messenger RNA (mRNA) molecule. The DNA molecule is 'opened up' by RNA polymerase allowing a complimentary mRNA molecule to be made from the strand of DNA. For every adenine (A) nucleotide on the DNA molecule, a uracil (U) nucleotide is added to the mRNA. For every guanine (G), cytosine (C) and thymine (T) on the DNA strand, a C, G and A nucleotide is added to the mRNA molecule respectively. The sequence of nucleotides on the DNA molecule is termed the genetic code. 

In order for transcription to occur the cell needs:

• Promoters
• Enhancers or Silencers
• Transcription factors
• and RNA polymerase (RNAP)

Promoters:

Promoters are DNA sequences located upstream of a gene that direct and define where and in what direction transcription is to commence. They consist of a short sequence of elements, for example the CAAT-box, the TATA-box, or the GC-box. Promoters bind RNAP and transcription factors. Promoters must bind to transcription factors in order for them to work and they are unique to each gene. 

Enhancers:

Enhancers are regions of DNA which determine how frequently and when transcription occurs. They bind to specific transcription factors or enhancer DNA binding proteins and elevate the rate of transcription initiation. Enhancers can be found long distances away from promoters and can be either upstream or downstream from the start site of transcription. The binding of transcription factors to enhancers increases the rate of transcription, this is known as transcription synergy. When several transcription factors are bound to the enhancer sequences upstream of the promoter, the increase in transcription rate is higher than that expected from an additive effect.

Silencers: 

Silencers are DNA sequences that a repressor protein binds to and causes an inhibition of transcription. 

 Transcription Factors:

Transcription factors are proteins that bind to the promoter and to RNAP to switch on protein synthesis. Transcription factors have at least 2 domains:

• An activation domain: interacts with the components of RNAP and with other regulatory proteins, effecting the efficiency of DNA binding.
• DNA binding domain: this consists of amino acids that recognise specific DNA bases near the start of transcription.

Transcription factors "recognise" specific segments of DNA in the major and minor grooves and interact with them via hydrogen bonds, ionic bonds and hydrophobic forces. Transcription factors have different structural motifs, eg. the zinc finger, helix-turn-helix, and Leucine zipper. 

 RNA Polymerase:

RNAP doesn't need an RNA primer and recognises and binds to promoter sequences. RNAP 'opens' a short segment of DNA which then binds the initiating triphosphate during the formation of mRNA from DNA.

Transcription Factors and Disease:

An example of a disease which results from problems with a transcription factor is Pituitary Dwarfism. Pituitary Dwarfism is caused by a mutation in the Pit 1 transcription factor. Pit 1 activates the transcription of Growth Hormone in the body. The mutation prevents Pit 1 from binding to the promoter which prevents the production of Growth Hormone. 

And that's it :)

Autonomic Nervous System

Our next topic in Veterinary Physiology 1 is about the Autonomic Nervous System (ANS). This post will be discussing the the main divisions of the nervous system and the major structural and functional differences between the somatic and autonomic nervous systems. I'll describe the functions of the ANS in an organism as well as explain the concept of dual innervation. I'll finish off with comparing the two branches of the ANS. Enjoy!

The Main Divisions of the Nervous System. 

The divisions of the Nervous system can be summarised in the diagram below.

 The Somatic and Autonomic Nervous Systems

There are several differences between the somatic nervous system (SNS) and the autonomic nervous system (ANS). The primary function of the ANS is to maintain homeostasis in the body. Somatic responses are faster than those of the ANS, however, responses from the ANS can be more diverse and are able to coordinate the activity of many body systems. In addition, the ANS has 2 neurons between the central nervous system and the target organ while the SNS has only one neuron. Also, the ANS uses acetylcholine and noradrenaline as a neurotransmitter while the SNS only uses acetylcholine. The ANS can also be inhibitory or stimulatory while the SNS can only be stimulatory. This can be summarised in the table below: 

	Somatic NS	Autonomic NS
Function	Voluntary control of movement	Control of involuntary functions
Action	stimulatory	Inhibitory/stimulatory
Effector Organ	Skeletal muscle	Smooth muscle, heart, glands
No. of neurons between CNS and target	1	2
Transmitter	acetylcholine	Acetylcholine/noradrenaline
Transmitter released from	Axon terminals	Axon terminals and varicosities
Receptor type	ionotropic	Metabotropic  and ionotropic

 Roles of the ANS

The main role of the ANS is to maintain homeostasis and to respond to stress. The ANS is able to direct the body's resources when in times of need. An example of this is the redirection of blood flow from the digestive system to the skeletal muscles during strenuous exercise.

Dual Innervation

The ANS consists of two branches: the Sympathetic Nervous System and the Parasympathetic NS. These two divisions usually exist as separate nerves each innervating the same organ. The sympathetic nervous system is activated when the body prepares for stress (a flight or fight response). The parasympathetic nervous system is activated in order to maintain normal body function during times of rest (the rest-and-digest response). These two divisions are constantly at work but at different proportions depending on the situation. Dual innervation is essential to maintain homeostasis. 

Sympathetic and Parasympathetic Nervous Systems

As I said earlier, there are two divisions of the ANS, the sympathetic and parasympathetic nervous systems. Their anatomy is compared in the diagram below:

The Sympathetic (red) and Parasympathetic (blue) Nervous Systems

Their differences can be summarised in a table form:

	Sympathetic	Parasympathetic
Spinal origin of preganglionic cell	Thoracolumbar	Brain stem and sacral region
Ganglia	Sympathetic chain ganglia or collateral ganglia or adrenal medulla	Parasympathetic ganglia
Location of ganglia	Near spinal column	Near target organ
Preganglionic nerve length	short	Long
Focus point	Adrenal gland	Parasympathetic nerves

And that's it for this post, if you have any question please feel free to ask :)