Thursday, 31 May 2012

Neuromuscular Anatomy: Categories of the Nervous System

Hello :) In this post we'll be tackling neuromuscular anatomy. In our course, one of the major things we need to understand is how to define the categories of the nervous system, so that's what this post will cover. Enjoy!

Categories of the Nervous System

Before we start, it is important to understand that in reality the nervous system is integrated and forms a whole. However, it may be helpful to divide it up into parts. 

If we were to consider mainly structure and the relationship of the nervous system and to other body parts we could divide it into the Central and Peripheral Nervous systems (CNS and PNS, respectively). The CNS consists of the brain and spinal cord (sometimes called the neuraxis) while the PNS consists of the cranial, spinal and autonomic nerve trunks and their associated ganglia. 

Another way to categorise the nervous system would be to consider function. Using this method the nervous system (NS) can be divided into afferent and efferent systems. The afferent NS transmits nerve impulses to the brain and spinal cord while the efferent NS transmits impulses away from these. Within the PNS, afferent nerves are considered sensory while in the spinal cord they are considered ascending. This is because they conduct impulses from "lower" (caudal) to "higher" (cranial) areas of the CNS. In the PNS, efferent nerves are known as motor neurons while in the spinal cord they are considered descending. This is because they travel from cranial to caudal areas of the CNS. 

If we look at the type of information that is conveyed by the nerves we can categorise the nervous system in another way. The somatic system refers to the functions that determine the relationship of the organism to the outside world. The visceral system involves functions which relate to the internal environment. The visceral system also contains the autonomic nervous system which includes sympathetic and parasympathetic divisions which work antagonistically.

Below is a diagram which integrates these categories and sums them up nicely:
Even further divisions are possible, however none of these were mentioned in our lectures and so probably aren't that important for this unit so I won't describe them here. 

That's it for this post, let me know if you have any questions :)

Sunday, 27 May 2012

The Pancreas and Liver

Hello :) In this post, we'll be discussing the roles of the pancreas and liver. I'll describe the general structure of the exocrine pancreas, list the main enzymes produced by the pancreas and what they do. I'll also explain the mechanisms of pancreatic duct secretion and the neurohormonal regulation of secretion. We'll also go over the structure of the liver, as well as take a look at bile salts and bilirubin.

Just briefly before we begin, it's important to understand the general role of the pancreas and liver. Digesta that is emptied from the stomach (or abomasum in ruminants) enters the duodenum. Here it is modified by secretions from the exocrine pancreas and liver. The bicarbonate secreted in pancreatic fluids is particularly important because it works to neutralise the acidic digesta which has come from the stomach. This spares the duodenal mucosa from acid damage and provides an optimum pH for pancreatic enzyme activity.

The Structure of the Exocrine Pancreas

The exocrine pancreas is arranged anatomically like a salivary gland. Its functional unit is the acinius and draining ductule. The acinar cells synthesise and secrete digestive enzymes which are stored in the zymogen granules positioned on the apical side of the cells. The basolateral membrane of the cells have receptors for hormones and neurotransmitters that regulate secretion. Duct epithelial cells are responsible for secreting bicarbonate ions. The basolateral membrane of the duct epithelial cells also have receptors for hormones and neurotransmitters that regulate secretion. Fluid flows along these ducts and empties into the duodenum.

Pancreatic Enzymes

 The proteolytic enzymes include trypsin, chymotrypsin and carboxypeptidase. These are secreted in their inactive forms. Trypsinogen is converted to trypsin by an enzyme called enterokinase. Trypsin then activates the other two proteolytic enzymes. Trypsin and chymotrypsin split the proteins into peptides but do not release individual amino acids. Carboxypeptidase splits some proteins into the component amino acids. The acinar cells which secrete the proteolytic enzymes also produce a trypsin inhibitor which prevents these enzymes from damaging the pancreas. 

The amylase enzymes include α-amylase which is secreted by the pancreas and the salivary glands. These digest starch to maltose and maltotriose while complete hydrolysis to monosaccharides is done by the brush border enzymes in the small intestine. The secretion of amylase is stimulated by diets high in starch.

The main lipolytic enzyme is lipase which is important in fat digestion. However, in order for fats to be digested bile salts are also required. In the presence of bile salts the hydrolysis of fats by lipase allows for the formation of water-soluble micelles. The secretion of lipase is stimulated by diets high in fat or high in protein.

 The Mechanisms of Pancreatic Duct Secretion

 Bicarbonate, water and electrolytes are mainly secreted from the epithelial cells of the duct system. As the concentration of bicarbonate increases in the fluid, the concentration of Cl- decreases. In addition to bicarbonate, pancreatic fluid also contains water, sodium and potassium.
 The mechanism of secretion is as follows: 
  • Carbon dioxide enters the duct cell and mixes with water. 
  • This is converted to carbonic acid by carbonic anhydrase. Carbonic acid then breaks down into H+ and HCO3-.
  • This bicarbonate exits the apical membrane of the cell through a HCO3-/Cl- counter transporter. Bicarbonate also enters the cell through the basolateral membrane through a type 1 sodium/bicarbonate co transporter (NBC-1) and exits the cell in the same way. 
  • Cl- exits through the cystic fibrosis transmembrane conductance regulator (CFTR).
  • The H+ exits the basolateral membrane via a type 1 sodium-hydrogen exchanger (NHE-1). Here the H+ combines with HCO3- to form carbonic acid which breaks up into carbon dioxide and water. This carbon dioxide enters the cell through the first step. 
  • A Na+/K+ pump also exists on the basolateral membrane. This exports Na+ out the cell and creates a concentration gradient which allows the NBC-1 and NHE-1 transporters to work. 
The faster the pancreatic fluid flows through the ducts, the more bicarbonate and less chloride will be present in the fluid. However, the concentrations of sodium and potassium will remain the same. Sodium concentrations will remain fairly high while potassium concentrations are low.

Cholecystokinin (CCK) and Acetylcholine are the main regulators of pancreatic enzyme secretion. In the cephalic and gastric phases of pancreatic secretion, vagal cholinergic nerve fibres stimulate M3 receptors in the acnini and this stimulates enzyme secretion. During these phases of secretion, only small amounts of  water and electrolytes are secreted. During the intestinal phase of secretion, secretin is released from S cells in response to H+ in the gastric chyme entering the duodenum. This stimulates copius amounts of bicarbonate and water to be secreted from the ducts. Secretin induced secretion requires sholinergic input. Also during the intestinal phase, CCK is released from I cells in response to fat entering in the gastric chyme. This mediates acinar enzyme secretion and also requires cholinergic input.  

The Liver

The liver receives blood from both the hepatic artery and portal vein and in healthy animals uses about 25% of the cardiac output. The liver performs many functions, particularly the metabolism of carbohydrates, proteins and fats, and secretes bile. Bile has an important role in the digestion of fats. The liver is also the body's first line of defence against toxins and other chemicals absorbed via the GIT. 


The liver consists of sheets of six-sided hepatocytes which are arranged into lobules and bathed by sinusoidal blood on two sides. Bile flows through cannaliculi which are situated between each row of hepatocytes. The composition of bile is changed within the biliary ducts by the addition of water and bicarbonate. This website has a diagram of the microscopic structure of the liver which you may find useful :)

Blood flows towards the central vein of the lobule while bile flows in the opposite direction.

Bile Acids

Bile acids are synthesised from cholesterol by hepatocytes and thus have a chemical structure which is similar to cholesterol. Bile acids have both a hydrophilic and hydrophobic side and this enables them to make lipids soluble in water (they emulsify them). The representative bile acid is Cholic acid, its structure is shown below. 

The Structure of Cholic Acid
In the liver the bile acids are conjugated with taurine or glycine, this decreases the dissociation constant which means they are excreted in the bile as bile salts. 

Because bile salts are not fat soluble they remain in the lumen of the small intestine and this allows them to form micelles which are important in fat absorption. The bile salts are reabsorbed through an active process in the distal ileum or are degraded to secondary bile acids by intestinal bacteria. 95% of bile acids are recycled to the liver via portal circulation.  

When the bile is produced by the hepatocytes it has a similar ionic composition to blood. However, the volume and ionic composition is altered during the flow through the ducts and storage in the gall bladder. In ducts, secretin stimulates the secretion of bicarbonate while in the gall bladder bile is concentrated by the active reabsorption of sodium, chloride and bicarbonate (which causes water to follow). 


Bilirubin is a product of the breakdown of haemoproteins from erythrocytes which are too old. The iron from the haemoglobin is recycled but the haeme pigments are broken down to bilirubin which is water insoluble. Thus, it is transported in the blood bound to albumin. It is then absorbed by the cells of the liver and conjugated into glucuronides. These are secreted in the bile and reduced by intestinal bacteria to form urobilinogen. Urobiliniogen is absorbed by the small intestine and is excreted in the urine or oxidised to stercobilin (this is responsible for the brown colour of stool). 

That's it for this post, please feel free to leave any questions or suggestions in the comments section below :)

The Rumen Stomach and Vomiting in Monogastrics

Hi :) In this post we'll be discussing the structure and development of the ruminant stomach, the structure and function of the oesophageal groove as well as the forestomach motility patterns in a ruminant.We'll also go over the sequence of events and neural pathways involved with vomiting in monogastric animals.

Structure and Development of the Ruminant Stomach

The forestomach of the rumen consists of the rumen, reticulum and omasum. The forestomach is lined with non-glandular mucosa. The fourth chamber is the abomasum and this acts like a monogastric stomach as it is lined with glandular mucosa and secretes acid. The structure is represented in the diagram below:
The Ruminant Stomach
Source. Please see this website if you'd like to use the diagram :)

The walls of all the chambers of the stomach contain smooth muscle.

At birth, the young ruminant derives all its nutrition from milk. Thus milk bypasses the immature forestomach and goes straight to the abomasum where digestion is initiated. As the animal gets older, the forestomach develops and becomes populated with microorganisms and it begins to feed off plant based foods instead of milk. The forestomach becomes fully functional at 2-3 months of age.

The Reticular Groove

In order to bypass the forestomach, the reticular groove acts as a tube to guide milk to the abomasum. This reflex is initiated by the act of suckling or drinking as well as by the presence of milk in the pharynx or even through conditioning. The reflex is lost when the ruminant stops suckling. The reflex occurs through several steps. First afferent impulses travel to the coordinating centre in the brain stem via the trigeminal nerve. Next, efferent impulses travel via the vagus nerve to the reticular groove and smooth muscle contraction turn the groove into a tube. This allows milk to pass from the oesophagus to the abomasum.

Forestomach Motility Patterns

The forestomach plays an important role in storage, maintaining a suitable environment for microbes, mixing eructation, further breakdown of plant material through rumination as well as the absorption of VFAs water and electrolytes.

There are several types of contractions which occur and these are quite important to remember.

A Word of Warning: The following lists of steps involved in these contractions may seem scary and intimidating! But don't worry :) I have only included the steps in this way because it breaks down the process into smaller steps and helps you to understand the processes a bit better. It's really not so bad :)

This website shows you the anatomy of the rumen. Its helpful to go through the following processes with this in mind.

Primary Contractions: Emptying:

  1. These start in the reticulum at a rate of 1-3/min. 
  2. The reticular wall contracts twice within 5-10 seconds. 
  3. The first reticular contraction reduces the reticular volume by 50% and this forces coarse material from the top of the reticulum to the central and dorsal parts of the rumen. 
  4. The reticulum then relaxes for one second.
  5. A second reticular contraction occurs and this almost completely empties the reticulum of the remaining fine material.
  6. Most of this fine material is transferred back into the atrium
  7. During the second contraction, the reticulo-omasal orifice opens for a few seconds and well digested fluid flows into the omasum. 
Primary Contractions: Mixing:

  1. These begin in the rumen after the biphasic contractions of the reticulum. 
  2. These contractions begin in the atrium and atrial pillar and spread caudodorsally to the dorsal sac. 
  3. The cranial pillar then contracts, placing it in a vertical position. This moves digesta into the relaxed reticulum.
  4.  The dorsal sac contracts and this moves digesta to the caudodorsal blind sac. 
  5. The contraction of the caudodorsal blind sac and caudal pillar pushes the digesta upwards and forwards and this completes the circular movement of the digesta. 
  6. Contractions in the ventral sac now begin. 
  7. These start cranially and move caudally to the caudoventral blind sac.
  8. This caudoventral blind sac contracts and completes the circular movement of the digesta. 
  9. Mixing now occurs between the dorsal and ventral sacs with the well digested material remaining in the ventral part of the rumen. 
  10. However, when the ventral sac contracts some of the digesta moves over the cranial pillar into the atrium. 
  11. This digesta is shuttled back and forth between the atrium and reticulum and eventually empties through the reticular-omasal orifice.  
Secondary Contractions: Eructation

  1. Secondary contractions usually follow a variable number of primary contractions.
  2. Usually, 2 or 3 primary contractions occur for every secondary contraction.
  3. The secondary contraction starts in the caudodorsal blind sac and moves cranially forcing the dorsal ruminal gas cap in the same direction. 
  4. At the same time, cranially-moving contractions occur in the ventral part of the rumen. This starts in the caudoventral blind sac and displaces gas dorsally.
  5. As the dorsal rumen contraction reaches the atrium, the cranial pillar elevates and this moves fluid away from the oesophageal opening, allowing gas to enter the oesophagus. 
  6. After entering the oesophagus, gas moves towards the oral cavity through retroperistalsis. This is followed by a peristaltic wave (towards the stomach) to clear any residual fluid from the oesophagus. 

  1. The first act of rumination is regurgitation.
  2. It starts with a reticular contraction (which lasts 2-4 seconds) that occurs just before the primary contractions begin.
  3. The contraction removes recently-ingested material from the oesophageal opening and replaces it with semi-digested material that has undergone some fermentation. 
  4. Simultaneously with this contraction, the lower oesophageal sphincter opens and there is an inspiratory excursion against a closed glottis. In other words, the animal tries to breathe in but it can't because the opening of the trachea is closed.
  5. This creates a negative pressure in the thoracic cavity which 'sucks' the digesta into the oesophagus. An antiperistaltic wave then propels the cud into the oral cavity through the upper oesophageal sphincter. 
  6. Once in the mouth, excess fluid is squeezed out of the cud by the tongue. This fluid is then swallowed. 
  7. The cud is masticated, saliva is added and is then swallowed. 
Regulation of Forestomach Motility

The forestomach contractions which I mentioned above are mainly regulated through long vagovagal reflexes. Sensory information from receptors in the forestomach are transmitted to the integrating centres in the medulla of the brain through the vagus nerve. The vagus nerve also conveys efferent signals from the dorsal vagal nucleus in the brain back to the smooth muscle of the forestomach.The stretch receptors in the forestomach are arranged in series with smooth muscle cells. Moderate distention of these receptors stimulates contractions while over-distension inhibits contractions.

There are also chemo receptors located in the epithelium of the forestomach. These respond to changes in pH, osmolarity, and the concentration of volatile fatty acids. In general, the activation of these receptors leads to the inhibition of contractions.

Vomiting in Monogastic Animals

Several events are associated with vomiting. The early signs include hypersalivation, cardiac rythm changes, and possibly defecation. Salivation stimulates swallowing and this is associated with the relaxation of the lower oesophageal sphincter. Antiperistalsis then begins in the small intestine. At first, the duodenum in relaxed, it then undergoes 'retrogade giant contractions' (RGCs) which move the intestinal contents into the stomach. Immediately after this RGC, duodenal motor activity is inhibited. Retching (which is forceful contractions of the abdominal muscles and diaphragm against a closed glottis, this produces an increased pressure in the GIT) begins with the onset of RGC.

These events are  followed by retrograde contractions of the antrum and relaxation of the corpus, oesophagus and the upper and lower oesophageal sphincters. The gastric contents are forcefully expelled by the contractions of the abdominal muscles and diaphragm. As the vomit passes through the pharynx, the glottis and nasopharyngeal openings close and this prevents aspiration and nasal regurgitation. 

Neural Pathways: 

The vomiting reflex involves neural pathways which synapse in the 'emetic'centre of the medulla in the brain. This 'emetic centre' is not a distinct object or area of the brain, instead it is pharmacologic entity that receives a range of information. It receives info from the peripheral visceral receptors, the chemoreceptor trigger zone in the brain, the vestibular apparatus and from other cortical centres in the brain. 

The emetic centre can be stimulated by several different things and once stimulated it triggers a series of reactions which lead to vomiting (as mentioned above). The emetic centre can be stimulated directly, by afferent nerves from the GIT acting on this centre. Examples of this type of stimulation include pharyngeal stimulation, bacterial toxins, upper GI irritation or distension. The emetic centre can also be stimulated indirectly via stimulation of the chemoreceptor trigger zone, located in the fourth ventricle of the brain. Various drugs stimulate the centre in this way, for example those which are used in the treatment of cancer. In addition, the centre can be stimulated indirectly via other pathways, such as the cerebral cortex, brain stem and vestibular apparatus.

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

Friday, 18 May 2012

The Monogastric Stomach

Hello :) In this post we’ll be taking a look at the structure and functions of the monogastric stomach. We’ll discuss the species differences in the composition of gastric mucosa, the motility patterns that occur in the stomach and how these assist the processing of digesta. In addition, I’ll explain the neurohormonal regulation of gastric emptying and the passage of digesta into the duodenum as well as the mechanism and regulation of acid and pepsin secretion. We’ll finish off by discussing the main mechanisms that protect the gastric lining from damage by the gastric secretions. If you have any questions please don’t forget to ask in the comments section of this post.

Structure and Functions of the Monogastric Stomach

The stomach functions in the storage and mixing of digesta with gastric secretions. It is also involved in the mechanical and chemical break down of food as well as the delivery of digesta to the small intestine at a rate optimal for digestion and absorption.

The stomach of a monogastric animal (such as a dog, pig or human) contains four regions:
  • Cardia 
  • Fundus: this section receives and stores food. 
  • Corpus (body): this acts as a mixing chamber.
  • Pyloric (antrum): this region is involved with emptying, trituration (grinding) and mixing. The wall of the stomach is thickest in the pyloric region because this is where most of the movement occurs.
There may be differences in the mucosa between species. For example, the oesophageal portion occupies about 30% of the equine stomach but much less in other species.  

The proximal region of the stomach acts as a reservoir to store food and its wall undergoes receptive relaxation and adaptive relaxation to accommodate the meal. The tonic contractions of the proximal gastric wall push the digesta towards the antrum. These tonic contractions are gentle and create a low pressure.

Motility Patterns in the Stomach

As mentioned earlier, the proximal region of the stomach undergoes receptive and adaptive relaxation. Receptive relaxation is triggered by swallowing and the stimulation of pharyngeal mechanoreceptors. Afferent nerve fibres carry impulses to the central nervous system and efferent vagal fibres innervate the inhibitory nerves in the gastric wall. During adaptive relaxation distension of the gastric wall activates stretch receptors which initiate a vagovagal reflex. Here, the efferent fibres also innervate the inhibitory nerves in the gastric wall. 

Motility also occurs in the distal stomach. Emptying of the stomach involves 3 steps:
1.       Contraction waves start in the corpus
2.       When this wave reaches the antrum, the pyloric sphincter opens and the pressure in the antrum moves the chyme into the duodenum.
3.       When the wave reaches the pyloric sphincter it closes. Antral contraction then propels the chyme back into the gastric body and this mixes the contents.

Sieving and trituration also occur in the stomach. Antral contractions grind large particles and moves them back into the gastric body where they are digested further. The antrum also acts like a sieve and prevents larger particles from passing into the duodenum.

In the stomach, slow waves of contraction are generated by the interstitial cells of Cajal which lie between the circular and longitudinal layers of muscle. These cells act as pacemaker cells for the stomach.


Gastric emptying is regulated by several factors. Emptying will be stimulated by:
  • Dilation of the stomach: this increases the activity of the stretch-sensitive sensory cells which leads to increased contraction of smooth muscle cells and the secretion of gastrin and emptying of the stomach increases. 
  • Peptides in the stomach: This also increases the secretion of gastrin which causes more smooth muscle cells to contract and causes the stomach to empty more.
When there is a high concentration of peptides, high pressure, and high osmolarity in the duodenal lumen, and a low pH the activity of the sensory cells in the duodenum increase. This is detected by the central nervous system which stimulates the sympathetic and inhibits the parasympathetic nerve fibres to the stomach. This results in less emptying of the stomach. In addition, a high fat content will cause the release of hormones from the duodenal epithelium (mainly CCK) and this produces the same effect.

Acid and Pepsin Secretion in the Stomach

Hydrochloric acid is generated by the parietal (aka. Oxyntic) cells in the wall of the fundus and body of the stomach. It is generated by the action of the enzyme carbonic anhydrase which is located inside the cell. This enzyme produces H+ and HCO3- from carbon dioxide and water. The H+ ions which are produced are secreted via the K+/H+ ATPase counter-transporter (this is often called a ‘proton pump’). The H+ is transported against a steep concentration gradient and so this process requires energy. The HCO3- which is produced diffuses into the extracellular fluid and blood plasma, increasing the pH of the blood. Some of this bicarbonate also diffuses into the mucosal capillary in exchange for a Cl- ion. It then diffuses into the mucosal cell and helps protect the cells from acid damage. The main role of gastric acid is to facilitate the conversion of pepsinogen to pepsin.

Gastric acid secretion is regulated by three substances:
  • 1.  Gastrin (which binds with a CCK-2 receptor) 
  • 2.       Histamine (which binds with a H-2 receptor) 
  • 3.       Acetylcholine (which binds to a M3 receptor)
The stimulation of all three receptors is necessary for the maximal secretion of acid. The blocking of any one of these receptors will greatly reduce the response of the other two.

Mechanisms That Protect the Gastric Lining

Mucus is continually secreted onto the surface of mucosal epithelial cells and acts as a physical barrier which ‘sticks’ to the epithelium. Bicarbonate, which is produced by parietal cells during acid secretion, reaches the mucosal epithelial cells via the blood stream. It is then secreted into the mucus layer and this produces a neutral pH next to the epithelial cells. The bicarbonate acts to neutralise the hydrogen ions that penetrate the mucus layer.

Glycoproteins and phospholipids are secreted by gastric epithelial cells and also help to protect the epithelial cells. The glycoproteins form a barrier which prevents pepsin from diffusing while the phospholipids provide a hydrophobic layer at the base of the mucus layer. This provides extra protection against water-soluble acids.

The cell membranes of the gastric epithelial cells also act as a barrier to acid damage. These cells also contain intracellular amounts of HCO3- and this protects the cell from acid that back-diffuses into the cell.

Another mechanism which protects the mucosa is the fact that the epithelial cells are continually being renewed. The surface mucus cells are replaced by new cells every three days. This cell renewal is mainly controlled by gastrin but other growth factors may be involved.

In addition, all defence mechanisms depend on the maintenance of mucosal blood flow. The actions of prostaglandins (PGs) have an important role here. Factors that compromise blood flow, such as shock or the production of PG’s predispose animal to ulcers.  

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

Wednesday, 16 May 2012

Prehension, Mastication and Deglutition

Hello :) This post will discuss the acts of prehension, mastication and deglutition. I'll describe the mechanics of prehension, mastication, and swallowing. We'll also take a look at the main salivary glands in animals as well as the main constituents of saliva and the process of salivary excretion. We'll finish off by looking at how the structure of the oesophageal wall may differ between species.  

Prehension and Mastication

Prehension is the act of getting food into the mouth. Domestic animals do this by using their lips, teeth, tongue and by head and jaw movements. Some animals may also use their front legs and digits to grip their food. Most animals drink by drawing water into the oral cavity with suction. Dogs and cats drink by lapping water with the tongue. Birds, on the other hand, fill the oral cavity with water and then raise the tip of their beak, draining water into the pharynx. Prehension is a voluntary reflex and the trigeminal, facial and hypoglossal nerves provide motor innervation to the lips, tongue and muscles of the jaw. Sensory information is also important and this is derived from olfactory, optic and trigeminal (sensation from oral mucosa, lips and teeth) input. 

Mastication involves the mechanical breakdown of food and allows mixing with saliva. This is also under voluntary control. The tongue and buccal muscles position the food within the mouth while the teeth cut or grind the food. Several nerves are involved in this process:
  • The trigeminal nerve provides sensory input to the teeth and motor input to the jaw muscles.
  • The facial nerve provides motor and sensory input to the tongue and pharynx.   
  • The glossopharyngeal nerve provides sensory input to the caudal third of the tongue.
  • The hypoglossal nerve provides motor innervation to the tongue. 

Most of the salivary secretion in animals comes from the paired parotid, mandibular and sublingual salivary glands. Dogs also have zygomatic glands. 

Saliva is formed in a two-step process:
  1. Acini secret fluid containing amylase, lysozyme, mucin and electrolytes in similar concentrations to those found in the blood plasma. 
  2. During the passage through the ducts of the salivary gland, ionic composition of the saliva becomes modified. This is because Na+ and Cl- are reabsorbed while K+ and HCO3- are secreted.
If saliva is flowing at a high rate, there is less time for its modification in the salivary ducts. This leads to an isotonic saliva. A low saliva flow rate leads to less Na+ and Cl- and more K+ in the saliva. Here the saliva is hypotonic. 

Saliva is mainly water (98%) but also contains mucin, which forms mucus when mixed with water and acts as a lubricant. Amylase is also present and initiates the breakdown of starch. Bicarbonate is there too and this neutralises acids produced by the bacteria in the mouth and prevents acid damage to the enamel on the teeth. Saliva is very important as a buffer in ruminants. Urea also diffuses from the blood into the saliva. In ruminants this is important as it acts as a nitrogen source for ruminal microorganisms. 

The major differences between species seen in terms of saliva composition is mainly the amount of bicarbonate secreted and the flow rate. Ruminant animals excrete much more bicarbonate in their saliva and produce much more saliva per day when compared to non-ruminant animals.

Regulation of Salivary Secretion

Salivary secretion is regulated by the autonomic nervous system. The volume and composition of saliva depends on the balance between the parasympathetic and sympathetic divisions of the ANS. Parasympathetic stimulation results in a high volume of saliva that has a watery consistency. Sympathetic stimulation results in constriction of the blood vessels supplying the salivary glands. This causes a low volume of saliva which has a viscous consistency to be produced.

Deglutition (Swallowing)

The act of swallowing occurs in several phases. The initial phase of swallowing is voluntary. However the remaining phases are under involuntary control. 
  • Oral Phase: following prehension and chewing, a bolus is formed from the food. The bolus is then moved caudally towards the pharynx. The upward movement and pressure of the base of the tongue pushes the bolus against the palate, moving it caudally. This involves the trigeminal, facial and glossopharyngeal nerves. 
  • Pharyngeal Phase: In this phase, the bolus is moved towards the oesophagus. The pathway back into the oral cavity is closed by the muscles of the mouth and tongue. The passage of the bolus into the nasopharynx is also prevented by the reflex elevation of the soft palate and apposition of the palatopharyngeal folds. The opening of the trachea is protected by the closure of the glottis and the tipping of the epiglottis. This diverts food away from the glottis. In addition, the swallowing centre of the medulla inhibits the respiratory centre which ceases respiration. All this involves the glossopharyngeal and vagus nerves which are initiated from the swallowing centre. 
  • Cricopharyngeal phase: In the absence of swallowing, the cricopharyngeus and thyropharyngeus muscles contract (this is caused by vagus nerve activity). This ensures that the upper oesophageal sphincter remains closed, preventing air from entering the oseophagus during respiration. During swallowing, the vagus nerve is inhibited and this causes the crico- and thyropharyngeal muscles to relax. This opens the upper oesophageal sphincter allowing the bolus to pass into the oesophagus. A mechanism in the central nervous system senses the size of the bolus and calculates the amount of time the sphincter is to remain open. After the bolus has moved into the oesophagus, the sphincter closes and this prevents the aspiration of the oesophageal contents. 
  • Oesophageal Phase: As the bolus enters the oesophagus, the primary peristaltic contraction wave is initiated by the swallowing centre. If the primary wave ends before the bolus reaches the stomach, a secondary wave is rapidly generated by local oesophageal distention. The pressure generated by these actions varies. It will be lower for liquids and higher for solids. 
  • Gastro-Oesophageal Phase: The muscles of the gastro-oesophageal region act as a sphincter and maintain a high pressure region between the oesophagus and the stomach. This prevents the reflux of gastric contents. This sphincter open to allow for the eructation of gas. This is mediated by the vagus nerve. 
The Structure of the Oesophageal Wall

  1. The oesophageal wall has four layers:inner mucosa
  2. submucosa
  3. muscularis
  4. outer connective tissue
In dogs and ruminants, the muscularis is entirely striated muscle. However, in the horse, cat and pig, the muscularis is striated at its origin but changes to smooth muscle as the oseophagus passes through the thorax. 

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

Introduction to the Gastrointestinal System

Hello :) This post will introduce the gastrointestinal (GI) system. We'll discuss at the main compartments of the GI system as well as their functions. We'll also go over the basic digestive processes as well as the anatomy of the enteric nervous system. We'll also take a look at the phases of digestion, some of the main hormones secreted in this system as well as some of the hormones that regulate appetite.

The Gastrointestinal Tract (GIT)

In monogastric animals, the GIT is composed of:
  • the oral cavity: this is where food enters the GIT. Some digestion of starches by amylase begins here however mechanical digestion via mastication (chewing) mainly occurs here. Saliva is also secreted and this lubricates the food (which is now called a bolus) as it moves down the GIT.
  • pharynx: this allows the passage of the food into the oesophagus and not into the trachea!
  • oesophagus: this is a muscular tube which directs food into the stomach.
  • stomach: here hydrochloric acid as well as some enzymes such as pepsinogen are secreted. The low pH allows for protein denaturation and creates a larger surface are for the action of pepsinogen. 
  • small intestine: this is the major site for nutrient absorption and digestion.
  • large intestine: this is the major site for water absorption
  • rectum: undigested food exits the body from here as feces.   
Basic Digestive Processes

Mechanical Digestion:

This involves the mechanical breakdown of food to increase the surface area on which the enzymes will act. This form of digestion occurs in the mouth through mastication and rumination. Mixing also occurs and this facilitates digestion and absorption. Mixing mainly occurs in the stomach of monogastrics (some grinding may happen here too) and the forestomach of ruminants. In the small intestine, mixing occurs and this allows the ordered passage of food through the intestine aborally (away from the mouth). In the large intestine mixing and retention occurs and this allows fermentation and the absorption of nutrients, water and electrolytes.

Chemical Digestion:

Glandular cells in the GIT secrete enzymes into the lumen and this enables intraluminal nutrient breakdown. The salivary glands, pancreas and liver also secrete substances and these reach the GIT via ducts. The enzymes which are secreted operate at an optimum pH. This pH will match the pH of the area of the GIT in which they work. Mucous is secreted and this lubricates the contents and protects the mucosal epithelium of the GIT.  

The nutrients which the animal ingests contains complex carbohydrates, proteins and fats which need to be broken down in order for them to be absorbed. The initial breakdown by enzymes occurs in the lumen of the intestine and further breakdown occurs on the surface of the epithelia. This is enhanced by the brush border which increases the surface area of the epithelium and hence allows more nutrients to be broken down.


Water, ions, vitamins and small molecules which are a result of the breakdown of the nutrients move from the GIT lumen to the blood and lymph. Absorption is optimised by the large surface area created by villi and microvilli and may occur via active or passive transport. Any material that is not absorbed is eliminated from the body as feces.

The Enteric Nervous System

The enteric nervous system is an intrinsic system that is integrated within the autonomic nervous system. It forms two plexuses:
  • Myenteric Plexus: this exists between the circular and longitudinal muscle layers of the GIT and primarily regulates motility.
  • Submucosal Plexus: this exists between the submucosal circular muscle layers and regulates secretion and reabsorption. 
The parasympathetic nervous system includes preganglionic (cholinergic) fibres which arise from the medulla via the vagus nerve and from the sacral spinal cord via the pelvic nerve. These fibres form synapses with the ganglion cells in the enteric nervous system and stimulate intestinal motility, secretion and release of hormones. The mediator at the target cells is usually acetylcholine. 

The sympathetic nervous system involves preganglionic cholinergic nerve fibres which synapse in sympathetic ganglia outside the GIT. From these ganglia, post ganglionic adrenergic fibres innervate cells in the myenteric and submucosal plexuses. Some of the post ganglionic nerves also innervate some blood vessels and the muscularis mucosae. The sympathetic nervous system constricts blood vessels and inhibits intestinal motility, secretion and hormone release.

The vagus nerve in the GIT is a mixed nerve, and is composed of approximately 75% sensory (afferent) fibres. The receptors in the mucosa and smooth muscle relay information back to the CNS via vagal afferent fibres. The signals communicated by the afferent fibres trigger the long vagovagal reflex, in which the efferent signal is also in the vagus nerve. Reflex signals from the vagus nerve are not consciously perceived. 

Approximately 50% of the GIT sympathetic nerves are afferent nerves. Information from the GIT is sent to the spinal cord, there is some reflex activity however most signals travel to the cerebral cortex where they are consciously perceived. These sympathetic nerves are involves in the transmission of signals from nociceptors to the brain where they are perceived as pain. 
The enteric system has both short and long reflexes. Long reflexes to the GIT involve a sensory neuron that sends an impulse to the brain where it is integrated and another impulse is sent to the digestive system. The stimulus may come from the GIT or another area such as salivary glands or the pancreas and liver and may travel along the vagus, pelvic or sympathetic nerves. Short reflexes occur when only the enteric nervous system receives, integrates and acts upon the stimulus. An example can be seen when sensory cells are stimulated in the wall of the GIT. These cells then send signals to the nerve plexuses in the GIT. 

Gastrointestinal Hormones

There are three main peptide hormones secreted in the GIT that we need to be familiar with:
  • Gastrin: this is released from G cells (G for Gastrin) in the antral and duodenal mucosa. Proteins and protein digestion products from a meal contact the antral mucosa and cause the release of gastrin. It is also released by vagal stimulation through gastrin-releasing peptide as well as through distention of the gastric wall. Its actions are to stimulate gastric acid secretion and growth of gastric oxyntic glands and colonic mucosa.
  • Cholecystokinin (CCK): this is released from I-cells in the duodenal and jejunal mucosa. It is released in response to fatty acids, peptides and amino acids. Its actions are to stimulate: gall bladder contractions, pancreatic enzyme secretion, growth of exocrine pancreas and gall bladder as well as pancreatic water and bicarbonate secretion. It also inhibits gastric emptying.
  • Secretin: This is released from S cells (S for Secretin) in the duodenal mucosa. It is released in response to acid to a lesser extent by fatty acids. Its actions are to stimulate: pancreatic and liver water and bicarbonate secretion, growth of the exocrine pancreas, and gastric pepsin secretion. It also inhibits gastric acid secretion and the gastric trophic (stimulating the activity of another endocrine gland) effects of gastrin.
 Phases of Contraction:

 There are three phases of digestion:
  •  Cephalic: this includes changes in secretion and motility that occur in response to sight, smell, taste and mastication of food. An example of this is when a dog drools saliva when it watches a person eat. This phase is affected by input from the CNS and is regulated via long reflexes. 
  • Gastric: this phase includes changes in GIT secretion and motility initiated in the stomach. Its stimuli include gastric distension and the release of peptides from protein digestion. It involves the release of gastrin and activation of both the long and short reflexes.
  • Intestinal: this includes changes in GI secretion and motility including pancreatic secretion. It is initiated by alterations in the volume and composition of digesta, particularly in the duodenum. It involves the release of secretin, CCK and the activation of both long and short reflexes.
The Hormones Which Regulate Appetite

Leptin is a hormone which is secreted by adipose cells. When the intake of energy from food exceeds the body's need for energy fat is deposited in adipose tissue. This tissue responds by secreting leptin. Leptin acts on the hypothalamus to reduce the sensation of hunger. It also increases the metabolic rate which reduces the amount of fat stored in adipose tissue. Leptin is important in the long-term maintenance of body weight.

CCK is also secreted by the intestinal mucosa in response to the ingestion of proteins and fat. This activates the receptors on the vagus nerve which sends a satiety signal to the hypothalamus in order to limit the size of the meal. Leptin and insulin may also increase the hypothalamus' sensitivity to CCK.

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

Monday, 14 May 2012

Renal Handling of Calcium and Phosphate

Hi :) In this post we'll have a look at how the kidneys handle Calcium and Phosphate. We'll also look at diuretics, kidney failure, and hyperparathyroidism. 

 Calcium Balance

Calcium is critical to the function of all cells but is particularly important in the heart, muscles and bones. The amount of calcium in the blood is regulated through the kidneys, the digestive tract, bone and skin. Calcium can be added to the blood by the reabsorption of bone (bone is broken down) or by absorption through the digestive tract. Calcium can be removed from the blood plasma by the calcification of bone (bone is formed) or through filtration at the kidneys.

Calcium can be transported in the blood plasma in three ways: free as Ca2+, complexed with other ions, or bound to carrier proteins. Ionised and complexed Ca2+ can be freely filtered at the glomerulus in the kidney. Ninety-nine per cent of the Ca2+ which is filtered at the glomerulus is reabsorbed. The reabsorption which occurs at the loop of Henle and the distal tubule are under hormonal control.

It is important to remember that calcium balance is highly regulated by hormonal control. In particular, three hormone regulate plasma calcium levels:
  1. Parathyroid Hormone (PTH): this is released from the parathyroid hormone in response to decreased plasma Ca2+ levels. PTH increases the amount of calcium in the blood by:
    1. stimulating the resorption of bone
    2. stimulating Ca2+ reabsorption in the ascending loop of Henle and distal tubules in the kidney.
    3. Stimulating the action of Calcitriol at the kidneys. This promotes calcium reabsorption at the gastrointestinal tract (GIT) as well as reabsorption at the kidneys.  
  2. Calcitriol (1,25-(OH)2D3): this is a steroid hormone synthesised from vitamin D3. It increases the absorption of calcium from the GIT as well as increasing the reabsorption in the distal nephron of the kidney.
  3. Calcitonin: This is a hormone secreted by the thyroid gland and its secretion is triggered by hypercalcaemia (too much calcium in the blood). It increases the calcium uptake by the bone and decreases the renal calcium reabsorption. Its nett effect is to decrease plasma calcium levels. It plays a much less important role in calcium balance when compared to PTH and Calcitriol.
Now, the ratio between calcium and phospate concentrations is very important and ideally it should be 2:1. The close association between calcium and phosphate means that factors regulating calcium balance also affect phosphate balance. 

Parathyroid Hormone has a particularly important influence on plasma phosphate concentrations. PTH an opposing influence on the plasma phosphate concentrations. It promotes bone reabsorption to increase the concentration of phosphate in the blood. It also reduces the amount of phosphate reabsorbed and this promotes phosphate excretion. This causes the plasma phosphate concentration to remain stable despite a decreased plasma calcium concentration. 


There are two types of hyerparathyroidism: primary and secondary. Primary occurs when the parathyroid works too hard and this increases PTH production. This leads to hypercalcaemia. Secondary involves a reaction of the parathyroid gland to a low calcium concentration in the blood. This leads to an increase in the amount of PTH. Overall, a loss of calcium from the bones is experienced and this leads to fragility and fractures, etc. There is also an abnormally low amount of phosphate in the blood plasma. 

The Effect of Diuretics

Diuresis is defined as the increased rate of urine output through increased excretion of solutes and therefore water. Hypokalaemia (reduced concentration of potassium in the blood) is a side effect of the long term use of diuretics. Two types of diuretics exist:
  1. Loop Diuretics (Frusemide): These inhibit the Na+/K+/2Cl- symporter at the thick ascending loop of Henle. This decreases the medullary gradient for water reabsorption which results in an increased flow in the distal nephron. 
  2. Potassium Sparing Diuretics (Spironolactone): these block the action of aldosterone in the late distal tubule and collecting duct. This causes the Na/K pump to not be induced which blocks Na reabsorption and K excretion. This results in diuresis because ADH release relies on the sodium concentration in the extracellular fluid.   
Kidney Failure 

Renal failure occurs when 75% of the nephrons of both kidneys fail to function. It is characterised by Isosthenuria and Azotaemia (Increased blood nitrogen levels). Acute renal failure is characterised by an abrupt decline in renal function which is usually due to an ischemic or toxic insult as well as an enlarged kidney. It may be reversible. Chronic renal failure occurs over weeks to years and the nephron damage is irreversible as it is replaced by fibrous tissue. It is characterised by a decrease in the size of the kidney.

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

Saturday, 12 May 2012

Fatty Acid Synthesis

Hello :) This post will cover the process of fatty acid synthesis or lipogenesis. We'll look at the function, regulation and special features of lipogenesis. Enjoy!


The function of lipogenesis is to synthesis long chain fatty acids which are the major store of energy in animals. Fatty acid synthesis occurs in the cytosol of the cells in all tissues. However, there are a few key places where lipogenesis occurs, this includes: the liver, adipose tissue and mammary glands. Lipogenesis essentially 'strings' together 16 CH2 groups together to form palmitic acid. The pathway gets its carbon from acetylCoA and its hydrogen atoms from NADPH. Lipogenesis occurs through the citrate cleavage pathway which is shown below:

The Citrate Cleavage Pathway
There are several key steps involved. Firstly, acetylCoA is created from glucose through glycolysis as well as through the citrate cleavage pathway where citrate is converted to oxaloacetate and acetylCoA by ATP citrate lyase. Oxaloacetate is converted to malate and then to pyruvate by NADP malate dehydrogenase. This involves the conversion of NADP to NADPH. AcetylCoA is then converted to malonylCoA and then to NEFACoA which is assembled into a fatty acid. This requires NADPH, half of which comes from the conversion of oxaloacetate to malate, the other half comes from the Pentose Phosphate Pathway.   

This pathway is regulated by several things:
  • Supply of substrate: the more glucose is available, the more fatty acids can be synthesised. 
  • Endocrine regulation of activity by covalent modification: Insulin stimulates the pathway while glucagon, adrenaline, ACTH and Growth Hormone inhibit the pathway. AcetylCoA carboxylase is also activated through dephosphorylation by Insulin. The pathway is also allosterically activated by citrate and inhibited by NEFACoA.
  • Endocrine regulation by enzyme expression: Insulin causes an increased synthesis of NADP malate dehydrogenase, ATP citrate lyase, acetylCoA carboxylase and fatty acid synthase. 

In ruminants, however, their fatty acids are synthesised from acetate. In order to do this they have some special features: they get their carbon source for this reaction from acetate. Acetate is also their source of NADPH via NADP isocitrate dehydrogenase found in the cytosol. 50% of their NADPH is derived from the Pentose Phosphate Pathway, the other 50% comes from the cytosolic NADP isocitrate dehydrogenase. This is inhibited by high levels of NEFACoA and stimulated by high levels of acetate. It is also regulated at the acetylCoA carboxylase step by the same mechanisms described above for non-ruminants.

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

Wednesday, 9 May 2012

Lypolysis and β-Oxidation

Hi, this post will cover how fat is used as an energy source.

Fat as a Substrate for Metabolism

Lipids are twice as energy dense as glycogen on a dry matter basis and are six times as energy dense on a wet matter basis. Thus, lipids are used to store energy in the body. It is known that an average person has enough glycogen to last for one day without eating, while they'll have enough lipids stored to last one or two months!
Lipids are used during:
  • a high fat diet
  • fasting
  • sustained exercise
  • lactation
  • late pregnancy
  • a cold air temperature
  • stress
  • and hibernation.
So, its quite clear that lipids are important to animals, but how does the body actually break down lipids in order to use them?

Lipids are stored as triacylglycerols (TAGs). One TAG molecule is converted to three non-esterified fatty acid molecules (NEFAs, see this post) and one glycerol molecule through the process of lipolysis which is catalysed by the enzyme lipase. An example of a triacylglycerol is shown below:

An Example of a Triaylglycerol
The reverse of lipolysis is called esterification and involves the conversion of 3 NEFAs and 1 glycerol molecule into a TAG molecule. Lipolysis occurs in two main areas in the body: in adipose tissue and in blood capillaries.

Lipolysis in Adipose Tissue:

Firstly, a hormone binds to a hormone receptor located on the surface of the cell. The hormone could be glucagon, adrenaline, growth hormone, adrenocorticotropic hormone or prolactin. This causes adenyl cyclase to convert ATP to cAMP. cAMP binds to cAMP dependent protein kinase which phosphoyrlates and activates hormone sensitive lipase. Lipase then catalyses the conversion of TAG to 3NEFAs and glycerol, as discussed earlier.

Lipolysis in Capillaries:

TAG molecules in the blood undergo lipolysis in the capillaries to deliver NEFAs to the tissues. However, because lipids are hydrophobic they can't dissolve easily in the blood plasma and so they need to be carried by lipoproteins. Lipoproteins are small spherical particles which solubilise lipids. Their structure is shown below:

Structure of a Lipoprotein

There are four classes of lipoproteins, which are classed by their density. (In order from least dense to most dense)
  1. Chylomicrons: these carry lipids from the gut
  2. Very Low Density Lipoproteins: carry lipids from the liver
  3. Low Density Lipoprotein
  4. High Density Lipoprotein
The first two mainly carry TAG molecules while the last two categories primarily carry cholesterol.

Many tissues, except the liver, have the enzyme lipoprotein lipase on the surface of their capillary epithelium. As the chylomicron or very low density lipoprotein pass the enzyme it binds to lipoprotein lipase and the TAG is cleaved into NEFAs and glycerol. The NEFAs can then pass into the tissue which is nourished by the capillary. Insulin stimulates lipoprotein lipase.

So in summary, lypolysis is the main regulator for the storage of fat; it occurs in adipose tissue and capillaries and these two sites of lypolysis are different in terms of regulation and mechanism. However, the overall result is the same, that is the delivery of NEFAs into the blood for use by tissues. 

Activation and Transport into the Mitochondrion.

Lypolysis involved the conversion of a TAG molecule into 3 NEFAs and 1 glycerol. Now that NEFAs have been produced they need to be carried into the mitochondrion so they can be oxidized. Before this can occur, the NEFA is converted to its active form,  NEFACoA according to the equation:
Once this has occured, the NEFACoA is transported accross the mitochondrial membrane by a molecule called carnitine according to the following pathway:

A note on nomenclature: different textbooks or sources often use several words which mean the same thing. A NEFA is another word for Acyl or free fatty acid (FFA).

In the diagram above AcylCoA and carnitine are converted to Acylcarnitine and this is catalysed by CPT1. This can be transfered to the mitochondrial matrix by translocase. Acylcarnitine and CoA are then converted to AcylCoA and carnitine by CPT2. This AcylCoA from this reaction can then be fed into β-Oxidation. The active form of carnitine is known as L-carnitine. The inactive form is called D-carnitine.

Once the AcylCoA has been transported inside the mitochondrion it can be fed into β-Oxidation. This pathway removes 2 carbons from the AcylCoA at each step to release AcetylCoA as well as NADH and FADH. These steps repeat until the fatty acid is completely broken down.

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

Tuesday, 8 May 2012

Renal Handling of Urea, Sodium and Potassium

Hello :) In this post we’ll take a look at how urea is handled by the body. I’ll describe the details of how the kidneys handle urea as well as why urea recycling is important. We’ll look at the differences between mammalian and avian excretion of nitrogenous wastes as well as how the kidney’s regulate sodium and potassium balance. In addition, we’ll discuss the key differences between aldosterone, ADH (antidiuretic hormone), and ANP. I’ll finish off by explaining why an increase in Na+ concentration does not increase K+ excretion. Don’t forget, if you have any questions about this post, please feel free to ask me in the comments section at the end of the page :)

The Handling of Urea

Urea is a nitrogenous end-product of protein catabolism and is excreted by the kidneys as waste. The breakdown of amino acids releases ammonia which is toxic to the body. Because of this, the ammonia is converted to urea which is less toxic. The concentration of urea in the blood is referred to as blood urea nitrogen (BUN). When elevated BUN and creatinine levels exist the situation is referred to as azotaemia. 

Handling of Urea at the Proximal Convoluted Tubule

About 50% of the urea which is filtered by the glomerulus is passively reabsorbed at the proximal convoluted tubule. Urea is reabsorbed at the PCT through several steps: 
  1.  It is freely filtered at the glomerulus 
  2.  Active reabsorption of the solutes then occurs, this increases the peritubular fluid and plasma osmolarity
  3. Water is then reabsorbed because it follows the movement of the solutes into the plasma
  4. This water reabsorption creates a urea concentration gradient. This is because the tubular fluid has a higher concentration of urea than the blood plasma.
  5. Passive urea movement then occurs from the tubule to the blood plasma. This is completely dependent on water movement.

Handling of Urea at the Distal Nephron

The loop of Henle, distal convoluted tubule and the collecting duct in the outer medulla are impermeable to urea and water reabsorption increases the concentration of the urea in the tubular fluid. The permeability to urea increases at the collecting ducts of the inner medulla and facilitated diffusion of urea occurs here. This diffusion is enhanced by antidiuretic hormone. 

Ten per cent of the urea which is filtered by the glomerulus is reabsorbed into the plasma at the collecting duct in the inner medulla. This occurs because the urea passively diffuses into the medullary interstitial fluid and into the plasma. Some of this urea re-enters the thin ascending loop of Henle and is ‘recycled’. The reabsorption of urea in this way decreases during times of reduced water reabsorption and when ADH is absent.

Mammals vs. Birds

As described earlier in this post, mammals excrete urea in order to get rid of their nitrogen. Birds, on the other hand, excrete uric acid in order to get rid of nitrogen. Uric acid requires less water to make when compared to urea and is made mainly by the birds’ reptilian-like nephrons. Birds do not have bladders, instead they have a cloaca. In the cloaca, birds are able to adjust the water and salt content and regulate the osmolarity of their waste.  

Sodium Balance

Because sodium is the main solute in the extracellular fluid, it is important for its balance to be regulated so that normal osmolarity can be maintained. When sodium levels in the blood plasma are higher than normal, the condition is known as hypernatremia. When lower than normal it is known as hyponatremia. Sodium levels are regulated through absorption in the kidneys.

More than 99% of the Na+ which is filtered at the glomerulus is reabsorbed. 60-65% of this occurs unregulated at the proximal tubule; 25-30% occurs in the thick ascending limb of the loop of Henle; while 10% happens in the distal nephron under control of aldosterone.

Reabsorption at the Proximal Convoluted Tubule

Here, reabsorption is unregulated. It is driven by the Na+/K+ pump which actively transports sodium across the basolateral membrane into the blood plasma. This creates a low concentration of Na+ in the proximal tubule epithelial cell. This allows Na+ to move across the apical membrane into the epithelial cell from the tubular fluid using co-transport with other solutes and counter transport with H+.

Reabsorption of Sodium at the Distal Nephron

Reabsorption at the distal nephron occurs through Na+/K+ ATPase which creates a very low intracellular sodium concentration. Sodium then moves along its concentration gradient across the apical membrane through co-transport with other solutes (eg. Cl-) and through ion channels (which is coupled with K+ secretion).  Reabsorption here is regulated by aldosterone and atrial natriuretic peptide (ANP).

Aldosterone is a steroid hormone which is produced and released at the adrenal cortex and its release is stimulated by the presence of Angiotensin 2. Aldosterone regulates Na+ reabsorption and K+ secretion at the distal nephron and indirectly leads to increased water reabsorption through increased ECF osmolarity. 

Aldosterone binds to the receptors in the cytosol of the principal cells in the late distal convoluted tubule and collecting ducts. This binding stimulates the synthesis and opening of Na+ and K+ channels at the apical membrane. The synthesis and insertion of Na+/K+ pumps occurs at the basolateral membrane.  This has the effect of simultaneously increasing sodium reabsorption and potassium excretion.  

ANP is secreted from the atrial walls in response to distension associated with an increased blood volume. 
ANP inhibits sodium reabsorption. It also increases the filtration, and thus the secretion, of sodium by increasing the glomerular filtration rate by dilating the afferent and constricting the efferent arteriole. It decreases the reabsorption of sodium by limiting the number of open sodium channels on the apical surface of the principal cells. It also inhibits RAAS by decreasing the renin and aldosterone secretion.  

Potassium Balance

The ratio of intracellular to extracellular potassium concentrations is very important to the function of excitable cells. Small changes in the concentration of potassium can affect nerves as well as cardiac, skeletal and smooth muscle. Hyperkalaemia refers to a situation where the potassium concentrations in the blood are higher than normal. Hypokalaemia is when potassium levels in the plasma are lower than normal.

At the glomerulus, potassium ions are freely filtered from the blood and both secretion and absorption occur within the tubule. Unregulated active reabsorption occurs at in the proximal convoluted tubule (55%) and the loop of Henle (30%). Regulated secretion and reabsorption occurs in the late distal tubule and collecting duct and is dependent on the dietary intake of potassium. However, the regulation of potassium levels in the blood occurs through secretion at the distal nephron.

Reabsorption at the Proximal Tubule

Active Na/K+ pumps on the basolateral membrane of the tubule epithelial cell pump K+ from the peritubular fluid into the epithelial cell. An unknown mechanism also transfers K+ from the tubular fluid in to the epithelial cell. K+ then moves down its concentration gradient across the basolateral membrane into the peritubular fluid. K+ can also be reabsorbed through paracellular diffusion.  

The Handling of Potassium at the Distal Nephron

If the animal’s diet has high amounts of potassium, potassium will be excreted at the principal cells in the distal nephron. If the diet is low in potassium, reabsorption will occur at the intercalated cells. This is also where sodium reabsorption occurs.  

At the principal cells K+ moves from the peritubular fluid into the cell through the Na/K pump across the basolateral membrane. This is an active process. Potassium also moves down its concentration gradient through ion channels into the renal tubule across the apical membrane. This is a passive process.

Now, aldosterone increases the amount of Na/K on the basolateral membrane and the amount of K+ channels on the apical membrane. This aldosterone is regulated by the RAAS and the concentration of potassium. High potassium levels in the extracellular fluid stimulate the release of aldosterone.

At the intercalated cells, potassium is reabsorbed while H+ is secreted when there is a depletion in potassium. This occurs through an H+/K+ exchange at the apical membrane.

That’s all for this post, see you next time :)

Saturday, 5 May 2012

Water Balance and Micturition

Hi :) In this post we'll take a look at an overview of water balance and the factors affecting changes in osmolarity and water movement in the body. We'll also discuss normo-, hypo- and hypervolaemia as well as how water is reabsorbed in various regions of the nephron. I'll explain how the medullary osmotic gradient is generated and maintained and why this gradient is important. I'll also discuss how ADH regulates water reabsorption in the nephron as well as the micturition reflex.

Water Balance

The amount of water in the body is balanced when the input of water equals the output. A positive water balance occurs when input exceeds output and a negative water balance occurs when output exceeds input. Water input largely comes from ingestion while a small amount is a result of cellular metabolism. Output is due to mainly excretion and other losses (such as sweating, from the breath etc).

Normovolaemia = a normal blood volume
Hypervolaemia = an increased blood volume
Hypovolaemia = a decreased blood volume

Water Reabsorption

 The kidneys are able to adjust the rate at which water is excreted to compensate for the changes in plasma volume and osmolarity. Seventy percent of water is reabsorbed at the proximal convoluted tubule where water reabsorption is unregulated, that is no hormones are involved. Here water follows the movements of solutes especially Na+. The distal tubule and collecting ducts of the nephron also reabsorb water, however, here the water excretion is regulated by Antidiuretic Hormone (ADH) which allows the kidneys to vary the volume of water excreted by the nephron. This is the place where concentration is fine-tuned.

To enable water balance, the kidneys regulate the osmolarity of the urine that they produce. Now, the normal osmolarity of blood plasma is 300mOsm. To get rid of excess water the kidneys excrete large volumes of dilute urine which has an osmolarity of 50mOsm. To conserve water, the kidneys concentrate the urine to approx. four times the osmolarity of plasma (~1400mOsm). The kidneys vary the urine volume and osmolarity by varying the water reabsorption at the distal nephron. The kidneys do this by creating and maintaining a medullary osmotic gradient. 

The Medullary Osmotic Gradient

The part of the medulla closest to the cortex has the lowest osmolarity (300mOsm) while the inner medulla has the highest osmolarity (1200-1400 mOsm). The distal nephron acts as a countercurrent multiplier. The fluid in the descending and ascending limbs of the loop of Henle (LOH) move in opposite directions. The descending limb of the LOH is permeable to water and no Na+, K+ or Cl- is transported there. The thick ascending limb of the LOH is impermeable to water and Na+, K+ and Cl- a transported by co-transporters.  The Medullary Osmotic Gradient is established in several steps:
  1. Fluid enters the tubule and the active transport of Na+, Cl- and K+ ions occurs. This causes these ions to move into the medullary interstitial fluid which increases its osmolarity. 
  2. This causes water to move out the descending limb of the LOH into the medullary interstitial fluid by osmosis.
  3. The fluid in the descending limb reaches an iso-osmotic state. That is the osmolarity of the fluid in the descending limb is equal to that in the medullary interstitial fluid. There is an osmotic difference between the descending and ascending limbs.
  4. More fluid enters the tubule and this pushes the existing fluid along the loop. More solutes are also pumped into the interstitial fluid. 
  5. Water moves out the descending limb by osmosis.
  6. The descending limb reaches an iso-osmotic state. An osmotic difference between the descending and ascending limbs exists. This cycle is repeated as the system is in a steady state. 
The osmolarity in the descending limb increases until 1400mOsm (in humans). The osmolarity of the ascending limb is always lower than the descending limb and decreases until it becomes hypo-osmotic. The osmotic gradient that is created does not dissipate because of the sluggish flow of blood through the vasa recta (the network of capillaries surrounding the distal nephron). This provides time for the osmotic gradient in the plamsa and interstitial fluid to equalise.

Because the fluid in the distal tubule and collecting duct is hypo-osmotic, water moves from the tubule to the interstitial fluid along an osmotic gradient, this is reabsorption. Water reabsorption requires a medullary osmotic gradient as well as permeability of the epithelium to water (this is dependent on ADH). The permeability of the epithelium to water is dependent on the presence of water channels in principal cells. Aquaporin-3 is always present in the basolateral membrane while Aquaporin-2 is present in the apical membranes when ADH is present in the blood.

Antidiuretic Hormone (ADH)

ADH (also known as vasopressin) is produced in the hypothalamus but is stored and secreted from the posterior pituitary gland. ADH is released into the blood in response to osmotic and baroreceptor signals. It acts on the cells of the distal nephron through several steps: 
  1. ADH binds to basolateral receptor
  2. Activates 2nd messenger
  3. Increased synthesis and insertion of Aquaporin-2 channels into apical membrane
  4. water permeability increased within 5-10 minutes. This causes the urine to be concentrated.
  5. Aquaporin 3 is always present on the basolateral membrane. 
ADH secretion is stimulated by: increased ECF osmolarity, hypovolaemia, decreased mean arterial pressure, stress, nausea and vomiting, nicotine. ADH release is inhibited by: decreased exctracellular fluid osmolarity, hypervolaemia, increased mean arterial pressure and alcohol. 

In the absence of ADH, the late distal nephron becomes impermeable to water and water remains in the tubules despite the medullary osmotic gradient. This results in a large volume of dilute urine to be produced. In the presence of ADH the late distal nephron becomes permeable to water and it moves into the peritubular fluid because of the osmotic gradient. This causes small volumes of concentrated urine to be produced.

Species Differences in Urine Concentrating Ability

The ability to concentrate urine is dependent on the ratio of cortical to juxtamedullary nephrons. The more juxtamedullary nephrons present, the more concentrated the urine can be. Consequently, humans, which have 17% juxtamedullary nephrons, can generate a urine concentration of 1400mOsm. Dogs and cats, on the other hand, can produce concentrations of 2400mOsm and 3300mOsm respectively due to their ratio of 80% juxtamedullary nephrons. This is because the more juxtamedullary nephrons are present, the longer the tubules become. This allows a higher osmotic gradient to be generated which leads to more concentrated urine production.

The Micturition Reflex

This is the reflex which is involved in urination. The kidneys produce the urine while the bladder stores it. The bladder has several muscles which are under involuntary and voluntary control. The detrusor muscle, which is located in the wall of the bladder is under involuntary control. The internal urethral sphincter is also involuntarily controlled while the external urethral sphincter is under voluntary control. 

When the bladder fills with urine the bladder wall expands and this activates stretch receptors located in the wall. These stretch receptors communicate with the spinal cord and work to:
  • Decrease the sympathetic activity: this causes the internal urethral sphincter to relax which causes it to open.
  • Increase parasympathetic activity. This causes the detrusor muscle to contract and also causes the internal urethral sphincter to open.
  • Decrease in somatic motor neuron activity. This causes the external urethral sphincter to relax and open. 
The opening of the internal and external urethral sphincters lead to micturition (urination). 

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