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Liver Pathophysiology and Liver Disease Markers

The liver is the largest glandular organ present in vertebrates and some other animals. It is reddish brown in colour with four lobes of unequal size and shape ( Fig.1.0). It is located at the right side of the abdominal cavity beneath the diaphragm.
The liver has a wide range of functions. It would be difficult to overestimate the its importance to the healthy functioning of the human body. It acts as a giant chemical processing plant , a battery, a filter, a warehouse and distribution centre.. The chemical reactions, called metabolism, are central in the regulation of body homeostasis. The liver is able to carry out its functions through the help of liver cells called hepatocytes ( Ramaori, et al., 2008). These cells contain essential enzymes that perform the vital metabolic functions.
The liver metabolises both beneficial and harmful substances. It stores nutrients and other useful substances, as well as detoxifying or breaking down harmful compounds. These can be then excreted from the body in bile via the liver; in urine via the kidney, or by other means. These cells are described as supermodels in the world of cellular metabolism.
In summary, the liver performs the following functions:
Metabolism of fats, proteins, and carbohydrates
Excretion of bilirubin, cholesterol, hormones, and drugs
Storage of glycogen, vitamins, and minerals
Bile production and excretion
Blood detoxification and purification
Enzyme activation
Synthesis of plasma proteins, such as albumin and globulin, and clotting factors
Pathophysiology of the Liver The functions of the liver described above occur in the normal functioning of the liver but in some cases ther are abnormal functioning of the liver due to disease conditions which can result from a wide variety of insults, including infections, drugs, toxins, ischemia, and autoimmune disorders.
Abnormalities of liver function can be divided broadly into two groups:
those caused by a malfunction of the liver cells (such as cirrhosis or hepatitis)
those caused by an obstruction of the biliary tract (such as bile duct stones or cancer of bile duct and haemocytes).
Most liver disorders cause some degree of hepatocellular injury and necrosis, resulting in various abnormal laboratory test results and, sometimes, symptomssuch as jaundice , acute GI bleeding . Some of the diseases lead to by impairment of biliary secretion; and cryptogenic cirrhosis, by liver fibrosis and resultant portal venous hypertension).
The diagnosis of the diseases and the general state of the liver is made by blood tests. These tests help to pinpoint the extent of liver damage. One of these blood tests is called Liver function tests.
Liver function tests. As the immune system, digestive tract, kidney, brain and cardio-vascular system all depend on a healthy and well-functioning liver, there is great need to know the state of the liver and also to know some of the key liver disease markers for effective management of this vital organ. The diagnosis of liver function is made by blood tests. The liver makes a number of chemicals when playing its vital roles. The blood levels of these chemicals are altered by various liver disorders as they pass into the bile and the bloodstream. One of the tests used for the measurement of these chemicals in the blood sample is called Liver function tests which assess the general state of the liver and bilarry system. It involves the measurement of bilirubin, a compound formed by the catabolism of hemoglobin; ammonia, a product of protein catabolism that is normally converted into urea by the liver before being excreted by the kidneys; proteins that are made by the liver including total protein, albumin, prothrombin, and fibrinogen; cholesterol and triglycerides, which are made and excreted via the liver; and the enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and lactate dehydrogenase (LDH). Other liver function tests include serological (tests to demonstrate antibodies) and DNA tests for hepatitis and other viruses, tests for antimitochondrial and smooth muscle antibodies, transthyretin (prealbumin), protein electrophoresis, bile acids, alpha-fetoprotein, and a constellation of other enzymes that help differentiate necrotic versus obstructive liver disease.
Key liver disease markers and how they aid diagnosis. Laboratory tests for total protein, albumin, ammonia, transthyretin, and cholesterol are markers for the synthetic function of the liver. Tests for cholesterol, bilirubin, ALP, and bile salts are measures of the secretory function of the liver. The enzymes ALT, AST, GGT, LD, and tests for viruses are markers for liver injury.
Some liver function tests are used to determine if the liver has been damaged or its function impaired. Elevations of these markers for liver injury or disease tell the physician that something is wrong with the liver. ALT and bilirubin are the two primary tests used largely for this purpose. Bilirubin is measured by two tests, called total and direct bilirubin. The total bilirubin measures both conjugated and unconjugated bilirubin while direct bilirubin measures only the conjugated bilirubin fraction in the blood. Unconjugated bilirubin is formed from heme in the reticuloendothelial cells in the spleen that remove old red blood cells from the circulation. The RE cells release the bilirubin into the blood where it is bound by albumin and transported to the liver. The bilirubin is taken up by liver cells and conjugated to glucuronic acid, which makes the bilirubin water soluble. This form will react directly with a Ehrlich’s diazo reagent, hence the name direct bilirubin. While total bilirubin is elevated in various liver diseases, it is also increased in certain anemias caused by increased red blood cell turnover. Neonatal hyperbilirubinemia is a condition caused by an immature liver than cannot conjugate the bilirubin. The level of total bilirubin in the blood becomes elevated, and must be monitored closely in order to prevent damage to the brain caused by unconjugated bilirubin, which has a high affinity for brain tissue.. Direct bilirubin is formed only by the liver, and therefore, it is specific for hepatic or biliary disease. Its concentration in the blood is very low and therefore, even slight increases are significant. Highest levels of direct bilirubin are seen in obstructive liver diseases. However, direct biliruibn is not sensitive to all forms of liver disease (e.g., focal intrahepatic obstruction) and is not always elevated in the earliest stages of disease, and therefore, ALT is needed to exclude a diagnosis.
ALT is an enzyme that transfers an amino group from the amino acid alanine to a ketoacid acceptor.. Although ALT is present in other tissues besides liver, its concentration in liver is far greater than any other tissue, and blood levels in nonhepatic conditions rarely produce levels of a magnitude seen in liver disease. The enzyme is very sensitive to necrotic or inflammatory liver injury. Consequently, if ALT or direct bilirubin are increased, then some form of liver disease is likely. If both are normal, then liver disease is unlikely.
These two tests along with others are used to help determine what is wrong. The most useful tests for this purpose are the liver function enzymes and the ratio of direct to total bilirubin. These tests are used to differentiate diseases characterized primarily by hepatocellular damage (necrosis) from those characterized by obstructive damage. In hepatocellular damage, the transaminases, ALT and AST, are increased to a greater extent than alkaline phosphatase. This includes viral hepatitis, which gives the greatest increase in transaminases (10-50 fold normal), hepatitis induced by drugs or poisons (toxic hepatitis), alcoholic hepatitis, hypoxic necrosis (a consequence of congestive heart failure), chronic hepatitis, and cirrhosis of the liver.
Aspartate aminotransferase is not as specific for liver disease as is ALT, which is increased in myocardial infarction, pancreatitis, muscle wasting diseases, and many other conditions( Hannah, 2007). However, differentiation of acute and chronic forms of hepatocellular injury are aided by examining the ratio of ALT to AST, called the DeRitis ratio. In acute hepatitis, Reye’s syndrome, and infectious mononucleosis the ALT predominates. However, in alcoholic liver disease, chronic hepatitis, and cirrhosis the AST predominates.
Alkaline phosphatase is increased in obstructive liver diseases, but it is not specific for the liver. Increases of a similar magnitude (three-to five-fold normal) are commonly seen in bone diseases, late pregnancy, leukemia, and some other malignancies. The enzyme gamma-glutamyl transferase (GGT) is used to help differentiate the source of an elevated ALP. GGT is greatly increased in bstructive jaundice, alcoholic liver disease, and hepatic cancer..
Some liver function tests are not sensitive enough to be used for diagnostic purposes, but are elevated in severe or chronic liver diseases. These tests are used primarily to indicate the extent of damage to the liver. Tests falling into this category are ammonia, total protein, albumin, cholesterol, transthyretin, fibrinogen, and the prothrombin time.
Conclusions Liver function tests done individually do not give the physician very much information, but used in combination along with a careful history, physical examination, and imaging studies they contribute to making an accurate diagnosis of the specific liver disorder. Different tests will show abnormalities in response to liver inflammation, liver injury due to drugs, alcohol, toxins or viruses, liver malfunction due to blockage of the flow of bile, and liver cancers.

Broiler Cockerel Production In Semi Intensive System

Every year billions of egg-type cockerels are produced in the world. The associated breeding industry has become prosperous for egg-type cockerels in terms of meat flavour compared to fast-growing-type broilers. Many researches have been carried out to evaluate the nutritional requirements of broilers; conversely, little research has been performed on the nutritional factors of egg-type cockerels. At present, most diets formulated are uneconomical for the producers of cockerels. Wang C. et al, 2005.
The desire of every poultry farmer is to produce large quantity of meat and eggs throughout the year irrespective of the environmental conditions. (Eilkheir S., Ahmed M., Gadir A., 2008) which explains why the production of laying cockerels is not given much importance. In Mauritius, the production of poultry grew by 4.8% in 2009 to reach 44,000 tonnes compared to 42,000 tonnes in the year 2008. (CSO, 2009 – 2010) The poultry industry has prospered due to an increase in purchasing power of Mauritians. This has resulted in the development of the poultry sector as an integrated industry with the private companies being involved from feed preparation to marketing of the poultry products through production of day old chicks. (FAO, Country Report, 2007). In the other hand, there hasn’t been much research on growth of layer cockerels because of their slow growth rate compared to the fast growing broilers.
To satisfy the higher demand for meat products on time, livestock production and densities of birds per square metre have significantly gone high, often close to urban centres. Industrial animal production has become more focused, using fewer livestock breeds who turn out to be more productive.
According to FAO Chief Veterinary Officer Joseph Domenech those developments have potentially serious consequences for local and global disease risks, which by now, have not been recognised by policy makers. As a result, the vast majority of chickens are now produced in houses with 15 000 to 50 000 birds in the industrialized countries. The trend towards industrialization of livestock production can also be seen in developing countries, where traditional systems are being replaced by intensive units, mostly in Asia, South America and parts of Africa (FAO, 2008). And thus, backyard poultry is decreasing together with indigenous chicken and cockerel production.
2.0 Literature Review 2.1 Cockerels
Cockerel coming from the word cock is known as a young cock not having an age older than one year. Cocks are also known as fighters without mercy since centuries. They can mate with 5-6 hens at a time and one cock or cockerel can stay with a family of five to six female birds. Cocks cannot accept another cock in their family, so they fight until one survives and takes possession of the family. So these skills of fighting start developing in early stages of the cockerels. Cockerels also like to be in higher positions from the soil, and thus they are seen on high trees. (Danae Olivier, 1990)
Cockerels the egg-type male chicks’ production is an essential component of family poultry development with the increasing trends of commercial layer farming. The layer farmers usually buy female chicks from the hatchery and a significant number of male chicks remains in the hatchery and are sold at a low price or destroyed since there is little or no facility to market these chicks. Cockerels can be grown as a source of meat as most consumers prefer cockerels as a source of poultry meat because of its hardness. (Huque Q. M. E. et al, 2004)
Cockerels from strains of laying hens take long period to grow. Despite this, cockerels are present in high number in developing countries where the accessibility and price of day old chicks are frequently constraints. The efficient supply of the animal category is very low in research activities. On the other hand, poultry feed represents 60 to 80% of the cost of inputs in commercial poultry production (Branckaert et al 2000).
2.1.1 Fate of cockerels
Domestic chickens produce eggs which hatch giving almost equal proportions of males and females. Long time ago, domestic chickens were bred for both egg and meat production. On the contrary, nowadays, commercial hybrid chickens are selected for one purpose only; either eggs or meat. Surplus day-old male chicks of the layer type are currently without significant commercial value and are at best used as food for e.g.carnivorous animals. All attempts to raise male chicks of the layer type for meat production have resulted in high consumption of feed and poor meat yield which is difficult to market at competitive prices. (Kaleta E. F. and Redmann T., 2008). Due to the inefficiency in producing meat in a short time, they are culled on the first day.
2.1.2 Cockerels as a source of poultry meat
Normally cockerels are mostly reared in backyard system and village poultry production. It is a source of income to women in villages, as well as it contributes to the food security in villages. In some places cockerels are also used as a barter system instead of money.
2.2 Broiler Industry
In order to produce a kilogram of broiler meat, 1.8 kg feed is required (Akbay, 1995) and broilers are one of the most efficient converters of grains to animal protein.
Growth of broilers at the beginning requires investments in significant amounts in the form of broiler houses and buying and storage of feed (Knoeber and Thurman, 1995).Broilers are genetically selected, then slaughtered when only 6 or 7 weeks (a healthy chicken’s lifespan is as many years) and never experience maternal care. Mass-produced chickens spend their short lives in huge windowless sheds and since they are motherless they have to fend themselves since day old (Webster J., n.d.). Meat chickens today can reach a weight of approximately 2kg in 35 days while consuming only 3.2kg of feed. With genetic selection there are still improvements in performance and the time it takes to reach market weight is gradually becoming shorter (Choct M., 2010).
2.3 Egg industry
2.3.1 Trend of commercial egg production
Compared to the broilers, the egg layers take much more time to grow. They can have a lifespan of up to 2 years.

The trends in Mauritius shows that, egg production has been decreasing significantly since 2006, though there have been improved breeds of egg layers, with increasing rate of laying eggs every year.
2.4 Feeding Difference for broilers
Recently, there has been an unexpected and high demand of certain elements in the feeding of poultry, due to the success of the research scientists in producing birds with enhanced productivity in every way, which overcomes the normal nutritional requirements of broilers. (David Sainsbury, 2000)

2.5 Cockerel production management compared to broiler production management
There is no recognized cockerel management guide till date, for profitable cockerel rearing and production system. Even then farmers begin cockerel husbandry with great interest for consumer’s choice, lower management cost, more organoleptic preference and easy management practices. Many consumers prefer the meat of the male chicks at a body weight of 600g to 700g and thus there is a better plan for the utilisation of the vast quantities of male chicks (Huque Q. M. E. et al, 2004).

2.6 Cockerel performance compared to broiler performance
2.6.1 Feed efficiency and growth rate
The growth rate is linked mainly to genetic factors, where the expression depends on environmental features (Gerken et al., 2003).
2.7 Market demand and consumer choice of preference for cockerel compared to broiler
2.7.1 Meat quality
The meat quality of cockerels is considered to be hardier than the broiler meat. The taste, flavor, juiciness and tenderness are more or less alike to the indigenous stocks. Due to its excessive abdominal fat properties, the broiler meat is less appealing if consumers have to choose between broiler meat and cockerel meat (Crawford, 1990). This can be considered as a great advantage for the rapid expansion of cockerel rearing in remote areas. The meat from male chicks of layer strains is believed to be more suitable for the preparation of chicken delicacies because of less abdominal fat property, juiciness and most importantly the desirable flavour of the meat. Due to its smaller size, recently there has been a great demand of cockerels in restaurants, hotels and consumer demands where both restaurant holders and consumers are benefited which is creating a prospect for cockerel production. (Haleem, 1987)
2.8 Types of production systems
In Mauritius we have 4 types of production systems which are the:
Industrial system
Intensive system
Semi intensive system
Backyard production system
2.8.1 The intensive system
The industrial system of production also form parts of the intensive system, where there are very large quantities of chickens are present in the grow-out farms. Food And Allied Limited is one of private companies which operate on an industrial system of production.
In this kind of production animals are kept in a fairly small area or at a high stocking density and the level of administration and inputs involved are high in this system of production. Though this system of production is completely dependent on use of concentrates manufactured locally, the raw materials are imported. The birds are under constant veterinary monitoring. All veterinary products including vaccines are imported. The birds are kept in large buildings where most favorable conditions are maintained and reared on the deep litter system (FAO Country Report, 2007)
2.8.2 The semi-intensive system
The stocking density is lesser in the semi intensive system compared to the intensive system of production but the level of management and inputs are low. In this system the birds can be of broiler type or layer type. They are fed concentrates and have little veterinary care. They are usually kept on deep-litter but on a small-scale and at the back of the house. They are fed concentrates and have little veterinary care. The birds are mostly kept in concrete buildings but the environment prevailing inside is very often poor. The products which are the eggs and meat from these farms are generally sold to the public in the locality through some middlemen (FAO Country Report, 2007)
2.8.3 The backyard/extensive system
In the backyard system all the birds are kept in the backyard and there is no input or if present, it is at a very low level. It also includes those units where the animals are left to roam and look for their feeds. In this system of production, the local chickens roam and look for food. There is a minimum of inputs, usually consisting of small amount of concentrates and in some cases of kitchen leftovers. There is no veterinary care provided and production is very low. Nevertheless the products from this system of production usually fetch a higher profit than those from commercial firms, both in case of meat and eggs (FAO Country Report, 2007). In the villages, the birds normally spend the night on trees in the backyard. Backyard poultry are the predominant livestock species in many rural areas of the developing countries and comprise mainly local unimproved poultry breeds and few improved strains. (Ahlers et al 2009) Backyard poultry production plays an important role in poverty alleviation and improvement of family food security in many poor rural households of the developing countries. (Adongo 2004)
In the year 2002, it was estimated that around 1000 farmers are involved in backyard family poultry production consisted of around 1000 farmers in Mauritius, and around 4000 in Rodrigues. The farmers in Rodrigues rear indigenous scavenging chickens, which are known as the ‘local’ breed, most probably a mixture of Rhode Island Red, Australorp and Naked neck breeds which were brought on the island a few centuries ago. (Jugessur, V. and Pillay, M. (2002)
2.9 Nutrition of birds
2.9.1 Water
Water is the most important nutrient for poultry as a shortage of water supply may affect the bird’s performance more quickly than a shortage of any other nutrient. Water is important in digestion and metabolism of poultry. The body of the bird comprises of 55 to 75% of water. There is a strong relationship between feed and water intake. Water softens feed in the crop to prepare it for grinding in the gizzard. The chemical reactions involved, require water to facilitate the processes of digestion and nutrient absorption (Damron B. L. and Sloan D. R., 2003).
2.9.2 Nutrients Proteins
Proteins, Fats, Carbohydrates, Vitamins and Minerals
The main sources of protein for poultry feeds are animal proteins such as fish meal and plant proteins such as soybean meal and corn gluten meal. On a dry-weight basis, the body of a mature broiler is more than 65% protein (Damron B. L. and Sloan D. R., 2003). Fats
Fats are important sources of energy for poultry diets because they contain twice the energy as any other feed ingredient. This characteristic makes fat an important tool for the proper formulation of starting and growing diets. Fat makes up about 17% of the dry weight of a market broiler (Damron B. L. and Sloan D. R., 2003). Carbohydrates
Carbohydrates make up the largest portion of a poultry diet. They are usually in the form of sugar, starches or cellulose. Carbohydrates are a major energy source for poultry and some important sources of carbohydrates can be obtained from grains such as corn, wheat, and milo (Damron B. L. and Sloan D. R., 2003). Vitamins
Vitamins are essential for life and they must be provided in proper quantities for chickens to grow and reproduce. Although some of these vitamins are abundant in feed ingredients, a vitamin premix is usually used by the nutritionist to ensure adequate strengthening of the birds.
The most widely recognized use of minerals is the formation of straight, strong and rigid bones (Damron B. L. and Sloan D. R., 2003). Minerals
Laying hens also need minerals, primarily calcium, for eggshell formation. As grains are low in minerals, poultry feeds are supplemented with with sources of minerals (Damron B. L. and Sloan D. R., 2003).
2.9.3 Feed Additives
Poultry feeds often contain substances that are not concerned with nutrient requirements. For example, an antioxidant may be included to prevent rancidity of the fat in the diet, or to shelter nutrients from loss by oxidation. Pellet binders may be used to improve the texture and firmness of pelleted feeds. Coccidiostats are often used in broiler feeds (Damron B. L. and Sloan D. R., 2003).
2.10 Feeding strategies
Ojewola G. S. And Ozuo U. K., 2006 carried out an experiment with cockerels of five weeks old by substituting Soyabean meal with palm kernel meal at different percentages of 0, 25, 50, 75 and 100%. Palm kernel meal is a by-product of palm oil extraction (Tewe O. O., 2003) and is abundant in many tropical regions (Onwudike O. C., 1986). Inclusion of 20% of palm kernel meal in the feed of cockerels was the best scenario in terms of weight gain and economic performance (Ojewola G. S. and Ozuo U. K., 2006).
2.11 Litter management
There two systems of litter management, which are the deep litter systemAccording to David Sainsbury, shavings should usually be placed at a depth of 150 mm or another material can be placed at the same depth. He also suggests that it is better to place the shavings at a depth of 70 mm and the rest to be put later. The litter should not be allowed to be caked. The addition of litter at a later stage dilutes the birds’ droppings, thus enhancing the activities of the birds. A high level of ammonia is dangerous for all birds at any age. It may cause respiratory problems later leading to blindness. (David Sainsbury, 2000)
The advantages of the deep litter method are:
It can be managed quickly and easily.
It can be used as compost in the end.
The birds get to scratch through the microbes and useful culture of the living compost litter material, which is beneficial for them.
It is safe and the birds stay healthy (Ware L., 2011.)
2.12 Health and diseases
Farmers consider that the cockerels are less vulnerable to diseases compared to broilers (Sil et al., 2002)
2.13 Heat stress
Heat stress has been one of the major problems which the broiler industry is facing in the tropical and subtropical areas. This is because broilers can only attain the desired final live weight in a stress free environment (Sabah et al., 2008). When exposed to high temperatures, broilers exhibit many behavioural changes which allow them to re-establish heat balance with their surroundings (Gray et al. 2003). But according to Fuquay (1981), in hot environment importance should be placed on diets to raise intake or alter the levels of proteins, amino acids or other nutrients to increase the conversion of feed to meat (Onu P. N., 2009).
2.14 Mortality
Early mortality in bird flocks may occur due to failure in adapting to the new environmental condition, disease, or disappearance of yolk sac in the intestine. Sometimes inaccessibility to feed and water the chicks do not begin to eat and drink, they may survive for few days with the yolk sac but once depleted, the chicks will soon die (Tabler, Berry and Mendenhall, 2004).

These data show that broiler mortality usually peaks at approximately 3 to 4 days after placement, declines until approximately day 9 or 10 then stabilizes until approximately day 30. (Tabler, Berry and Mendenhall, 2004).
2.15 Conclusion
Types of poultry industries (broiler and egg layers)
What are cockerels (nature, behaviour)
Fate of cockerels
CSO stats on status of cockerel production and poultry production for the last 10 yrs
Trends of egg layers produced, will give information on day old cockerels produced.
Cockerel breed
Number of small scale cockerels producers through extension services
Broiler breed
Systems of production
Organic farming
Traditional chicken production
Organic feed in case of cockerels
Performance of cockerels
Normal growing requirements of broilers
Brooding and rearing conditions
Space requirements
Vaccination and sanitation
Ventilation in growing poultry farms
Consumer preference towards meat quality and quantity
Energy, vitamin and protein requirement of poultry
Price of maize going high in the world market
Banning of feed additives
Growing chickens in tropics
Body weight and FCR
Slaughtering age of cockerels and broilers
Litter analysis (moisture content)
Village chicken production
Advantage of intensive production
Advantage of organic poultry
Cost effectiveness
CRD design in placing chicks