Sunday, 24 March 2013

Fat Soluble Vitamins

The fat soluble vitamins include vitamins A, D, E and K. In this post, we'll discuss the sources, forms, functions, metabolism and storage as well as the effects of deficiency and toxicity in each of these vitamins. 

Vitamin A


There are three functional forms of vitamin A: retinol (the alcohol), retinal (the aldehyde) and retinoic acid (the acid). The ‘all-trans’ (all the double bonds are in the trans configuration) form of retinol is the major active form of the vitamin. 


Vitamin A, in its pre-formed state, can only be found in animal tissues. Fish oils and offal, especially liver, are good sources. Provitamin A, which can be converted to vitamin A in herbivores, can be found in green pasture or plants. The provitamin in plants are called carotenoids. The more green the food, the greater the content of carotenoids. The most important form of the provitamins is beta-carotene. Vitamin A may also be produced synthetically for animal supplements. 

Most species can convert beta-carotene to vitamin A but a differing efficiencies. In theory, two molecules of vitamin A are produced from one molecule of beta-carotene. Cats, foxes, and minks cannot convert beta-carotene because they lack the enzyme needed to do this. Thus, they must get their vitamin A pre-formed from the diet. 

Metabolism and Storage

When food is digested, retinyl esters from animals and carotenoids from plants are absorbed by the intestinal mucosal cells. Here, the retinyl esters are converted to retinol and the beta-caretnoids are converted to retinal which is then converted to retinol. The retinol from the intestinal mucosal cells are then converted to retinyl palmitate and travel in chylomicrons in the lymph to the liver where it is stored. 


Vitamin A has several important functions including:

  • Vision: it is responsible for the formation of rhodopsin
  • Maintenance of epithelial cell differentiation and mucous production. 
  • Growth: especially bone 
  • Reproduction 
  • Immune response and healing (it is a scavenger of free radicals).

Vitamin A Deficiency

As a result, deficiencies in Vitamin A will lead to the following clinical signs:

  • Opthalmic disease, particularly night-blindness and xerophthalmia (dry eyes). 
  • Skin disease 
  • Bone lesions due to the excessive deposition of bone 
  • Increased CSF pressure 
  • Reproductive failure: teratogenesis, failure of spermatogenesis and the abortion of foetuses 
  • Failure of growth 
  • Death

Vitamin A Toxicity

Vitamin A toxicity may result if excess amounts of vitamin A are included in an animal’s diet. Signs of toxicity include:

  • Changes in the skin and mucous membranes:

o   Skin thickening
o   Scaly dermatitis
o   Swelling/crusting of eyelids
o   Sloughing of skin
o   Hair loss
o   Excess mucous production.

  • Nausea 
  • Headache 
  • Anorexia and weight loss 
  •  Decreased bone strength 
  • Haemorrhaging 
  • Malformed young 
  • Death

Vitamin D


There are many forms of vitamin D but not all occur naturally. The most important forms are D2 (ergocalciferol – found in plants) and D3 (Cholecalciferol – found in animal tissues).

Ergosterol is the provitamin of D2 and 7-dehydrocholesterol (7-DHC) is the provitamin of D3. UV radiation is required to convert the provitamin to the vitamin and this process occurs in the skin.


Pre-formed vitamin D3 is not abundant in foods. This is not usually an issue because vitamin D3 is produced by the skin in excess of what is required by mammals. Dietary supplements are only required when animals have little exposure to sunlight. Fish liver oils have high vitamin D content. Egg yolk, margarine, lard, shrimp and sardines have a medium amount of vitamin D. Foods that have a low amount of vitamin D include grain, vegetable oils, meat, butter, milk, cream and cheese.

Cats are unable to synthesis vitamin D3 even if their skin comes into contact with sunlight. This is because they lack the enzymes required for the conversion of the provitamin to the vitamin. Thus, they need to obtain their vitamin D preformed in the diet. Lactating cows may also need a higher level of vitamin D in their diet.

Metabolism and Storage

Vitamin D3 enters the plasma through absorption of pre-formed vitamin D in the small intestine or alternatively through the conversion of 7-DHC in the skin in the presence of sunlight. Once in the plasma it travels to the liver and then the kidneys where it is converted to calcitriol. This substance has a regulative activity on calcium use and absorption. 

Calcitriol stimulates the absorption of Calcium in the intestines as well as bone calcium resorption. These effects cause an increase in plasma calcium levels and unsurprisingly is most active when these levels are low.

Vitamin D Deficiency

A deficiency in vitamin D results in impaired absorption of calcium and phosphorus. Thus, clinical signs include abnormal skeletal development and inadequate calcification of bone.

Vitamin D Toxicity

Vitamin D is also toxic in excess and this involves the mineralisation of soft tissues such as the liver. 

Vitamin E


There are eight vitamers of vitamin E which belong to two groups: tocopherols and tocotrienes. “Natural vitamin E” is actually called d-α-tocopherol and is the most common form. Synthetic vitamin E refers to dl-α-tocopherol acetate. The stability of vitamin E is reduced by heat as well as exposure to sunlight and peroxidising lipids. 

Exercise, growth and the amount of polyunsaturated fatty acids in the diet all increase vitamin E requirements. Thus, growing as well as lactating animals require more vitamin E than other animals. Poly-unsaturated fatty acids (PUFAs) increase the requirement of Vitamin E because they are susceptible to peroxidation and the vitamin acts as an antioxidant. 


The main job of vitamin E is as an antioxidant to protect the body from damaging reactions (known as peroxidation) that are produced by many normal metabolic processes and exogenous toxins. The vitamin works as a free radical scavenger, it also protects membranes from damage and helps prolong the lifespan of red blood cells. It also is important for the function of the immune system. 

The presence of either vitamin C, beta-carotene or selenium enhances the antioxidant effects of vitamin E. Vitamin E also reduces the use of the liver’s Vitamin A stores.  


Good sources of vitamin E include vegetable oils, cold-pressed seed oils and wheat germ. Other sources of this vitamin include nuts, seeds, whole grains and leafy green vegetables. Although vegetable oils are a good source, this is normally not a large part of most livestock’s diet.

Metabolism and Storage

Vitamin E absorbed mainly from the jejunum where it is repackaged as chylomicrons to travel in the lymph. It is stored in fatty tissue, liver and muscle but not to the same extent as Vitamin A and so it is important to that Vitamin E is received from the diet regularly.

The presence of either vitamin C, beta-carotene or selenium enhances the antioxidant effects of vitamin E. Vitamin E also reduces the use of the liver’s Vitamin A stores. The presence of iron in the diet will reduce the availability of vitamin E to the body.  

Vitamin E Deficiency

Signs of Vitamin E deficiency include:

  •   Reproductive Failure

o   Embryos degenerate
o   Sterility and testicular atrophy
o   Ovarian failure

  • Derangement of Cell Permeability

o   This affects the liver, brain, kidneys and capillaries
o   It may be present as encephalomalacia and exudative diathesis.

  • Nutritional Muscular Dystrophy

o   This includes White Muscle Disease which affects the skeletal muscle of sheep, and Mulberry Heart Disease which effects the cardiac muscle of pigs.

  • Pansteatitis (also known as Yellow Fat Disease).

o   This is when fat becomes inflamed and starts to go necrotic. 

Vitamin E Toxicity

There are few reports of Vitamin E toxicity as it has little or no toxicity in metabolism. Vitamin E is also expensive which means that it is not likely to be given to animals in excess.

Vitamin K


Vitamin K has several different forms but what they all have in common is a menadione ring. Plants and bacteria can synthesise this ring but animals can’t. Vitamin K1 is also known as phylloquinone and is found in plants. Vitamin K2 is also called menaquinone and is made by bacteria, while K3 are the menadione compounds that are produced synthetically.


Vitamin K is involved in blood clotting as it is needed for the synthesis of prothrombin by the liver which is the inactive precursor of thrombin. Thrombin converts fibrinogen in the blood to fibrin which holds the blood clot together. Before prothrombin can be activated it must be bound to calcium. Vitamin K deficiency results in low levels of the amino acid responsible for this binding.


Good sources of vitamin K in the diet include fresh leafy plants; animal based feeds such as egg yolk, liver and fishmeal; as well as bacteria in the gut. It generally quite stable but may be rapidly destroyed by light.
Normally, the bacteria that live in the animal’s digestive tract produce vitamin K needed. However, animals that are being treated with antibiotics that may reduce the amount of vitamin-K producing bacteria may need vitamin K supplements. This is also true for birds that are housed on wire mesh and aren’t able to perform coprophagy. This is because faeces is a source of Vitamin K that has been produced by the bacteria in the gut. In birds, the vitamin K that is synthesised by bacteria may not be able to be absorbed because the site of production is too distal for adequate absorption.

Supplements are also required for animals that may be consuming vitamin K antagonists. An example of this is dicoumarol which is produced by fungi found in weather-damaged legume hay or silage.

Vitamin K Deficiency

Symptoms of vitamin K deficiency are not reported in ruminants, horses and pigs because of the bacteria in their gut which produces adequate amounts of this vitamin.
In birds, signs of deficiency include anaemia and delayed blood clotting.

Vitamin K Toxicity

There is little risk of vitamin K poisoning except when high levels are given by injection. 

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

Friday, 22 March 2013

Acute Inflammation: Outcomes and Terminology

Hello :) In this post we'll take a look at the terminology used to describe the classifications of acute inflammation. We'll also discuss the possible outcomes of this process. 
 Outcomes of Acute Inflammation

There are four possible outcomes of acute inflammation: complete resolution, healing via fibrosis, abscess formation, or the progression to chronic inflammation. The outcome depends on the severity of the tissue damage, the ability of the cells to regenerate as well as the characteristics of the damaging stimulus. 

A few events are involved in the resolution of acute inflammation. Firstly, normal vascular permeability it returned. Oedema fluid and proteins are then drained into the lymphatics and this may also be consumed by macrophages through pinocytosis. Dead neutrophils and necrotic debris are also phagocytosed and the macrophages are disposed of. Macrophages also release growth factors which initiate the process of repair.  

Types of Acute Inflammation

The classification of an acute inflammatory lesion depends on the anatomical site and nature of the exudate. The suffix "itis" is added to the end of the name of the organ to show that it is inflamed. For example, encephalitis, tonsillitis, meningitis, hepatitis etc. 

The major component of the exudate is then added to this base word. There are seven types of exudate that may be seen (the name of the exudate is in blue, examples are in red):
  1. Serous: this is serous fluid with increased amounts of cells and proteins. It is straw coloured and clots upon exposure to air (due to increased amounts of clotting factors). It is the mildest form of exudate. It is commonly seen in serous cavities (eg abdomen, thorax, pericardium etc) and may also be seen in burns. 
  2. Serofibrinous: this is similar to serous exudates but has strands and flecks of fibrin. It is associated with an increased inflammatory response. It may be seen in feline infectious peritonitis
  3. Fibrinous: this results from more extensive vascular leakage and clotting. In severe cases, the fibrin deposits within or over organs appears as white-tan, sticky, flaky material which may adhere to the material. It looks like butter has been smeared over the tissues. These exudates act to localise the lesion and as a scaffold for cell migration and healing. However, the reaction may become severe enough to enhance the initial injury (eg. fibrin deposition in the pericardium can restrict movement of the heart. An example of fibrinous inflammation is fibrinous pneumonia caused by acute Mannheima haemolytica infection.
  4. Mucoid or Catarrhal: the tissue response consists of the secretion or accumulation of a thick gelatinous fluid containing abundant mucous and mucins from a mucous membrane. It may be seen in mild forms of bronchitis and tracheitis.
  5. Haemorrhagic: this contains increased numbers of erythrocytes and appears as varying shades of dull red, brown or black. It is seen where there is damage to blood vessels. Eg  colitis in horses
  6. Suppurative or Purulent: This type of exudate contains large numbers of dead and dying neutrophils and necrotic tissue debris which is liquefied by the neutrophils. It is often referred to as 'pus' and is seen with bacterial infections. It appears as a thick, pasty-white (yellow/green/brown) exudate. 
  7. Diphtheritic: this occurs on mucous membranes which become necrotic and interwoven. Within the necrotic tissue is a fibrinous exudate. It appears as a sticky, yellow-brown exudate which adheres to the underlying surface. It may be seen in herpes virus in chickens.    
 The classification of the inflammation can be made more specific by including the time frame (acute, sub-acute or chronic). Eg acute suppurative hepatitis.

That's it for this post! See you next time :)

Acute Inflammation: Soluble Mediators

Soluble mediators, also known as chemical mediators, are the switches that cause the inflammatory response to be turned on and off. These substances are messengers that act on blood vessels and cells and control their actions. Their four main functions are to cause arteriolar dilation, increase vascular permeability, act as chemoattractants for leukocytes and to stimulate pain. There are three varieties of soluble mediators: circulating chemical mediators, those released from cells, and receptors on the surface of cells. In this post, we'll take a look at each type of chemical mediator as well as how they work together in the inflammatory response.

Circulating Soluble Mediators

These mediators are present in the plasma as precursors and have to be activated before they will work. There are three groups of these proteins that are inter-related: the complement, kinin and clotting systems. Together these are known as the plasma proteases. Each system has a series of proteins which become activated in sequence to generate a large number of chemical mediators which act to greatly increase the acute inflammatory response.

Complement Cascade

This is a sequence of molecular events that occur in the vascular system. It causes inactive plasma proteins which are produced by the liver to be activated after a tissue has been injured. The cascade triggers the formation of many molecules which have proinflammatory, chemotactic, opsonising (allowing foreign substances to be phagocytosed), permeability and microbicidal effects.

The cascade eventually causes the formation of a membrane attack complex (MAC). The MAC forms a tube like structure which perforates the cell membranes of foreign cells and some host cells. This allows water, small molecules and ions to pass into the cell via osmosis and cause lysis. 

The video below shows an interesting illustration of this process.


The Kinin Pathway

Like the clotting cascade, the kinin pathway is activated by factor XII (also known as Hageman Factor) which is triggered by contact with basement membranes or endotoxins. The kinin pathway consists of proteins which are split from their precursors by enzymes known as kallikreins which may be derived from tissue or plasma. There are several kinins but bradykinin is the major product of the system. Bradykinin causes vasodilation, pain, increased vascular permeability and smooth muscle contraction. Bradykinin  can be broken down by kinase to control its effects. 

A substance called prekallikrein enhances the activation of Hageman factor and amplifies the system.

The Coagulation Pathway

 This was discussed in detail in this post. The end-product of this pathway is fibrin which essential in the inflammatory response as it acts as a mechanism for inflammatory cells to use to assist migration. It serves to localise the agents which cause inflammation and also assists in healing by increasing the proliferation of fibroblasts and collagen production. 

Fibrin degradation products (FDPs) also have several actions:
  • they are chemoattractants for neutrophils,
  • they increase vascular permeability, 
  • smooth muscle contraction
  • inhibit the action of thrombin on fibrinogen
  • Inhibits platelet activation and adhesion.

 Cell-Derived Chemical Mediators

These mediators may exist pre-formed in granules or the cells may be stimulated to synthesise the chemical mediators.

Preformed Chemical Mediators

There are two groups of preformed chemical mediators: vasoactive amines and neuropeptides.

Vasoactive Amines:

These are histamine and serotonin which are released by mast cells, basophils and platelets. They cause arteriolar dilation, extravascular smooth muscle contraction, venule permeability by rounding up endothelial cells, and pain. Several factors cause the release of these substances including physical injury, immune reactions, fragments of the complement cascade, neuropeptides, cytokines, and histamine-releasing proteins from leukocytes. Histamine is also a chemoattractant for eosinophils.  

They are rapidly degraded and histamine receptors become refractory after 30 minutes.


Neuropeptides have a similar role to vasoactive amines and are small peptides found in the central and peripheral nervous systems. An example is Substance P which function to transmit pain signals, regulate blood pressure, stimulate secretion by immune cells and increase vascular permeability. 

Induced Chemical Mediators

These require cells to be induced to make them. There are 5 groups of these mediators: Cytokines, Eiconasoids and platelet activating factors, Nitric Oxide, Oxygen Derived Free Radicals, and Heat Shock Proteins.


This group includes tumour necrosis factor (TNF), interleukins, interferons and chemokines. These substances are able to activate leukocytes which produce more cytokines and amplify the response. They may act locally or at long distances. The major cytokines that mediate inflammation include interleukins, and Tumour Necrosis Factor. They are stimulated by bacterial endotoxins and immune complexes, physical injury and other inflammatory stimuli. Their most important actions are:
  • endothelial activation
  • leukocyte activation
  • fibroblast recruitment
  • priming of neutrophils.  
Other cytokines that are involved in acute inflammation include interferons and chemokines.

The interleukins and TNF work together in the acute phase response. When gram negative bacteria activate macrophages interleukins and TNF are released. This has several effects which may:
  • act on the liver and cause it to produce acute phase proteins (which can be detected clinically)
  • act on the precursor cells in the bone marrow to increase the production of neutrophils and may cause increased phagocytosis by neutrohils. 
  • act on the brain to induce fever, decrease appetite and increase the desire to sleep.
  • At very high levels, these substances have systemic effects leading to shock.


These are derived from polyunsaturated fatty acids within cell membranes. During the metabolism of eiconasoids, cyclooxygenase and lipoxygenase convert arachidonic acid into four types of eiconasoids: prostaglandins, thromboxanes, leukotrienes, and hydroxyacids.

These substances have a variety of effects on the body including vasodilation, chemotaxis of neutrophils and increased vascular permeability. 

Corticosteroids prevent the first step (phospholipase) of this metabolism and prevent the formation of leukotrienes and prostaglandins. Non-steroidal anti-inflammatories (NSAIDs) inhibit cyclooxygenase and prevent the formation of prostaglandins. 

Nitric Oxide

This is produced by endothelial cells, macrophages and neurons and causes vascular smooth muscle relaxation and vasodilation. It also reduces platelet aggregation and adhesion, inhibits mast-cell induced inflammation, regulates the recruitment of leukocytes and facilitates microbial killing.

Oxygen Derived Free Radicals

These are released from leukocytes during the inflammatory process. Low level release can increase the expression of cytokines and leukocyte adhesion molecules and amplify the inflammatory response. High levels can cause damage to the body.

Heat Shock Proteins

These cells may be induced by infection with intracellular pathogens. They may be referred to as "molecular chaperones" as they modify the destiny and function of other proteins. They prevent the premature and senseless interaction between molecules and assist in the folding and unfolding of proteins. 

Receptors on the Surfaces of Cells

 The receptors on the surfaces of cells involved in acute inflammation belong to a family called the 'pattern recognition receptors' (PRR). These receptors detect the molecular patterns that are characteristic of certain types of microbial infections by recognising the patterns of molecules that are contained in the DNA of pathogens. Activation of PRRs results in an increase in the production of inflammatory mediators, increased phagocytosis, in addition to an increased Th1 lymphocyte response and an increase in the number of chemokine receptors and chemoattractants. 

 There are many pattern recognition receptors, however a classic example is the TLR4 (Toll-like Receptor 4). This receptor only binds to the lipopolysaccharide of bacteria and results in the production of cytokines and reactive oxygen intermediates which activate leukocytes which then kill the microbes. 

So in summary, there are three categories of soluble mediators: plasma-derived mediators, cell-derived mediators, and receptors on the surfaces of cells. These categories are inter-related and work together to cause acute inflammation. 

That's all for now, please let me know if you have any questions :)

Sunday, 17 March 2013

Nutritional Secondary Hyperparathyroidism

In this post we'll take a look at the pathogenesis behind secondary nutritional hyperparathyroidism as well as the clinical signs of the disease and how it can be treated. 

This is a disease caused by the excess production and release of parathyroid hormone (PTH) into the blood in response to low calcium levels in the blood. 


Nutritional Secondary Hyperparathyroidism (NSH) is caused by several factors including:
  • diets with an absolute calcium deficiency, 
  • diets with low calcium bioavailablilty (due to the presence of phytate and oxalates), 
  • excess phosphorus intake, 
  • and low calcium to phosphorus ratios

Low calcium levels cause the release of PTH in order to increase the amount of calcium in the blood and maintain homeostasis. This results in increased calcium reabsorption from the kidneys and increased resorption from bone. In addition, there is increased conversion of vitamin D to Calcitriol which increases calcium reabsorption from the gut and resorption from bone. 

When calcium and phosphorus are mobilised from the bones, the mineral matrix is replaced with connective tissue. Excessive resorption of bone leads to osteodystrophia fibrosa. 

Clinical Signs

Young, growing bone is most susceptible to osteodystrophia fibrosa and may become brittle. Fractures may also be common and are unlikely to heal well. In addition, excessive fibrous deposition in the bones may leads to swelling and softening of the bone which is more severe in non-weight bearing bones (such as the head and jaw – this is why this NSH is sometimes called ‘big head disease’ in horses). The spine and long bones become affected in chronic cases. Lameness is also common. 

Interestingly, blood concentrations of affected patients do not reflect a dietary deficiency of calcium. This is because the PTH works to increase plasma calcium levels. Plasma inorganic phosphorus levels in the blood may also be higher than normal. Serum alkaline phosphatase is also increased. 


Treatment involves correcting the ration to supply sufficient calcium, maintain the dietary Ca:P between 1:1 and 1:2, and reduce oxalates and phytates.

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