Metabolism
is derived from the Greek word for “change” it represents the sum of the
chemical changes that convert nutrients the “raw material” necessary to nourish
living organisms into energy and the chemically complex finished products of
cells (Garrette et al. 2005).
Metabolism consist of literally
hundred of enzymatic reactions organized into discrete pathways, these pathways
proceed in a stepwise fashion transforming substance into end products through
many specific chemical intermediates (Garrette et al, 2005).
Nutrients of Human metabolism,
Carbohydrate, lipids and proteins are the major constituents of foods and serve
as fuel molecules for the human body. The digestion of these nutrients in the
alimentary tract and the subsequent absorption of the digestive end products
make it possible for tissues and cells to transform the potential chemical
energy of food into useful work (Andrea et
al, 2010).
The
major absorbed end product of food digestion are monosaccharide mainly glucose
(from carbohydrate) monoacyglycerol and long chain fatty acids (from lipid) and
small peptides and amino acids (from protein). Once in the blood stream,
different cell can metabolize these nutrients (Andrea et al, 2010).
CARBOHYDRATE
METABOLISM
After meal, carbohydrates are stored mainly in the liver
and in the skeletal muscles as polymers of glucose known as glycogen. The
glycogen store in muscle is used by contracting muscles and cannot be converted
to glucose because of the absence in muscles the enzyme glucose-6-phosphatase
which converts glucose-6-phosphate to glucose (Ezeilo, 2002). On the other
hand, the glycogen store in the liver serves for the maintenance of blood
glucose concentration in between meals for use by other tissues (Ezeilo, 2002).
The conversion of glucose to glycogen or the synthesis
of glycogen is known as glucogenesis while the break down of glycogen to
glucose (in the liver) or lactate and pyruvate (in muscles) is known as
glycogenolysis (Ezeilo, 2002).
Anaerobic glycolysis in the cytoplasm
The
process for the catabolism of glucose begin in the cell cytoplasm with an
anaerobic phase called glycolysis in which the glucose molecule is split into 2
equal halves of 3-carbon chains which are converted to acids (Pyruvic or
lactic). This is the embden-mejerhof pathway for glycolysis and it generates a
net energy of 2ATP molecules per molecule of glucose (Ezeilo, 2002).
Grafted into the EMP glycolysis, is
another cytoplasmic pathway for glycolysis known as the pentose phosphate
pathway which occurs in many tissues, but not in skeletal muscles. This pathway
oxidizes the carbonation in glucose one at a time, producing the reducing agent
known as NADPH required for the synthesis of fats and steroids as well as
essential intermediates for synthesis of nucleotides (Ezeilo, 2002).
Oxidative phosphorylation in the
mitochondria
In
the presence of oxygen, lactic acid is not formed instead pyruvic acid enters
mitochondria where it is completely oxidized to carbon dioxide (Co2)
and water (H2O). The process in the mitochondria leading to this
complete breakdown of pyruvic acid constitute the Kreb’s cycle (citric acid
cycle) and the H+ released during the oxidation is passed through
the flavoprotein-cytochrome respiratory chain cycle to combine with oxygen to
form water (Ezeilo, 2002).
The passage of H+ through
the respiratory chain is coupled with the phosphorylation of ADP to ATP. From
the citric acid cycle, 36 molecules of ATP are additionally released from the
full oxidation of pyruvic acid, which brings to a total of 38ATP molecules from
one glucose molecules when glucose is broken down in the presence of oxygen
(Ezeilo, 2002).
Transport of glucose into cells
Three
mechanisms by which glucose enters the cells:
1) Secondary
Active transport: In the small intestines and in the nephrone, glucose
transport is linked to the facilitated diffusion of sodium by a symport carrier
protein known as SGLT1. The transport derives energy from a primary active
transport of sodium on the basal and basolateral membrane hence it is also
known as secondary active transport (Ezeilo, 2002).
2) Simple
Diffusion: In the liver, which receives all the glucose absorbed from the gut,
the cells are freely permeable to glucose and entry is by simple diffusion
(Ezeilo, 2002).
3) Facilitated
Diffusion: Glucose uptake in skeletal muscle, cardiac muscle, adipose tissue,
brain, placenta, red blood cell and to some extent in the kidney and small
intestines occurs by (Uniport carrier) facilitated diffusion. The glucose
transported for facilitated diffusion in their locations are designated as GLUT1
through GLUT4 which are quite distinct from sodium cotransporter. GLUT1 is found
in all cells, GLUT2 in liver, pancreatic β-cell, intestine and kidney, GLUT3 in
the brain and GLUT4 in the insulin sensitive transporter in muscles and adipose
tissues (Ezeilo, 2002).
FAT METABOLISM
The
triglycerides is a lipid found in plants and animals and there are major energy
reserve and the principal natural derivative of glycerol found in animals
(Ramlingan, 2001).
The triglycerides derived from
intestinal absorption of fat are contained in complexes known as chylomicrons,
together with triacylglycerol synthesized
by the liver are transported in the blood as very low density lipoprotein
(VLDL, rich in lipid (Ezeilo, 2002). They must be hydrolyzed into fatty acids
and glycerol before they can be catabolized. The hydrolysis of these
triacylglycerol occurs intervascularly by the action of vascular lipoprotein
lipase located in the capillary endothelium of various organs (heart, adipose
tissue, lungs) (Ezeilo, 2002).
The free fatty acids are transported
by albumin and metabolized as fuel extensively by the heart, but practically
all tissues can also oxidize them to co2 and H20, in
adipose tissue, fatty acids may be stored in fat cell as triacylglcerides, the
triacylglycerides, are broken down into fatty acids (FA) and glycerol (Ezeilo,
2002). The enzyme for intracellular hydrolysis of triacylyglycerides is the
CAMP-dependent kinase regulated lipase known as the hormone sensitive lipase
(Ezeilo 2002).
Oxidation of fatty acids
The
first step in the oxidation of fatty acid is the activation of the fatty acid
by a combination with co enzymes A (catalyzed by acyl. COA. Synthetase, with
energy from ATP) to from fatty acid COA. The activated fatty acid enters the
mitochondria, and in the case of long chain fatty acid which cannot enter
readily, they combine with a transporter substance known as carnitine which
ferries them across (Ezeilo, 2002). The oxidation of the activated fatty acid
within the mitochondria occurs at the β - carbon hence it is called a β-
oxidation, and leads to the production of β - keto fatty acid COA (Ezeilo,
2002).
Next is the process of thiolysis in
which terminal 2 carbon units are cleaved off by the action of a β - keto
thiolase utilizing further COA. The 2- carbon units remain attached to COA and
are known as acetylCOA, which is oxidized on the citric acid cycle to CO2
and H2O. The total energy yield from complete oxidation of fatty
acids is 9kcal/g compared with 4kcal/g for carbohydrate or protein (Ezeilo,
2002).
PROTEIN METABOLISM
Unlike
carbohydrate and fats which serves principally to provide energy and are stored
in cells, proteins serve principally to provide amino acids which are used to
build and maintain tissues (one half of the dry weight of the body protein);
from enzymes, hormones, anti- bodies and provide some amount of energy (Ezeilo,
2002). There are no special stores of proteins, instead tissue proteins are
being constantly synthesized and degraded and the amino acid pools in the blood
and tissue derived from amino acids from the gut or from breakdown of tissue
proteins more rapidly than others example the liver, intestinal mucosa and
blood. Although, the proteins turnover rate in skeletal muscle is relatively
low, the overall effect is large because of its large size (Ezeilo, 2002).
In general, amino acids in excess of
the requirements for the formulation of structural proteins, enzymes, hormones
etc are deaminated in the liver to form different amino acids. The ammonia is
converted to urea, while the keto acids are eventually oxidized to Co2
and H2o with a release of energy which is stored as ATP. Adequate
supplies of carbohydrate and fat spare the utilization of protein for energy,
but during fasting as the glycogen store is used up, energy is derived from fat
and proteins with fat supplying about 85%. When the fat reserves are exhausted,
and energy supply depends on protein alone, the large increase in tissue
destruction leads rapidly to death (Ezeilo, 2002).
PHYSIOLOGY
OF THE WHITE BLOOD CELL
White blood cells are colourless transparent
cells which unlike other blood cell contain nuclei (Ezeilo, 2002). They are
cells of the immune system involved in defending the body against both
infectious diseases and foreign material (Leafeur, 2008).
There are 5 different types of
leucocytes, but they are all produced and derived from a multipotent cell in
the bone marrow as a hematopiotic stem cell. The normal count of white blood
cell is somewhere between 4,000 and 10,000/mm3. They have a short
lifespan ranging from a few days to a few weeks. These cells offer defensive
properties to blood in order to fight against infections and the invading
foreign bodies such as bacteria and viruses (Reshman, 2011). If the white blood
cell is below normal, it is known as “leucopenia” while if the number of
leucocytes increases to more than the normal count, the condition is known as
“Leucocytosis”. There may be a decrease in individual leucocyte percentage eg
Neutropenia (decrease in neutrophil). The reduction of all types of white blood
cell is known as “Panleukopenia” (Reshman, 2011 and Maton et al 2008).
CLASSIFICATION OF LEUCOCYTES
1) Morphological Grouping.
2) Functional Grouping.
Morphological grouping: Morphologically, white blood cells
are classified into granulocyte and Agranulocytes based on the presence and
absence of granules (Ezeilo, 2002).
1) Granulocytes
are leucocytes which have granules in their cytoplasm namely neutrophil,
basophil and eosinophil. The individual name is derived from the color of the
granules when stained with Ramanowsky stains which contains a basic dye
(methylene blue) and an acid like stain (eosin) (Ezeilo, 2002). The granulocyte
have segmented nuclei, hence they are called poly morphonuclear leucocytes (Gartner
et al, 2007)
2) Agranulocytes
: Are leucocytes characterized by the apparent absence of granules in their cytoplasm. Though they lack
granules, these cells do contain non – specific azurophilic granules which are
lysosome (Gartner et al. 2007). The
cells include lymphocyte, monocytes and macrophages, they are also called
mononuclear leucocytes (Gartner et al.
2007).
Functional classification
Leucocytes
are mainly grouped into phagocytes and lymphocytes (Ezeilo, 2002). Phagocytes destroy
foreign bodies by engulfing and digesting them within the cell (phagocytosis).
These group include all leucocytes except lymphocytes. Lymphocytes destroy
foreign bodies by secreting antibodies against them or by directly killing or
neutralizing them (Ezeilo, 2002).
Neutrophils
Neutrophils defend the body against bacterial or
fungal infection and other very small inflammatory process that are usually
first responders to microbial infection (Gartner et al. 2002). They are the most common cell type seen in the early
stages of acute inflammation, and make up 60 – 90% of the total leucocyte count
in human blood (Alberts, 2005).
Mature neutrophils are characterized
by multiple segmentation of the nucleus, beginning with 3 lobes joined by
chromatin strand and increasing to 5 lobes as the neutrophil gets older. The
cell is 10 – 15cm in diameter (Ezeilo, 2002) with lifespan of about 4 – 5 days
(Pillay et al, 2010).
Eosinophils
Eosinophils
primarily deal with parasitic infections. Eosinophils are also the predominant
inflammatory cells in allergic reactions. The most important causes of
eosinophilia include allergies such as asthma, hay fever and hives and also
parasitic infection. Their nucleus is bilobed and their cytoplasm is full of
granules with a pink – orange color when stained with eosin (Ezeilo, 2002).
Basophils
Basophils are chiefly responsible for allergic and
antigen response by releasing the chemical histamine causing vasodilation. The
nucleus is bilobed or trilobed, but it is hard to see because of the number of
coarse granules which hide it. They are characterized by their large blue
granules (Ezeilo, 2002).
Lymphocytes
Lymphocytes
are much more common in the lymphatic system. Lymphocytes are distinguished by
having a deeply staining nucleus which may be eccentric in location and a
relatively small amount of cytoplasm.
The
blood has 3 types of lymphocytes.
β
- Cells: β – cells make antibodies that bind to pathogens to enable their
destruction. They do not only make antibodies that bind to pathogens, but after
an attack, some B – cells will retain the ability to produce an antibody to
serve as a memory system. (Pantaleo et al,
1994).
T
– Cells
1) CD4+
(helper) : T – cells having co – receptors CD4 is known as CD4+ T cells. These
cells bind with the antigen having MHC11 receptors on its surface. They present
this antigen to β – cells. β – cells produce anti – bodies to destroy antigens.
The CD4+T cells is also known as antigen presenting cells. T – cells co –
ordinate the immune response and are important in the defense against
intracellular bacteria (Pantaleo et al,
1994)
In acute HIV infections, these T – cells are the main
index to identifying the individual’s immune system activity. Research has
shown that CD8+ cells are also another index to identifying human’s immune
activity (Pantaleo et al. 1994).
2) CD8+
cytotoxic T cells: Are able to kill virus infected and tumor cells. T cells
having co – receptors CD8 are known as CD8+ T cells. These cells kill damaged
or cancerous cells. CD8 binds with MHC 1 receptors of damaged cells (carrying
antigens). All nucleated cells possess MHC1 on its surface (Pantaleo et al, 1994).
3) YdT
–cells: possess an alternative T cell receptors as opposed to CD8+ and CD8+αβT
cells and share characteristics of helper T-cells, cytotoxic T-cells and
natural killer cells (Pantaleo et al,
1994).
4) Natural
killer cells: Natural killer cells are able to kill cells of the body which are
displaying a signal to kill them, as they have been infected by a virus or have
become cancerous (Pantaleo et al,
1994).
Monocytes: Is usually the largest leucocytes and is about 15 –
20um in diameter. The Nucleus is often indented or kidney shaped and tends to
be pushed to one side of the cell (eccentric). It has a fine meshwork of
chromatin which distinguishes it from large lymphocytes.
The cytoplasm has blue – grey
frosted appearance after staining and may be vacuolated (Ezeilo, 2002).
WHITE BLOOD CELL COUNT
Is
the number of white blood cells in a volume of blood. Normal range varies
slightly between laboratories but it is generally between 4,300 and 10,800 cells
per cubic millimeter (cmm). This can also be referred to as the leucocyte count
and can be expressed in international units as 4.3 to 10.8 x 109
cells per litre (Siamak, 2011).
White blood cell differential counts
comprises of several different types of cells that are differentiated or
distinguished based on their size and shape. The cells on a differential counts
are granulocytes, lymphocytes, monocytes, eosinophil and basophils (Siamak,
2011).
The
differential and white blood cell counts in Caucasians and African (mean values
for differential counts in bracket) is shown below.
WBC
type
|
Caucasians
|
Africans
|
Total
WBC
|
4500
– 11,000/ul
|
2000
– 9000/ul
|
Neutrophil
%
|
50
– 70 (65)
|
10
– 60 (40)
|
Lymphocytes
%
|
20
– 40 (25)
|
22
– 80 (45)
|
Monocytes
%
|
2
– 8 (6)
|
0
– 7 (4)
|
Eosinophils
%^
|
1
– 4 (3)
|
0
– 30 (10)
|
Basophils
%^
|
< 1 %
|
<
1 %
|
(Ezeilo,
1972)
FACTORS THAT AFFECTS THE WHITE BLOOD CELL
COUNT
1) Age
2) Exercise
3) Pregnancy
4) Diurnal variation and menstrual cycle
5) Emotion
6) Nutritional factors
Majority of Negro Africans have on the average lower leucocyte counts
compared with those of Caucasians. The low counts are due to lower absolute
counts of neutrophils in the Africans. In addition, their eosinophil counts are
higher. This alters their differential W.B.C values such that the lymphocytes
rather than the neutrophil, is the most abundant leucocyte (Ezeilo,2002).
Studies have shown that Africans are
not neutropenic at birth, and when their diets were changed to Caucasian
pattern, remarkable corresponding changes occurred in their leucocytes pattern:
an increase in their neutrophil counts with a fall in the eosinophil counts.
Studies in experimental animals have shown that changes in diets can have
profound effects on blood leucocyte pattern in animals. The neutropenia is
therefore believed to be of dietary origin (Ezeilo, 2002).
DISORDERS OF THE WHITE BLOOD CELLS
1) Leukemia: Also called blood cancer is a
group of disease that is caused due to increased number of blood cells.
Uncontrolled growth of any blood cell leads to leukemia. Most forms of the
disease are caused due to high white blood cell counts. The bone marrow
produces a large number of immature white blood cells that cannot function
properly. The following is a list of different types of leukemia that occurs
due to increased white blood cells in the blood.
1) Acute
myeloid leukemia
2) Chronic
myeloid leukemia
3) Acute
lymphocyte leukemia
4) Chronic
lymphocyte leukemia (Mayuri, 2012)
2) Lymphoma: is characterized by malignant
tumors of lymphocytes that are usually not associated with a leukemia blood
picture. Instead enlargement of lymph nodes, spleen, both are characteristics.
The lymphomas are classified into 2 main groups;
1) Hodgkins Disease.
2) Non – Hodgkin Disease.
Hodgkin disease usually begins with a painless swelling
of any lymph nodes; it may involve lymph nodes anywhere in the body.
Non
– Hodgkin lymphoma arises from either β – lymphocytes or T– lymphocytes
(Maxwell et al 2010).
3) Leucocytosis: Means an increase in
white blood cell counts above the normal range. It may be due to an increase in
any cell type eg Neutrophilia or a lymphocytosis and may be physiological or
pathological. Pathological leucocytosis may be due to inflammation in which mediators
are released from macrophage, neutrophils, endothelial and fibroblast cells
which stimulate the marrow to increase leucopoiesis or it may be due to a
neoplastic disorder of leucocyte production, a condition known as leukemia
(Ezeilo, 2002)
4) Leucopenia: means a decrease in white
blood cell count below normal which may be due to a fall in a particular cell
type, e.g. Neutropenia. A sever Neutropenia (Neutrophil count < 500/ul) may
cause recurrent pyogenic infections especially in the areas where micro –
organisms are in contact with the body, the skin, the anus, mouth and
respiratory passages (Ezeilo, 2002).
EFFECTS OF CARBOHYDRATES, PROTEIN AND LIPIDS
ON THE LEUCOCYTES
1) Sanchez
et al (1973) reported the “role of
sugars in human neutrophilic phagocytosis”, showing that ingesting 100g of
simple sugar lowers white blood cell activity for up to 5 hours. He got this
result using processed honey, table sugar and processed orange juice. This
translates into a 50% reduction in the ability of W.B.C to engulf bacteria.
Lowered W.B.C activity means that the immune system and its ability to fight
infection is impaired.
2) Sugar raises
the insulin level which inhibits the release of growth hormones which in turn
depresses the immune system. An influx of sugar into the blood stream upsets
the body’s blood sugar balance triggering the release of insulin, which the
body uses to keep blood sugar at a constant and safe level. Sugar can produces
a significant rise in triglycerides which have been linked to cardiovascular
diseases (Bernstein, 1977, Leeper, 1998).
3) The
effects of dietary proteins and amino acid on the immune system have been
documented previously. In particular, dietary caesin proteins are known to
enhance the immune system and promote host protection against the development
of intestinal cancer (Wong et al,
1995, Mcintosh et al, 1995, Kunz et al . 1990, Parker et al 1984).
Soy is a common plant source of dietary proteins for
humans and many mammalian species. It contains a range of phytochemical such as
Isoflavons, which influence the activity of the immune system and have anti –
tumor activities in animals. For example, Isoflavones influences the signal
transduction process of macrophages and other phagocytic cells and the activity
of cytotoxic T – lymphocyte, thus influencing both non – specific and specific
immune response (Rumsey et al, 1994
and steward et al, 1997).
4) White blood
cells require proteins from the diet to combat antigens. One of the ways immune
cells fight against pathogens is by increasing their numbers.
To increase immune cell proliferation, you need
proteins and amino acids. To achieve the healthiest possible immune system,
consume 0.8 – 1g of proteins per kg of body weight (Eric, 2010).
5) Diets
containing different amounts of caesin (3, 6, 9 and 18%) were fed ad libitum on
rats to determine the effects of diet varying in quantity and quality on the
white blood cell. At the 3% level, a decrease occurred in the white blood cell
count where as the other three (6, 9 and 18) percentages initiated a
regeneration of leucocytes, its degree being more or less in proportion to
casein content. Therefore protein increases the white blood cell regeneration
(Guggenheim 1949).
6) Johnson
et al. (2001) studied the influence
of westernized and traditional African diets on biochemical and haematological
profiles in vervet monkeys (cercorpithecus aethiops). 12 adult male vervet
monkeys, all over 4 years of age and weighing more than 5kg each, were divided
into 2 groups of 6 individuals. These monkeys were fed for 8 weeks on diets
containing milk solids (17.2%) maize and legume (17.4%) as source of protein.
High protein diets had no significant effect on serum biochemical indices and
heamatological parameter (W.B.C) for the African diet. Compared to the group
that were given the traditional African food, the animals on the western type
milk solid diets showed significant elevation in a number of important
biological indicators like (Total cholesterol, low density lipoprotein and
triglycerides).
7) The
effect of diet on the differential white blood cell counts in rat was studied
by Ogunranti, 1994. Twenty rats were divided into 4 dietary groups. Group 1(Control) rats fed on pallets, group 2
rats fed on Millet, group 3 rats fed on
Peanuts and group 4 rats fed on a
special diet containing high cholesterol and saturated fatty acids from
coconuts, egg yolk, milk and Danish butter. After 3 months, group 4 rats had
significantly higher total white blood cell counts and percentage neutrophils
in addition to higher serum cholesterol levels and higher weights.
8) Haematological
values determined in 3 groups of Africans on different diets were compared with
those of groups of European and Asians. Neutropenia was most common in African
on native diets (88%), less common in those who periodically had European diets
(55%) and least common (25%) in those having only a European diet. Lymphocyte
and eosinophil values were higher in the African groups, but the values for
Africans on European diets were closest to those of Europeans and Asians. These
results suggest that Neutropenia in Africans is non - genetic in origin
(Ezeilo, 1972)
9. Oji,
2011 Studied the influence of different diets on blood leucocyte patterns. He
reported that diets high in carbohydrates and low in saturated fat and animal
protein are suggested to be responsible for Neutropenia in Africans.