physiology

الرحيم الرحمن الله بسم

” الل�ه ِإ ل�ى يه ِف ُع�وَن� َج� ُت�ر� ا َي�و�ًم� وا اُت�ُق� َو�اَل� َو�ُه�م� َب�ْت� َك�س� ا ًم� َن�ْف�ٍس% َك�ُّل( ُت�و�ِف�ى ُث�م�

“َي�ْظ�ل�م�وَن�

الَبُقرة , 281َية آسورة

Nutrition, Digestion, MetabolismNutrition

What is Nutrition:Nutrition is the study of how our bodies use the food that we eat.What are Nutrients:Nutrients are chemical substances in food that require for performance of various life activities, and necessary for reproduction and growth. One of the most important function of macronutrient is the production of energy. The balanced diet:It is the diet which must be composed of carbohydrates, lipids, proteins, vitamins, minerals and water in proportionate amounts. We require food:■ To provide fuel for our body or energy to accomplish daily activity (Carbohydrates & Lipids).■ To provide the necessary materials for building or maintenance of body tissue and organs. (Proteins). ■ To provide the substances needed to regulate body functions and vital processes. (Vitamins, Minerals & Water).Food Types and Feeding Mechanisms:Animals fit into one of the following three dietary categories. Herbivores: such as cows and many snails, eat mainly autotrophs (plants, algae). Carnivores: such as sharks, spiders, and snakes, eat other animals. Omnivores: such as cockroaches, bears and humans consume animal and plant or algal matter.

Nutrients are classified into:Macronutrients: Nutrients required in relatively large amounts, e.g. carbohydrates,

lipids, and proteins.Micronutrients: Nutrients required in smaller amounts, e.g. vitamins and minerals.

Carbohydrates Carbohydrates are organic compounds which contain carbon, hydrogen, and

oxygen in which the last two elements are always present in the same proportions as in water (CnH2nOn).

Classification of carbohydrates:They are classified according to the number of units of mono-sugar into:

(1) Monosaccharides: Monosaccharide composed of a single sugar unit. They are classified according

to the number of carbon atom into: trioses (3C), tetroses (4C), pentoses (5C) as ribose sugar , hexose's (6C) as glucose (presents in diet in the form of disaccharides and polysaccharides, Galactose (presents in the form of lactose) & fructose [in fruits, honey (50% fructose, 50% glucose].

(2) Disaccharides: Disaccharide is formed by the condensation of two monosaccharides with

elimination of a molecule of water and formation a glycosidic bond.■ (Milk sugar) Lactose (glucose + galactose) ■ (Cane sugar) Sucrose (glucose + fructose). ■ (Malt sugar) Maltose ( glucose + glucose).

(3) Polysaccharides: On chemical bases, polysaccharides can be divided into two broad classes:

a- Homopolysaccharides: The constituent sugars are the same. Examples are:■ Glycogen [12 -18 units of glucose]. It is found in animal cells (In

human and other vertebrates. Glycogen is stored primarily in the liver and muscle cells.

■ Starch [200 - 300 units of glucose]. It is found in plant cells. ■ Cellulose [up 2000 units of glucose]. It is found in plant cell wall.

b- Heteropolysaccharides: The constituent sugars may take several forms.

Examples are:■ Chitin: It is found in arthropod shells, cuticle of mollusks and

annelids. It is a polymer of acetylglucosamines units. ■ Hyaluronic acid: It is found in synovial fluids of joints, vitreous

humor of eye,….. It contains N-acetylglucosamine and glucuronic acid.

■ Chondroitin sulfate:It is found in tendons, cartilage, and bones.

An example shows the chemical structure of glucose (a monosaccharide carbohydrate)

Biological significance of carbohydrates:1- They form about 50-60% of human diet. 2- Stored as glycogen in both liver(6%) and

muscles(1%).3- Act as a source of energy (4.2 Kcal/g).4- They may be converted to fats or proteins.5- The pentose (ribose) sugar is a part of DNA

and RNA.6-Cellulose (dietary fibers) stimulates

contraction of the intestine, peristalsis (wormy-like movement) that helps passage of food a long through the digestive canal.

Lipids Lipids (like carbohydrates) contain carbon,

hydrogen and oxygen, but the proportion of oxygen in them is much less.

Classification of lipids: Simple lipids………….[ fats as butter & waxes as

bee wax]. (Fats) are ester of fatty acids with glycerol. (Waxes) are ester of fatty acids with alcohol

other than glycerol. Compound lipids......................[phospholipids].Derived lipids ...........[Cholesterol and bile acids].

Biological significance of lipids:1- The most important source of energy. Oxidation of 1g of fat (triglycerides)produces about 9.3 kcal.3- Lipids are the most common storage materials,

and have the following functions: a- Subcutaneous fats provide an insulating layer

that protects from heat loss in cold weathers. b- Lipids have a role in protection and fixation of

internal organs as kidney.4- Lipids are source of fat-soluble vitamins,

essential fatty acids & steroid hormones.5- Lipids are essential components in the structure

of cell membranes.

Proteins■ Proteins are composed of carbon,

hydrogen, oxygen, and nitrogen; and they frequently contain sulfur, or phosphorous, or iron.

■ Protein molecules consist mainly of amino acids which linked together in chains called polypeptide. The linkage between the amino acids is called peptide bond.

The amino acids

• An important feature of the amino acid is that each individual amino acid contains two characteristic groups of atoms -COOH and -NH2. The simplest amino acid, glycine which has the formula, CH2NH2COOH. There are two types of amino acids:

The essential amino acids : which can not be synthesized inside the body of either

animals and humans but synthesized by the plants. They are: phenylalanine – histamine – isoleucine – lysine –methionine – valine – threonine – leucine – tryptophan.

The non-essential amino acids: which can be synthesized inside the body are: alanine - arginine - aspartic acid – cysteine - glutamic acid – glutamine – glycine – proline – serine – tyrosine – asparagine – selenocysteine.

Classification of proteinsProteins are classified according to the chemical structure

into:(1) Simple proteins: which on hydrolysis give rise amino

acids only. e.g. albumin, globulin, collagen, and keratins.

(2) Conjugated proteins: which on hydrolysis give rise amino acids and a non- protein group called prosthetic group.

• Phosphoproteins……………….Casein of milk.• Glycoproteins..………………….Heparin. • Chromoproteins .. ……………...Haemoglobin.

• Nucleoproteins…………………..Nucleic acids.• Hormoproteins…………………..Insulin –Prolactin.

(3) Derived proteins: which obtained as a result of partial hydrolysis of natural proteins as: peptones, proteoses, and peptides.

Biological significance of proteins:1- Provide the body with essential amino

acids.

2- Build up new tissues during growth, pregnancy, and lactation.

3- Proteins are important for synthesis of some hormones and all enzymes.

4- Proteins maintain the pH of blood (7.4).

5- Proteins provide the body with energy when needs [4 kcal/g].

VitaminsDefinition:The vitamins are organic compounds, which must be present in the

food in minute quantities to enable growth, health, and maintenance of life.

Nomenclature: • The word vitamin is from vital amine, and it means amine of life .• First named alphabetically vitamin A , B,C,D,E,K……….etc.• Given common names also Thiamin, Riboflavin, Niacin,………etc.• Chemical names, Ascorbic acid, Folic acid,……………… ….etc.

Sources: • Foods, are the major dietary sources. • Exposure to sunlight (UV), triggers vitamin D synthesis in the skin.• Intestinal bacteria are able to synthesize a sufficient quantity of

some vitamins like vitamins E and K.

Classification of vitamins

There are two types of vitamins:

(I) Fat – soluble vitamins [A,D,E and K].

(II) Water – soluble vitamins [B and C].

VitaminsPurposeSourcesVitamin A(Retinal & Retinol)

(Produced from the plant precursor ß-Carotene).

1- Normal cell differentiation & growth.

2- Protects the linings of the digestive, urinary and respiratory tracts (It helps secretion the mucous).

3- Maintain healthy vision at night.

4- Antioxidant.(Fights free radicals that causing DNA damage.)

Deficiency: • Growth retardation.

• Changes in skin epithelia, dry, horny and more susceptible to infections.

• Night blindness, as a result of rhodopsin deficiency which responsible for night vision.

Liver,

Carrots,

Sweet, potatoes, Spinach, Cantaloupe, Broccoli, Mangos

(I) Fat – soluble vitamins

VitaminsPurposeSourcesVitamin D

The active form

1,25-dihydroxy

cholecalciferol

■ Helps intestinal absorption of calcium and phosphorus for healthy bones and teeth.

Deficiency:* Rickets in children.

* Osteoporosis & Osteomalacia.

* Sunlight, promotes synthesis of vitamin D under the skin.

* Cod liver oil

* Salmon

* Sardines

Vitamin E

(Antisterility)

Alpha-tocopherol is the most

biologically active compound

■ Helps form blood cells.

■ Antioxidant, so it protects DNA from free radical damage.

Deficiency:■ Female abortion and male sterility, only in experimental animals.

■ Hemolysis of red blood cells, degeneration of sensory neurons.

■ Deficiency symptoms are rare occurrence in human being because the intestinal bacteria are able to synthesize the vitamin in a sufficient amount.

■ Plant oils, seeds, nuts, wheat germ, green leafy vegetables.

■ Synthesized by intestinal microorganisms.

Vitamins PurposeSourcesVitamin KAnti-hemorrhagic

Phylloquinone

■ It helps in the production of blood-clotting-factor proteins that participate in a series of reactions to form a blood clot [prothrombin (factor II), factors VII, IX, and X, and proteins C, S, and Z].

■ It also participates in the production of bone proteins  [osteocalcin, also called bone Gla protein (BGP), matrix Gla protein (MGP)].

Deficiency:■ Prolongation of the time of blood clotting

formation (hemorrhage may occur). ■ A primary deficiency of vitamin K or E is rare, but a secondary deficiency may result from:

■ Fat malabsorption syndrome.

■ Prolonged use of antibiotics can destroy the intestinal bacteria that produce these vitamins.

Green vegetables Spinach,

Broccoli,

liver .

synthesis by intestinal microorganisms.

Vitamins Purpose Sources

Vitamin C Ascorbic Acid

■ It is used in the production of collagen

(bone, tendons, cartilage, and skin).

■ It improves the immune system.

(Moderate doses alleviate the symptoms of colds).

■ Acts as an antioxidant (destroying free radicals).

■ Strengthens blood vessel walls.

■ It enhances the absorption of iron.

Deficiency: Scurvy disease

Its symptoms are:

• Loss of hair and teeth.

• Bleeding gums.

• Very slow healing of wounds.

citrus,

tomatoes,

broccoli,

potatoes,

green peppers,

cabbage

(II) Water – soluble vitamins

VitaminPurpose Sources

B1 Thiamin

■ Essential for energy production, because it is required for the metabolic reactions of foods, especially carbohydrate. The energy is essential for the functions of nervous system. The metabolic reactions catalyzed by thiamin are decarboxylation reactions.

Deficiency: Beri beri disease

• Pain and loss of sensation in the hands and feet. So, paralysis of the legs may occur.

• Muscle wasting (weakness) and gradual loss of function.

• Brain damage and eventually death.

legumes,

whole grains,

wheat germ,

nuts

VitaminPurpose Sources

B2Riboflavin

■ It converted in the body to the active forms flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), which they act as cofactors for dehydrogenase enzymes.

■ It plays an important role in the metabolism of carbohydrates and proteins.

[dehydrogenation reactions]

Deficiency: Dermatitis.Thickening and rough skin, especially in the mouth, with cracks and inflammation at the corners of the lips, a painful tongue.

Milk Dairy products.

Whole grains,

Eggs, Fish,

Green leafy,

Vegetables

B3Niacin,

nicotinamide

■ In the form of NAD or NADP, the vitamin plays a vital role in energy production in cells. fat, protein, and carbohydrates metabolism. [dehydrogenation reactions].

Deficiency: Pellagra (Pella = skin, agra = rough)

Its symptoms are: diarrhea, dermatitis, dementia خبل, and death.

Meat, fish,

poultry, eggs,

peanuts,

legumes

grains

VitaminPurpose Sources

B5PantothenicAcid

■ It plays a vital role in metabolism of foods (carbohydrates, lipids, and proteins), particularly in the production of energy in cells, because it represents a part from the vital molecule coenzyme A.

Deficiency: In animal only:

■ Impaired growth and reproduction, dermatitis, nervous symptoms.

■ Naturally occurring pantothenic acid deficiency is very rare, since it is so widespread in the diet.

Chicken, beef,

potatoes, tomatoes,

liver, kidneys, eggs, broccoli, whole grains

(such as brown rice)

B6 Pyridoxine

■ It catalyzes the reactions of conversion of some amino acids (decarboxylation, transamination, deamination……….)

■ It also plays a role in fat metabolism and in carbohydrate metabolism.

Deficiency: Impaired growth, anemia, dermatitis, and neuromuscular problems such as convulsion in children

Meat, poultry,

fish, grains, bran,

wheat germ,

egg yolk, legumes, green

leafy vegetables

VitaminPurpose Sources

B9Folic Acid

■ Synthesis of hemoglobin.

■ Synthesis of DNA & RNA.

Deficiency: ■ Failure of normal cell division. e.g. in the cells lining the digestive system, this can lead to loss of appetite and diarrhea.

■ In the bone marrow leads to a type of anemia called megaloblastic anemia (large, immature blood cells).

Meat, eggs, fish, green vegetables, beans,

asparagus, yeast

B12Cobalamin

■ vital for cell division, especially in the bone marrow.

Deficiency: ■ Leads to production of large, immature blood cells which do not have the normal oxygen-carrying capacity.

■ Damage in nervous system.

(Pernicious anemia)

Meat, liver poultry, fish, dairy

products

VitaminPurpose Sources

Biotin (Vitamin B7)

■ It plays a major role in metabolism, addition of CO2 (synthesis of fats, urea formation, ……..)

Deficiency:Deficiency syndromes are not normally seen in man. Experimentally, they include hair loss, dermatitis, and depression.

Egg yolk, milk,

legumes, peanuts,

bananas

Minerals

• Both vitamins and minerals are essential in the diet in small quantities, so they are often grouped together as micronutrients.

• Minerals cab be divided into:

(I) Major minerals: which required in relatively large amounts such as calcium (Ca), phosphorus (P), potassium (K), sodium (Na), chlorine (Cl), magnesium (Mg), sulfur (S).

(II) Trace elements: which required in smaller amounts such as iron (Fe), manganese (Mn), copper (Cu), iodine (I), cobalt (Co), zinc (Zn), florine (Fl), selenium (Se), chromium (Cr), molybdenum, bromide, aluminum.

MineralSourceUse in the body

Calcium

(Ca)

Dairy products, dark green vegetables legumes.

• It is necessary for bone and teeth formation.

• It contributes to nerve and muscle action.

• It contributes to blood clotting.

Phosphorus (P)

Meat, poultry, whole grain foods..

• It serves as components of bones, teeth, phospholipids, ATP, phosphoproteins, and nucleic acids.

Magnesium (Mg)

Whole grains foods, green leafy vegetables.

• It acts as coenzyme in several enzymes such as adenosine triphosphatase (ATPase), phosphodiesterase, hexokinase,…..

)I (Major minerals

MineralSourceUse in the body

Sodium

(Na)

Table salt, widespread in the diet.

• It is a major cation of extra-cellular fluid.

• It participates in the muscle and nerve functions.

• It contributes to maintenance of water balance in the body.

Potassium

(K)

Widespread in the diet, especially in meats and grains, fruits, vegetables.

• It is necessary for muscle and nerve function,

• It represents a major component of intracellular fluid.

Chloride

(Cl)

Table salt.• It plays a role in the acid-base balance.

• It is required for stomach acid formation.

• It is necessary for maintenance of body water balance.

Sulfur

(S)

Meat products• It is a component of some amino acids and (like methionine and cysteine) and many proteins (like insulin and keratine).

)II (Trace elementsMineralSourceUse in the body

Iron

(Fe)

Green leafy vegetables, Whole grains, legumes, meats, eggs.

• It is needed for synthesis of hemoglobin, myoglobin, and certain enzymes like cytochrome P450.

• So, it required for oxi-reduction reactions.

Copper

(Cu)

Seafood, nuts, legumes.

• It stimulates iron absorption.

• It activates many enzymes, particularly oxidative enzymes.

• It represents a part of the respiratory pigment of blue color called hemocyanin (similar to hemoglobin) in invertebrates like crabs, shrimp,……….etc.

Iodine

(I)

Iodized salt, marine fishes.

• It is a part of the thyroid hormones (thyroxine and triiodothyronine).

Zinc

(Zn)

Whole grain foods, Meats, seafood.

• It is activates many enzymes such as carbonic anhydrase.

Fluorine

(F)

Fluoridated water, tea, seafood..

• It accounts for the maintenance of teeth from decay (perhaps the maintenance of bone as well).

Water

• The amount of water in a human body depends on age, gender, body type, and level of physical activity.

• The body of an adult male is approximately 62 percent water, while an adult female is 51 percent water. 10-15% loss of water will result in death.

Water balance: It refers to the balance between the amount of water consumed and the amount of water excreted.

Water functions :• Both the spaces between cells (intercellular spaces) and the spaces inside cells

(intracellular spaces) are filled with water.• Water is the medium in which materials are transport to and from cells and tissues.• Water is the solvent of our nutrients through digestion.• Water is the medium in which toxic substances are excreted from the kidney. Much of

the water lost each day is through the excretion of toxic waste materials.• Water is a participant in hundreds of metabolic processes.• Water lubricates and functions as a shock absorber for joints, spinal cord, and our

eyes. • Water maintains appropriate blood volume.• Water also helps the body maintain a constant temperature by acting as a thermostat.• When a person is too hot, whether from being in a hot environment or from intense

physical activity, the body sweats. When sweat evaporates, it lowers the body temperature.

The digestive system

• The digestive system consists of (I)The alimentary canal.(II)The accessory organs.

• The alimentary canal is a long tube that extends from the mouth to the anus. It includes the mouth, pharynx, esophagus, stomach, small intestine, and large intestine.

• The major accessory organs are the salivary glands, liver, and pancreas. These organs secrete digestive juices into the alimentary canal.

Structure of digestive system

(I) Alimentary canal: It consists of:1. The mouth: It contains the teeth, the tongue, the salivary

glands. 2. The pharynx: In humans, it leads to both the trachea and

the esophagus. The epiglottis blocks the trachea and the uvula blocks off the nose, while food is being swallowed.

3. The esophagus: It is the muscular tube which extends from the pharynx to the stomach. Food is moved easily along the esophagus by peristalsis, and mucus secretion. There are sphincter muscles at the top and bottom of the esophagus.

4. The stomach is a J-shaped muscular sac, which lies on the left side of the upper abdomen. The stomach can expand to hold about 2 L of food. The stomach has two sphincters: the cardiac sphincter closes off the top end of it and the pyloric sphincter, which closes off the bottom.

5. The small intestine: It has a length of about 6 m. The surface of the small intestine is wrinkled and convoluted to produce a greater surface area for absorption. The total surface area is about 300 m2. The small intestine includes: ▪ the duodenum, the first portion. ▪ the jejunum, the second portion. ▪ the ileum, the third portion. 6. The large intestine or colon: It begins with a blind pouch called the cecum. In humans, cecum terminates in the appendix, a finger-like extension which may function in the immune system. The rectum is the terminal portion of the large intestine and functions for storage of the feces. It leads to external opening called the anus.

Accessory glands

■ Salivary glands There are 3 pairs of salivary glands: the parotids,

submandibular, and sublingual. Salivary glands secrete about 1-1.5 L/day of the saliva in the adult.

■ The liver. The liver is the largest gland in the body, attached to the

under surface of the liver is a gall bladder containing a green colored fluid called bile. When the chime from the stomach enters the duodenum, the gall bladder contracts and bile is discharged on the foods.

■ The Pancreas. The pancreas is a slightly pink-colored glands which lies

between the stomach and the duodenum. but contains cells that secrete in to the blood stream as well as those that discharge via the pancreatic duct into the gut.

DigestionDigestion is a biochemical process by which the complex compounds

in foods like carbohydrates, proteins, and lipids are changed into more simple soluble units (glucose, fructose, galactose, amino acids, fatty acids, and glycerol), which can be easily absorbed through the intestinal wall.

• The breakdown of these food chemicals is brought about by biochemical catalysts called enzymes. An enzyme is a chemical substance (special proteins) which accelerates a chemical reaction without itself being changed.

Factors affecting digestive enzymes activity: • Each enzymes has an optimum temperature. • Each enzyme has an optimum pH. • Each enzyme acts upon a specific type of food called substrate. • Each enzyme is secreted as a pro-enzyme (zymogen), inactive form. • Each enzyme has an specific activator and specific inhibitor. • Most enzyme names are written with the suffix-ase, e.g. Maltase

– Sucrase - Lactase.

Digestion in buccal cavitySalivary glands: • There are 3 pairs of salivary glands: the parotid,

submandibular, and sublingual. • Salivary glands secrete about 1-1.5 L/day of the

saliva in the adult. • The salivary glands pour there secretion in the

mouth cavity. • The saliva is colorless, and has a pH 7.4.

Constituents of saliva: • It consists of about 99.5% water, 0.2% inorganic

materials [chloride, phosphate, bicarbonate, Na, K, and Ca] and 0.3% organic solids [mucin, albumin, and enzymes].

Functions of saliva:● The mucous acts as a lubricant which facilitates mastication and swallowing.● The food is moistened and softened.● When the body loses too much moisture the flow of saliva is stopped, a sensation of thirst is created and the feel to drink water is created.● Saliva dissolves certain substances which are then able to stimulate the taste buds of the tongue and give the sensation of taste.● Saliva contains the following digestive enzymes: Salivary amylase: It initiates the digestion of a part of soluble starch into maltose. Maltase: It converts maltose sugar into glucose. Lysozyme: It has anti-bacterial effects, so it destroys microorganisms which enter the mouth.

Digestion in the stomach ▪ Control of gastric juice secretion:

(1) Reflex stimulation of the vagus nerve.

(2) Hormonal stimulation:

- Gastrin stimulates acid secretion.

▪ The volume of the gastric juice is 2-3 L / day, pH 1-2.

▪ The gastric glands contain different types of secretory cells:

- Oxyntic (parietal) cells .………………....secret HCl.

- Mucous cells …………………………….secret mucin.

- Peptic (chief) cells…………………………….....secret enzyme pepsinogen.

- G cells………………secret gastrin hormone which released to the blood.

▪ Functions of gastric digestive enzymes:

Functions of HCl:• It gives the optimum pH of stomach (1-2).• It activates the pepsinogen enzyme into pepsin. • It has antibacterial action.• It converts carbohydrates into mono-, di-, and

polysaccharides; and proteins to meta-proteins.

Digestion in the small intestine Most of the digestive action that takes place in the small

intestine is carried out in the duodenum and brought about by secretions from liver, pancreas, and intestine itself.

Hormonal control of juices secreted into intestine: • When the acidic chyme reaches to the duodenum, the

later secretes the following hormones from special cells. - Secretin: It stimulates both pancreas and liver to secret

alkaline juices (rich with bicarbonate). - Cholecystokinin (the old name is pancreozymin): It

stimulates secretion of the bile juice; and the pancreatic juice rich with enzymes.

- Entrokinin: It stimulates the intestinal wall cells to secret the intestinal juice.

The pancreatic juice▪ The pancreatic juice is alkaline (pH 7.5-8.0), and its

volume is about ¾ L / day.

▪ It contains digestive enzymes for proteins, carbohydrates, and lipids:

The bile juice▪ It is secreted by the liver cells and stored in the gall bladder . ▪ The bile is a viscous fluid which contains about 98% water, mucin, bile salts (sodium salts), bile pigments (as billirubin and billiveridin), and cholesterol.

Role of bile juice in digestion▪ Sodium salts cause: - alkalinity of digestive juice. - breakdown the fats into minute droplets, so the fat becomes emulsified. ▪ Mucous acts as a lubricant.

The intestinal juice

▪ It secrets from the wall of the intestine itself. ▪ The volume of the juice secreted per day is about 3 L. ▪ The juice contains the following enzymes. [1] Peptidases: They convert peptides into amino acids (aminopeptidase, tripeptidase, and dipeptidase) [2] Intestinal lipase: It hydrolyzes the emulsified fats into glycerol and fatty acids. [3] Disuccharidases: - Sucrase, which hydrolyzes sucrose into glucose and fructose. - Maltase, which hydrolyzes maltose into glucose and glucose. - Lactase, which hydrolyzes lactose glucose and galactose.▪ The juice contains also mucin which protects the intestinal wall from either the digestive enzymes or the acidity of the food coming from the stomach.

AbsorptionAbsorption means passage of the molecules of food from

the intestinal lumen into the body's interior after digestion. Pathways of absorption: There are two pathways:(1) The veins of the portal system. Where amino acids

and glucose pass into the bloodstream.(2) The lymphatic (lacteal) vessels. Where the fatty acids

and glycerol are transported into the lymphatic system and then to the blood stream at the thoracic region.

Mechanisms of absorption: Fluids and nutrients are absorbed by different mechanisms (methods).

(1) Osmosis: Osmosis means the movement of water through a partially permeable membrane down a concentration gradient from a dilute solution (where there is a high concentration of water) to a concentrated solution (where there is a relatively low concentration of water).

(2) Diffusion: ▪ Diffusion means the movement of particles (solutes) from an area of high concentration to an area of low concentration down a concentration gradient.Diffusion and osmosis are both types of passive transport - i.e., no energy is required for the molecules to move into or out of the cell.Diffusion may be simple or facilitated. In facilitated diffusion, a large molecules such as glucose and amino acids cross the plasma membrane by the help of carrier proteins. While in simple diffusion, a small molecules (CO2 & O2) are passed through the membrane without the need of carrier proteins.

(3) Active transport:

▪ It means the movement of substances against the concentration and electrical gradient, with consumption of energy.

▪ In active transport, a special carrier protein in the cell membrane is used to transport the particle from one side to the other side of the membrane.

Sites of food absorption ▪Stomach: Absorption of some short-chain fatty acids.

: ▪Small intestine - Duodenum: Absorption of vitamins A and B1, iron,

calcium, glycerol, fatty acids, monoglycerides, amino acids, and monosaccharides.

-Jejunum: Absorption of glucose, galactose, amino acids, glycerol, fatty acids, copper, zinc, potassium, calcium, magnesium, phosphorus, iodine, iron, fat-soluble vitamins D,

E, and K, most of the B complex, and vitamin C . -Ileum: Absorption of sodium, potassium, chloride,

calcium, magnesium, phosphorus, iodine, vitamins (e.g., biotin and vitamin K), and water.

▪Colon: Absorption of sodium, potassium, water, acids, gases, some short-chain fatty acids metabolized from plant,

fibers and vitamins synthesized by micro-organisms .

MetabolismMetabolism: It is the set of life-sustaining chemical trans-formations within the cells of living organisms. In other words, it refers to all chemical reactions that occur in living organisms, including digestion, transport of substances into and between different cells, and uses of these substances in various biochemical activities.Metabolism is usually divided into two categories: * Catabolism: It refers to the breakdown of organic matter into small intermediates with production of energy, for example conversion of fats into carbon dioxide, water, and ATP. * Anabolism: It refers to the uses of energy and small intermediates to construct components of cells such as manufacture of proteins from amino acids.

Carbohydrates Metabolism

Calculation of number of ATP molecules produced during glycolysis of one molecule of glucose

I- During aerobic glycolysis:ATP consumed = 2 ATP

ATP produced = 2 + 2 + (3x2) = 4 + 6 = 10 ATP[Where, in the presence of O2, NAD NADH+ + H+ To respiratory

chain 3 ATP (3 ATPX2 = 6 ATP)]Net production of ATP = 10 – 2 = 8 ATP

II- During anaerobic glycolysis:ATP consumed = 2 ATP

ATP produced = 2 + 2 = 4 ATPNet production of ATP = 4 – 2 = 2 ATP

■ Number of produced ATP per oxidation of 2 moles of pyruvic acid into acetyl-CoA = 2x3 = 6 ATP molecules

Calculation of number of ATP molecules produced during glycolysis of one molecule of glucose

I- During aerobic glycolysis:ATP consumed = 2 ATP

ATP produced = 2 + 2 + (3x2) = 4 + 6 = 10 ATP[Where, in the presence of O2, NAD NADH+ + H+ To respiratory

chain 3 ATP (3 ATPX2 = 6 ATP)]Net production of ATP = 10 – 2 = 8 ATP

II- During anaerobic glycolysis:ATP consumed = 2 ATP

ATP produced = 2 + 2 = 4 ATPNet production of ATP = 4 – 2 = 2 ATP

Total number of ATP produced per oxidation of one mole of glucose into CO2 and H2O:

● In aerobic glycolysis: 8 ATP molecules● In conversion of pyruvate to acetate: 6 ATP molecules

● In citric acid cycle (oxidation of acetate into CO2 and H2O): 24 ATP molecules

Total number of ATP = 8 + 6 + 24 = 38 ATP molecules

Metabolism of Keto Acids:

1- It converted by decarboxylation to acetyl-coA which enters citric acid cycle and produces energy (ATP), in addition to CO2 and water.

2- It used in synthesis of glucose and glycogen.

3- It used in synthesis of fats.

Blood vesselsArteries carry oxygenated blood away from the heart. Artery aorta, a massive and thick-walled artery receives the blood from left ventricle Major arteries Tissue arteries Arterioles Capillaries.Veins carry oxygen-poor blood back to the heart. Deoxygenated blood is collected by capillaries Venules Tissue veins Two major veins: the superior vena cava (from areas above the heart) and the inferior vena cava (from areas below the heart) Right atrium. Capillaries ▪ Help to join tissue with arterioles. ▪ Help in distribution and passage of blood oxygen and nutrients to all body cells.▪ Help in collection of metabolic wastes from all body cells (e.g. CO2, urea,…….).

Types of circulations(1) Pulmonary circulation● In this circulation, oxygen-depleted blood is pumped away from the right ventricle of the heart, via the pulmonary artery, to the lungs and returned, oxygenated, to the left atrium of the heart via the pulmonary veins.● Gas exchange occurs in the lungs, where CO2 is released from the blood into the lungs, and O2 is absorbed from the lungs alveoli into the blood. The pulmonary veins return the oxygen-rich blood to the left atrium.

(2) Systemic circulation● Systemic circulation transports oxygenated blood through the aorta from the left ventricle to the different parts of the body (except the lungs), and returns oxygen-depleted blood back to the heart.● Arteries bring oxygenated blood to the tissues. As blood circulates through the body, oxygen diffuses from the blood into cells surrounding the capillaries, and carbon dioxide diffuses into the blood from the capillary cells. ● Veins bring deoxygenated blood back to the heart.

(3) Coronary circulation● The coronary circulation provides a blood supply to the myocardium (the heart muscle). ● It arises from the basis of aorta by two coronary arteries, the left and the right. The right coronary artery supplies blood mainly to the right side of the heart. The left coronary artery, which branches into the left anterior descending artery and the circumflex artery, supplies blood to the left side of the heart. The left side of the heart is larger and more muscular because it pumps blood to the rest of the body.● After nourishing the myocardium, blood returns through the coronary veins into the coronary sinus and from this one into the right atrium. The smallest cardiac veins drain the blood directly into the heart chambers.

Anatomy of the human heart

Weight: The heart weighs between 200 to 425 grams. Size: The normal average size of adult heart equals to clenched adult fist. Location: Human heart is located in the center of the chest between right and left lungs, behind and slightly to the left of sternum.

Membranes of the heart: ▪ The heart is covered by the pericardium, which is made of a double-layered membrane like a sac that surrounds the heart and its major blood vessels. ▪ The outer layer of the pericardium (parietal pericardium), is slightly thicker, surrounds the roots of the heart's major blood vessels and is attached by ligaments to vertebral column, diaphragm, and other parts of the body. ▪ The inner layer of the pericardium (epicardium or visceral pericardium) is attached to the heart muscle. It's a thin, glossy membrane. ▪ There is a small amount of fluid between the pericardium membranes that acts as lubricant, and to reduce friction between the heart and the pericardium when the heart beats. ▪ Another smooth, glossy membrane, called the endocardium, covers the inside surfaces of the four chambers of the heart, plus the valves and the muscles that attach to the valves.

The Exterior of the Heart & Blood circulation in the heart

The Right Side of the Heart◘ It contains both the right atrium and right ventricle, and the blood vessels connected to them.◘ The superior and inferior vena cavae are connected to the right atrium, and carry the deoxygenated blood collected from the tissues back to the atrium. ◘ The superior vena cava carries deoxygenated blood from the upper parts of the body, including head, chest, arms, and neck. The inferior vena cava carries deoxygenated blood from the lower parts of the body.◘ The deoxygenated blood from the vena cavae flows into the right atrium and then into the right ventricle, from which the blood is pumped through the pulmonary artery to the lungs, where oxygenation of the blood occurs.◘ The oxygenated blood passes from the lungs back to the heart through the pulmonary veins.

The Left Side of the Heart● It contains both the left atrium and left ventricle, and the blood vessels connected to them. ● The left atrium receives oxygenated blood from the lungs via pulmonary veins, and pumps it into the left ventricle. ● The left ventricle pumps oxygenated blood through the aorta to the rest of the body.

The Interior of the HeartThe septum▲The heart are divided internally into right and left sides by an internal wall of tissue called the septum. ▲ The area of the septum that divides the atria is called the atrial or interatrial septum. ▲ The area of the septum that divides the ventricles is called the ventricular or interventricular septum.The heart chambers ■ The inside of the human heart is divided into 4 chambers. ■ The two upper chambers of the heart are called the left and right atria. The atria receive and collect blood. ■ The two lower chambers are called the left and right ventricles (their walls are more thicker than the two atria). The left ventricle is the largest and strongest chamber in the heart (its wall is thicker than right ventricle), so it has enough force to push blood into the circulatory system to other parts of the body.

This figure shows a cross-section of a healthy human heart and its inside structures. The blue arrow shows the direction in which oxygen-poor blood flows from the body to the heart then to the lungs. The red arrow shows the direction in which oxygen-rich blood flows from the lungs to the heart, then to the rest of the body.

The Heart valvesHeart contains four valves which regulate blood flow through the heart. They permit the blood flow in ONE direction only. 1-The tricuspid valve permits the deoxygenated blood flow from right atrium to right ventricle, but not vice versa. 2-The mitral valve permits the oxygenated blood flow from the left atrium to left ventricle, but not vice versa. 3-The pulmonary valve permits deoxygenated blood flow from the right ventricle into pulmonary artery.4-The aortic valve permits the oxygen-rich blood to pass from the left ventricle into the aorta.

Blood flow in the heart and the role of the valvesThe right atrium pumps blood into the right ventricle the pulmonary artery the lungspulmonary veins the left atrium the left ventricle the aorta the rest of the body.

● The blood flows in the heart in one direction only, and the valves make this possible. ● Healthy valves open and close in an exact coordination with the pumping action of the atria and ventricles. ● Each valve has a set of flaps called leaflets or cusps that seal or open the valves. This allows pumped blood to pass through the chambers and into the arteries without backing up or flowing backward.

A cross-section of a human heart showing the four types of the valves (1,2,3,and 4), and their location inside the heart.

Electrical conduction system of the heart

● The electrical signal begins in the sinoatrial (SA) node, located at the top of the right atrium. The SA node is sometimes called the heart's "natural pacemaker" .منظم ضربات القلب● When an electrical impulse is released from this natural pacemaker, it causes the atria to contract. ● The signal then passes to the atrioventricular (AV) node. The AV node sends the signal through the bundles of His to the Purkinje fibers and finally to the muscle fibers of the ventricles, causing them to contract.

Heart Sounds Heart sounds result from the closing of the heart valves.● When the heart beats, it makes a "lub-dub" sound. Between the time of hearing "lub" and “dub", blood is pumped through the heart and circulatory system. ● The first heart sound (lub) results from the closure of the atrioventricular valves (tricuspid valve and mitral valve). ● The second heart sound (dub) produced when the semilunar valves shut (pulmonary valve and aortic valve).● The right and left atrioventricular valves do not close at precisely the same time. Nor do the semilunar valves. A physician can, therefore, listen to each valve individually and determine whether it is functioning properly.

Heart rate It is the number of heartbeats per unit of time, typically expressed as beats per minute (bpm). Each heartbeat has two basic parts: diastole or relaxation, and systole or contraction. Normal heart beat:At rest, the SA node causes the heart to beat about 50 to 100 times each minute. Exercise, emotions, fever and some medications can cause the heart to beat faster, sometimes to well over 100 beats per minute. Measurement of the heart rate:You can tell how fast your heart is beating (your heart rate) by feeling your pulse. You will need a watch with a second hand.▲ Place your index and middle finger of your hand on the inner wrist of the other arm, just below the base of the thumb, where the  radial artery passes.▲ You should feel a tapping or pulsing against your fingers. Count the number of taps you feel in 30 seconds. ▲ Multiply that number by 2 to find out your heart-rate for one minute.

Heart rate It is the number of heartbeats per unit of time, typically expressed as beats per minute (bpm). Each heartbeat has two basic parts: diastole or relaxation, and systole or contraction. Normal heart beat:At rest, the SA node causes the heart to beat about 50 to 100 times each minute. Exercise, emotions, fever and some medications can cause the heart to beat faster, sometimes to well over 100 beats per minute. Measurement of the heart rate:You can tell how fast your heart is beating (your heart rate) by feeling your pulse. You will need a watch with a second hand.▲ Place your index and middle finger of your hand on the inner wrist of the other arm, just below the base of the thumb, where the  radial artery passes.▲ You should feel a tapping or pulsing against your fingers. Count the number of taps you feel in 30 seconds. ▲ Multiply that number by 2 to find out your heart-rate for one minute.

Blood Pressure ■ Blood pressure is the pressure (force) exerted by circulating blood upon the walls of blood vessels. It is principally due to the pumping action of the heart. ■ Blood pressure varies throughout the cardiovascular system, being the highest in the aorta and the lowest in the capillaries and veins. Low blood pressure in the capillaries enhances the rate of exchange between the blood and the tissues.■ Blood pressure is maximum during systole, when the heart is contracted, and minimum during diastole, when the heart is relaxed. It is therefore expressed in terms of the systolic pressure over diastolic pressure, and is measured in millimeters of mercury (mmHg).■ Normal values are: 120/80 in adult male, and 115/75 in adult females. ■ Blood pressure changes in relation to a person’s activity and stress levels, and the age.

Factors affecting the arterial blood pressure

(1) Total blood volume in the circulatory system.(2) Volume of cardiac output of blood.(3) Peripheral resistance. It is affected by some factors such as, ▪ The viscosity of the blood.   ▪ Vasoconstriction , which decreases the radius of the peripheral vessels.(4) Elasticity of the blood vessels walls.

Measurement of blood pressure ■ The cuff طرفof the sphygmomanometer is wrapped around the arm just above the elbow and pumped up to block off blood flow (the pressure exerted by the cuff is higher than the systolic pressure). ■ The pressure in the cuff is gradually decreased, and when it equals the person’s systolic pressure, the heart can force blood under the cuff, and a sound is heard (systolic pressure). Here, record the value of systolic pressure on the column of mercury.■ As the pressure in the cuff is lowered, when it equals the diastolic pressure, blood can flow freely, so the sound disappears (diastolic pressure). Here, record the value of diastolic pressure on the column of mercury.

Hypertension■ Hypertension occurs when either the systolic pressure is greater than 145 to 160 mm Hg and/or the diastolic is greater than 90 to 100. ■ Major contributing factors include the high level of salt intake , cholesterol (and other lipids), and sugar in the diet; and the lack of exercise the person gets.

Thrombus & Embolus Definition: Thrombus is a blood clot which is formed within a blood vessel (vein or artery) and blocks the blood flow. ▪ These can result from surgery or from conditions like atrial fibrillation. ▪ When a clot (thrombus) breaks off and travels to another part of the body, it may cause vessel obstruction elsewhere and called embolus. ▪ If thrombi or emboli stabilize in an artery supplying blood to the heart, this can cause a coronary embolism or heart attack or myocardial infarction. ▪ If one of these becomes lodged in an artery in the lungs, it is also a life-threatening pulmonary embolism, and if in the brain, a cerebral (or cerebellar) embolism or stroke or cerebro-vascular accident.▪ When a thrombus occupies more than 75% of cross-sectional area of the lumen of an artery, blood flow to the tissue supplied is reduced enough to cause symptoms because of decreased oxygen (hypoxia) and accumulation of metabolic products like lactic acid. More than 90% obstruction can result in anoxia, the complete deprivation of oxygen, and infarction, a mode of cell death.

A hemorrhage is bleeding, which can be severe if it occurs internally.

A hematoma is a local swelling or tumor filled with blood; e.g. a bruise كدم[[[ة, especially a large one. Sometimes, if the injury is extensive, it can calcify leading to a hard lumpكتل[[ة ص[[ل[بة , which may need to be surgically removed.

The Respiratory SystemFunctions of respiratory system1- The primary role of the respiratory system is to maintain a continuous supply of tissues with atmospheric oxygen (O2) for oxidation of foodstuffs in the cells and excreting carbon dioxide (CO2) and water (H2O) from cells to atmosphere.2- The secondary roles of the respiratory system include: a- Control of acid-base balance (blood pH), by utilizing the bicarbonate buffer. Acidosis activates the respiratory center to increase respiratory rate and depth, which eliminates more CO2 and causes blood pH to rise. Alkalosis depresses the respiratory center, resulting in CO2 retention and a fall in blood pH. b- Protection of the body against inhaled particles, e.g. bacteria. c- Regulation of body temperature especially in panting animals (= animals without sweat glands) during summer. d- Supply of air to the larynx for purpose of voice production.

Divisions of respiratory processes(1) External respiration: It includes; a- Exchange of gases between the environment and the lungs. b- Exchange of gases between the lungs and the blood, across the respiratory membrane.(2) Transport of respiratory gases: The carriage of O2 and Co2 by the blood to and from the body cells. (3) Internal respiration: The exchange of O2 and Co2 between the blood and tissues. It is also involves the intracellular O2 utilization through the metabolic biotransformations, and production of CO2.

Divisions of the respiratory tractAnatomically:I- The upper Respiratory Tract: It includes the nostrils, nasal cavities, pharynx, epiglottis, and the larynx. II- The Lower Respiratory Tract: It consists of the trachea, bronchi, bronchioles, and the Lungs.

Physiologically:I- Conducting zone▪ Respiratory passages that carry air to the site of gas exchange. Filters, humidifies, and warms air.▪ It includes the nostrils, nasal cavities, pharynx, epiglottis, larynx, trachea, bronchi, terminal bronchioles. II- Respiratory zoneSites of gas exchange, which composed of:Respiratory bronchiolesAlveolar ductsAlveolar sacs

The diaphragm

▲The diaphragm is a sheet of muscles that lies across the bottom of the chest cavity. ▲ As the diaphragm contracts and relaxes, breathing takes place. When the diaphragm contracts, oxygen is pulled into the lungs, while when it relaxes, carbon dioxide is pumped out of the lungs.▲ In mammals, the diaphragm divides the body cavity into two parts: (1) Abdominal cavity, which contains the viscera (e.g., stomach and intestines). (2) Thoracic cavity, which contains the heart and lungs.

The pleural (A two-layered structure) ▲ The parietal pleura, which lines the walls of the chest cage and covers the upper surface of the diaphragm.▲ The pulmonary pleura, or visceral layer, which tightly covers the surface of the lungs. ▲ The two layers, which are in fact one continuous sheet of tissue, are generally connected (adhered) to each other.▲ There is a slight amount of watery fluid within the pleural cavity that lubricates the pleural surfaces and allows the lungs to slide freely over the inner surface of the thoracic wall during breathing.▲ If air is introduced between them, the adhesion is broken and the natural elasticity of the lung causes it to collapseتنهار . This can occur from traumaصدمة .

Breathing (Respiration)

There are two phases of breathing:Inspiration (inhalation) – air inExpiration (exhalation) – air out

Mechanisms of Quiet Respiration (Eupnoea)During eupnoea (respiration during rest in healthy subject), respiration is underlying 2 mechanisms:A- Central mechanisms: They involve the changes in the activity of the respiratory centers in the brain which control the peripheral activity. This will be discussed later.B- Peripheral mechanisms: They involve the changes in the size of the thoracic cavity and lungs leading to rush of the air into or out of the lungs.

Peripheral mechanismsI- During inspiration (inhalation)The external intercostal muscles contract, causing the ribs to move upward and laterally. The sternum moves out. This increase the thoracic cavity laterally and in anterior and posterior dimention (circumference). The dome shaped diaphragm flattens as it contracts. This increases the height (superior to inferior dimension) of the thoracic cavity.II- During expiration (exhalation)The processes occurred during inspiration are passively reversed.The natural elasticity of the lungs returns them to their normal volume. At rest, we breath 15-18 times per minute exchanging about 500 ml of air per one time.

Boyle's Law: As the volume occupied by a gas increases, the pressure of that  gas decreases. This means that the pressure of any gas and the volume it occupies are inversely proportional (P  =  1/V).The entry and exit of air during breathing■ When the lung stretches out, its volume is increased thereby the pressure of air in the intrapulmonic space decreases to a level below atmospheric pressure (760 mmHg), causing air moves into the respiratory tract from the outside producing inspiration.■ When the respiratory muscles relax, the thorax cavity becomes smaller.  This causes the  pressure of the air in the intrapulmonic space to exceed the air pressure outside.  This results  in air moving out of the respiratory tract producing passive expiration.

Lung Volumes (Respiratory Air Volumes) 

Lung volumes refer to the physical differences in lung volume during inspiration or expiration in relation to differences in the respiratory conditions.There are 4 terms of air volumes (lung volumes). Most of them are determined by the Spirometer.1)    Tidal volume (TV): It is the volume of air inspired or expired during rest. It equals 5oo ml.2)    Inspiratory Reserve volume (IRV): It is the maximum volume of air which can be inspired after normal inspiration. It equals 3000 ml.3)    Expiratory reserve volume (ERV): It is the maximum volume of air which can be expired after normal expiration. It equals 1000 ml.[N.B. The above 3 volumes can be measured by the Spirometer.]4)    Residual volume (RV): It is the volume of air that remains in the lungs after maximal expiration. It can't be expelled to atmosphere except after opening of the chest wall and squeezing the lungs. It equals 1200 ml.

Lung capacities:Lung capacity equals 2 or more of lung volumes.Most of the lung capacities are also determined by the Spirometer. 1. Inspiratory capacity (IC): It is the maximum volume of air which can be inspired after normal expiration. It equals T.V (500) + I.R.V (3000) = 3500 ml.2. Functional Residual capacity (FRC): It is the volume of air remaining in the lung after normal expiration. It equals ERV (1000) + RV (1200) = 2200 ml. This air is used for gases exchange.3. Total lung capacity (TLC): It is the volume of air contained in the lungs after deepest inspiration (maximum expansion of lungs). It equals all lung volumes = 5700 ml.4. Vital capacity (VC): It is the volume of air given out by maximal expiration after maximal inspiration. It equals IRV (3000) + TV (500) + ERV (1000) = 4500 ml. VC = IRV+TV+ERV=TLC-RV

Anatomic Dead Space: It is the portion of the airways, (from the mouth or nose to the terminal bronchioles) which conducts gas to the alveoli. No gas exchange is possible in this space. The volume of this space is approximately 150 ml in the average adult human.

Physiologic Dead Space: It is the anatomic dead space plus the volume of any non-functional areas of the lungs (alvioli which are less efficient in gas exchange). In young, health lungs, the volume of the anatomic dead space and physiologic dead space are equal.

Lung capacity and high altitudes● A person who is born and lives at sea level will develop a slightly smaller lung capacity than a person who spends their life at a high altitude. ● This is because the partial pressure of oxygen is lower at higher altitude which, as a result means that oxygen less readily diffuses into the bloodstream. In response to higher altitude, the body's diffusing capacity increases in order to process more air.● When someone is living at or near sea level travels to locations at high altitudes (e.g. The Tibet & The Himalayas) that person can develop a condition called altitude sickness. The severity of these conditions varies from a minor headache to life threatening swelling of the brain and lungs. because their lungs remove adequate amounts of carbon dioxide but they do not take in enough oxygen. (In normal individuals, carbon dioxide is the primary determinant of respiratory drive).

Oxyhemoglobin dissociation curve  ● This curve describes the relationship between partial pressure of oxygen (PO2) on the horizontal axis, and the amount of hemoglobin saturated with oxygen (SO2 or % saturation) on the vertical axis .● At high PO2, hemoglobin binds to oxygen to form oxyhemoglobin, as in the pulmonary capillaries, hemoglobin is nearly 100 % saturated.  ● When the blood is fully saturated all the red blood cells are in the form of oxyhemoglobin.  ● As the red blood cells travel to tissues the oxyhemoglobin releases the oxygen to form hemoglobin, due to decreased PO2 in the tissues. The reaction of oxygen with the iron molecule of the haem group is an oxygenation reaction, not oxidative, and the iron remains in the ferrous (2+) state.

The sigmoidal shape (S-shaped) of the oxygen dissociation curve is a result of the co-operative binding of oxygen to the four polypeptide chains.  Co-operative binding is the characteristic of hemoglobin to have a greater ability to bind oxygen after a subunit has bound oxygen.  This means that binding of the 1st O2 molecule increases the affinity of hemoglobin for oxygen and hence facilitates the binding of the 2nd O2 molecule. Binding of the 2nd O2

molecule facilitates the binding of the 3rd O2 molecule and so on. The affinity of hemoglobin for the 4th O2 molecule is approximately 300 times that for the 1st.

Factors that affect oxygen dissociation curve 1. Hydrogen ion concentration◘ A decrease in pH from a value of 7.4 (increase in  H+ ion concentration) shifts the standard curve to the right, while an increase shifts it to the left. ◘ The reason for this is that H+ and O2 both compete for binding to the hemoglobin molecule. Therefore, with increased acidity, the hemoglobin binds less O2 for a given PO2 (Bohr effect).

2. Effects of carbon dioxide• Most of the CO2 content (80–90%) is transported as bicarbonate ions. • The formation of a bicarbonate ion will release a proton into the plasma. • Hence, the elevated CO2 content creates a respiratory acidosis and shifts the oxygen–hemoglobin dissociation curve to the right (Bohr effect). i.e. it decreases the affinity of hemoglobin to bind to O2.

In exercising tissues, PCO2 is high and hydrogen ion concentration, [H+], is also high due to the formation of carbonic acid which dissociates to form bicarbonate ions and hydrogen ions. This increase in CO2 and decrease in pH shifts the dissociation curve to the right for a given PO2, releasing more oxygen to the tissues.In the lungs, PCO2 is low and hydrogen ion (H+) concentration is also low. This decrease in CO2 and increase in pH shifts the dissociation curve to the left for a given PO2, enhancing oxygen uptake.

3. Effects of 2,3-disphosphoglycerate (2,3-DPG)◘ 2,3-DPG is an organo-phosphate, which is created in erythrocytes during glycolysis. ◘ High levels of 2,3-DPG in red blood cells shift the curve to the right, while low levels of 2,3-DPG shift the curve to the left. ◘ This is because 2,3-DPG lowers hemoglobin's affinity for oxygen by binding preferentially to deoxyhemoglobin.

4. Temperature● Increases in temperature, such as in exercising tissues, causes a rightward shift, while hypothermia causes a leftward shift.● This is because increasing the temperature denatures the bond between oxygen and hemoglobin.

5. Carbon monoxide● Carbon monoxide (CO) binds with hemoglobin (hem group) forming carboxyhaemoglobin (COHb). CO has about 200–250 times the affinity of O2 for Hb. 

● The presence of CO on one of the 4 hem sites causes the oxygen on the other hem sites to bind with greater affinity with O2.● This causes either difficult for the hemoglobin to release oxygen to the tissues or shifting the curve to the left. ● With an increased level of CO, a person can suffer from severe tissue hypoxia while maintaining a normal PO2.