Biology unit 1, whole unit cards

• A disease is defined as a physical or mental disorder or malfunction with a characteristic set of signs or symptoms.
• Diseases may be caused by a single factor such as a pathogenic microorganism or be multifactorial and have many causes some of which may depend on lifestyle.

• Pathogenic microorganisms include bacteria, viruses and fungi.
• Each pathogen has a specific method by which it causes disease.  Some such as the influenza virus damage host cells whereas others, such as Vibrio cholera produce toxins which have a harmful effect on the body.
• The ability of the pathogen to cause disease depends on
  • Location - what tissue is colonised
  • Infectivity - how easily a bacterium can enter the host cell
  • Invasiveness - how easily a bacterium or its toxin spreads within the body
  • Pathogenicity - how a bacterium causes disease
• Common entry points for pathogens are the gas exchange and digestive system.

• A healthy lifestyle involves:
  • Maintaining a healthy weight
  • Taking regular exercise
  • Eating a balanced diet
  • Drinking a limited amount of alcohol
  • Not smoking
• Lifestyle has an effect on human health:
  • Exposure to carcinogenic chemicals (i.e. those found in tobacco smoke) or radiation (i.e. X-rays) may increase a person's chance of contracting cancer
  • Coronary heart disease is associated with diets that are rich in fat and a sedentary lifestyle
  • Alterations to a person’s lifestyle can have a dramatic effect on the likelihood of them contracting these conditions

The incidence of heart disease has been steadily increasing as our lifestyles become more sedentary and our diets have changed.  There are many causes of heart disease but the condition which most people associate with this disease is the sudden onset of a heart attack.  This section will examine the cause of these myocardial infarctions (Doctor speak for heart attack).

The heart muscle is supplied with freshly oxygenated blood from the coronary arteries.  Any disruption to this supply will mean that the heart muscle cells do not have enough oxygen and glucose to contract efficiently and can lead to death of the muscle tissue.  The severity of a heart attack will depend on the size of the area of muscle cells affected - blockages in larger coronary arteries will affect larger areas of cells.

The most common cause is a blood clot. A blood clot is called a thrombus and the process of forming a blood clot, thrombosis.  If a clot forms in the coronary arteries it is called coronary thrombosis.

The clot blocking the coronary artery may not have formed actually within the heart itself, it may have travelled in the bloodstream from another site. In this situation the clot is called an embolus and the blockage of the coronary artery an embolism.

A process known as atherosclerosis increases the tendency of thrombosis within arteries.  Essentially it is a build up of fatty deposits within and a thickening of the wall of the arteries, narrowing the lumen, making the wall less elastic and preventing blood flow thus encouraging the formation of blood clots. 

atherosclerotic plaques form by:

• Cholesterol is transported around the body in lipoproteins (LDLs).Excess cholesterol leaks from lipoproteins (LDLs)
• Deposited on arterial walls
• Macrophages (white blood cells) are trapped within cholesterol
• Release free radicals which damage the arterial wall
• Activates blood platelets which stick to damaged areas releasing clotting factors (thromboxanes)
• Forms a plaque which may rupture to produce a thrombus
• Circulating thrombus is called an embolus
• Embolus may lodge elsewhere in the circulation (brain - cause a stroke, coronary arteries - cause a heart attack, lungs - cause a pulmonary embolism)
• NB: healthy arteries produce anti-clotting factors (prostaglandins) → don't form clots

Coronary Heart Disease refers to a condition which develops when the coronary arteries themselves become damaged and narrowed by atherosclerotic plaques.  Atherosclerosis causes arteries to become narrowed.  This means that:

• More force required to move blood through narrowed vessels
• Blood pressure increases to compensate for this
• Increased blood pressure was an initial cause of atherosclerosis so it could result in further damage.

Development of atherosclerosis can lead to the development of angina:

• ↑exercise leads to ↑oxygen requirements by heart
• Narrowed arteries prevent more blood to pass through
• Shortage of blood to heart muscle causes chest pain
• Cells do not die as some blood can still pass through
• Pain only occurs during activity but not at rest

Heart failure is caused by the prolonged blockage of a coronary artery which causes damage to heart muscle.  Frequent heart attacks will cause this damage, but there are many other causes of heart failure.  The damage to the heart muscle results in a decrease in the number of contractions / a reduced cardiac output / lower pressure generated / less blood leaves heart.  This means that more blood is stored on the right side of the heart and in the veins leading to swelling and enlargement of the heart and liver.  At this point, a patient’s only option would be a heart transplant.

Another effect of atherosclerosis is that it can weaken the artery wall.  If this happens then the artery could, when placed under pressure burst or deform.   This is called an aneurysm.  If this happens in the brain then it will also result in a stroke.  Again, it’s worth looking online for images or animations showing the formation of these aneurysms.  Some are truly spectacular.  Just as the severity of an embolism depends on its location, the severity of an aneurysm is location dependent.  An aortic aneurysm would obviously be life threatening!  If this weakening is discovered by a doctor, then there are procedures which can help.  Stents can be used to support the blood vessel, ensuring that they are not harmed by mechanical stress.

Cholesterol is needed for many things in the human body including:

• Vitamin D production in skin
• Sex hormone production in gonads and adrenal glands
• Making cell membranes
• Produce bile acid (salts)

It has properties similar to fats → soft, waxy, and insoluble (difficult to remove if deposits form).  As mentioned before, it is transported in blood from liver to tissues.  It is carried by lipoproteins (soluble fatty proteins which wrap themselves around cholesterol). 

There are two different forms of lipoprotein, LDL (Low Density Lipoprotein) and HDL (High Density Lipoprotein) which have slightly differing roles.

LDL

• Carries cholesterol from liver to tissues
• Normally, some cholesterol 'leaks' from the lipoprotein and is absorbed to build cell membranes
• Excess LDL/cholesterol → too much cholesterol leaks out and causes atherosclerosis

HDL

• High density lipoprotein
• Picks up cholesterol from arterial walls and carries it away from tissues
• Travels to liver where cholesterol is removed with bile
• A diet low in cholesterol is therefore recommended for anyone concerned about heart disease.

• Nicotine constricts arteries causing platelets to stick together → vasoconstriction → heart must work harder to force blood through → increases BP
• ↑BP causes damage to blood vessel lining / endothelium / collagen
  • Leads to rise on blood platelets and makes them more sticky / form a plug / adhere to collagen fibres
  • Release of thromboplastin/thrombokinase
  • Fibrinogen converted to insoluble fibrin
  • Platelet plug trapped by fibrin mesh
• Raises conc. of fibrinogen (in blood) → increased risk of clotting
• ↑LDL causes more cholesterol to leak out in blood
• Carbon monoxide reduces the efficiency of the blood in terms of carrying oxygen
  • Haemoglobin combines with CO more readily than with oxygen → forms carboxyheamoglobin
  • Associated with plaque formation
• Principle CHD = heart muscle receives inadequate amount of blood or oxygen/(coronary) blood supply reduced

• Medication
  • Beta blockers reduce heart rate and reduce oxygen required by heart
  • Aspirin prevents blood clotting and thrombosis formation
  • ACE inhibitors stabilize plaques → prevent thrombus to break off
  • Statins reduce LDL and increase HDL
• Angioplasty
  • Deflated balloon-like device is passed up to the heart via the aorta
  • Guided into damaged coronary artery and inflated to stretch the artery
• Heart by-pass graft
  • Leg veins and arteries from chest are used to by-pass the blocked region of the coronary artery
  • Involves open heart surgery
• Reperfusion therapy after a myocardial infarction
  • Angioplasty done within 90 minutes of onset of chest pain
  • May prevent irreversible damage to the heart muscle

This topic involves learning a lot of new terminology. Below is a list of the terms which you will need to be comfortable using:

Pathogen

Fever

Inflammation

Phagocytosis

Neutrophils

Macrophage

Immunological memory

Self and non-self

Complement proteins

Immunoglobulin

Antigen

Plasma cell

Memory cell

Major Histocompatibility complex

T-helper cell

Cytokines

Primary immune response

Secondary immune response

T-lymphocytes

B-lymphocytes

Natural immunity

Artificial immunity

Active immunity

Passive immunity

Polyclonal antibodies

Monoclonal antibodies

Vaccine

After studying this topic you should have an understanding of how the body is equipped to keep most microorganisms out and how it responds to and destroys any microorganisms which do manage to get through the body’s barriers.

• Species resistance - many microorganisms are  specific and will not cause infection in us.
• Physical and chemical barriers - pathogenic organisms (those which can cause disease) might enter the body at any point where there is an ‘interface’ with the external environment. Your body has several physical and chemical barriers which try to prevent this:
  • Eyes are protected by tear production - contain antibacterial enzyme - lysozyme
  • Ears secrete wax - antiseptic properties
  • Sweat - contains an antiseptic
  • Stomach acid - many bacteria cannot withstand the low pH environment
  • Urine - antiseptic properties
  • Digestive tract - contain large numbers of harmless bacteria which out compete the pathogenic microorganisms. This is known as your natural flora. Any disruption to this can lead to infection - the cause of stomach upsets whilst taking antibiotics.
  • Airways - epithelial cells lining the respiratory system produce mucus and are ciliated. Bacteria are trapped in the mucus and wafted up towards the oesophagus by the cilia.
  • Blood clotting 
• Immune responses - if a pathogenic microorganism does make it past the physical and chemical barriers listed above then the body’s immune system mounts a response. This can be non-specific or specific as you will discover shortly.

The entire immune response depends on the body detecting the difference between self and non-self antigens:

• Self-antigen
  • Only found on the host's own cells and does not trigger an immune response
  • As these are proteins, their structure depends on the amino acid sequence
  • The gene for this sequence is highly polymorphic, having several alleles at each loci
  • There is great genetic variability between individuals
  • Thus, antigen is different in other people → injection would cause an immune response
  • There is only 25% chance that siblings will possess an identical antigen (transplant will not be rejected)
• Non-self-antigen
  • Found on cells entering the body (e.g. bacteria, viruses)
  • Can also be displayed by cancer cells
  • May cause an immune response

Once a foreign antigen has been detected, the non-specific immune response is triggered. The temperature of the body will rise - FEVER - This higher temperature causes damage to the pathogenic cells. The site of infection will become swollen - INFLAMMATION - The area will be red, swollen, painful and feel hot to the touch. This is because the blood vessels in the affected area become more permeable thus allowing more white blood cells and important blood proteins such as antibodies to flood into the infected area and deal with the infection. Any pathogenic microorganisms found will be engulfed and destroyed -PHAGOCYTOSIS - by phagocytic cells entering the infected area. Damaged or infected tissue releases chemical mediators which attract the neutrophils and macrophages (most common phagocytic white blood cells).

• Neutrophils primarily engulf bacteria
• Macrophages engulf larger particles; including old and infected red blood cells

Another event in the non-specific immune response is the activation of the complement protein cascade. The complement proteins are blood proteins, which due to inflammation enter the site of infection. Damaged tissue is capable of activating this biochemical cascade which results in the formation of a protein complex which is then able to lyse (burst) the invading microorganism. Looking at an image will help you to understand this system better - again an internet image search will help.

If, despite the initiation of the non-specific response (FEVER, INFLAMMATION, PHAGOCYTOSIS) the infection still remains, the specific immune system will begin to act. This as its name suggests depends on recognition of SPECIFIC antigens present on the invading microorganism. Activation of this response results in the formation of antibodies and immunological memory to protect you from further infection by that SPECIFIC microorganism.
There are two types of specific immune response:

• The Humoral, or antibody-mediated response
• The Cell-mediated response

The Humoral Response

The humoral response is mainly involved in the elimination of pathogenic microorganisims which do not enter body cells - bacteria. As mentioned above, this response relies on the production of antibodies. Antibodies are secreted by B-lymphocytes and produced in response to a specific (foreign) non-self antigen. The B-lymphocyte's receptor site will match the non-self-antigen. Each antibody is produced by one type of B-lymphocyte for only one type of antigen. In diagrams you can recognise the antibody as they are a Y-shape. An internet image search for a diagram of an antibody would help here:

• The two ends of the Y are called the Fab fragments
• The other end is called the Fc fragment
• Fab fragments are responsible for the antigen-binding properties
• Fc fragment triggers the immune response

The antigen binds to specific Fab fragment of B cell receptor immunoglobulin

• This produces a short and weak response
• T helper cells are required to trigger the true potential of B cells

Once activated, the B cell grow and produce many clone cells. The clone cells have the same Fab fragment that recognizes the same antigen. Most of these clone cells differentiate into plasma cells which secrete large amounts of antibodies. Some of the clone cells differentiate into memory cell.
The antibodies which are released are specific for the original antigen and are capable of a variety of effects:

• Agglutination - making the pathogens clump together
• Acting as an antitoxin - to neutralise toxins produced by bacteria
• Lysis - digests bacterial membrane, killing the bacterium

Opsonisation - the pathogen is coated in protein that identifies them as foreign cells making them more obvious targets for phagocytosis and destruction

Exposure of same antigen causes activation of memory cells. They are present in the glandular tissue and will immediately recognize the antigen if presented with it. They are capable of producing larger amounts of antibodies in a much quicker time meaning that the pathogenic microorganisms are destroyed quickly and the infection never takes hold. This is immunological memory.

Cell-Mediated Response

Pathogens that quickly enter cells (viruses, tuberculosis) are more difficult to remove. The only way of clearing the infection is to destroy infected cells. No antibodies involved in the cell-mediated response. It is done by binding to the self and non-self antigen which prevents destruction of harmless body cells. The self antigen is a MHC (Major Histocompability Complex) protein present on almost all body cell and the non-self antigen (from viruses, bacterium, cancer, foreign cell, parasite) is an antigen which has been processed and displayed on the surface of the infected cell.

A macrophage engulfs the pathogen and processes its foreign antigen. The non-self antigen is transported to the plasma membrane surface of the macrophage. This cell is now called an antigen presenting cell (APC). Activated B-cells can also act as antigen presenting cells.

T Helper cells (Th cells) recognise the foreign antigen present on the APC. They then activate cytotoxic T cells and B cells to destroy the infected cell:

• T killer cells (cytotoxic T cells)
  • Must recognize self and non-self antigen to attach to infected cell
  • Directly kill pathogen by injecting proteases into the infected cell
  • Detach to search for more foreign cells
• T-Suppressor cells switch off the T and B cell responses when infection clears otherwise your T killer cells would destroy your healthy body cells long after the infection had gone. This is the basis of autoimmune disease. Experiments with mice have shown that destroying their T-suppressor cells leads to the development of conditions very similar to human autoimmune diseases such as multiple sclerosis and rheumatoid arthritis.

As with the humoral response, this involves the development of memory cells. Some of the T cells differentiate into T-memory cells which remain in the circulation and respond quickly when same pathogen enters body again.

HIV

The HIV virus has specific proteins which recognise the T helper cells. It enters and destroys these cells and therefore immunosuppress the patient as:

• Other immune cells are not activated
• The humoral response cannot be launched without Th cells / require co-stimulation of Th cells

AIDS develops as the immune system becomes totally suppressed. A patient with end stage AIDS will have multiple opportunistic infections (caused by microorganisms usually present but non pathogenic on or in the body) and possibly large numbers of tumours as a result of the suppressed immune system.

If antibodies are acquired by an individual then this is an example of passive immunity. Natural passive immunity happens when antibodies are passed from mother to foetus across the placenta and from mother to baby in the colostrums and milk during breast feeding.Artificial immunity can be initiated in individuals. Artificial active immunity is the result of vaccination. If a patient is given an ‘agent’ containing the same antigens as the pathogenic microorganism then their body will produce antibodies against the pathogen. There are many different types of vaccine used:

• Live attenuated: organism is alive but has been modified/weakened so that it is not harmful eg. MMR (measles, mumps, rubella)
• Inactivated: dead pathogen but antigen is still recognised and an immune response triggered eg. Pertussis (whooping cough) andPoliomyelitis
• Toxoid: vaccine contains a toxin eg. Diphtheria andTetanus
• Subunit: contains purified antigen that is genetically engineered rather than whole organism eg. Haemophilus influenza b - causes epiglottitis, meningitis and Meningococcal C - causes serious septicaemia, meningitis and Pneumoccocal - causes meningitis which results in permanent disabilities in >30%!

A vaccine may cause swelling, mild fever, and malaise and you should NEVER give live vaccines to children with an impaired immune system!

Active (Antibodies made by the human immune system, long term acting due to memory cells)

Passive (Given-Antibodies, short term acting)

Natural

- Response to disease
- Rejecting transplant

- Acquired antibodies
(via placenta, breast milk)

Artificial(immunisation)

Vaccination
(Injection of the antigen in a weakened form)

- Injection of antibodies from an artificial source, e.g. anti venom against snake biter

Differences

- Antibody in response to antigen
- Production of memory cells
- Long lasting

- Antibodies provided
- No memory cells
- Short lasting

Monoclonal antibodies are produced by just one type of B cell. They are therefore highly specific and are suitable for use in many research situations. The methods used to produce them are outlined below.

Hybridoma

• B cells are fused with tumour cells in the lab
• Divide rapidly to form a clone of identical cells
• Specific monoclonal antibodies are continuously produced and useful as
  • Tumour markers (antigens not present on non-cancer cells / attach to cancer cells only)
  • Anti-cancer drugs attached to monoclonal antibodies - deliver drug directly to cancer cells, fewer side effects

• Monoclonal antibody is an antibody that is of just one type
• Used to target the treatment of cancer cells or to screen (AIDS) in contaminated blood
• Antibody direct enzyme prodrug therapy techniques (ADEPT)
  • Monoclonal antibodies are tagged with an enzyme that converts the prodrug (inactive drug) to an active form that kills cells (i.e. is cytotoxic)
  • The prodrug is injected in high conc
  • Attached to a monoclonal antibody, enzyme activates the drug and kills only cancer cells
• In immunoassays, they can be labelled (radioactively) making them easy to detect
• In the enzyme-linked immunosorbant assay (ELISA) technique, they are immobilised on an inert base and a test solution is passed over them
  • Target antigen combines with immobilised monoclonal antibodies
  • Second antibody attaches with an enzyme and binds to the monoclonal antibodies and to the target antigen as well
  • Substrate is added which is converted to a coloured product by the added enzyme
  • Conc. of colour tells us the amount of antigens present in the test solution

• Used to detect drugs in urine of athletics or in home pregnancy tests (where an antigen in human chorionic gonadotrophin (hCG) is secreted by the placenta)
• Transplanted organs have non-self-antigens triggering antibodies to attack the organ, leading to its rejecting
• T-Lymphocytes are needed for B-lymphocytes to function
• Monoclonal antibodies against T-lymphocytes can be used to prevent B-lymphocytes from functioning, thus blocking the rejection of transplanted organs
• [EXAM] Helping to diagnose between two pathogens because
• Antigens are on cell-surface membrane
• Monoclonal antibody reacts with specific antigen only
• Thus, detects presence of special bacteria because of a different antigen on another, different bacteria

The digestive system is a tube through which food passes from the mouth where food is ingested to the anus where it is egested. It consists of a series of organs, each with a distinct structure and function. During the digestive transit food is broken down into substances suitable for absorption into the bloodstream.
The gut wall has the same basic structure along its length. There are three main layers:

• An outer, muscular layer. Circular and longitudinal layers of smooth muscles are present. Alternate contraction of these muscles moves food along the digestive tract (peristalsis)
• A middle layer of connective tissue - submucosa
• An inner layer - mucosa

Oesophagus

• Muscular tube carrying food from the mouth to the stomach

Stomach

• Elastic and muscular organ which can expand
• Highly folded mucosa
• Gastric pits secreting gastric juices containing digestive enzymes (proteases)
• Contraction and relaxation of the muscular wall mix the food thoroughly

Small Intestine

• The site of chemical digestion and absoption of the products of lipids, polysaccharides and proteins
• Highly folded mucosa - arranged in villi (finger like projections to increase surface area for absorption)
• Epithelial cells lining the small intestine have a folded cell membrane -microvilli to further increase the surface area for absorption

Large Intestine

• The site of absorption of water
• Undigested food matter forms faeces

Rectum

• Faecal matter is stored here before egestion

• Large molecules (starch, proteins, TAG) are too big and insoluble to be absorbed
  • Polymers have to be broken down into monomers
  • With help of hydrolytic enzymes - reaction requires H2O
  • Note: TAGs are not polymers but also need to be broken down
• Different enzymes break down different food
  • Work best at body temperature (37°)
  • Work in different conditions at different pH (stomach is acidic, intestine is alkaline)
• Hydrolysis
  • Proteins → amino acids
    • Essential amino acids: cannot be synthesised and must be present in diet
    • Non-essential amino acids: synthesised from essential amino acids by transamination in the liver
  • TAG → glycerol and fatty acids
  • Polysaccharides → monosaccharides

• Proteins are made up by different combinations of 20 amino acids
  • Common structure -COOH group -NH2 group
  • Amino acids differ in their R-group
• Tertiary structure
  • Complex globular 3D shape
  • Folding and twisting of polypeptides (H-bond, ionic bonds, disulphide bridges)
  • Polypeptides contain many peptide bonds
• Same amino acid sequence → ALWAYS same shape
• Bonds found in proteins
  • Hydrogen bonds, Between R-groups, Easily broken, but present in larger numbers. The more bonds, the stronger the structure
  • Ionic bonds, Between -COOH and -NH2 groups
  • Disulphide bridges, Between two sulphur-containing cysteine side chains. Strong bonds found in skin and hair
• Denaturation
  • Destruction of tertiary structure, can be done by heat
  • Protein structure is lost and cannot reform → dysfunctional

• All enzymes are globular proteins → spherical in shape. Control biochemical reactions in cells
• They have the suffix "-ase"
• Intracellular enzymes are found inside the cell
• Extracellular enzymes act outside the cell (e.g. digestive enzymes)
• Enzymes are catalysts → speed up chemical reactions
  • Reduce activation energy required to start a reaction between molecules
  • Substrates (reactants) are converted into products
  • Reaction may not take place in absence of enzymes (each enzyme has a specific catalytic action)
  • Enzymes catalyse a reaction at max. rate at an optimum state
• Lock and key theory, Only one substrate (key) can fit into the enzyme's active site (lock). Both structures have a unique shape
• Induced fit theory. Substrate binds to the enzyme's active site. The shape of the active site changes and moves the substrate closer to the enzyme. Amino acids are moulded into a precise form. Enzyme wraps around substrate to distort it
  •  
  • This lowers the activation energy
  • An enzyme-substrate complex forms → fast reaction
  • E + S → ES → P + E
• Enzyme is not used up in the reaction (unlike substrates)

• Changes in pH
  • Affect attraction between substrate and enzyme
  • Ionic bonds can break and change shape → enzyme is denatured
  • Charges on amino acids can change → ES complex cannot form
  • Optimum pH (enzymes work best) pH 7 for intracellular enzymes. Acidic range (pH 1-6) in the stomach for digestive enzymes (pepsin). Alkaline range (pH 8-14) in oral cavities (amylase)
  • pH measures the conc. of hydrogen ions → higher conc. will give a lower pH
• Enzyme conc
  • Proportional to rate of reaction, provided other conditions are constant
  • Straight line
• Substrate conc.
  • Proportional to rate of reaction until there are more substrates than enzymes present
  • Rate of reaction increases, Substrate binds to active site, but more enzymes are available. Rate increases if more substrate is added
  • Eventually, curve becomes constant (no increased rate)
    • Substrates occupy all active sites (all enzymes)
    • Adding more substrate won't yield more product, as no more active sites are available

• Increased Temperature
  • Increases speed of molecular movement → chances of molecular collisions → more ES complexes
  • At 0-42°C rate of reaction is proportional to temp
  • Enzymes have optimum temp. for their action (usually 37°C in humans)
  • Above ≈42°C, enzyme is denatured due to heavy vibration that breaks -H bonds
  • Shape is changed → active site can't be used anymore
• Decreased Temperature
  • Enzymes become less and less active, due to reductions in speed of molecular movement
  • Below freezing point
    • Inactivated, not denatured
    • Regain their function when returning to normal temperature
  • Thermophilic: heat-loving
  • Hyperthermophilic: organisms are not able to grow below +70°C
  • Psychrophiles: cold-loving

• Organic molecules which contain C, H and O
• Bind together in the ratio Cx(H2O)y
• Monosaccharides → single sugar (monomer)
  • Ribose found in RNA and DNA
  • Deoxyribose part of nucleic acids
  • Glucose is the main energy source in brain
  • Fructose is found in sweet-tasting fruits
• Disaccharides → two sugar residues (2 monomers)
  • Sucrose (glucose + fructose) → transport carbohydrates in plants
  • Maltose (glucose + glucose) → formed from digestion of starch
  • Lactose (glucose + galactose) → found in milk
  • Lactose intolerance
• Polysaccharides → many sugar residues (polymer)
  • Starch (alpha-glucose) → main storage of carbohydrates in plants
  • Glycogen (alpha-glucose) → main storage of carbohydrates inhumans
  • Cellulose (beta-glucose) → component of plant cell wall, important for digestion

• 
  Consists of amylopectin and amylose (both are made of α-glucose)
  • Amylopectin is branched via 1,6-glycosidic bonds
  • Amylose forms a stiff helical structure via 1,4-glycosidic bonds
  • Both are compact molecules → starch can be stored in small space
• The ends are easily broken down to glucose for respiration
• Does not affect water potential as it is insoluble
• Readily hydrolysed by the enzyme amylase produced by the pancreas and present in saliva
• Found in corn (maize), wheat, potato, rice

• Reducing sugars (all monosaccharides and some disaccharides) can be tested for using Benedict’s reagent. After placing the sample and the reagent in a hot water bath a brick red precipitate will be produced if reducing sugars are present.
• Non reducing sugars require a negative result using Benedict’s reagent. Add hydrochloric acid to the sample and heat. Neutralize the solution using sodium hydrogencarbonate and then test again with Benedict’s solution. A positive result will be found.
• Starch can be tested for using iodine. In the presence of starch iodine will turn blue - black.

The four chambers of the heart are continually contracting and relaxing in a sequence known as the cardiac cycle. Contraction of a chamber is SYSTOLE(pronounced sistolee) and relaxation DIASTOLE (pronounced diastole). The left and right sides of the heart actually contract simultaneously but in order to understand how blood moves through the circulatory system we will consider each half separately.

• Right atrium receives blood from
  • Superior vena cava (SVC) - carries blood from upper body (head, arms)
  • Inferior vena cava (IVC) - carries blood from lower body (chest, abdomen, legs)
• Blood flows from right atrium, across tricuspid valve, into right ventricle
• Blood leaves right ventricle and enters pulmonary artery
  • Backflow into RV prevented by semilunar pulmonic valve
  • Deoxygenated blood arrives at lungs via pulmonary artery
  • Oxygenated blood leaves lungs via pulmonary vein
• Blood from pulmonary vein enters left atrium
• Blood flows from left atrium, across mitral valve, into left ventricle
• Left ventricle has a thick muscular wall / generates high pressures during contraction
• Blood from LV is ejected, across aortic valve, into aorta

The problem of backflow:

• Between each chamber of the heart are valves which prevent the blood being forced back into the chamber from which it was just pushed out. Between the atria and the ventricles are the tricuspid and mitral valves (mitral is on the left and tricuspid on the right). These are known as the atrioventricular valves. If you’ve dissected a heart you will have seen fibrous strands leading from ‘flaps’ at the top of the ventricles. These strands (cordae tendinae) are attached to papillary muscles which contract during ventricular systole which generates tension pulling the AV valves shut.
• The pulmonary artery and the aorta also contain valves to prevent the blood from these vessels falling back into the ventricles. These are known as the Semilunar valves (pulmonic and aortic). They do not work in the same way as the AV valves. Instead, the pressure of blood within the vessel actually causes the closure of the semilunar valves.

At several points so far, pressure has been mentioned. It is an important aspect of the cardiac cycle and a factor which can be used to identify which stage of the cardiac cycle a heart is in. In fact, examiners love to provide you with pressure graphs and ask you to analyse the cardiac cycle. It is therefore worth us spending a little time going over the principles of ‘Isovolumetric contraction’ - it sounds worse than it is!

As a chamber fills with blood, the pressure is going to rise. When a chamber contracts, the pressure is going to rise. Changes in pressure affect whether a valve is open or closed. Fluids always move from areas of high pressure to areas of low pressure. Let us think through the cardiac cycle in terms of pressure:

• As the blood passes into the atria, the valves are open so most will fall immediately into the ventricle. There is a gradual rise in pressure in the atria until the end of atrial systole when the blood has moved into the ventricles.
• The intraventricular pressure rises as the ventricles fill with blood. This closes the AV valves.
• Contraction of the ventricles means that the intraventricular pressure is higher than the pressure in the artery which forces the blood out of the ventricle and into the aorta or pulmonary artery (depending on which side of the heart you’re looking at).
• The increase in pressure of the artery causes the closing of the semilunar valves preventing the back flow of blood into the ventricle.

The heart has a unique ability to beat (contract) on its own. The cardiac muscle cells are therefore myogenic. Regulation of this contraction though is required to ensure that the muscle cells contract in a specific way and that your heart can respond to meet the energy demands of your body. Nervous and hormonal stimulation both have an effect on the way that the heart contracts.On the right atrium is a structure called the Sinoatrial Node, or the SAN. This bundle of cells acts as a pacemaker controlling the rate of contraction - the heart rate. Stimulation of this node initiates a wave of electrical impulses which spread aross the atria causing atrial systole. If cardiac cells are stained with a voltage sensitive dye then a wave of contraction can be seen rippling across the atria (all muscular contraction relied on electrical changes).

The electrical signal in the atria is picked up by a second node, the AtrioVentricular Node (or the AVN) which passes the signal down to the apex of the heart (bottom of the ventricles). This is passed through specialised conducting cardiac muscle fibres called the Bundle of His. From the apex, the electrical activity is spread throughout the ventricles along Purkinje fibres. This means that the ventricles contract from the bottom up once they have filled with blood.

Air comes into the respiratory system through the nose. The air is filtered in the nostrils due to the presence of small hairs. It is also moistened and warmed by the nasal cavities and the mucus present traps foreign particles which are then propelled towards the throat by the cilia on the epithelial cells.From the nose, the air passes into the pharynx and is drawn into the larynx and then the trachea. The epiglottis is found within the larynx. This structure prevents food and drink passing into the respiratory system. When swallowing, the larynx is pulled up and the epiglottis flaps back to block the entrance of the larynx.The trachea contains C-shaped cartilage rings which prevent the tube collapsing due to the change of pressure. It divides into 2 tubes with smaller diameter called bronchi. Each bronchus is lined with ciliated epithelia to waft mucus upwards towards the throat. There is asymmetry in the respiratory system - the right bronchus is bigger than the left one and at a more vertical angle. This makes it a common site for inhaled foreign bodies.The bronchi further divide into bronchioles. These are important because their diameter can be controlled by smooth muscles contraction or relaxation. The bronchioles terminate with alveoli (100µm in diameter) which are the site of gas exchange.

The process of breathing in and out is known as ventilation. Breathing in (inhalation) relies on air being drawn into the lungs because the air pressure in the lungs is lower than that in the atmosphere. This lower pressure is created by the contraction of the diaphragm and the external intercostal muscles. This flattens the diaphragm and moves the ribs up and out. The volume of the thorax therefore increases, decreasing the pressure and allowing air to enter into the lungs.

Exhalation (breathing out) requires the air pressure in the lungs to be increased. As with inhalation this occurs because of changes in the diaphragm and intercostal muscles. The diaphragm and external intercostal muscles relax, raising the diaphragm back up into a dome shape and pulling the ribs down and in. These changes reduce the volume of the thoracic cavity. This rise in air pressure in the lungs means that air is moved out of the lungs. If exhalation is forced then the internal intercostal muscles contract further raising the pressure in the thoracic cavity.

Fick was a busy man, he has both a law and a principle named after him AND is credited with the invention of the contact lens! Fick’s law states that:

The rate of diffusion across a fluid membrane is proportional to (surface area x conc. difference) / distance

Efficient gas exchange therefore requires: Large surface area, Large concentration, Short diffusion pathway (thickness of the membrane molecules must travel to diffuse across)

Large organisms have a small surface area : volume ratio, Decreases the rate of diffusion, Large animals loose less heat than small animals, Don't require a high metabolism to maintain body temperature, Feed only once. 

Small organisms have a large surface area: volume ratio, Lose heat very readily, Need a high metabolism to maintain body temp, Must feed continuously. 

The greater the partial pressure of O2 in alveolar air the more O2 will dissolves in blood (Henry's Law)

It seems that Henry was a master of stating the obvious! Let’s try to further understand the process of how oxygen moves across the alveolus and into the blood.

The alveoli - the site of gas exchange in the lungs is composed of epithelial cells. This has evolved to allow efficient diffusion of gases (large surface area short diffusion pathway) down their concentration gradients. O2 therefore diffuses from air to blood where it then associates with haemoglobin and CO2 diffuses from blood to the air in the alveolus.

A protein called surfactant is produced by the alveoli, which prevents the alveolar surfaces from sticking together when they deflate. The alveoli also contain phagocytes to kill bacteria that have not been trapped by mucus which may later cause disease.

At least one in ten people suffer from asthma at some point during their lives with the majority of cases presenting in childhood. The condition is caused by inflammation of the bronchioles. In an asthma attack:The smooth muscle in the bronchiole wall contracts which narrows the lumen. The epithelial cells lining the bronchiole secrete more mucus than normal which obstructs the movement of air through the respiratory system. Breathing rate increases but the tidal volume is reduced, Gas exchange in the alveoli is reduced. Asthma attacks can be triggered by many different stimuli. Common triggers include:

• Some diseases e.g. the common cold and flu
• Exposure to air pollution or dust
• Exposure to known allergens such as pollen, animal fur or certain foods
• Exercise - especially in cold air
• Psychological factors such as stress

There is no ‘cure’ for asthma but the condition can be treated and managed through the use of inhalers which administer drugs to the respiratory system. Normally an asthma sufferer would have two inhalers to be used in different ways. They will have one ‘Preventer’ which when used release anti-inflammatory drugs such as steroids to reduce the underlying inflammation and hopefully reduce the likelihood that a person will have an asthma attack. They will also be given an inhaler which should be used to relieve symptoms during an attack. This contains substances which dilate the bronchioles which should make breathing easier.

Fibrosis is the scarring of body tissue in this case - the lungs. The scarring causes a loss in elasticity of the tissue between the alveoli and contorts the bronchioles and alveoli. These pathological effects reduce lung capacity. The condition is highly linked to occupational hazards such as working with substances such as asbestos, coal dust and metal dust. Widespread fibrosis caused by inhalation of harmful substances is called emphysema. Infectious diseases such as tubercolosis can also leave small regions of the lungs with scarring. Fibrosis therefore refers to the consequence of diseases which produce lung damage.

A patient suffering from pulmonary fibrosis would have shortness of breath and/or a cough. At present there is no treatment for this condition and a lung transplant is the only treatment option which will improve long - term survival.

This condition is caused by rod-shaped bacteria: Mycobacterium tuberculosisOR Mycobacterium bovis.

Symptoms:, persistent cough, tiredness, loss of appetite and weight loss, fever, coughing up blood.

This disease is spread through the air in droplets released when an infected person coughs or sneezes. Coughs and sneezes really do spread diseases! Unusually the bacterium causing TB can survive for a long period of time even in dried droplets. This means that close contact with an infected person over a period of time can lead to transmission of the disease.

People most at risk of contracting TB are those who: are in close contact with infective individuals. live or work in care facilities, are from countries in which TB is prevalent. have reduced immunity (the very young or very old, those with AIDS, people taking immunosuppresants, malnourished individuals, alcoholics, homeless people)

Once inside a person’s respiratory system there is a plentiful supply of oxygen allowing rapid growth and division of the bacteria. At this early stage the person often develops pneumonia. The white blood cells of the immune system respond rapidly to the infection to try and prevent the bacteria from spreading. This process results in the formation of scar tissue which contains the infection in an inactive state.

If the body’s immune system becomes weakened the TB bacteria can break through the scar tissue resulting in the return of pneumonia and the spreading of the bacteria to other parts of the body (the kidneys, bone and linings of the brain and spinal cord are the most common sites affected).

Symptoms and Treatment:

There is a relatively long time between the time of infection and the onset of symptoms. A patient will present with tiredness, weight loss, fever, coughing, chest pain and shortness of breath (this is due to the presence of scar tissue in the lungs).

Inactive TB may be treated with an antibiotic and active TB will usually require several antibiotics to combat the infection.

Emphysema can be an inherited condition but most cases arise as a result of smoking. The toxins passed into the lungs when smoking trigger an immune response which ultimately leads to the destruction of the lung tissue.Your lungs contain white blood cells which ‘patrol’ the lungs phagocytosing any harmful pathogens or particles which are inhaled. These phagocytes release enzymes which catalyse the breakdown of proteins found in the connective tissue between the alveoli and bronchioles. This makes it easier for them to move around the lung tissue to engulf and kill the invading pathogen or particle.. The smoke from cigarettes contains several chemicals which stop lung cells from producing. This means, that the destruction of elastin will increase, damaging the elastic tissue of the lungs making it harder for a person to exhale. Other proteins are also destroyed by the enzymes secreted by the pathogens meaning that the alveoli walls can be damaged and the surface area available for gas exchange is reduced.A reduced area for gas exchange means that a person with emphysema’s blood will contain a reduced concentration of oxygen. This will limit the amount and rate of aerobic respiration achievable by their cells making any activity a great effort.

Microvilli

• Adaptation of cells to increase surface area for absorption or secretion
• Found on epithelium of the small intestine

Nucleus

• Contains DNA
• DNA arranged into long thin threads known as chromosomes
• In most cells the chromosomes are arranged in homologous pairs
• Surrounded by nuclear envelope
• This has pores to allow communication between the nucleus and cytoplasm

Plasma Membrane

• Sea of phospholipids - arranged as a bilayer
• Intrinsic and extrinsic proteins float within the phospholipids
• Selectively permeable barrier - controls movement of substances betweenthe internal and external environments

Ribosomes

• 20-30nm in size
• Small organelles often attached to the ER but also found in the cytoplasm
• Large (protein) and small (rRNA) subunits form the functional ribosome
  • Subunits bind with mRNA in the cytoplasm
  • This starts translation of mRNA for protein synthesis (assembly of amino acids into proteins)
• Free ribosomes make proteins used in the cytoplasm. Responsible for proteins that
  • go into solution in cytoplasm or
  • form important cytoplasmic, structural elements
• Ribosomal ribonucleic acid (rRNA) are made in nucleus of cell

• Rough ER
  • Have ribosomes attached to the cytosolic side of their membrane
  • Found in cells that are making proteins for export (enzymes, hormones, structural proteins, antibodies)
  • Thus, involved in protein synthesis
  • Modifies proteins by the addition of carbohydrates, removal of signal sequences
  • Phospholipid synthesis and assembly of polypeptides
• Smooth ER
  • Have no ribosomes attached and often appear more tubular than the rough ER
  • Necessary for steroid synthesis, metabolism and detoxification, lipid synthesis
  • Numerous in the liver

• Stack of flattened sacs surrounded by membrane
• Receives protein-filled vesicles from the rough ER (fuse with Golgi membrane)
• Uses enzymes to modify these proteins (e.g. add a sugar chain, making glycoprotein)
• Adds directions for destination of protein package - vesicles that leave Golgi apparatus move to different locations in cell or proceed to plasma membrane for secretion
• Involved in processing, packaging, and secretion
• Other vesicles that leave Golgi apparatus are lysosomes

• Microscopy
  • Magnification → increases the size of an object
  • Resolution/resolving power → ability to distinguish between adjacent points
• Calculating magnification
  • X = size of picture (measure the size of the diagram in the question)
  • Y = size of object in real life (often given in exam question)
  • Make sure Y has the same unit as X!
    • If X = mm and Y = μm
    • Convert mm to μm = X * 1000

Feature

Optical microscope

Electron microscope

Radiation

Light

Electrons

Magnification

400x (max1500)

≈500 000x

Resolution

2µm

1nm / 0,001µm
Electrons have a small wavelength
Thus, higher resolution

Vacuum in microscope

Absent

Present

Specimen is

- Alive or dead
- Stained

- Dead (vacuum!)

Transmission microscope:
Electrons pass through internal
structure of specimen

Scanning microscope:
Beams of electrons are reflected
off specimens surface. Allows a
three dimensional view

• Easily dissolved in organic solvents but not in water
• Triglycerides (fats and oils), Also called triacylglycerides (TAG)
  • Consists of 3 fatty acids linked by ester bonds to glycerol, Require 3 condensation reactions (but are not polymers!). Glycerol contains 3 -OH groups. One fatty acid contains a -COOH group.
  • Excess energy available from food is stored as TAG
  • Can be broken down to yield energy when needed
  • Contain twice as many energy stored per unit of weight as carbohydrates
• Saturated fatty acids -COOH group without double bonds in the carbohydrate chain
  • May cause blockage of arteries which can lead to strokes and heart attacks
  • High melting point / solid at room temperature (fats) / typicalanimal fats
• Unsaturated fatty acids
  • -COOH group with double bonds in the carbohydrate chain
  • Low melting point / liquid at room temperature (oils)
  • Found in plants
• Phospholipids, Found in cell membrane
  • Formed by replacing one fatty acids in a triglyceride with a phosphate group
  • Phosphate is polar / hydrophilic / does mix with H2O
  • Fatty acid tails remain non-polar / hydrophobic / insoluble, does not mix with H2O

• Membranes consist of a phospholipid bilayer studded with proteins, polysaccharides, lipids
• The lipid bilayer is semipermeable - H2O and some small, uncharged, molecules (O2, CO2) can pass through
• Phospholipids have two parts
  • "Head": hydrophilic → attracts and mixes with H2O
  • Two "fatty acid tails": hydrophobic

• Uses energy from moving particles (kinetic energy)
• Substances move down their conc. gradient until the conc. are in equilibrium
• Fick's law → rate of diffusion across an exchange surfaces (e.g. membrane, epithelium) depends on
  • Surface area across within diffusion occurs (larger)
  • Thickness of surface (thinner)
  • Difference in conc. gradient (larger)
  • (surface area * difference in conc.) / thickness of surface
• Microvilli
  • Extensions of the plasma membrane
  • They increase the surface area of the membrane
  • Accelerate the rate of diffusion

• Temperature increases rate of diffusion due to increasing K.E. (kinetic energy)

• transmembrane proteins form a water-filled ion channel
  • Allows the passage of ions (Ca2+, Na+, Cl-) down their conc. Gradient
  • NB: this is a passive process → no ATP required
  • Some channels use a gate to regulate the flow of ions
  • Selective permeability → not all molecules can pass through selective channels
• Transport mechanism
  • Carrier protein binds to substrate (specific molecule)
  • Molecule changes shape
  • Release of the diffusing molecule (product) at the other side of the membrane

• Special term used for the diffusion of water through a differentiallypermeable cell membrane
• Water is polar and able to pass through the lipid bilayer
• Transmembrane proteins that form hydrophilic channels accelerate osmosis, but water is still able to get through membrane without them
• Osmosis generates pressure called osmotic pressure
  • Water moves down its conc. gradient
  • When pressure is equal on both sites net flow ceases (equilibrium)
  • The pressure is said to be hydrostatic (water-stopping)

• Movement of solute against the conc. gradient, from low to high conc.
• Involves materials which will not move directly through the bilayer
• Molecules bind to specific carrier proteins / intrinsic proteins
• Involves ATP by cells (mitochondria) / respiration
  • Direct active transport - transporters use hydrolysis to drive active transport
  • Indirect active transport - transporters use energy already stored in gradient of a directly-pumped ion
• Bilayer protein transports a solute molecule by undergoing a change in shape (induced fit)
• Occurs in ion uptake by a plant root; glucose uptake by gut cells