Grade 12 Lesson Plan

PHOTOSYNTHESIS

 

//is a solar energy acquiring pathway occurring in autotrophic plants. It consists of two parts:

 

·        The light dependent pathway or reaction: Occurs in the grana of chloroplasts. They trap the sunlight’s energy and convert it to chemical energy ATP and NADPH.

 

·        The light independent pathway or reaction: Occurs in the stroma of chloroplasts. They take the chemical energy and use it to make glucose. Sunlight is not directly used in this pathway.

 

Do plants respire?

Review the structure of the leaf and stomata (p141-2)

Review the structure of a chloroplast (P143).

The light independent pathway was known as the Dark Reaction. Why was this changed?

What is photophosphorylation?

What is chlorophyll a and chlorophyll b?

What is a photosystem? Discuss the two types.

 

PHOTOPHOSPHORYLATION  //The phosphorylation of ADP to ATP in the light dependent pathway of photosynthesis.

 

THE PHOTOSYSTEM:  is a cluster of chlorophyll and proteins. It consists of two parts: the Antenna complex consisting of chlorophyll embedded in the thylakoid membrane which transfers energy to the Reaction Centre by passing it along a series of pigments to reach a chlorophyll a molecule in the Reaction Centre; and The Reaction Centre which is a transmembrane protein with a chlorophyll a molecule that begins the process of photosynthesis.

 

Photosystem I contains a chlorophyll a in the Reaction Centre that is called P700 because it maximally absorbs light at this wavelength.

Photosystem II contains a chlorophyll a in the Reaction Centre that is called P680 because it maximally absorbs light at this wavelength.

 

A. THE LIGHT DEPENDENT PATHWAY

·        Occurs in the grana i.e. the piles of thylakoids in the chloroplast.

·        Uses photosystems embedded in the thylakoid membranes.

·        In Non-cyclic photosynthesis, the only form we will deal with, the sun hits Photosystem II and this excites electrons.

·        The electrons enter an electron transport chain in which some of the energy is taken out of the electrons. This energy will be used to make ATP.

·        The same electrons are then accepted by the second photosystem, called photosystem I.

·        For the second time the electrons are excited by sunlight, and enter a second electron transport chain, in which some of the energy is again released from the electrons. This will be used to make more ATP.

·        The electrons, still containing the sun’s energy, are finally accepted by NADP and this, together with H ions, forms NADPH. The sun’s energy is trapped in the electron of the H atom.

 

·        Photolysis: Z protein uses the sunlight to split water into:

a.      H ions which will be used for making ATP

b.     Electrons which replace the excited electrons lost from the chlorophyll

c.     Oxygen which is respired

 

·        The H ions are pumped by the energy released from the electron transport chains to one side of the thylakoid membranes. This creates an electrochemical gradient that allows the H ions to run through H-ATPase pumps and thus generate ATP (chemiosmosis).

 

At the end of this pathway, NADPH and ATP have been formed and will be passed into the stroma of the chloroplasts for the second pathway.

 

b. THE LIGHT INDEPENDENT PATHWAY:

·        Occurs in the stroma of the chloroplast

·        The pathway is called the Calvin cycle and involves three phases:

 

1. Phase one: Carbon fixation

There are two options to phase one of the Calvin cycle: C3 photosynthesis and C4 photosynthesis:

 

Carbon Fixation in C3 photosynthesis:

·        Ribulose biphosphate (RuBp) (5-C) bonds to CO₂ to form an unstable 6-C intermediate (CO2 is fixed). The enzyme catalyzing the carbon fixation is rubisco. 

·        This splits into two 3-C molecules: 3-phosphoglycerate (PGA).

·        This process happens three times over, so that:

3CO₂ + 3RuBp à 6 PGA

It is called C3 photosynthesis because a three carbon compound is formed at the start of the Calvin cycle.

 

Carbon Fixation in C4 Photosynthesis

·        This occurs in sugar cane, corn and many grasses

·        Essentially the difference is an extra step before the one above. The carbon dioxide is stored before it is released into the Calvin cycle. The plant stores the carbon dioxide by attaching it to phosphoenolpyruvate to make oxaloacetate, a 4 carbon compound. This is why it is called C4 photosynthesis: the first step of the Calvin cycle involves a C4 compound.

·        The oxaloacetate is converted to malate and then when the plant wants to release the carbon dioxide, the malate is converted to pyruvate and carbon dioxide is released to ribulose biphosphate as above. The pyruvate is converted back to phosphoenolpyruvate for reuse.

·        These plants are also different in that the Light Independent pathway occurs in the cytoplasm not the stroma of the chloroplast. The carbon is fixed in mesophyll cells, and then the malate is pumped to special cells around vascular bundles called bundle sheath cells, where the carbon dioxide is released into the Calvin cycle. We say the first and second steps of the Calvin cycle are spatially separated.

·        The disadvantage is that the process is endothermic.

·        The advantage is that the rubisco is continually given a supply of carbon dioxide ensuring continual photosynthesis and minimising respiration or the breakdown of glucose back to carbon dioxide. It also means the plant can store carbon dioxide, and so close stomata to minimise transpiration.

 

NOTE: There is another type of plants called a CAM plant (succulents), which keeps its stomata open at night and closed during the day. At night it takes in carbon dioxide and fixes it just as the C4 plant does. The fixation is called Crassulacean acid metabolism (CAM). The difference with these plants is the carbon fixation occurs during the night, and the later release to rubisco for the rest of the Calvin cycle occurs during the day. This is called Temporal separation.

 

2. Phase 2: Reduction Reaction

·        Add ATP energy:

                The 6PGA + 6ATP à 6 molecules of     

                                   1,3 biphosphoglycerate

 

·        Add NADPH:

              6 molecules of 1,3 biphosphoglycerate + 6NADPH à

                                          6glyceraldehyde -3-phosphate (G3P)

 

3. Phase 3: RuBp regeneration

·        5 G3P are rearranged to form 3RuBp, using 3ATP

·        One G3P is left over

·        The three phases are repeated to make another G3P

·        The two G3P molecules will bond to form glucose

       (two 3C à 6C compound)

 

Overall process:

12H₂O + 6CO₂ + SUNLIGHT à 6O₂ + C₆H₁₂O₆ + 6H₂O

 

 

 

 

 

 

NUTRIENTS

 

MACRONUTRIENTS

• Required in large amounts
• Measured in g/ kg body mass per day (g/kg body/day)
• Carbohydrates, protein and fats or tryglycerides

 

MICRONUTRIENTS

• Required in small amounts
• Measured in mg or microg/kg body mass/day
• Vitamins and minerals

 

Note

1. Carbohydrates and fats provide us with energy
2. Protein, fats and minerals are important structural components of our body
3. vitamins and minerals enable our enzymes to catalyse biochemical reactions. Vitamins are also antioxidants

 

CARBOHYDRATES

 

//Compound of carbon and water: C_xH_2nO_n

The name usually ends in –ose

 

1. MONOSACCHARIDE (C₆H₁₂O₆):

• The simplest sugar
• Other sugars are broken down to this form by the body during digestion so that they can be absorbed.
• Includes glucose, fructose and galactose

 

2. DISACCHARIDE (C₁₂H₂₂O₁₁):

• Two monosaccharides bonded together
• glucose + glucose = maltose

broken down by maltase

found in sprouting grains

• b. glucose + fructose = sucrose

broken down by sucrase

cane sugar

also found in beets, pineapple and carrots

• c. glucose + galactose = lactose

broken down by lactase

lactose intolerance is due to a lack of lactase enzyme

milk sugar

 

3. POLYSACCHARIDE (C₆H₁₀0₅)_n + n(H₂O) )

• Many simple sugars joined together.
• “Complex carbohydrate”

1. starch: many maltose units bonded together. Made by plants
2. cellulose: many glucose units joined by a bond humans cannot break, and therefore cannot use for energy. Fibre.
3. Glycogen: glucose bonded together and formed by animals to store energy in the muscles for exercise and the liver to replenish blood glucose.

 

 

FATS/LIPIDS/TRIGLYCERIDES

• Cannot dissolve in water
• Consist of carbon, hydrogen and oxygen
• Are made up of 3 fatty acids and one glycerol molecule.
• Saturated fats are the animal fats that are stable and solid at room temperature. Palm and coconut oil are also saturated.
• Unsaturated fats are plant fats that are liquid at room temperature (oils). Fish oil is also unsaturated. Monounsaturated oils like olive oil and peanut oil are quite stable but the polyunsaturated oils like the seed oils and fish oil are very unstable and easily break down when exposed to heat, light and oxygen. They should never therefore be exposed to these three elements, or else they will become toxic free radicals.

The polyunsaturated oils include the essential fatty acids which must be included in the diet to maintain health – these are the omega 6 and omega 3 oils found in nuts, seeds and oily fish.

 

 

 

PROTEINS

• Are made up of amino acids.
• Amino acids are made up of nitrogen, cargon, hydrogen, oxygen, phosphorus and sulphur

(NCHOPS)

• Amino acids are joined into long peptide chains (primary structure). These are over and over to give the secondary, tertiary and quartenary structures.
• The essential amino acids are lysine, isoleucine, leucine, valine, methionine, phenylalanine, tryptophan and threonine. They must be in the diet, they cannot be made in the cells and they are essential to health.
• All proteins are rated for their quality in two ways:

1. complete vs incomplete protein: complete proteins contain all the essential amino acids in the right proportions
2. biological value (B.V) scale: is a measure of the body’s ability to retain and use the nitrogen in the protein per gram of protein eaten.

• Quality proceeds in the following way: animal >legume>cereal>vegetable

 

 

Vegetarians that eat eggs and dairy will get all the essential amino acids and are getting good protein. But Vegans that only eat vegetables will not get complete protein unless they combine grains, legumes, nuts and seeds in such a way as deficiencies of amino acids in one are compensated by another. They still need to eat a lot to get enough good quality protein, and a lot is lost to the reduced digestibility of this diet. They also lack vitamin B12 (only made by microbes and animals) and iron as animal iron is the most absorbable.

 

 

METABOLISM

P58-68 of Nelson

 

//METABOLISM is the sum of all anabolic and catabolic processes in a cell or organism. Energy is either used or released in this process. Energy is the ability to do work. Work is the transfer of energy from one place to another.

 

FIRST LAW OF THERMODYNAMICS: Energy is neither created nor destroyed, but is converted from one form into another. Losses and gains balance out.

 

METABOLIC REACTIONS

1. If the energy absorbed from breaking bonds is greater than the energy released in forming the product bonds, there is a net absorption of energy: Endothermic reaction (endogonic reaction).
2. If more energy is released during bond formation than that absorbed during bond breaking there is a net energy output. This is an Exothermic reaction (exogonic reaction). Here the bonds of the products are more stable than those in the reactants. These reactions are therefore more likely to occur spontaneously.

 

The overall energy change that occurs in a chemical reaction is called the Enthalpy (H) of a reaction . H is + for Endothermic and – for Exothermic reactions.

 

3. COMBUSTION is an exothermic reaction (-H_combustion) . Organic compounds react with oxygen to produce CO₂ and H₂O: e.g. C₆H₁₂O₆  + O₂ à 6CO₂ + 6H₂O

 

4. Whether a reaction occurs spontaneously depends on:
a. Enthalpy – exothermic are more likely to be spontaneous.

b. entropy// a measure of the change in randomness/disorder (S)

Entropy increases when disorder increases. It increases when:

• Solids become liquid/gas
• Catabolism
• Diffusion: Solutes move from high [ ] to low [ ] until they are uniformly distributed

 

4.GIBBS FREE ENERGY (G)//energy that can do useful work.

In the late 1800's, Josiah Gibb drew a relationship between heat energy, entropy and temperature.

He showed that free energy (G) of a system can be defined as

G = H - TS

where H is the heat energy of the system, T is the temperature, and S is entropy.
Every chemical reaction results in a change in free energy which we can measure as

G = G_products - G_reactants = H_products - H_reactants - T(S_products - S_reactants) = H - TS

The net direction of a chemical reaction will be from higher to lower energy. In other words, if the energy of the reactants is higher than the energy of the products, G_reactants > G_products, the reaction will occur spontaneously. In such a case, G < 0, and the free energy of the system decreases with the reaction. In the opposite case, G > 0, and energy is required for the reaction to occur.

 

5. All changes in the universe either directly or indirectly result in an increase in entropy of the universe. This is the second law of thermodynamics: the entropy of the universe increases with any change that occurs. S (change in entropy) > 0.

 

6. METABOLIC REACTIONS

• Are enzyme catalysed
• Are all reversible.

If the reaction reaches eqlm, change in Gibb energy is zero – this is a dead cell.

 

ADENOSINE TRIPHOSPHATE

·         Purine nitrogenous base adenine

·         Pentose sugar ribose

·         3 phosphate groups   ….see p65 of Nelson

·         ATPase catalyses the hydrolysis of the last phosphate with the release of 54kJ/mol (under standard lab conditions this is 31kJ)

·         Phosphorylation is the attachment of inorganic phosphate to ADP

·         There is enough ready formed ATPof 5mmol/kg muscle, enough for a few seconds. In addition there is 15mmol/kg creatine phosphate.

·         One mole of glucose = 180g = 3000kJ = 100moles of ATP if there was a 100% efficiency – however, only 40 moles are produced due to a 40% efficiency in energy conversion.

 

REDOX REACTIONS

1. Oxidation is the loss of electrons, loss of hydrogen or the gaining of oxygen.

2. Reduction is the gaining of electrons, gain of hydrogen or loss of oxygen.

3. A redox reaction involves the transfer of electrons from atom to atom

4. A reducing agent reduces another atom, and is itself oxidized. It loses an electron and gives one to another atom

5. An oxidizing agent oxidizes another atom and is itself reduced. It gains an electron from another atom.

6. The electron transfer chain is a redox reaction that removes energy from the electron to form ATP

METABOLIC RATE

//the amount of energy consumed by an organism in a given time. It is a measure of the speed of internal aerobic respiration.

• Basal metabolic rate is the energy used for breathing, maintaining body temp, contracting posture muscles, and maintaining brain function. It accounts for 60 – 70% of energy used a day. It is measured in kJ/m²/h. It changes with growth, development and age. BMR reaches a max of 220kJ/m²/h by age one (100 at birth) and then decreases. BMR varies with gender and health. A healthy male is 167, a woman 150. It drops with age because the body becomes more efficient at doing the same tasks over and over and because activity declines; muscle tissue decreases; energy needs decrease.
• BMR is estimated in direct calorimetry by measuring heat loss over time in a human Benzinger calorimeter. This is an insulated vessel containing a known mass of water and a thermometer. The person lies still  and heat from the body is transferred to the water causing its temp to rise. The heat energy is calculated by knowing that 4.2J is required to raise the temp of 1g of water by 1^oC. The calculated enrgy is proportional to the BMR. Body surface area can be calculated from:

            BSA = m^0.425 >< h^0.725  >< 0,007 184 (mass in kg; height in

                                                                                                     cm)

            A nomogram can be used instead (see p112)

            See table 2 p112 for average energy expenditures for different human activities

·         Indirect calorimetry can also be used to measure energy expenditure by calculating energy produced from measured oxygen consumption. 1L of oxygen produces 20kJ of energy.

·         Energy expenditure is affected by BMR, the specific dynamic action of food (eating), climate, weight and exercise. 

EXERCISE PHYSIOLOGY

 

1. Aerobic fitness: you can train and improve the following:

·         Increase stroke volume and decrease heart rate. Drop blood pressure

·         Improve vascular compliance

·         Increase the number of blood vessels and blood delivery to muscle. This will increase oxygen delivery and increase the use of fat as the energy sources thus sparing blood glucose and increasing endurance.

·         Increase the amount of haemoglobin

·         Increase the amount of sweating in heat acclimatisation – the amount and earlier onset

·         Improve muscle endurance – the type of fibres and amount don’t change. In aerobic fitness the slow twitch are favoured.

·         Lung volume doesn’t change – it depends on body size – but it is never a limiting factor in exercise anyway.

·         There is a limit to how much VO₂ max can be increased. It is genetically set. VO₂ max is the maximum rate of oxygen consumption by mitochondria in aerobic conditions. It determines performance ability (power, output)

·         Raises the lactate turning point/the onset of blood lactate accumulation (OBLA). This is the percentage of VO₂ max at which there is an accumulation of products of anaerobic respiration. This improves endurance. Exercise  intensity increases.

·         Max heart rate cannot be changed.

2. Anaerobic fitness: you can train and improve the following:

·         Muscle strength – the fast twitch fibres are favoured and can increase in diameter

·         Lactic acid/low pH tolerance improves

·         Lowering of lactic acid production, because turning point increases or the point ries. untrained have a LT at 60% of VO₂ max. This can go up to 80%.

·         Cori cycle removes lactic acid faster.

 

3. Factors that cannot really improve with either aerobic or anaerobic fitness:

·         Lung volume

·         Max heart rate

·         Type of muscle fibres

·         Number of muscle fibres

·         VO₂ max

·         Mechanical efficiency

These are related to genetics, sex, age and body size. These sort the supreme athletes out in a group of very fit athletes.

 

 

 

Genetic engineering//altering the sequence of DNA molecules. In 1976 Herbert Boyer and Stanley Cohen co-founded Genentech, the first biotech company to go public on the stock exchange. In 1978, somatostatin was produced. Today, insulin and growth hormone (somatotropin) are synthesized in large amounts by bacteria. Bovine somatotropin (BST) is used in the US (not Canada) to boost milk production in cows (an insulin-like growth factor that is carcinogenic).

Bioremediation//use of living microbes to transform undesirable and harmful substances into nontoxic compounds e.g using bacteria to degrade oil spills into carbon dioxide and water.

Restriction endonucleases or enzymes// Bacterial enzymes that cleave DNA into fragments by recognizing specific recognition sites. In bacteria they are used like a crude immune system – it scans the bacterial DNA for viral fragments of a bacteriophage. The bacteria puts a methyl group at its own recognition sites preventing the splicing of its own. About 2500 have been isolated and are specific for about 200 different target sites. Over 200 are available for use in labs. They are used to cut DNA. See p278-9 in Nelson

Most recognition sites have 4-8 bases that are palindromic (//both strands have the same base sequence when read in the 5’ to 3’ direction).

·         The shorter the recognition site (e.g. 2 base pairs) the more frequent the cuts (4><4 : 4 being the possible bases)

·         the longer the recognition site (e.g. 6 base pairs) the less frequent the cuts (4><4><4><4><4><4).

·         If there are lots of cuts the gene may be cut and would have to be isolated in fragments. 

·         If the frequency is lower the fragments may be too big.

·         So 6 base pair recognition is most often used.

When cut, two situations arise:

·         Sticky ends form//short single-stranded overhangs result from the cleavage. These are more useful because they can be joined easily to other sticky ends

·         Blunt ends form//the ends of the cut are fully base paired

 

NAMING ENZYMES:

1. BamH1 = B: bacillus; am = species amyloliquefaciens;

H = strain; 1 = first isolated.

 2. Hind11: H = haemophilus; in = influenzae; d = strain Rd;

11 = second isolated.

Group work: in pairs work on p281 # 1 – 5

 

DNA Ligases recreate the phosphodiester bonds and so reform the DNA. Ligases join complementary sticky ends produced by the same restriction enzyme. T4 DNA Ligase is an enzyme from a T4 bacteriophage that is used to join blunt ends. (e.g. p 282 of Nelson)

 

GEL ELECTROPHORESIS (see page 282 fig 5 Nelson): separates DNA fragments. The DNA is loaded into wells at one end of the gel. The gel is placed in an electric field and the fragments move from the – electrode (DNA is negative due to its phosphate group) to the + electrode. The rate of migration depends on the size of the fragment. The gel is like a molecular sieve – short fragments will travel faster because it can get through the pores easily. A dye added to the solution of fragments allows visualization of the DNA solution. The current is turned off before the loading dye reaches the end of the gel, and so the fragments are separated according to size. The fragments are made visible using ethidium bromide a carcinogenic stain that fluoresces under uv light. The results are compared to known separations, and the desired fragments found by comparison are excised from the gel.

 

 

PCR: POLYMERASE CHAIN REACTION

 

// amplify the DNA sequence by continually separating and replicating it so that essentially many copies are made: exponential DNA fragment photocopying. Each cycle takes minutes. After 20 cycles 2²⁰ copies are produced = 1 048 576. It was developed in the late 1980’s. It is a direct method that doesn’t require the use of plasmids.

 

1. The DNA is separated using heat (95^oC)

2. The temp is brought down to 50 – 65⁰ C to allow the primer to anneal to the template DNA.

3. Taq polymerase (isolated from Thermus aquaticus), DNA primers start the complementary strand and polymerase 111 builds the strand.

4. The cycle is repeated.

Small amounts of forensic evidence can be copied. It can also improve medical diagnosis.     It can be used for fossil remains to see if species are closely related.

 

RFLP: RESTRICTION FRAGMENT LENGTH POLYMORPHISM

 

·        Polymorphism//is an difference in the DNA sequence – coding or noncoding sections – that can be detected between individuals. Organisms of the same species carry the same genes but different alleles. So their genomes are polymorphic unless they are identical twins. This is used in forensic identifications.

·        RFLP

 

// a technique in which DNA regions are digested using restriction enzymes to produce fragments.

 

1. The fragments are run on a gel.

2. This produces a long smear because there are so many fragments nearly the same length.

3. So the gel is subjected to a chemical that denatures the DNA into single stands.

4. They are transferred onto a nylon membrane with a positive charge behind it, which transfers them to the membrane (called Southern blotting).

5. The membrane is emersed in a solution with radioactive nucleotides that are complementary only for some chosen regions (eg a noncoding region that is highly individualistic especially variable number tandem repeats in the noncoding area).

6. These are  complementary DNA probes to compare the differences in the fragments lengths between two people.

7. The radioactive bases (complementary probes) will bond to the fragments if present (hybridization has occurred).

8. The membrane is placed against an X-ray film.

9. The hybridized areas will show up (called an autoradiogram).

10. The pattern is compared to the  evidence to see if the suspect matches.

 

Comparison of PCR and RFLP

 

	RFLP	PCR
State of sample	Large and fresh (blood size of quarter; semen a dime)	Minute – 1 cell Degraded
Size of sample	Whole genome	Target sequence
Time	Three weeks	One day
Basic premise	Cleave DNA then subject to radioactive probes	Build complementary strands using replication
Result medium	Autoradiogram	Gel
Tools	Restriction enzymes; radioactive probes; nylon membrane, Xray, gel electrophoresis	DNA polymerase, nucleotides, primers, gel electrophoresis
Sensitivity and accuracy	very	quite

 

DNA SEQUENCING: THE SANGER DIDEOXY METHOD

//determining the exact sequence of base pairs for a gene using a method developed in 1977 by Fred Sanger and colleagues at Cambridge University.

·        They sequenced the genome of a bacteriophage for the first time.

·        It uses the principles of DNA replication.

·        The DNA is treated so it becomes single stranded. A radioactively labeled primer is added to the end of the template.

·        Identical copies of the DNA strand are placed in 4 test tubes.

·        Each tube contains DNA polymerase and complementary nucleotides to make a complementary strand. All four deoxynucleoside triphosphates are present (dATP; dTTP; dGTP; dCTP).

·        Each tube also contains dideoxy analogues of one of the deoxynucleosides (the deoxyribose sugar is missing a hyroxyl group on the 2’ and the 3’ carbon), which is also radioactively labeled in low concentration (ddATP or ddTTP or ddGTP or ddCTP – one in each tube)

·        Whenever the dideoxy analogue is incorporated in the complementary strand, it acts as a stop or chain terminator.

·        This results in different lengths of DNA produced. In each tube, it marks the place of that particular dideoxy analogue or where one of the four bases is. Each tube is marking its own base.

·        The strands are separated by electrophoresis. The sequences can be read off in ascending order. Each lane stands for one of the four bases. See p 302 figure 6

·        In the human genome project each ddNTP was fluorescently tagged eg G green, A yellow, T red and C blue. Thousands of automated seqencer machines worked 24 hrs every day.

 

APPLICATIONS

1. Quick HIV testing.

2. Genetic screening for mutations

3. Gene therapy//altering the gene sequence to prevent  or treat a genetic disorder. In its infancy.

1.    Pain control: If a therapeutic gene can be inserted into a cell that expresses antinociceptive transmitters//signal molecules that dampen pain signals sent to the brain. Another method is the use of Antisense oligonucleotides which are short segments of DNA or RNA that recognize and deactivate complementary mRNA. Antisense RNA that is complementary to pronociceptive transmitter(molecules that amplify pain sensation transmission) DNA can inhibit the formation of this protein.

2.    Transgenic plants//Foreign genes in plant cells. In 1981, Eugene Nestor and Mary Dell Chilton used the Ti (tumour inducing) plasmid of soil bacteria agrobacterium tumefaciens as a vector. The bacteria infects a wounded plant and causes a tumour or crown gall to form. The T region on the plasmid becomes incorporated into the plant cell DNA. This area can be used to carry foreign DNA into a plant.

·        It has been used to increase yield, hardiness, insect and virus resistance and herbicide tolerance.

·        Antisense technology was used to reduce the production of  polygalacturonase that causes the ripening of tomatoes.

·        Genes can be inserted into cotton to result in the production of a polyester polymer blend.

·        Corn produces Bt toxin – a toxin produced by Bacillus thuringiensis. It acts as a pesticide against the European cornborer. The problem is the pollen of this transgenic corn dusts other plants and it is thought to be killing monach butterfly larvae.

·        40 genetically modified foods have been approved in Canada since 1994. Health Canada and the Canadian Food Inspection Agency approve these and develop labeling laws under the Food and Drug Act. Labelling only need be on foods ONLY if it is considered a safety concern.

·        See the frost gene p321 Nelson #27. Discuss in class.

3.    BST (bovine somatotropin or growth hormone – which stimulates the liver to produce somatomedins -  iinsulin-like growth factor) is given to cows to increase milk production. Thought to be carcinogenic. Not approved in Canada (because it would drive milk prices down?)

4.    Discuss p 321 Nelson #28

8. DNA fingerprinting looks at the pattern of bands on a gel from RFLP or PCR (not Sanger) and compares it to a suspects pattern. It looks at the noncoding regions that are so individualistic. They differ in the quantity of variable number tandem repeats. The probability of matching in six or so areas of these regions with someone else is very low. DNA databases are shared among criminal institutions in Canada and the US.

 

 

 

GENERAL NOTES ON DNA

 

1.      The helix winds in a clockwise direction.

2.      The helix makes a turn every 3.4nm.

3.       See p 216 of  Nelson # 3, 6-9

4.      95% of the genome does not code for proteins. Noncoding areas have Variable Number tandem repeats (VNTRs) or Microsatellites. They repeat base pairs over and over (e.g. TAGTAG) (tandem means repeating segments adjacent to each other. They are the most variable and the most individualistic parts of the genome and are used for DNA fingerprinting.

 

5.      The ends of chromosomes have VNTRs called telomeres that act like knots, preventing the loss of valuable DNA. They bind proteins that stop the ends from being degraded. VNTRs also make up the centromere.

 

6.      Pseudogenes look like genes but they don’t express as proteins either. They may be crippled copies of some functioning gene. There are two kinds:

a.      LINEs (long interspersed nuclear elements)  ….5000 – 7000 bases

b.       SINEs (short interspersed nuclear elements).  …. 300 base pairs.

These are used to work out evolutionary phylogenic connections, because the presence of similar pseudogenes in a primate, for example, shows a link to a common ancestor.

 

History:

·         Friedrich Miescher a Swiss chemist first investigated the chemistry of DNA using pus in 1869.

·         In the 1920’s it was clear that chromosomes carried our genetic traits. But was it the protein or the DNA that was the genetic material?

·         In 1929, Frederick Griffith was able to show that a pathogenic bacteria, even when dead, can send some ‘transforming principle’ to non-pathogenic bacteria to make them pathogenic: bacterial transformation. He didn’t know what was transferred.

·         Joachim Hammerling a Danish biologist conducted experiments in the 1930’s on Acetabularia, a unicellular green alga to identify that  hereditary information was inside the nucleus. See p 207.  This work did not identify whether it was protein or DNA that carried the hereditary info.

·         In 1944 Oswald Avery repeated Griffith’s experiments with purified DNA and protein. He found it was DNA not the protein responsible for transformation.

·         In 1952 Alfred Hershey and Martha Chase used bacteriophages  to identify whether it was the protein or the DNA that carried the info. The protein capsule of one viral batch was tagged with a sulphur isotope and the phosphorus of the DNA of a second batch of virus with a P isotope. The phages were allowed to infect and multiply in a bacteria. They were then centrifuged so only the actual bacteria remained. Only the bacteria infected by the P isotope showed radioactivity. This showed that only the DNA of the virus entered the bacterial cell and was responsible for the replication, not the protein capsules.

·         Erwin Chargaff (1947) developed Chargaff’s rule: in DNA the amount of A equals T and G equals C. This suggested they were paired. The four percentages together will equal 100%

·         The DNA structure was tackled by Linus Pauling in California, Rosalind Franklin and Maurice Wilkins in London and James Watson and Francis Crick at Cambridge University. Franklin (mainly) and Wilkins used X-ray diffraction analysis in which a molecule is bombarded with X-rays which are deflected by the molecule producing lighter and darker bands on a photographic film. The 3-D structure is deciphered using math. It showed the helix is about 2nm in diameter and makes a complete turn every 3.4nm. (1nm = 10^-9m/10^-6mm). James Watson, Francis Crick and Wilkins got the Nobel Prize in 1962 – Franklin had died in 1958 at the age of 37 from cancer, and the committee don’t award prizes to deceased scientists. See p211-2 Nelson.

 

 

DNA REPLICATION

1.      DNA helicase unwinds the DNA by disrupting the H-bonds

2.      The bases want to anneal//pair up and bond again, so they are kept apart by Single Stranded Binding Proteins (SSBs)

3.      DNA Gyrase-like enzymes (gyrase is found in bacteria) relieves the tension produced by the unwinding. It cuts both strands of DNA, allowing them to swivel and then reseals the cut strands (much like undoing the coils on a central vac pipe by chopping and turning).

4.      Replication begins in two directions from the origin or replication fork//the region where the replication enzymes are bound to the untwisted DNA. It is the point where the single strands are joined to the joined DNA.

5.      There is more than one origin that opens up along the DNA and so many replication forks spread out in opposite directions. A Replication Bubble is found where 2 replication forks are close to each other.

6.      DNA polymerase III builds the complementary strand  along the template strand. It adds nucleotides at a rate of 50 per second. This happens at many sites so that the entire process takes 5 to 10 hrs.

7.      The synthesis occurs in the 5’ to 3’ direction. An RNA primer of 10-60 bases is first made using Primase, and then polymerase III starts adding free deoxyribonucleoside triphosphates to the elongating complemenatary strand. Energy is derived from the breaking of the phosphate bonds for the dehydration reaction.

8.      Because the DNA can only be built in the 5’ to 3’ direction, only the complementary strand that uses the 3’ to 5’ template can be built continuously. This is the Leading strand and is built toward the replication fork.

9.      The strand that uses the 5’ to 3’ template and therefore is a 3’to 5’ strand itself must be built discontinuously in Okazaki fragments (100 – 200 nucleotides in length) away from the replication fork. It is called the Lagging strand (see p220-1 Nelson). A polymerase has to be used for each fragment and each starts with a primer.

10.  DNA polymerase 1 removers the RNA primers from the fragments and the leading strand, and replaces them with appropriate deoxyribonucleotides.

11.  DNA ligase joins the Okazaki fragments.

12.  Each twists back into a helix.

13.  DNA polymerase 11 and 1 proofread the new strand. If there are mistakes, they can function as exonucleases//cut out the incorrect nucleotides. It is replaced immediately.

 

 

THE HUMAN GENOME

The Human Genome Project started in 1990 and was deciphered in 2001. Craig Venter and co at Celera Genomics did a private mapping, and Eric Lander and co at Whitehead Centre in Massachusetts did a publicly funded mapping. Only about 42 000 protein-encoding genes are present. The rest doesn’t code for genes. Some genes are clustered, but over half are dispersed among long, often repeat sequences of noncoding DNA. We share many protein families with other animals. 3 billion base pairs make up the genome.

See course pack p 173 – James Lupske: The human genome project.

The identification of genes is done using microarray technology: mRNA that is transcribed is taken and and translated into a single-stranded complementary DNA (cDNA). This is placed against glass slides of known DNA sequences, and the cDNA will bond with its complementary DNA. We can then identify which part of the genome was turned on and was being used to make a protein.

 

 

 

MICROEVOLUTION//changes in allele frequency and phenotypic traits within species, that could result in the formation of a new species.

 

MACROEVOLUTION// large scale evolution making changes that warrant the classification of lineages into genera or higher taxa.

 

RATE OF EVOLUTION

a.      Gradualism//macroevolution is the result of the accumulation of small, ongoing change. We should find, if we go with this theory, transitional forms. But many distinct species appear suddenly. The only way around this is to say that the intermediates were not preserved.

b.     Punctuated equilibrium//macroevolution involved rapid spurts of change followed by long periods of no/little change. Niles Eldridge and Stephen Jay Gould:

·        Species evolve rapidly. It may be an environmental change that results in extinctions and the opening of niches. Disruptive selection results in speciation.

·        Speciation usually occurs in small isolated populations and so intermediate fossils are rare

·        Species don’t change over long periods of time. The species are well adapted with stabilizing selection.

Both are probably at work.

 

Divergent evolution//species evolve different traits, due to selective pressures or genetic drift, and diverge. Also called adaptive radiation if rapid and in many directions.

 

Convergent evolution//once divergent species become similar in phenotype due to similar selective pressures.

 

Co-evolution//one species evolves in response to the evolution of another. For e.g without the wasp the fig cannot reproduce and the fig wasp can only reproduce  in modified fig flowers. So the modified figs have coevolved together with the behaviour of the wasp.

 

 

 

 

 

In the 1930’s, evolution and genetics were put together in what has become The Modern Synthesis.

 

Genome//complete set of chromosomes containing all its genes. See p545 for examples of genomes.

 

HARDY-WEINBURG PRINCIPLE

In 1908 G.H. Hardy (English) and G. Weinberg (German) simultaneously said that in a large population of random mating, and in the absence of forces that change the proportions of alleles for a particular trait, the original proportions of the genotypes would remain constant. The genotypes are in a Hardy-Weinberg equilibrium.

    Assume only two alleles: one dominant and the other recessive

    The equation is a binomial expansion: (p + q)² = p² + 2pq + q²

    It allows prediction of what proportion of genotypes will be homozygous and  heterozygous for a gene.

    It measures allele frequency //the proportion of copies in a population of a given allele. frequency = #alleles in the category/total # alleles considered.

    The two alleles are equal to 1 (100%).

 

For a gene with two alleles (A and a), ‘A’ frequency is expressed as ‘p’, and ‘a’ frequency is expressed as ‘q’ in the binomial expansion: (p + q)² = p² + 2pq + q²

p² = homozygous dominant

pq = heterozygotes

q² = homozygous recessive

 

Do p549 Nelson #1-3

 

To remain in a constant Hardy-Weinberg equilibrium the following conditions must be met:

·        Large population

·        Equal mating opportunities

·        No mutations

·        No migration

·        No natural selection (everyone has equal reproductive success)

 

 

5 factors change the Hardy-Weinberg equilibrium:

This results in microevolution. See p147 course pack

FACTOR	DESCRIPTION
Mutation	Cannot alone change gene frequency , because the rates are so low. Many genes mutate 1-10 times per 100 000 divisions. Mutation is the ultimate source of variation. A neutral mutation has no immediate effect on fitness and most are silent or occur in noncoding DNA. Harmful mutation reduces fitness. Beneficial mutation is more rare – cells gain the ability to produce a new or improved protein, giving selective advantage.
Migration – Gene flow	The movement of individuals from one population to another. A potent agent of change. Alleles removed from one population are added to another.
Genetic drift – in small populations	In small populations, the frequencies of particular alleles can change drastically by chance alone. A subset of this is the founder principle in which a few individuals disperse and become founders of an isolated population – rare alleles may be enhanced in the new population (e.g porphyria in Afrikaners). Drift can also cause fixation of alleles, increasing the incidence of homozygotes and reducing diversity. Genetic drift can also be the result of bottlenecks//a dramatic temp. Reduction in population size resulting in significant gene drift as only a small sample of alleles survives to form the new population.
Nonrandom Mating	Inbreeding is the most common form – gene frequency isn’t altered, but there are less heterozygotes (Mendel got his pure breds this way – homozygotes). It promotes homozygous recessives. Many genetic disorders are recessive e.g xeroderma pigmentosum, albinism, tay-sachs, ichtyosis. Individuals preferred as mates will pass on their alleles in greater numbers.
Natural selection	In artificial selection the breeder selects the desired characteristics, in natural selection the environment imposes conditions for selection. Selection acts only on the phenotype, not on rare recessive alleles in the genotype.

 

Hardy-Weinberg: Do p549 Nelson #1-3; p581 #3, 4; p583 #19, 20, 2

 

Modes of Natural Selection:

a.      Stabilizing selection: When an environment is stable the extremes are not favoured. Selection against variation too far from the population average e.g birth weights. Most common form of selection, and kicks in once species adapt to the environment.

b.     Directional selection: selection that favours those that deviate from the average. This occurs when the habitat changes creating new forces of selection p 558

c.     Diversifying or Disruptive selection: selection against the intermediate form and favouring the adaptation of two extremes. Leads to polymorphism which can eventually become isolated separate gene pools/two different species.

d.     Sexual selection: differential reproductive success due to variation in the ability to get mates. Usually will result in sexual dimorphism//differences in the physical appearance of males and females, as well as in mating/courtship behaviour. The most common situation is females choosing males and males competing with each other.

 

Complex structures are thought to develop by CUMULATIVE selection//the accumulation of many small changes over very long periods of time.

 

MODES OF SPECIATION

Speciation// the evolutionary formation of a new species. There are two kinds of speciation:

·        Allopatric: evolution of new populations into separate species due to geographic isolation. Barriers like canyons, rivers, highways, dams can form.

·        Sympatric: evolution of new populations within the same geographic area into separate species. A mutation can split a species into two both capable of adapting to the same niche. The mutation could be polyploidy that results in reproductive isolation.

 

Species//an interbreeding group that are reproductively isolated form other groups and evolve independently. This is not easy to apply. So usually classification is done on physical appearance (morphology), and sometimes on behaviour, or on the mechanisms that isolate them reproductively.

 

MECHANISMS THAT ISOLATE SPECIES REPRODUCTIVELY:

These are behavioural, structural or biochemical blocks:

MECHANISM	EXAMPLE
	PREZYGOTIC MECHANISMS
	PREVENTION OF MATING
Ecological isolation	Ground squirrels in different habitats.
Temporal Isolation	Similar plants bloom at different times of the day (cacti), or different seasons (irises).
Behavioural Isolation	Different attracting signals.
	PREVENTION OF FERTILIZATION
Mechanical Isolation	Pollen sacs of lady slipper orchid attach to insects but can’t be removed by any other flower
Gametic Isolation	Gametes in water – clam sperm and egg, recognize each other by molecular markers
	POSTZYGOTIC MECHANISMS - RESULT
Zygotic Mortality	Fertilized zygotes cant develop to maturity.
Hybrid Inviability	Hybrids offspring are unlikely to live long
Hybrid infertility	Offspring are strong but sterile e.g mule

 

 

Phylogeny//the theoretical evolutionary history of a species or group

 

Linnaean taxonomy//grouping according to morphology/structure

 

Darwinian taxonomy/cladistics//grouping according to phylogeny. Related organisms are in a monophyletic group or clade. The arrangement shows evolutionary distances.

 

Phylogenetic tree/cladogram//diagram of the evolutionary relationships by descent of groups of species. These are based on synapomorphies//shared traits that evolved only once and have been inherited by two or more species. The cladogram provides information on the sequence in which species split. The lines do not represent the end-point animal for their entire length only the branching point of the ancestor of that end-point animal.

·        An ingroup is the group having one or mode synapomorphies.

·        An outgroup is the first group that diverged from the other members of the clade studied.

·        Each member of the ingroup is compared to the outgroup. Traits found in the ingroup and not the outgroup are shared traits.

·        Once the derived traits are tabulated (p608) check the vertical columns and add up the number of species with the trait: the more = the earlier it is in the cladogram. As the numbers drop, so it represents the divergence of those organisms without it. Eventually there will be only 3 or 2 with a trait – they will be at the end of the cladogram. The sequence is from most found to least found traits, and between each trait the branching off of divergent species must be drawn.

 

Cladograms can be built on other evidence – amino acid sequences (chemical makeup) or DNA base sequences (genetic makeup).

·        In amino acid sequences for a shared protein e.g cytochrome c, the fewer the sequence differences, the more the two species are phylogenetically related. This applies to DNA bases too.

·        An easier way to look at DNA is to look at DNA that becomes inserted into the genome – SINE (short interspersed elements) and LINE (long interspersed elements). For example viral DNA can be inserted into the germ cell DNA, and becomes inherited junk DNA. If two species have the same insertions at the same position, they could be assumed to have a common ancestor.

 

Try p622#9.

Lab exercise 13.4.1 p629: Looking for SINEs of evolution. Work in groups and write up answers individually for hand-in.

 

Activity: What can Pseudogenes Tell us About common Ancestry – why do we need vitamin C in our diet.

 

 

 

EVOLUTION:

// the process in which significant changes in the inheritable traits (genetic makeup) of a species occur over time (see also course pack pg 206).

 

Archbishop James Ussher of Armagh (1581-1656): earth was created Sunday October 23 4004 B.C. This persisted as the accepted immutable nature of life.

 

Palaeontology

//the study of fossils, began in the 18^th century.

Evidence for change on earth: FOSSILS

//fossils are any preserved remains or traces of an organism or its activity. These can be hard body parts like shells, bones and teeth. They can be impressions of burrows and footprints and chemical remains. Some fossils are permineralised i.e. the cells are replaced by minerals. This occurs when decomposition is very slow. Fossils occur when bodies become trapped in sediments that then become compressed into strata that harden into sedimentary rocks. Tar pits, volcanic ash, peat bogs, permafrost, amber allow intact preservation.

 

Baron Georges Cuvier’s investigations showed that

• many fossils were of extinct species (til then it was thought all fossils were of living species). Less than 1% live today.
• More complex forms are found in shallower deposits. These were also more likely to resemble living species.
• Each layer seemed to contain distinct species not found above or below it
• Deeper deposits were older and contained more ancient fossils: relative age

 

Because he believed all life was created at one time, the way he explained this is catastrophism//local catastrophes caused localized extinctions, to be replaced by migrating species. This didn’t explain increasing complexity.

 

1795 James Hutton (Scottish geologist) introduced ACTUALISM//the theory that the same geological processes occurring now happened in the past.

 

Sir Charles Lyell (1797-1875) introduced UNIFORMITARINISM//the earth surface has and will change through gradual processes.

 

Comte Georges Buffon (1707-1788), Carl Linneaus and Erasmus Darwin (1731-1802) proposed that species could change over time and this could lead to new organisms.

 

Jean de Lamarck (1744-1829) reasoned in the 19^th century that species will survive over long periods of time only if they adapt to changing environmental conditions. Species gradually became complex, and at the same time simple species were continually created by Spontaneous generation//life from non-living matter. The changes became acquired traits that could be given to the next generation: theory of the inheritance of acquired characteristics.

 

Thomas Malthus (1766-1834) in his ‘Essay on the Principle of Population’ observed that plants and animals produce far more offspring than survive, and this led to what Darwin termed in his autobiography “a struggle for existence”. It was this idea that underpinned Darwin’s theory of Natural Selection. (www.ucmp.berkeley.edu/history/malthus.html)

 

AGING FOSSILS AND THE EARTH

There are two basic principles to determine the age of rocks:

1. Principle of superposition: younger sedimentary rocks are deposited on top of older sedimentary rocks.
2. Principle of Cross-cutting relations: any geologic feature is younger than anything else that it cuts across. 

 

Parent isotope	Daughter isotope	Half-life (yrs)	Effective dating range (yrs)
C-14    (6)	N-14    (7)	5730	100 – 100 000
U-235   (92)	Pb-207   (82)	713 million	10 mill – 4.6 bill
K-40      (19)	Ar-40  (18)/Ca-40 (20)	1.3 billion	100 000 – 4.6 bill

 

 

ISOTOPES

Elements with a different number of neutrons are called isotopes. Radioisotopes are atoms of an element that spontaneously decay into smaller atoms, subatomic particles and energy.

The half-life is the time it takes for one half of the nuclei in a radioactive sample to decay.

symbol	Atomic #	Mass #	protons	neutrons	Relative abundance	Structural stability
C-12 C-13 C-14	6 6 6	12 13 14	6 6 6	6 7 8	98.9% 1.1% trace	Stable Stable radioactive
H-1 H-2 H-3	1 1 1	1 2 3	1 1 1	0 1 2	99.8% 0.2% trace	Stable Stable radioactive

 

Carbon-14 enters the body through the food chain. During life, the ratio of C-12 to C-14 is the same as in the atmosphere. When death occurs, the C-12 doesn’t change but the C-14 decays. Measuring the ratio allows us to calculate the time of death.

You will receive a handout worksheet on this.

 

Radioisotopes decay at a constant rate, unaffected by temp, moisture and environment. The half-life is the time it takes 50% of a sample of parent isotope to decay to daughter isotope.

• Lava initially contains K-40 but not Ar-40 because gases all escape when lava is hot. So the accumulation of Ar-40 is a good indicator of the age of igneous rock.
• A fixed proportion of the atoms in a given sample of carbon consists of C-14. C-14 is produced from C-12 by particle bombardment.All living organisms get the C-14 from the atmosphere during life. The carbon in living bodies consists of these fixed proportions. After death the organism is no longer incorporating C, the C-14 decays to C-12.

 

Activity: counting M & M’s.

 

Other forms of analysis:

1. Varve analysis: the retreating Scandinavian ice sheet deposited fine sediments in the lakes at the time of the annual summer melt. The thickness depended on the summer.
2. Tree rings
3. Sea bed silts
4. Paleomagnetism: the magnetic north and south poles have wondered over time. As igneous rock cools, magnetite or magnetic minerals line up according to the field at the time. We measure the direction and degree of particle alignment.
5. Electron-spin resonance (ESR) measures the vibration or resonance of electrons within a magnetic field. Microwaves are passed through and electron spin is affected as microwave energy is absorbed.

 

Go through example and practice # 1 and 2 on p515 on dating.

Try #5, 6, 7 pg540, and pg 516 # 4.

 

 

 

LESSON ON HOMINOID EVOLUTION

 

Earliest primates: 60 million yrs ago – long snouts, sharp teeth, large eyes, arboreal, insectivorous. They developed 3 important traits:

·         Flat molars for plants

·         Grasping hands and feet with opposable thumbs for brachiation

·         Forward-directed eyes for binocular vision and depth for moving quickly through trees.

 

Characteristics of mammals:

·         Homeotherms

·         Hair

·         Four-chambered heart and double circulation

·         Internal fertilization

·         Milk

·         Monotreme mammals: egg-laying mammal. Duck-billed platypus and echidna (egg is transferred to a pouch til hatching). No fossil record.

·         Marsupials: mammals in which young are born early (even 8days after fertilization) and retained in a pouch. 100 million year old fossils.

·         Placental mammals

 

The monogenesis hypothesis: hominids only evolved in Africa. The human genome project and work done on maternally inherited mitochondrial DNA suggest this is the more likely idea, as it seems all races of living humans are descended from one “eve” in Africa about 200 000 years ago, as apposed to the hypothesis of multiregional and parallel development of hominid lines. Genetic diversity seems greatest in sub-saharan Africa, suggesting that humans existed in Africa the longest.

 

SEQUENCE IN THE PHYLOGENETIC TREE:

(refer p616 and p618 of textbook)

·         50 million years: Anthropoids (monkeys, apes, humans): diurnal, feed on fruit and leaves, large brain, colour vision, societies, prolonged caring for young.

 

·         40 million yrs ago: 3 way split:

*     old world monkey (non-prehensile tails),

*     new world monkey (isolated in south America, flared nostrils, only arboreal and have prehensile tails),

*     hominoids (gibbons, orangutans, gorillas, chimps, humans – all lack tails).

 

·         Gibbons split about 35 million years ago

 

·         Orangutans split about 15 million years ago

 

·         Gorillas, chimps and hominids diverged about 5.5 million years ago

 

·         6 species of Australopithecines lived in africa between 5-1 million yrs ago. Bipedal movement came before large brains. They were about 20 kg and 1.3 metres tall. The brain was about 400 cm³.

·         Australopithecus africanus found in Sterkfontein caves and Kromdraai in South Africa. Best preserved fossils: Mrs Ples and Taung boy skull.

 

·         About 4 million yrs ago, A. anamensis gave rise to the Homo line and the rest of the Australopithecus line.

 

·         Best fossil of Homo afarensis is Lucy from the Afar triangle in Ethiopia (Dr. Johanson)

 

·         Homo habilis evolved about 1.8 million years ago. It has been found in East (Tanzania) and South Africa.  It had a brain about 700cm³, smaller jaws and longer legs. It used stone tools routinely. It regularly climbed trees. It lived for about 500 000 years.

 

·         Homo habilis gave rise to Homo erectus about 1million yrs ago. The brain was about 1000cm³. It gradually spread out of Africa to Europe and Asia.

 

·         Homo erectus was around from 1.7 million to 500 000 in Africa and 250 000 years ago in Asia. They were about the size of our species. He used fire from about 1.4 million years ago.

 

·         Homo sapiens appeared about 130 000 yrs ago. One type,the Homo neanderthalensis lived in Europe and Western Asia from 70 000 to 32 000 years ago. They were hunter-gatherers. They were powerful, short and stocky. They used spearheads, hand axes, and hides for clothing. They lived in hut like structures or caves. They took care of their injured and sick and buried their dead. Cro-magnon (from Africa?) seemed to replace the neanderthalensis by 40 000 years ago, across Europe either coexisting or even interbreeding for several thousand years. They made tools from bone, ivory, antler. They may have had the first fully modern language. They painted caves. The time they lived in was cooler. Grasslands were found across Europe during this time with large herds.

 

·         Humans of modern appearance spread across Siberia to North America  about 12 000 years ago. About 10 000 years ago, there were 10 million people in the world.

 

 

 

 

UNDERSTANDING NATURAL SELECTION

 

PRELUDE TO THE THEORY OF NATURAL SELECTION

Evolution has nothing to do with “perfect adaptation”. Indicators of this are imperfect contrivances – structures modified and used for functions different from their ancestors’ functions of the same structures (refer to the ‘panda’s thumb’ S.J. Gould). Other indicators are:

1. preadaptation: a characteristic that met the needs of prior conditions, and now provides the initial stage for evolution of new characteristics under different conditions e.g. birds’ flight feathers from feathery scales on dinosaurs where they were insulation.
2. Vestigial structures: found in living (extant) species with now no function  but are homologous to functioning structures in closely related species. E.g. pelvic bones and rudimentary legs in pythons; hipbones in some whales; dew claws in dogs; human appendix; wings in flightless insects like earwigs; eye sockets in blind cave-dwelling fish and amphibians; upland geese with webbed feet that never go into water, ear-wagging muscles in humans.

 

Other indicators of change over time is homologous and analogous features:

Homologous features//structures that share a common origin but now serve different functions in modern species

Analogous features//structures similar in function but not in origin or anatomical structure.

 

Work in groups on Activity 11.5.1 pg 535: Looking for Homologies.

 

The findings of Charles Darwin on the five year journey of HMS Beagle to the Galapagos islands and around the world, and his life work.

1. Each island supported unique species of plants and animals.
2. There was distinct variations within species of say finch or tortoise.
3. Species on an island closely resembled those on the closest landmass.
4. Continents separated by large distances would have entirely different species occupying the same/similar niche. The species adapted to that niche from a different starting point (gene pool). For example, grassland animals on one continent look more like animals in a nearby tropical forest than to grassland animals on another continent.
5. Fossils bore resemblance to living species in the same region they were collected, causing him to think they were the ancestors.
6. A single ancestral species could give rise to similar but distinct new species when introduced to a nearby land e.g. different finch species on the different islands. He began a notebook in 1837 on “transmutation of species”
7. His work led to the study of biogeography//the observation and analysis of the geographic distribution of organisms.
8. He observed homologous, analogous and vestigial features
9. People have altered the behaviour and appearance of animals and plants through artificial selection.

 

He could not work out how nature  chose desirable variations for reproduction until he read Thomas Malthus (1798) ‘Essay on the Principle of Population’ (refer): Plants and animals produce more offspring than can survive. Competition for survival would occur. Those with even a slight advantage would have the best chance of surviving and procreating. The favourable variables would tend to be preserved and the unfavourable would not. “A struggle for existence”.

 

NATURAL SELECTION:

(Refer page 207-8 in course pack)

 

1. Evolution proceeds by a process of variation, a genetically random process; and selection, an environmentally driven non-random process.
2. Organisms do not get what they “need through inner wants” or through “use and disuse”. Individual intentions do not play a role.
3. Acquired characteristics are not passed on to offspring.
4. Mutations are not directed for the benefit of the individual.

 

//Natural selection is the differential reproduction of genotypes in response to factors in the environment.

 

REMEMBER:

·         Variation is random. Selection is not.

·         Environmental pressures determine the “fitness” of a variation.

·         Traits that are selected for (are “fitter”) will be passed on to the offspring.

 

HOMEWORK

 P528 # 11, 12, 14, 15, 17.

 

 

 

Endocrine System

 

The endocrine system is a group of structures that release hormones from ductless glands. 

 

Hormones are specialized chemical messengers which are secreted by specific endocrine gland cells in response to certain stimuli and are carried by the blood to other sites in the body where they alter cell activity.  Hormones are effective at very low blood concentrations.

 

Endocrine glands are different than exocrine glands.  An example of an exocrine gland is the salivary glands.  All exocrine glands have ducts and substances produced by the gland are excreted through the duct.

 

Hormones regulate most of the body’s main functions such as:  basal metabolic rate, blood glucose concentration, growth, water and electrolyte balance, and sex development.

 

Normal Action of Hormones

 

            Stimulus à endocrine gland à hormone released into bloodstream à target area (cells with receptors for hormone) à hormone action

 

3 types of hormones

1. protein or peptide (most hormones)
2. steroid (produced by adrenal cortex, testes, ovaries and placenta) – cholesterol is common precursor of all  steroid hormones
3. amines (derived from the amino acid tyrosine)  - thyroid hormone, epinephrine and norepinephrine

 

Hormone actions

1. increase or decrease the activity of certain enzymes
2. alter the permeability of membrane to specific substances
3. increase or decrease the activity of certain genes – alter proteins made by the cell  (steroid hormones)

 

Hormones must reach a certain concentration in order to be effective i.e. females have some testosterone but the levels are low and it is continually destroyed by enzymes in blood and tissues therefore it does not produce maleness in females.

 

Hormone Action – Cellular Level

 

Steroid Hormones 

 

1. steroid enters the receptor site
2. these cells contain a transporting protein which picks up the steroid
3. the steroid is transported through the cytoplasm and this cytoplasmic protein releases the steroid into the nucleus, where it attaches to a particular gene and either increases DNA transcription or inhibits it.

 

Protein and Amine Hormones

1. protein hormone enters receptor site but, does not enter cell
2. the hormone-receptor interaction triggers a complex series of reactions – the host membrane releases an enzyme called adenyl cyclase
3. Adenyl cyclase converts available ATP to cyclic AMP
4. Cyclic AMP then acts inside the cell to alter the rate of enzyme activities or transport processes

 

 

THE ENDOCRINE SYSTEM

 

 

      There are two main types of hormones:

x        STEROID HORMONES: are formed from cholesterol. They are estrogen, progesterone, testosterone, aldosterone, dihydroepiandrosterone (DHEA) and the corticosteroids. They are produced by the adrenal cortex, the testes, ovaries and placenta. Steroid hormones are very inter linked, and can be converted from one to the other. They dissolve in phospholipids and pass through cell membranes. Once inside the cell, they stimulate the DNA and new proteins are synthesised.

x        NONSTEROID HORMONES: are divided into:

1.         AMINE HORMONES: derived from an amino acid. The two main amine series are (i) serotonin and  melatonin, derived from tryptophan, and (ii) dopa, dopamine, norepinephrine and epinephrine, and thyroid hormone, all derived from tyrosine.

2.         PEPTIDES: ADH and oxytocin

3.         PROTEINS: most hormones are protein. They include insulin, glucagon, somatotropin (growth hormone), parathyroid hormone, calcitonin, ACTH, prolactin, hypothalamic release hormones, and digestive hormones.

4.         GLYCOPROTEINS: FSH, LH, TSH.  

                        Nonsteroid hormones act as first messenger molecules and attach to receptor sites on the cell membrane, stimulating the release of adenyl cyclase. This secondary messenger then moves into the cell, and initiates the changes instigated by the hormone. These hormones do not actually enter the cell. 

 

 

x        CONTROL OF HORMONE RELEASE: Many hormones are controlled directly by feedback from the substance that they control. For example, insulin and glucagon release is controlled by glucose levels; parathyroid hormone and calcitonin by calcium levels. ADH secretion is stimulated directly by the osmolarity of the blood.

            Others are controlled by a gland to gland axis, which starts in the hypothalamus. The hypothalamus secretes the hormone which stimulates the pituitary to secrete the hormone which stimulates the end or target endocrine gland. In this type of control, the end hormone levels will feed back in what is known as a negative feedback loop to the hypothalamus or pituitary to stop hormone production when the level of the target hormone is adequate.

            For example, the release of cortisol starts with the release of corticotropin release hormone (CRH) from the hypothalamus, which causes the release of adrenocorticotropic hormone (ACTH) from the pituitary, which then stimulates the adrenal cortex to secrete cortisol. Once cortisol levels are high enough, the cortisol circulating in the blood will reach the hypothalamus and switch off CRH production. Similarly, to increase thyroid hormone levels, the hypothalamus must secrete thyrotropin release hormone (TRH), which then stimulates the pituitary to release thyrotropin (TSH), which then stimulates thyroid hormone secretion from the thyroid gland. Once the levels are raised, it is the thyroid hormone which switches off the axis. The problem with these axes from a diagnostic point of view is that when the end hormone levels are low in the blood, it has to be established if the problem lies at the hypothalamus, the pituitary or the end endocrine gland. One has to ask the question why such a complicated process even evolved. The intriguing answer is that it allows for multiple inputs in the stimulation of hormone release, including those coming from areas of the brain. This is why hormone release is so sensitive to one’s state of mind, and emotions.

            There is an axis separate from the hypothalamus. This is the renin-angiotensin-aldosterone axis that controls aldosterone function. Here renal blood flow controls the release of renin by the kidney (if the renal blood flow is low, renin is released), which then stimulates angiotensin production, and angiotensin stimulates the adrenal cortex to release aldosterone. In this axis, there is no negative feedback from aldosterone to the kidney. Instead, once renal blood flow is improved, renin release is switched off.

 

THE PITUITARY GLAND

            The pituitary gland is a pea sized structure on the inferior aspect of the brain lying in a saddle of the sphenoid bone called the sella turcica. The gland is divided into two discrete sections - the anterior and posterior pituitary. The posterior pituitary is actually an outgrowth from the hypothalamus, and is connected to it by neural tissue. The hypothalamus produces the hormones which are stored in the posterior pituitary. The hypothalamus also releases its own hormones which reach the anterior pituitary via the circulation, and control it.

 

A. ADENOHYPOPHYSIS/ANTERIOR PITUITARY

            Six hormones are produced in the anterior pituitary. Two of the six, growth hormone (GH), also called somatotropin, and prolactin, exert their effects on non-endocrine targets. The other four, thyrotropic hormone (TSH), adrenocorticotropic hormone (ACTH), and the two gonadotropic hormones called follicle stimulating hormone (FSH) and luteinising hormone (LH) are all tropic hormones, which means they stimulate other endocrine glands to secrete hormones, which then effect end organs and tissues. 

            The pituitary is called the master gland because it controls the secretion of so many other glands. However, the hypothalamus is the true master, because it secretes hormones that control the anterior pituitary.

            Most of the hypothalamic release hormones stimulate the pituitary to secrete its  hormones. The exception are two inhibitory hormones, called growth hormone inhibitory hormone (somatostatin), and prolactin release inhibiting hormone. The hypothalamic hormones:

a.         Corticotropin releasing hormone (CRH) stimulates the secretion of ACTH

b.         Thyrotropin releasing hormone (TRH) stimulates the secretion of TSH (thyrotropin)

c.         Growth hormone releasing hormone (GHRH) stimulates the secretion of GH

d.         Somatostatin (growth hormone inhibitory hormone, GIH) inhibits the secretion of GH

e.         Gonadotropin releasing hormone (GnRH) stimulates the secretion of LH and FSH

f.          Prolactin releasing hormone (PRH) stimulates the secretion of prolactin

g.         Prolactin release inhibiting hormone (PIH ) is actually dopamine. It inhibits the secretion of prolactin

 

            GH has dual roles. It stimulates the release from the liver of a group of growth-promoting peptide hormones called somatomedins (e.g. insulin-like growth factor 1), and it also exerts direct effects on growth by stimulating protein, lipid and carbohydrate metabolism all over the body. Its major effect in children is on the growth of skeletal muscles and long bones. In adults it no longer affects growth in this way, but is still anabolic. It is classed as a stress hormone, in that it mobilises fats for energy, thus sparing glucose utilisation. It spares protein stores from being used as a fuel source and stimulates protein synthesis (muscle growth). GH levels increase during and immediately after exercise, and during sleep. Athletes can actually manipulate GH release by constructing complicated schedules of exercise, sleep, and eating routines. The diet has to have enough protein, because negative nitrogen balance reduces the amount of somatomedins released from the liver in response to GH. In addition, some specific amino acids (e.g. arginine, ornithine, glycine, glutamine, tryptophan and valine) can boost GH release. The release of GH under these circumstances will build muscle, and prevent that muscle from being catabolised, whilst also mobilising fat for enhanced performance. For body builders this means good muscle definition and increased lean body mass. (6)

            In childhood, under secretion of GH causes the proportional dwarf, over secretion causes the proportional giant. In the adult, over secretion causes acromegaly (growth in soft tissue and thickening of the bones of the face, hands and feet). The proportional dwarf often lacks gonadotropins as well, and does not mature (a few do reach a delayed puberty). GH replacement would be the answer, but some children develop a resistance to it.  Dysproportional dwarfism has nothing to do with the endocrine system, but is due to achondroplasia which is failure of the growth plates of long bones to respond to GH, or it can be the result of rickets (2 p1023).

            In both gigantism and acromegaly, soft tissues, including internal organs, enlarge. Initially there can be increased muscularity and abnormal strength, sexual precocity in children and increased libido in adults. Later, the pituitary tumour producing the GH gets so large, it destroys much of the gland, and other hormones start to drop. In time, there is muscle wasting and weakness. Glucose tolerance is abnormal and there may be diabetes mellitus. The heart is enlarged and the blood pressure is raised. Acromegaly often ends in heart failure. (2 p 1009-1011)

            FSH and LH have different functions in males and females. In the female FSH is important for ovum development and estrogen formation, whilst LH is important for ovulation and progression to the secretory phase (second half of the menstrual cycle) and progesterone production. In the male FSH controls sperm formation, and LH stimulates testosterone formation in the testes. Infertility in either males or females needs to be investigated. One possible cause could be low or high levels of these two hormones (see chapters 11 and 12). A prolactin excess can also lead to infertility. Prolactin is a hormone involved in milk production for breast feeding. But the fact that it is found in men too suggests it has other functions. For example, it often rises in response to stress, and can be considered one of the stress hormones.

            Excess or deficient secretion of either TSH or ACTH will affect end hormone production. In each case, it must be ascertained whether the cause is hypothalamic, pituitary or end organ. Conditions are discussed under the relevant end endocrine glands.

            If the entire anterior pituitary fails, the condition is called simmond’s disease or sheehan’s syndrome. This can occur in women following childbirth. The first sign is failure to lactate, followed by loss of axilla and pubic hair, amenorrhoea, sterility and no libido. Hypothyroidism then starts to develop, and ACTH deficiency leads to weakness, hypotension, and even collapse. There is fasting hypoglycemia. Skin pigment decreases and the skin looks waxy. This condition requires lifelong treatment with thyroxin, corticosteroids and sex hormones (2 p1012-3).

 

B. NEUROHYPOPHYSIS / POSTERIOR PITUITARY

            This is actually an outgrowth of the hypothalamus and is neural tissue. The axons of two hypothalamic neurons pass through the connecting stalk and end in the posterior pituitary. The two peptide hormones stored here are oxytocin and anti diuretic hormone or vasopressin (ADH).

            Oxytocin causes the smooth muscle of the uterus and mammary glands to contract. It  is given intravenously or as a nasal spray (syntocinon), or sublingually as pitocin to induce labour, treat uterine haemorrhage or uterine hypotonic inertia. Oxytocin stimulates a milk letdown in lactating women. The baby therefore will get this hormone in the milk, and it is thought to increase bonding. Later on in life, this same hormone is released when we feel bonded to others, either in friendship or in love. If  this is missing from our lives, or we feel alienated from others, the lack of oxytocin can cause us to resort to food (mother’s milk) as a way of filling the gap. It appears we are programmed for this genetically, sothat it occurs even if there was no breast feeding in infancy.

            ADH is a peptide hormone secreted in response to blood osmolarity i.e. if the solute concentration is too high, there is a need for more water to be absorbed by the kidney. It makes the collecting ducts in the kidney permeable, increasing passive water reabsorption along the osmotic gradient created by a complicated renal tubular counter current mechanism.

(8 PG 7). Failure to secrete ADH in response to hyper osmolarity is called diabetes insipidus. It presents with polyuria, a dilute urine, polydipsia and dehydration (refer chapter 6). These are also the symptoms of diabetes mellitus. In the latter case, the name means lots of sweet urine, and in the former case, it means lots of insipid urine. In diabetes insipidus, the polyuria is due to an inability to concentrate the urine, whereas in diabetes mellitus the polyuria is due to the osmotic effect of having sugar in the urine. Diabetes insipidus tends to occur in young adults, especially males. Primary diabetes insipidus is a defect in the posterior pituitary (or rather the hypothalamus that makes the hormone), and may be familial. It can be inherited as a dominant trait. Secondary diabetes insipidus can be due to destruction of the posterior pituitary by trauma, infection, a tumour or a vascular accident (stroke). Nephrogenic diabetes insipidus is due to a defect in the renal tubules, which can be an inherited condition, or can be acquired after pyelonephritis, or amyloidosis. This type would be unresponsive to ADH administration.

 

THE THYROID GLAND

                        The thyroid is located in the neck over the trachea. It consists of two lateral lobes connected by an isthmus. The thyroid gland secretes three hormones:

1.  thyroxine (T4)

2. triiodothyronine (T3)

3. the C cells secrete calcitonin

            T4 contains four iodine atoms and two tyrosine molecules. T3 has three iodine atoms. These two hormones do not exist in a free state in the gland but are part of a large protein molecule called thyroglobulin. In the plasma, more than 99% of these hormones are bound to thyroxine binding globulin. There is a small free fraction, which regulates TSH secretion. T3 is metabolically more active. T4 is converted to T3 peripherally, and the conversion requires selenium.

            T3 and T4 increase the rate of protein synthesis and energy release from cells. They regulate the rate of growth and sexual development, the rate of metabolism, and the maturity of the nervous system. They also regulate the number of pressure receptors (baroreceptors) in blood vessels and so help maintain blood pressure. They increase the sensitivity of the cardiovascular system and central nervous system to catecholamines, so affecting heart rate and hence cardiac output. T3 uncouples oxidative phosphorylation i.e. it increases oxygen utilisation relative to the rate of formation of ATP, thus releasing energy as heat, which keeps the body warm. (2 p1016)

            Thyroid function tests most commonly involve assessing the levels of protein-bound and free T4. Other tests are plasma TSH levels, plasma T3, and protein-bound iodine levels. Radio-iodine uptake tests are done using iodine-131, which gives an index of thyroid activity. Thyroid scans can be done, and thyroid antibody levels if there is a suspicion of an autoimmune condition. (8 p159-172)

 

A. CRETINISM

            Cretinism occurs in infants. They usually appear normal at birth, because they received maternal hormone in utero. But the low T3 and T4 levels they themselves produce appear as symptoms of slow mental and physical development within a few weeks or months. there is stunted growth, thickened facial features, abnormal bone growth and mental retardation. The hair is scanty and the skin dry because they cannot convert beta carotene to vitamin A, and there are probably also blocks in EFA metabolism. They have a large protruding tongue, a pot belly and an umbilical hernia. Replacement of thyroid hormone will reverse the symptoms within two months. (2 p1021).

 

B. HYPERTHYROIDISM - THYROTOXICOSIS

            Excess T3 and T4 results in a speedy metabolism, with tremour, weight loss, tiredness and weakness but also restlessness, sweating, diarrhoea, anxiety and emotional instability, a rapid bounding pulse, arrhythmias and eventually heart failure. Osteoporosis and increased calcium excretion in the urine can occur.

The causes are:

x        GRAVE’S DISEASE, an auto immune condition commonest in females, in which thyroid hormone secretion is stimulated by auto-antibodies (long-acting thyroid stimulating antibodies, or LATS) which latch onto the TSH receptor sites, and mimic TSH stimulation. There is diffuse hyperplasia of the thyroid.  For reasons not well understood, giving iodine can reverse the hyperplasia temporarily. A fatty infiltration into the extrinsic muscles of the eye cause exophthalmos, and additional oedema of the orbital tissue will cause extreme bulging or proptosis of the eyes. The mechanism  is not well understood, but there are inflammatory infiltrations into these tissues.

x        TOXIC THYROID ADENOMA, a tumour that secretes T3 and T4.

x        TOXIC NODULAR GOITRE, a glandular enlargement involving many discrete foci of intense hormone formation. This occurs in people over fifty years who have had a non-toxic goitre for many years. They may present with cardiac arrhythmia or failure.

x        Thyroid hormone secreting tumours in the ovary or pituitary

x        The ingestion of exogenous thyroid hormone

x        Excess pituitary TSH or hypothalamic TRH secretion        (above from 2 p1025-1030;8 p159-171)

 

C. HYPOTHYROIDISM

            The condition covers a spectrum from mild sub clinical hypothyroidism to the severe condition called myxoedema, and so the symptoms will also vary from mild to severe. Myxoedema usually develops insidiously. The symptoms are fatigue due to a slow metabolism, mental dullness, physical slowness, dry skin and hair (beta carotene cannot be converted to vitamin A), inability to tolerate the cold, muscle weakness and cramps, orange colouration of the skin and especially the palms, yellow bumps on the eyelids due to fat deposition, recurrent infection, and depression.

            Mucoproteins accumulate in the dermal connective tissues causing the coarsening of features and a non-pitting oedema. They can also be deposited around nerves, impairing peripheral nerve functioning, and causing carpal tunnel syndrome and deafness. The same deposition in the tongue and larynx causes a slurred hoarse voice. There is weight gain in spite of a poor appetite, a slow pulse, constipation and cold extremities. Cholesterol is raised due to reduced excretion. Libido is low, and menorrhagia (excessive menstrual flow) occurs due to a failure to ovulate and so a prolonged proliferation of the endometrium. It can lead to eventual coma, with profound hypothermia.

            Some of the causes are:

x        AUTOIMMUNE THYROIDITIS with progressive destruction of the gland. This can be           divided into idiopathic/primary myxoedema without a goitre, and hashimoto's thyroiditis that presents with a firm moderate-sized goitre. Auto-antibodies are found and the gland is infiltrated with inflammatory cells. The condition is often associated with autoimmune gastritis and autoimmune addison’s disease (refer to section). There seems to be a cell-mediated auto immune reaction to mitochondrial antigens as well as antibodies, and this is non-organ specific, accounting for these multiple effects. Primary myxoedema occurs with greater frequency in those with HLA B8 (2p1023-4)

x        The result of radioactive therapy or thyroidectomy.

x        DYSHORMONOGENESIS associated with a  goitre. A congenital absence of some enzyme involved in the formation of the hormone results in a metabolic failure to produce the hormone. The gland is very enlarged and nodular.

x        Inhibition by exogenous goitrogens and drugs.

x        Decreased pituitary TSH or hypothalamic TRH secretion  

 

D. EUTHYROID /NONTOXIC OR SIMPLE GOITRE

            This is a goitre, or enlargement of the thyroid gland, in which the thyroid hormone levels are normal and there is no inflammation in the thyroid. The typical cause is an iodine deficiency (low ingestion, or low levels in the soil and hence in crops), resulting in impaired synthesis of T4. Only the peptide part of the hormone is put out, which is non-functional and so cannot produce negative feedback inhibition to TSH release. The pituitary responds to low functional thyroid hormone levels by releasing TSH, and without feedback inhibition,  levels remain high and continue to stimulate the thyroid. The thyroid tissue hypertrophies, and there is enough compensation in this way to maintain normal or only slightly reduced hormone levels.

 

E. CALCITONIN

            Specialised C cells embedded in the thyroid secrete calcitonin in response to high levels of blood calcium ions. Calcitonin lowers blood calcium by decreasing the conversion of cholecalciferol to 1,25 dihydrocholecalciferol (active vitamin D), thereby decreasing the absorption of calcium by calbindin-D in the gut, and it increases calcium uptake into the bones, thus removing it from the circulation.

 

THE PARATHYROID GLANDS

            There are four tiny parathyroid glands on the posterior surface of the thyroid gland. They respond directly to low calcium ion levels in the blood by releasing parathyroid hormone (PTH). PTH raises blood calcium levels by: increasing the conversion of 25-hydroxycholecalciferol to 1,25 dihydroxycholecalciferol (active vitamin D), thereby increasing gut calcium absorption; and increasing osteoclastic activity in bone, thereby increasing uptake of calcium from bone back into blood.

 

ADRENAL GLANDS

            These are two adrenal glands, each sitting above a kidney. Each gland is divided into the cortex, and medulla.

 

A. THE CORTEX

            The cortex secretes three types of steroid hormones. Each hormone is formed in a different tissue or zona in the cortex.

x        THE ZONA GLOMERULOSA

            This zona secretes the mineralocorticoid aldosterone, which affects sodium exchange across all cell membranes, but its major influence is in the renal tubular cells, where it increases sodium reabsorption in exchange for either potassium or hydrogen  ions (depending on whether it is compensating for pH changes). Water follows sodium and is also reabsorbed. Aldosterone has the nett effect of increasing body fluid volumes.

            Aldosterone is secreted in response to an axis that begins when the juxtaglomerular apparatus near the glomerulus responds to low renal blood flow by secreting a hormone called renin. Renin acts on alpha one globulin in the blood to form angiotensin 1. Angiotensin 1 is converted in the lung to angiotensin 2. Angiotensin 2 causes vasoconstriction, and stimulates aldosterone release.

            There is additional control by atrial natiuretic factor, released by  the atrium of the heart. It prevents aldosterone release, to reduce blood volumes as a way of dropping pressures that the heart has to deal with. Finally, low sodium or high potassium ions in the blood directly stimulate aldosterone release. This means that low sodium can cause water retention.

x        THE ZONA FASCICULATA AND ZONA RETICULARIS

            These zonae secrete glucocorticoids (corticosterone, cortisone and cortisol) and androstenedione respectively. They are stimulated by pituitary ACTH.  The glucocorticoids stimulate gluconeogenesis or glucose formation from glycogen, protein and fat breakdown. The result is a rise in blood glucose as a form of ready energy for handling stressful situations. They are long-term stress hormones. The glucose is seldom burnt up in the type of stress we have today, and so, if cortisol is continuously secreted, it destabilises blood sugar and stresses the pancreas to handle the glucose load by releasing insulin. The liver converts the large amounts of glucose into triglycerides and cholesterol, and much of this gets deposited as truncal adiposity.

            The nett affect of chronic stress (corticosteroid release) is: a loss in lean body mass with a resultant drop in the basal metabolic rate; a change in body shape and composition; and a tendency toward diabetes and cardiovascular disease because cells become insensitive to the high amounts of insulin produced, and because the high glucose creates lots of free radicals that damage the blood vessels. This is called the allostatic load. In addition to being a stress hormone, cortisol is also a natural anti-inflammatory. It suppresses the immune system, and inhibits prostaglandins.

            Androstenedione (dihydroepiandrosterone or DHEA) is responsible for protein synthesis, and secondary sexual characteristics. DHEA becomes important to a women postmenopausally, as it can be converted in the peripheral adipose tissue into estrogen and progesterone. It can also be important to men in addressing testosterone/estrogen imbalances that occur with ageing.

x        DISORDERS OF THE ADRENAL CORTEX

Ai. CUSHINGS DISEASE

            Cushings disease is the result of high cortisol and corticosterone secretion. It occurs most often in women and is commonly due to an adrenal tumour secreting cortisol, or a pituitary tumour secreting increased ACTH. The condition can also be induced by long-term administration of high doses of cortisol as an anti-inflammatory.

            It presents with obesity of the trunk, a moon face and thin limbs. This is due to the mobilisation of fat and protein from the periphery to the liver for conversion to glucose, and the resultant high glucose stimulates insulin secretion, which the liver responds to by converting it all back to fat and depositing it centrally on the body. Loss of subcutaneous fat and a growth in abdominal girth creates purple striae on the abdomen. The increased protein breakdown thins the skin, making it very delicate, and results in osteoporosis. The muscles are wasted and weak and the basal metabolic rate drops.

Aii. ADDISON’S DISEASE

            Addison’s disease is due to a chronic failure to secrete aldosterone, the adrenal hormone involved in sodium and water reabsorption in the kidneys. Sodium and water are therefore lost in large amounts in the urine. This results in tiredness, weight loss, low blood pressure, mineral imbalances, and if the water is not replaced orally, dehydration and haemoconcentration. There is also raised blood potassium because this is usually excreted in exchange for the sodium reabsorption. The kidneys also cannot compensate for metabolic acidoses, because this again relies on the sodium reabsorption process (hyrogen ions are excreted in exchange for sodium reabsorption).

 

Aiii. CONN’S DISEASE

            This is due to uncontrolled and excessive aldosterone secretion, usually from an adrenal tumour. The sodium and water retention that follows causes hypertension and hypokalemia (low blood potassium). The latter can cause arrythmias, cramps, and impaired renal concentrating ability.

 

Aiv. VIRILISATION.

Excess secretion of adrenal androstenedione causes precocious puberty in males and virilism in girls and women.

 

B. THE ADRENAL MEDULLA

            The medulla secretes the catecholamines adrenaline (80% of the secretion) and noradrenaline (20%). Adrenaline stimulates alpha, beta 1 and beta 2 receptors, and the nett effect is to prepare the body for fighting or for flight. It increases the cardiac output by increasing heart rate and stroke volume; it shunts blood away from non-vital areas like the digestive tract to vital organs that will save you like the heart and skeletal muscle. It converts glycogen to glucose, which floods into the blood and is available for energy. It bronchodilates, enabling enough air to get into the lungs and hence ensuring enough oxygen for glucose combustion and ATP formation (for energy). It dilates the pupils to allow maximum light entry so that the danger can be perceived, and it puts all the senses on alert. Adrenaline also stimulates ACTH secretion, so that cortisol, another stress hormone can be released.

            Inappropriate excessive adrenaline secretion can be due to a tumour (a phaeochromocytoma), and the symptoms include excessive sweating, nervousness, tremours, headache, palpitations, weight loss and even psychosis.(2 p1046-7)

 

OTHER ENDOCRINE GLANDS

1.         The ovaries secrete estrogen. The corpus luteum formed each month in the ovary secretes progesterone and estrogen. The placenta secretes estrogen, progesterone,     and human chorionic gonadotropin (HCG). In early pregnancy, HCG is produced by the placenta to maintain the corpus luteum in its production of estrogen and progesterone. In the third month, the placenta takes over this task. It also produces human placental lactogen which works with estrogen and progestorone to prepare the breast for lactation, and relaxin to relax the ligaments of the pelvis.

2.         The testes secrete testosterone and other androgens.

3.         The pineal gland in the mid brain on the roof of the 3rd ventricle, is attached to the thalamus, and secretes melatonin, which regulates day-night cycles, mating behaviour, and the secretion of other hormones. Melatonin is derived from serotonin which is formed from tryptophan. In winter, the longer dark cycle increases melatonin production. This depletes serotonin levels and this is thought to be the pathogenesis of seasonal affective disorder (SAD).

 

DIABETES MELLITUS

            Roughly translated, diabetes mellitus means lots of sweet urine. The essential problem is an inability to move blood glucose into the cells of the body, where it can be used or stored as glycogen or fat. Because of this, it reaches high levels in the blood, resulting in a high fasting blood glucose. The large volumes of glucose flowing into the kidney are more than its absorptive ability can handle, and glucose, plus lots of water pulled along with it, are excreted (an osmotic diuresis, with a urine that is sweet). The result is excessive urination, and an accompanying thirst and appetite.

            Pathognomonic for both diabetes I or II is the presence of three symptoms: hyperglycaemia, polyuria and polydipsia (excess thirst).

            To understand the difference between type I and type II, some physiology must be covered. Two vital factors must be present for glucose to enter cells:

1.         The presence of insulin  - which is like a key that unlocks the door for glucose to enter.                                                                         

2.         A sensitivity on the part of the cell membranes to respond to insulin, and allow glucose to enter.

                                               

A. TYPE I DIABETES: This is called insulin-dependent diabetes (IDD), and starts in childhood. In type I diabetes, factor one (above) is affected: the pancreas is not secreting enough insulin. The cause of this is not certain, but it may be linked to a viral infection or an autoimmune process.        One theory holds that bovine albumen (present in cow’s milk), absorbed through an immature gut lining, produces an antibody response. In some people, the cell antigen on the surface of the beta islets of langerhans looks similar to bovine albumen antigen, and so when these antibodies encounter the pancreatic tissue, they treat it as if it were foreign and attempt to destroy it.

            Because there is no insulin, glucose cannot enter cells, and accumulates in the blood. Its only outlet is via the urine, and so polyuria, dehydration and polydipsia, already described, results. The cells become starved of their most easily accessible source of energy. The brain is also starved of its major fuel source, blood glucose (it can make use of ketones to some extent).

            Other fuels such as fat stores and lean body mass (protein) must be mobilised as sources of energy. This results in weight loss in spite of an increased appetite. The large amounts of fatty acids that are broken down by beta oxidation to acetyl CoA cannot all be accommodated in the krebs cycle, but are shunted off to ketone formation. These ketones are excreted in the urine and on the breathe, but their high levels in the blood drop the pH to low levels, and affect brain and enzyme function to such an extent that a hyperglycaemic ketotic coma can result. Note that although there is plenty of glucose in the blood, the brain is seriously deprived of glucose, and cannot continue functioning. 

            The excess ketones impairs enzyme functioning, and so all biological pathways including those in oxidative phosphorylation are affected. The result is fatigue, which is also brought about by the dehydration, and the inability to use glucose.

            Type I diabetes requires insulin replacement, either as multiple daily injections, or the use of a continuous supply insulin pump. This, together with continual monitoring of blood glucose levels, is used in an attempt to mimic the moment to moment control that the pancreas has over blood glucose levels. It is not easy to get anything like the glucose balance that a normal pancreas achieves.

            Type I diabetics can get two kinds of coma. One is already described: the hyperglycaemic ketotic coma. The other is the result of taking too much insulin, either because of a frank overdose, or because the individual did not eat enough, or did too much exercise, and so the insulin was too much relative to his needs. This is a hypoglycemic hyperinsulinaemic coma. If a diabetic seems to be losing consciousness, and it is not possible to find out which of the two comas he has, the best is to give him glucose (a sweet). This will immediately turn the tide if he is hypoglycemic, and if he is hyperglycaemic, what difference will a little more glucose make? But it also serves to make the diagnosis, and so his needs then become apparent.

           

B. TYPE II DIABETES:   This is called non-insulin dependent diabetes (NIDD) or adult-onset diabetes. In Type II diabetes,  factor  two (above) is affected. The pancreas is not the problem, and is usually secreting excessive insulin. The problem lies with the resistance that the cells have to insulin, and so great stress is put on the pancreas to push out enough of the messenger (insulin), until the receiver of the message, the cells, listen. It takes years of eating simple sugars, putting on weight and not getting enough exercise to create this disease. As the percentage of fat on the body, and the size of the adipose cells increases, so there is a corresponding decrease in insulin sensitivity. In fact, many people with poor lifestyle habits are either well on their way to this disease, or have it without being aware of it.

            Before the onset of this type of diabetes, there is typically a phase called syndrome X (refer section above). The essential difference between type II diabetes and syndrome X is the degree of insulin resistance. By the time it has progressed to diabetes, very little glucose can get into the cells, and so instead of getting periods of hyperglycaemia and hypoglycemia in response to meals, as is the case with syndrome X, there is perpetual hyperglycaemia, as the glucose simply has nowhere to go beyond the bloodstream. After a meal, the blood glucose rises to over 200 mg/100ml, and although it does come down (a little goes into cells, and the rest is lost in the urine), it doesn’t come down to fasting levels of 80-90 mg/100 ml. Also, because a little glucose does get into cells, this type of diabetic is less likely to become ketotic or go into a coma.

            Putting Type II diabetics onto insulin injections, will of cause not alleviate the condition  Instead, this group respond best to healthier food choices, supplements which increase insulin sensitivity, weight loss and exercise. Doctors also prescribe oral hypoglycemic (blood glucose lowering) drugs. These include sulfonylureas like chlorpropamide (diabinese) and tolbutamide (orinase). They work by stimulating an already over stimulated pancreas to pump out more insulin, and they increase insulin sensitivity. The long-term success with these drugs in maintaining blood glucose and hence avoiding complications is estimated at about 30% (above from 10 p15-16).

 

C. COMPLICATIONS

            Diabetes is not a simple disease. If the blood glucose is kept at normal levels, the complications are far less, and we say the disease is well controlled. Hyperglycaemia leads to the complications that plaque this disease. The long term effects of high blood glucose are devastating to the body:

1.         Glucose binds to proteins in a process called glycosylation. This changes the structure                  and the function of the protein:

a)         It binds to low density lipoproteins (LDL) which carry cholesterol around the body. LDLs then cannot bind to their receptors. It is the binding of LDL to its receptor which creates negative feedback inhibition to HMG coA reductase             in the liver to stop cholesterol production. The liver also converts the excess blood sugar into cholesterol and triglycerides which circulate in the blood. Diabetics have high blood cholesterol, high triglycerides and low HDLs.  

b)         It binds to haemoglobin, affecting normal transport and utilisation of oxygen in the body, and hence normal energy production (ATP production by oxidative phosphorylation).

c)         It binds to the myelin sheath which surrounds nerves and contributes to the degeneration of nervous functioning in the body. This can cause loss of touch and position sense, so that a diabetic can easily hurt himself. It can affect gait, normal digestion and urination. It can contribute to impotence, which depends on the parasympathetic nervous system, or ejaculation which is a sympathetic nervous system function.

2.         Glucose is metabolised by the enzyme aldose reductase to sorbital, which accumulates in cells. When it builds up in the lens of the eye, it contributes to cataract formation. It also accumulates in the nerves, leading to myo-inositol loss, and affecting the speed of nervous transmission.

3.         Glucose is very bioactive and will oxidise to produce large amounts of free radicals. Free radicals damage the linings of blood vessels as well as oxidise the LDLs flowing in the blood, and it is this that so contributes to heart disease. Once this damage has occurred, atheromatous plaques are formed to in an attempt to “fix the damage”, and cholesterol, calcium, platelets and other debris get deposited in the arteries and arterioles. The atherosclerosis decreases the compliance of the vessels, resulting in increased total peripheral resistance, and a raised blood pressure. The heart has to work harder against this pressure, and becomes enlarged. The coronaries are themselves blocked, so although the heart is working harder, its blood supply is diminished. This results in angina, myocardial infarcts, and congestive cardiac failure.

            The eyes and kidneys are affected by the hypertension, and blindness and kidney                          damage are common complications

4.         Free radicals damage and cause thickening of the basement membranes of small vessels, and this, together with the atherosclerosis, decreases overall blood flow to the periphery, especially to the hands and feet. This slows wound healing.  The sugar is also a good breeding ground for micro-organisms, and so diabetics can develop serious, even gangrenous infections.

                        Free radicals can also damage enzymes, cells and the DNA.  Diabetics therefore have a great need for antioxidants to quench these molecules.    

            Reduced amounts of serum antioxidants has been shown to contribute to increased oxidative stress in diabetics. Hyperglycaemia reduces endogenous intracellular antioxidants like glutathione peroxidase, catalase and superoxide dismutase. Free radicals formed by the auto-oxidation of glucose and glycosylated proteins have even been implicated in the pathogenesis of diabetes.

 

x        EXERCISE

            Exercise is essential, and should become a part of a diabetics daily lifestyle. It alleviates stress, reduces weight and increases insulin sensitivity.

            However, hyperglycaemia can occur, because exercise causes the release of adrenaline and suppresses insulin. So the general rule is: if the blood glucose is under good control (between 100 to 150 mg/100ml) go ahead and exercise. If it is already over 250 mg/dl and there are ketones in the urine, the control has to be improved before exercising. It is vital to check blood glucose always before exercising, especially for diabetics on insulin, as exercise will affect blood glucose levels.

            A Diabetic should also look to other forms of stress management, as the stress hormones affect blood glucose control, and chronically elevated cortisol levels (a stress hormone) is often associated with diabetes and heart disease.

 

MENSTRUAL CYCLE

 

 

DEFINITION: The menstrual cycle is a 28 day cycle which prepares the female body for a possible pregnancy.

        

NOTE: MENSTRUATION is not the same as the menstrual cycle. Menstruation is the shedding of the endometrium (lining of the uterus) when a pregnancy does not occur.

 

NOTE: MENARCHE is the first menstruation i.e. the start of the fertile period          

 

 MENOPAUSE  is the last menstruation i.e. the end of the fertile period

 

1. THE FOLLICULAR PHASE: DAY 1 TO 14

1. The pituitary secretes Follicle Stimulating Hormone (FSH). This:

·         Stimulates the development of a follicle in the ovary

·         Stimulates the ovary to secrete estrogen

2. Estrogen stimulates the growth of the endometrium

 

 

2. OVULATION : DAY 14

The pituitary gland secretes Luteinising Hormone (LH) in a sudden surge (The “LH Surge”). This surge causes the follicle to release its developed ovum.

 

 

3. LUTEAL PHASE: DAY 14 TO 28

1. The follicle now changes into the Corpus Luteum, which secretes Progesterone
2. The ovary continues to secrete estrogen
3. The estrogen and progesterone stimulate further growth of the endometrium. It also becomes a secretory endometrium, secreting nutrients into the uterine cavity which nourish the zygote until it implants about 6 days after it is fertilised.
4. If a zygote is formed it implants about day 20 and begins to secrete Human Chorionic Gonadotrophin (HCG) a hormone that keeps the corpus luteum alive for another 2 months until a fully functioning placenta can take over the production of estrogen and progesterone. These 2 hormones then are secreted by the placenta and maintain the pregnancy to full term.
5. If conception (fertilisation) does not occur, the corpus luteum dies off and estrogen and progesterone levels drop at about day 28. The endometrium can now no longer be maintained, and shedding (menstruation) occurs.

 

 

 

NERVE CELLS

 

Two kinds:

a. The Glial cell: non-conducting cell that provides support

                             metabolically and structurally for neurons.

b. The Neuron: Come in different shapes. See page 413 text.

                          See p114 course pack (multi-polar motor neuron).

·        The Schwann cell wraps around the axon to create the myelin sheath and outer neurilemma. This forms the myelin.             See p 115 of Course pack.

·        The neurilemma allows for axon regeneration in the PNS.

·        In the CNS, the myelin is formed by a glial cell called an Oligodendrocyte. Myelin Associated Glycoprotein (MAG) inhibits regeneration of neurons.

·        Action potentials jump from Node of Ranvier to Node of Ranvier. This is called Sultatory conduction. This speeds up transmission.

·        In Multiple Sclerosis, an autoimmune disease, demyelination results in slow transmission. Symptoms are muscle weakness, foot dragging, clumsiness, visual disturbance, parasthesias.

 

PERIPHERAL NERVOUS SYSTEM

SOMATIC NERVES

 

    There are 12 pairs of cranial nerves and 31 pairs of spinal nerves. Most are mixed sensory and motor.

    See p438 for the receptors of the body.

 

The structure of a peripheral nerve

    See p 414 of the textbook

    Axons, each covered by a neurilemma are grouped into a fascicle. A perineurium surrounds the fascicle. Many fascicles are grouped together and are surrounded by an epineurium. This makes a nerve. Blood vessels are also found in the nerve.

 

 

NERVES

 ACTION POTENTIAL

//A rapid alteration in the membrane potential that may last only one millisecond. The membrane changes from -70mV to +30mV. Only a few types of cells have plasma membranes capable of producing action potentials. These membranes are called excitable membranes, and their abililty to generate action potentials is known as excitability. The propagation of action potentials is the mechanism used by the nervous system to communicate over long distances (Vander, p199).

 

The action potential is similar to the flow of current in a wire, but neural transmission is different from electrical transmission in that:

a. the axon cytoplasm provides great resistance to flow

b. the nerve impulse remains equally strong from starting point to end point

c. cellular energy is used to generate the current.

 

RESTING MEMBRANE POTENTIAL

Every cell has a resting membrane potential of –70mV on the inside of the membrane.

 

REASON: The charge is created by an unequal distribution of positive charge inside and outside of the cell. A sodium-potassium pump keeps K ions high inside the cell and Na ions high outside of the cell. But both these positive ions want to diffuse down their concentration gradients – Na in and K out – through protein channels. But the membrane is much more permeable to K, and so much more K moves out of the cell than Na moves into the cell. As a result the inside of the cell membrane  becomes negative because it has lost more positive ions than it has gained.

 

NOTE: The negative ions tend to stay put, being too big to move through the membrane.

 

 

EXCITABLE TISSUE

Only neurons have a membrane that can become excited, although all cell membranes are charged. So when a nerve is excited, the potential on the inside of the membrane changes from –70mV to +40mV. This only remains for a few milliseconds in any one place on the membrane.

 

THE IONIC HYPOTHESIS OF IMPULSE TRANSMISSION

The steps are as follows:

The nerve becomes excited because it receives a message from another neuron, a receptor or the central nervous system.

a. The Na gates open and the membrane becomes more permeable to Na⁺. Sodium flows into the cell along its concentration gradient.

 

b.The inflow of Na⁺ reverses the cell membrane potential: it has become depolarized (reverses polarity becoming positive on the inside and negative on the outside)

 

c.The Na⁺ channels close and the K⁺ channels open. K⁺ diffuses out of the cell, down its concentration gradient. This brings the membrane potential back toward the resting potential.

 

d. But the ions are in the wrong places. So the Na-K pump pumps 3 Na⁺ out for every 2 K⁺ in. The resting potential is restored and we say that  repolarisation has occurred. During this time the nerve is refractory i.e. it cannot be activated. The refractory period lasts 1 –10ms.

 

e. The depolarization occurs in one spot, and then as that spot goes through its refractory period the next adjacent spot is depolarized. The electrical changes in the first spot cause the Na⁺ channels to open in the second spot. A wave of depolarization moves down the axon followed by a wave of repolarisation.

 

f. In myelinated nerves, action potentials do not occur along the sections of membrane protected by myelin. They occur only at the nodes of Ranvier. So action potentials jump from one node of ranvier to another in what is known as salutatory conduction. This speeds up propagation.

 

g. The action potential is only generated if the stimulus is at threshold level

 //the minimum required to produce a response. If it is at this level or  above, an action potential is generated.

 

h. The nerve response is an all-or-nothing response ie it responds completely or not at all.

 

i. If the response is always the same, how does variation occur?

·         The more intense the stimulus, the greater the frequency of impulses, which the brain interpretes as different intensity

·         Different neurons have different thresholds. A single nerve has many axons. A temp of 40^oC may cause only a few axons to reach threshold, but the higher the temp the more higher threshold axons are activated, and more impulses reach the brain.

 

 

 

SYNAPSES

//Synapses are connections between nerves or between nerves and end organs. Synapses contain a small gap (cleft) between nerves, or between a nerve and an end organ. The impulse has to jump across this gap, and neurotransmitters are chemicals that achieve this jump.

 

Neurotransmitters are found in small vesicles at the presynaptic membrane. They respond to an incoming impulse by moving to the synaptic membrane and by a process of exocytosis are released into the synaptic cleft. They travel from the presynaptic membrane to the postsynaptic membrane. The greater the number of synapses the slower the speed of transmission as the chemical must diffuse across the spaces.

 

Acetyl choline (ACH) is the neurotransmitter found at the neuromuscular (NMJ) and at many of the autonomic synapses. It is excitatory and opens Na⁺ channels that allow depolarization to occur at the postsynaptic membrane. It is broken down by the enzyme cholinesterase in the cleft, allowing the synapse to recover.

 

Sometimes ACH can be  inhibitory by opening K⁺ channels and resulting in hyperpolarisation //the resting potential becomes more negative and it is harder to reach threshold. In the CNS, inhibitory impulse can help to prioritise information.

 

The amount of neurotransmitters from different presynapses can summate to bring a postsynapse to threshold.

 

Other neurotransmitters are:

·         Serotonin and dopamine (both monoamines broken down by monoamine oxidase – see MAO inhibitors and depression). Note that dopamine is the same as hypothalamic prolactin inhibitory factor.

a.        Note that dopamine is the same as the hypothalamic prolactin inhibitory factor

b.       Serotonin is low in depression, SAD, migraine, and obsessive-compulsive behaviour. It is high in mania, schizophrenia.

c.        Dopamine is formed from tyrosine (derived from phenylalanine). Dopamine is converted to adrenaline and noradrenaline

d.       Tricyclic antidepressants block monoamine uptake, and so prolong the effect of these neurotransmitters e.g. Trofranil, Norval

e.        Monoamine oxidase inhibitors (MAO inhibitors) are antidepressants that prevent the breakdown of these monoamines and prolong their effect.

f.         SSRI’s (selective serotonin reuptake inhibitors) like Prozac (Fluoxetine), Paxil, Sarafem, Zoloft, prevent serotonin reuptake and so prolong their effect.

·         GABA – gamma amino butyric acid – usually inhibitory (in the brain it dampens and coordinates motor movement. Parkinsons is due to a loss of dopamine. But the dopamine is needed to make GABA and so GABA levels are also low in this disease. It is the GABA that reduces the incoordinated tremours)

·         Glutamic acid

·         Norepinephrine

 

 

 

CENTRAL NERVOUS SYSTEM:

Made up of brain and spinal chord (review the spinal chord cross-section)

The Brain

1. The cerebrum.

·         The cortex is the grey matter and has folds (gyri) and fissures (sulci).

·         There are two hemispheres

·         The corpus callosum joins the hemispheres.

·         Each hemisphere has four regions (see p429 table 1 and figure 3).

·         The sensory cortex (postcentral gyrus) and the motor cortex (precentral gyrus) are made up of sections that respond to the control of certain parts of the body (see course pack p127)

Complete the handout on the cerebral anatomy

 

·         Buried deep in the white matter of the cerebrum are the basal nuclei which regulate voluntary motor activity by modifying impulses sent to the skeletal muscles from the motor cortex. Problems here result in Huntingtons chorea (genetic disease with jerky continuous movements) and Parkinsons disease (pill rolling tremour, tremour at rest, can’t start, cog-wheel rigidity) With huntingtons dopamine has to be blocked, with Parkinsons dopamine must be given.

 

2. Below the cerebrum is the diencephalon  (interbrain):

·         Thalamus: encloses the third ventricle and relays sensory imput, and gives an initial crude sense of pleasant vs unpleasant

·         Hypothalamus: autonomic system center; regulation of temp, osmoregulation, metabolism. Centre of drives and emotions and is an important part of the limbic system (emotional-visceral brain): thirst, appetite, sex, pain, pleasure. It also regulates pituitary gland and produces ADH and oxytocin

·         Pituitary

·         Epithalamus: roof of third ventricle. Composed of pineal gland and the choroids plexus of the  third ventricle (forms CSF). See notes on the pineal gland.

Refer to the handout and fill in.

 

3. The midbrain is found around the cerebral aquaduct that connects the third ventricle to the fourth ventricle. Around it is the cerebral peduncles and the corpora quadrigemina. This is all relay centers

Refer to handout and fill in.

 

4.The  Pons is made up of fibre tracts and is involved in controlling breathing.

Refer to handout and fill in.

 

5. The Medulla Oblongata merges into the spinal chord. It is a fibre tract area and contains many nuclei that regulate autonomic activities like heart rate, BP, breathing, swallowing, vomiting.

NOTE: The brain stem is made up of the midbrain, pons and medulla oblongata. It also has nuclei that belong to the cranial nerves. Extending its length is the reticular formation involved in motor control of visceral organs. A special group of reticular formation neurons are the reticular activating system (RAS) which controls awake/sleep cycles.

 

6. Cerebellum: 2 hemispheres with outer cortex of gray matter and inner white matter. It provides precise timing, balance and eqlm. It creates smooth coordinated movement. Fibres from the eqlm apparatus in the inner ear (8^th cranial nerve), the eye and proprioceptors are compared to the brains intentions. It sends appropriate corrective messages if necessary. VANISH DDT

Fill in handout

 

BRAIN IMAGING

1. PET: positron emission tomography: requires radioactive isotopic labeling of water or glucose placed into the blood stream. It measures which parts of the brain are active. The positrons are attracted to negative electrons in atoms. A brain map is created (see article)

2. Magnetic Resonance Imaging (MRI) and functional MRI are computer generated 2 and 3 dimensional pictures. fMRI measures brain function not structure. Powerful magnets align the nuclei of water molecules and then knocks them out of alignment with a radio wave. The hydrogens of the water spring back into alignment because they are under the consistent influence of the magnet, and so emit radio signals detected by the scanner. Soft tissues have lots of water and appear more opaque than dense bone with little water.

3. computerized tomography (CT) produces thin x-ray sections through the body. These can also be combined to form a 3-D.

 

Look over the summary of the CNS: p434

 

 

NEPHRON FUNCTION

1. Filtration

·        //blood coming in along the afferent arteriole in the glomerulus is under hydrostatic pressure and is selectively filtered in a way that creates a glomerular filtrate that appears in the Bowmans capsule.

·        Glomerular filtration is passive. The filtrate contains everything except proteins and protein-bound plasma products. Minerals like Na, K, Ca2+ is the same as in plasma. Glucose and amino acids are also filtered into the capsule. If proteins appear in the urine, it indicates that the glomerular capillaries are damaged, allowing large molecules to appear in the filtrate. This indicates kidney disease.

       (See the filtrate in table 1 p349)

 

2. Selective Reabsorption (to retain useful substances):

·        GLUCOSE AND AMINO ACIDS are actively reabsorbed in the proximal convoluted tubule. None should appear in the urine. If plasma glucose concentrations exceeds the reabsorption ability of the tubules, renal threshold is reached and glucose is found in urine. This indicates diabetes.

·        SODIUM

       (i) About 70% is reabsorbed in the proximal tubule, ascending loop of henle and collecting duct by an active process. Chlorine follows passively. 

                   (ii) Na⁺  is exchanged with H⁺ or K⁺ under the control of aldosterone in the distal convoluted tubule. This depends on pH.

·        PHOSPHATE is incompletely reabsorbed in the proximal tubule.

·        URATE (URIC ACID) is completely reabsorbed in the proximal, and resecreted actively later in the distal tubule. Uric acid is formed when nucleotides are broken down in the body.

·        POTASSIUM is actively reabsorbed in the proximal tubule, and in exchange with Na⁺ in the distal tubule.                     

·        WATER is absorbed in the proximal tubule along with the absorption of solutes to maintain osmolarity (isosmotic reabsorption). 200L of water are filtered a day in the glomerulus. About 140-160L is reabsorbed in the proximal tubule.

Water is absorbed differentially in the loop of henle and collecting duct according to the needs of the body (osmoregulation).

 

THE TWO PHASE SYSTEM: PREVIOUSLY CALLED THE COUNTERCURRENT EXCHANGE OR COUNTERCURRENT MULTIPLIER

This system controls water reabsorption by the nephron.

 

1. Phase one: sodium chloride is actively reabsorbed in the ascending Loop of Henle. It is absorbed directly into the medulla and makes the medulla very concentrated and hypertonic. The ascending Loop of Henle is impermeable to water. 

2. Phase two: The descending Loop of Henle is permeable to water. It is impermeable to sodium and other solutes. Because the medulla is so concentrated, there is a steep gradient for water absorption. The water goes directly into the peritubular capillaries (vasa recta) and cannot dilute the medulla. The medulla therefore retains its hyperosmolarity and water absorption from the descending Loop of Henle is maintained.

3. The bottom of the Loop of Henle therefore contains the most concentrated filtrate.

4. The filtrate flowing into the Distal Convoluted Tubule and early Collecting duct is dilute.

5. As the Collecting duct descends down the medullary pyramid, water can be drawn out of it by the hypertonic medulla but only in the presence of the hormone ADH.

·        When ADH is absent, the Collecting duct’s lining is impermeable to water and a dilute urine will be formed.

·        If the blood is too concentrated (stimulus), the osmoregulators (receptors) in the hypothalamus (control centre) respond. This control centre will secrete ADH (anti-diuretic hormone) which will make the Collecting duct lining (effector) permeable to water reabsorption. This is a homeostatic negative feedback loop to maintain steady blood osmolarity. 

 

A second homeostatic control is the secretion by the kidney of a hormone Renin.

Stimulus: low renal plasma blood flow

Receptor: the juxtaglomerular apparatus near the afferent arteriole

It secretes Renin. Renin reacts with angiotensinogen made by the liver and converts it to angiotensin one. In the lung this is converted to angiotensin 2. Angiotensin 2 is a vasoconstrictor (will raise the lowered blood pressure).  Angiotensin 2 stimulates the adrenal gland.

Control Centre: The adrenal gland responds to the angiotensin 2 by secreting aldosterone.

Effector: the Distal convoluted tubule to aldosterone by increasing sodium reabsorption. Water follows passively.

Result: water and sodium reabsorption increases plasma volume, restores renal plasma flow and increases blood pressure. 

 

Note: Natriuretic hormone: inhibits Na⁺ reabsorption. It is secreted by the cardiac atrium.

Note: Excessive curbing of dietary salt will cause  increased reabsorption of Na.

 

URINE: 95% water, 5% solids

·        organic wastes: urea (from the breakdown of amino acids when they are used for energy), ammonia, uric acid (from nucleic acid breakdown) and creatinine (from creatine).

·        Ions include Na⁺, K⁺, Mg²⁺, Ca²⁺, Cl^-, S^2- and PO^4-.

·        Hippuric acid is derived from benzoic acid, often found in fruits and vegetables.

·        Ketones. urobilinogen.

·        PH 4.6 to 8.0, with average 6.0 depending on diet

·        Volume on average: 1 to 2 litres but variable

 

See page 350, 351 for figures and summary tables.

 

ANTIDIURETIC HORMONE

The hypothalamus has osmoreceptors that respond to changes in blood osmotic pressure.

Alcohol decreases ADH release. There is a diuresis, and the hangover is largely due to this.

 

pH Regulation

Only the kidney is responsible for the excretion of H^+. The lungs can only handle H⁺ indirectly by excreting CO₂. Whether the hydrogen comes from CO₂, H₂PO₄ or organic acids it is excreted by the kidney. It does this to maintain pH of blood at 7.3-7.5

 

	H+	CO2	Cause of CO2 change
Respiratory. acidosis	Up	up	Primary lung abnormality (retaining CO2) - renal compensation
Respiratory alkalosis	down	down	Primary lung Abnormality (hyperventilating) - renal compensation
Metabolic acidosis	up	down	organic acids-ketones, lactic acid, renal failure. Results in reflex ventilatory compensation hence low CO 2
Metabolic alkalosis	down	up	Vomiting. Results in reflex decrease in ventilation to increase CO2

 

See Davenport diagram for compensation

There are three main buffers in operation in the kidneys.

When there is an acidosis:

1.      In tubular cells:

CO₂ +H₂O à H₂CO₃ à H⁺ + HCO₃^- à H⁺ + NaHCO₃

(see p355). The H⁺ is secreted into the tubule where…...

2.      In the lumen: The buffering of H⁺ by HPO₄^-2 à H₂PO₄^- which is excreted.

                               and the buffering of H⁺ by NH₃ à NH₄⁺

                               The  H⁺ is then excreted.

If there is an alkalosis, the first reaction is reversed to allow for H⁺ formation. CO₂ is absorbed from the blood and used to generate H⁺. H⁺ is reabsorbed and not secreted.

 

 

HEAT STRESS

Stimulus: raised environmental or core temperature (exercise)

Receptor: skin and core (brain) thermoreceptors   ….. afferent nerve to:

Control centre: hypothalamus in the brain   …… efferent nerve to:

Effectors: (a) blood vessels – vasodilate (this drops diastolic blood pressure

                                              – total peripheral resistance has decreased)

                 (b) sweat glands in skin – sweating

Result: brings core heat to surface and evaporation dissipates the heat.

This switches the receptors’ response off.

This whole process is called negative feedback i.e. restores the original state.

 

COLD STRESS

Stimulus: decreased environmental temperature

Receptors: skin thermoreceptors   ……. afferent nerve to:

Control centre: Hypothalamus of brain  …… efferent nerve to:

Effectors: blood vessels – vasoconstrict

                 Smooth muscles in skin – pilorection

                  Striated muscles of body – shivering

                  (long term: increase thyroid gland activity – increase thyroid

                  hormone to increase metabolic rate).

Result: Heat is generated and core temperature rises. This switches off the thermoreceptors. A process of negative feedback has occurred i.e. the original state is restored.

 

Textbook p341 gives a summary.

Activity: With your lab partner, do # 6, 7 and 10 p341 of textbook. 

 

RESPIRATORY CONTROL/ HOMEOSTASIS

 

Stimulus: Exercise results in an increase in the use of oxygen and in the

                 production of  carbon dioxide.

Receptors: peripheral (PO₂) and central (PCO₂/H⁺) chemoreceptors respond

                    to fallen oxygen and higher carbon dioxide... Afferent nerves to:

Control Centre: respiratory centre in the medulla and pons of the brain 

                              …   efferent  nerves to:

Effector: diaphragm and intercostals muscles contract at a faster rate.

Result: increased respiratory rate will increase oxygen levels and drop carbon dioxide levels thus returning these to normal. Negative feedback has restored the original balance.

Note: other stimuli can send messages to the control centre: raised core temperature, conscious anticipation of exercise (cerebral cortex), pain and emotion.

 

CARDIOVASCULAR CONTROL/HOMEOSTASIS

 

Stimulus: (1) Chemoreceptors

                 (2) Increased muscle pumping increases venous return to the

                       heart. (Frank-Starling Law of the Heart)

                 (3) decreased total peripheral resistance due to vasodilation

                       caused by the  response to heat.

Receptors: (1) The stimulated respiratory centre of the medulla

                          …. Send message to:

                   (2) The increased end-diastolic volume stretches cardiac muscle

                    (3) baroreceptors in carotid bifurcation and aortic arch 

                          … send message to:

Control centre: (1) The cardiovascular control centre in the medulla

                           (2) The cardiac muscle itself responds directly to the stretch

                           (3) The cardiovascular control centre in the medulla

Effector: (1) Efferent nerves carry message to heart to increase heart rate

                     (pulse rate) and stroke volume. This increases cardiac output

                     (HR >< SV = CO) and increases the systolic blood pressure.

                 (2) The cardiac muscle responds directly by increasing the

                       strength of contraction thereby increasing stroke volume.

                  (3) Efferent nerves carry message to heart to increase heart rate

                        and stroke volume.

Result: The systolic blood pressure increases. Note that the diastolic blood pressure decreases, so that mean arterial blood pressure (cardiac output + total peripheral resistance) stays about the same. This meets the needs of the exercising muscles for more oxygen because it is transported with a greater speed and in greater volumes of blood through dilated blood vessels to the muscles. PO₂ and PCO₂ is maintained within the ranges required for life.

So a negative feedback had occurred to restore balance.

 

 

 

WHAT IS RESEARCH?

 

QUESTIONS

1. What is an independent variable?
2. What is a dependent variable?
3. What are interfering variables?
4. How are interfering variables controlled?
5. When designing a study/an experiment/doing a piece of research, what are we trying to do with all of these variables?
6. How do we write a hypothesis?
7. What are the weaknesses in controlled experiments? Where could errors occur?

 

ANSWERS

1. The independent variable is the factor in the experiment that is manipulated by the researcher. It is what the experimenter is “doing”.

 

2. The dependent variable is the factor in the experiment that changes in response to the independent variable. It is the outcome or effect. It is the “then this will happen”.

 

Remember that

·        both the independent and the dependent variables have to be measurable variables i.e. the variables in an experiment have to be testable.

 

3.  The interfering variables are all the factors that could effect the relationship between the independent and dependent variable. Because we are trying to measure the relationship between these latter two variables, it is important to control the interfering variables.

 

4. Interfering variables are controlled in two ways:

(i)                  By inclusion and exclusion criteria. These are choices made right at the start as to who/what will be accepted into a study and who/what will not. These choices are based on the interfering variables identified, which then become part of what is excluded from the study.

(ii)                By using study and control groups. A study group is the group that gets the manipulation and the control is the group that does not. The initial sample subset taken from the population is randomly assigned to one or the other group. In this way it is hoped that the two groups will be the same, and that the same interfering variables are present to the same extent in both groups. If this is achieved there should be no measurable differences between the two. The manipulation is then applied only to the study group. If the two groups are compared with each other, it is logical to assume that any measurable differences between them would have to be due to the manipulation and none of the interfering variables. In this way, the interfering variables have been controlled in that they do not affect the outcome.

 

5. We are trying to measure the relationship between the independent and dependent variable, and keep any other variables from getting in the way of this.

 

6. The hypothesis, or educated guess as to what the outcome will be, is written in the following way: If …..(I do this i.e. the independent variable is put here ) …., then ….(this will happen i.e. the dependent variable is put here).

For example: If  humans take daily vitamin C supplements, then they will decrease their changes of getting a cold.

 

Remember that:

·        A hypothesis is a testable prediction or educated guess on the outcome of the experiment. It really doesn’t matter if this is the final outcome of the experiment – a rejection of a hypothesis does not mean the experiment has failed. The outcome is valid in its own right – the hypothesis was just a guess.

 

7.There are many inherent weaknesses and in study design, as well as chances for errors to occur:

(i)                  We cannot control all variables. Many times we don’t know all these variables. We cannot screen them all out, and if we use control and study groups we can never be sure if they are the same in all respects and that some bias hasn’t crept into the experiment.

(ii)                The more we control the variables, the less like life it becomes. This becomes a problem when we extrapolate our findings back to the entire population. However, the more we control variables, the more confident we are in any association we see between the independent and dependent variable. This is the catch-22 of research.

(iii)               Errors can result from the instruments used to measure variables (precision problems) or the accuracy with which the measurements were taken.

(iv)              All experimentation is ultimately subjective. It is also influenced by the society and the age within which that work was done.

 

 

WRITING A LAB REPORT

 

1. Title Page:

State the following on a cover page:

• the title of the investigation
• your name and the instructor’s name
• the course code and the due date.

 

2. Purpose:

In a sentence or two, make a brief statement about why you did the investigation.

 

3. Hypothesis:

Make an educated guess about the outcome of the investigation.

It must take the following form:

If ….(I do this manipulation/the independent variable), then ….(I expect this outcome/the dependent variable).

 

4. Materials:

Make a detailed list of materials you used. Be specific about sizes and quantities.

 

5. Procedure:

Write the procedure in detail, in the correct order in which it was done. It must be listed in point form.

 

6. Results:

Record the outcome in sentences, tables, charts, labelled diagrams or graphs. Do not discuss or explain the results.

 

7. Discussion:

Explain the results. Use theory or give a theory to support or interpret your results. If you were assigned questions, answer them in this section.

Include sources of error and design weaknesses in this section. In other words, explain why your experiment may be inaccurate. All experiments and observations have some degree of error.

There are different types of error:

1. Instrument error: measuring devices can be malfunctioning or calibrated incorrectly. All measuring devices have limitations with respect to the accuracy of the measurements which can be attained from them, and so the number of significant digits that can be quoted is also limited.
2. Uncontrollables: In real life there are always many interfering variables that can affect the outcome of an experiment or piece of research that is trying to establish a relationship between the independent and dependent variables. As much as possible these other variables should be controlled, but it is hard to control all of them. Any interfering variables should be identified and discussed here.
3. Human error: Any known human error should be included here.

 

8. Conclusion: Accept or reject your hypothesis and briefly say why.

 

 

HOMEOSTASIS UNIT

 

OVERALL EXPECTATIONS

·       Describe and explain the physiological and biochemical mechanisms involved in the maintenance of homeostasis

·       Analyse, through experimentation and the use of models, the feedback mechanisms that maintain chemical and physical homeostasis in animal systems

·       Analyse how environmental factors (physical, emotional, microbial) and technological applications affect/contribute to the maintenance of homeostasis, and examine related societal issues.

 

ENDOCRINE SYSTEM

NERVOUS SYSTEM

URINARY SYSTEM

IMMUNE SYSTEM

 

HOMEOSTASIS

//process that goes on all the time in the body to maintain constant biological ranges even as the external environment changes and challenges this balance. Any change in the internal environment initiates a reaction to minimize the change. This reaction would be called a compensating regulatory response.

 

A dynamic equilibrium. The body maintains a constant balance or steady state

 

For example homeostasis involves balancing: blood glucose; body temp; blood pressure; water balance and therefore concentration of dissolved minerals and organic molecules like proteins; blood gases; blood pH; blood hormones; metabolic rate.

 

 

Homeostasis

 

Homeostasis is a condition of active balance where the body processes fluctuate within a range considered normal.

 

Each major process in the body has a way of detecting change (outside of the normal range), and the activity level of the process increases or decreases, as necessary, to maintain conditions within the range required for normal functioning.  This process is called a feedback mechanism. 

 

Negative feedback mechanism  – this mechanism restores the conditions to within their normal range, to reverse the change

                                                       -    most body systems employ this type of feedback

            mechanism i.e. thermoregulation

  

Positive feedback mechanism – this mechanism reinforces the change and continues to keep

                   the body condition outside of the normal range

    - there are a few positive feedback systems in our body i.e.

       lactation and birth process

 

For each feedback system to operate 3 components are necessary:

 

1.      receptor – detects the change

2.      control center – selects appropriate adjustment

3.      effector – carries out action

 

The messages transmitted between each of the 3 components may be chemical or neural.

 

Feedback control loops out at different speeds depending on the number of hormones involved in the chain and the time it takes for each to act.  i.e. digestive system hormones are a quick-response to food in the stomach, menstrual cycle takes about 28 days to complete one feedback control loop.