Sunday, 3 July 2011

Topic 11 - Human health and physiology II

11.1 Defense against infectious diseases II

11.1.1 Describe the process of blood clotting.

Limit this to the release of clotting factors from platelets and damaged cells resulting in the formation of thrombin. Thrombin catalyses the conversion of soluble fibrinogen into the fibrous protein fibrin, which captures blood cells.

      First platelets collect at the site of injury, where platelets and the damaged cells release the ‘clotting factor’ thromboplasin.
      In the presence of the clotting factor as well as calcium ions and vitamin K present in the plasma, prothrombin in the plasma converts to thrombin.
      Thrombin is an enzyme which converts soluable fibrinogin to insoluable fibrin fibres. Fibrin fibres get caught in the clump of platelets, creating the semi-liquid structure of the blood clot.

11.1.2 Outline the principle of challenge and response, clonal selection and memory cells as the basis of immunity.

This is intended to be a simple introduction to the complex topic of immunity. The idea of a polyclonal response can be introduced here.

Challenge and response
      Lymphocytes in our body develop immunocompetence and have the ability to recognize one specific antigen. However, the immune system must be challenged by an antigen during the first infection in order to develop an immunity. All cellular events (involving macrophages helper T-cells and B cells) are part of the response which leads to immunity to this pathogen.

Clonal selection
      This describes the identification of the leukocytes (e.g. particular plasma B cells) that can help with a specific pathogen and the multiple cell divisions which occur to build up the numbers of that same cell type. Simply put, your immune system selects the type of cell that will be useful and initiates cloning of that cell.

Memory cells
      These are the cells that provide long term immunity. You must experience a pathogen (antigen) once in order to produce memory cells and have true immunity to that specific pathogen.

11.1.3 Define active and passive immunity.

Active immunity is immunity due to the production of antibodies by the organism itself after the body’s defence mechanisms have been stimulated by antigens.

Passive immunity is immunity due to the acquisition of antibodies from another organism in which active immunity has been stimulated, including via the placenta, colostrum, or by injection of antibodies.
      Transfer of antibodies from mother to fetus through the placenta.
      Aquisition of antibodies through mother’s colostrum (breast milk).
      Antibody injections such as with antivenoms to treat poison from spiders or snakes.

11.1.4 Explain antibody production.

Limit the explanation to antigen presentation by macrophages and activation of helper T-cells leading to activation of B-cells which divide to form clones of antibody-secreting plasma cells and memory cells.

      First, a macrophage identifies an antigen and engulfs it by phagocytosis.
      Inside, the antigen is combined with an MHC protein, and this is presented on the plasma membrane of the macrophage.
      A helper T-cell with the corresponding receptor can bind to the presented antigen on the macrophage. Once it does, the macrophage sends a signal that activates the helper T-cell.
      B-cells are activated once a corresponding antigen binds to a corresponding antibody on its cell surface, and then an activated T-cell binds to it as well. The T-cell causes the activation of the B-cell, which then begins to continuously divide by mitosis to produce plasma cells (clones).
      The plasma cells secrete the antibodies in significant quantities.

11.1.5 Describe the production of monoclonal antibodies and their use in diagnosis and in treatment.

Production should be limited to the fusion of tumour and B-cells, and their subsequent proliferation and production of antibodies. Limit the uses to one example of diagnosis and one of treatment.

Detection of antibodies to HIV is one example in diagnosis. Others are detection of a specific cardiac isoenzyme in suspected cases of heart attack and detection of human chorionic gonadotrophin (HCG) in pregnancy test kits. Examples of the use of these antibodies for treatment include targeting of cancer cells with drugs attached to monoclonal antibodies, emergency treatment of rabies, blood and tissue typing for transplant compatibility, and purification of industrially made interferon.

      B cells are obtained by injected an antigen that correspond to a desired antibody into an animal, and then extracting the antibody from the animal. Monoclonal antibodies are produced by the fusion of B-cells and tumour cells. Tumour cells divide indefinitely,  so the resulting hybridoma cells divide to form clones. These then secrete antibodies in significant quantities.
      Monoclonal antibodies are used in pregnancy kits to detect human chorionic gonadotrophin (HCG) in order indicate pregnancy, because the urine of pregnant women is rich with HCG. Mobile, blue coloured monoclonal antibodies in the pregnancy kit will bind to HCG protein in the urine and this is what produces the ‘blue’ colour on the kit that indicates pregnancy.
      Monoclonal antibodies have been developed for tumour-associated antigens on cancer cells.

11.1.6 Explain the principle of vaccination.

Emphasize the role of memory cells. The primary and secondary responses can be clearly illustrated by a graph.

Precise details of all the types of vaccine (attenuated virus, inactivated toxins, and so on) for specific diseases are not required.

      A vaccine is a modified form of a disease-causing microorganism that stimulates the body to develop immunity to a disease without having fully developed the disease.
      A weakened or dead version of a pathogen is injected into the body, causing the immune system to mount a primary response.
      The first vaccination causes some antibody production and the production of B memory cells. Booster shots may follow.
      Memory cells should persist to give long-term immunity.
      When the real pathogen strikes, a secondary response occurs, aided by the memory cell production of pathogen-specific antibodies.
      This response is faster and there is greater production of antibodies.

11.1.7 Discuss the benefits and dangers of vaccination.

The benefits should include total elimination of diseases, prevention of pandemics and epidemics,
decreased health-care costs and prevention of harmful side-effects of diseases. The dangers should include the possible toxic effects of mercury in vaccines, possible overload of the immune system and possible links with autism.

general statements: [3 max]
 vaccinations stimulate antibody production / immunity;  against/resistance to specific pathogens / artificial immunity;  use either weakened pathogens or specific antibodies;  primary response to first vaccination / secondary response to second vaccination;  memory cells (are cloned) maintain long-term immunity;

benefits: [3 max]
 eradicated some diseases e.g. smallpox / polio;  decrease child mortality;  MMR/mumps, measles and rubella prevent long-term health problems; e.g. deafness / blindness / heart damage from rubella / male infertility from mumps;  prevent epidemics / pandemics;

dangers: [3 max]
 too many vaccinations may lower body’s immunity to new diseases;  immunity may not be life-long / may have severe version as adults e.g. measles;  some vaccines may cause serious side effects; e.g. whooping cough vaccine may cause encephalitis / toxic effects (Hg) in some vaccines / allergic reactions;  may contract disease from vaccine; 

11.2 Muscles and movement

11.2.1 State the roles of bones, ligaments, muscles, tendons and nerves in human movement.

      Bones provide a firm anchorage for muscles. They also act as levers, changing the size or direction of forces generated by muscles.
      Ligaments connect bone to bone, restricting movement at joints and helping to prevent dislocation.
      Muscles provide the force needed for muscle contraction. They do this when they contract.
      Tendons attach muscle to bone at their point of anchorage. They are chords of dense connective tissue.
      Nerves stimulate muscles to contract at a precise time and extent, so that movement is co-ordinated.

11.2.2 Label a diagram of the human elbow joint, including cartilage, synovial fluid, joint capsule, named bones and antagonistic muscles (biceps and triceps).

11.2.3 Outline the functions of the structures in the human elbow joint named in 11.2.2.

      humerus, radius and ulna: the bones of the skeleton, together with the muscles attached across joints, function as a system of levels to maintain body posture and bring about actions, typically movements
      biceps muscle: anchored to shoulder blade and attached to radius so contraction flexes the lower arm (and stretches triceps)
      triceps muscle: anchored to shoulder blade and attached to ulna so contraction extends the lower arm (and stretches biceps)
      ligaments: hold bones (humerus, radius, and ulna) in correct positions at the point (combats dislocation)
      capsule: contains and protects joints without restricting movement, and encloses the synovial cavity
      synovial membrane: secretes synovial fluid
      synovial fluid: lubricates the joint to reduce friction, nourishes the cartilage, and removes any (harmful) detritus from worn bone and catilage surfaces
      cartilage: firm, flexible material - a slippery covering that reduces friction and absorbs compression

11.2.4 Compare the movements of the hip joint and the knee joint.

Hip joint
Knee joint
synovial ball and socket joint
synovial hinge joint
articulating bones include the acetabulum of the pelvic girdle and the femur (head), and no additional bones
articulating bones include the femur and the tibia, including the patella as an additional bone
freely movable
freely movable
angular motions in many directions - circumduction
angular motion in one direction - flexion and extension
ball-like structure fits into a cup-like depression
convex surface fits into a concave surface

11.2.5 Describe the structure of striated muscle fibres, including the myofibrils with light and dark bands, mitochondria, the sarcoplasmic reticulum, nuclei and the sarcolemma.

      Skeletal muscles are made of bundles of striated muscle fibres. Muscle fibres are long, multi-nucleate cells.
      Each muscle fibre consists of many parallel myofibrils within a plasma membrane called the sarcolemma, together with sarcoplasm (cytoplasm of muscle cell).
      Sarcolemma infolds to form the sarcoplasmic reticulum, which is a system of transverse tubular endoplasmic reticulum arranged around individual myofibrils.
      A sacromere is the subunit of a myofibril. Sacromeres have light and dark bands which extend across the myofibril and give  muscle fibre its striated appearance.
      At either end of a sacromere is a Z line, to which the thin actin filaments attach. In the centre of the sacromere is the thicker myosin filaments. Actin filaments make up the light bands and myosin filaments make the dark bands.
      There are mitochondria packed between the myofibrils.

11.2.6 Draw and label a diagram to show the structure of a sarcomere, including Z lines, actin filaments, myosin filaments with heads, and the resultant light and dark bands.

11.2.7 Explain how skeletal muscle contracts, including the release of calcium ions from the sarcoplasmic reticulum, the formation of cross-bridges, the sliding of actin and myosin filaments, and the use of ATP to break cross-bridges and re-set myosin heads.

1.     The myofibril is stimulated to contract by the arrival of an action potential. This triggers the release of calcium ions from the sarcoplasmic reticulum, which subsequently surround the actin molecules.  Calcium ions bind to troponin on the actin filaments, which removes tropomyosin and thereby exposes myosin-binding sites.
2.     Each myosin head is ‘charged’ with ADP + Pi attached to it. When a myosin head reacts with the binding site on an actin molecule, the Pi is released. This forms a cross-bridge. 
3.     ADP is released, and this triggers the ‘rowing movement’ of the myosin head, which tilts by about 45°, pushing the actin filament along. This is the power stroke and the myofibril has been shortened (contraction).
4.     A new ATP binds to the myosin head. ATPase on the myosin head catalyzes the hydrolysis of ATP into ADP and Pi, which makes the myosin head ‘charged’ again. This causes the myosin head straighten and detach from actin, thereby breaking the cross-bridge.
5.     The process repeats further along the actin molecule is action potentials are present.

11.2.8 Analyse electron micrographs to find the state of contraction of muscle fibres.

Muscle fibres can be fully relaxed, slightly contracted, moderately contracted and fully contracted.

11.3 Kidney

11.3.1 Define excretion.

Excretion is the removal from the body of the waste products of metabolic pathways.

11.3.2 Draw and label a diagram of the kidney.

Include the cortex, medulla, pelvis, ureter and renal blood vessels.

11.3.3 Annotate a diagram of a glomerulus and associated nephron to show the function of each part.

The functional unit of a kidney is the nephron.

      Glomerulus: a capillary bed within a nephron which filters various substances in the blood.
      Bowman’s capsule: a capsule that surrounds the glomerulus and receives filtrate during ultrafiltration by the glomerulus,
      Proximal convoluted tubule: reabsorption of useful substances like glucose, salts and water occurs here.
      Loope of Henle: creates a hypertonic environment in the renal medulla for the passive reabsorption of water.
      Distal convoluted tubule: reabsorption of salt.
      Collecting ducts: reabsorption of salt, water and urea, where the reabsorption of water is controlled by ADH (antidiuretic hormone).

11.3.4 Explain the process of ultrafiltration, including blood pressure, fenestrated blood capillaries
and basement membrane.

      The pathway towards the lumen of the nephron involves three layers which make a fine sieve-like structure: first, the fenestrated epithelial wall of the glomerulus, then the basement membrane, and lastly the epithelial wall of the Bowman’s capsule which is made of a network of fenestrated podocytes.
      High blood pressure in the glomerulus drives ultrafiltration. Blood pressure here is high because blood passes into the wide afferent tubes and out of the narrow efferent tubes, which drives substances through the fenestrations of the glomerulus.
     Ultra filtration excludes larger particles (RBCs, WBCs, platelets, proteins) from entering nephron, keeping them within the blood vessels
     Ultra filtration is nonselective, allowing water, urea, glucose, amino acids, salts, vitamins, hormones, minerals, and any other small particles to enter the nephron

11.3.5 Define osmoregulation.

Osmoregulation is the control of the water balance of the blood, tissue or cytoplasm of a living organism.

11.3.6 Explain the reabsorption of glucose, water and salts in the proximal convoluted tubule, including the roles of microvilli, osmosis and active transport.

      Many useful molecules are filtrated by the glomerulus, and selective re-absorption into the blood is necessary. Selective re-absorption occurs in the proximal convoluted tubule.
      The walls of the PCT are a single layer of cells with microvilli projecting into the lumen. This significantly increases the surface area for absorption.
      Cells are packed with mitochondria and pumps are embedded into the membrane -- these drive the active transport of useful substances.
      Normally, 100% of the glucose is reabsorbed by active transport.
      About 80% of the mineral ions are reabsorbed by active transport. facilitated diffusion or exchange of ions.
      Since solutes are reabsorbed, water is also reabsorbed by osmosis. About 80% of the water us reabsorbed.
      Ultimate effect of selective reabsorption is the return of essential substances to the blood that had left the blood during ultrafiltration

11.3.7 Explain the roles of the loop of Henle, medulla, collecting duct and ADH (vasopressin) in maintaining the water balance of the blood.

Details of the control of ADH secretion are only required in option H (see H.1.5).

Loop of Henle
      The purpose of the loop of Henle is to create a hypertonic environment in the tissue fluid of the medulla, which allows for subsequent osmoregulation in the collecting ducts.
      The loop of Henle uses a countercurrent multiplier mechanism with its descending and ascending loops.
      The ascending loop is impermeable to water but permeable to salt ions, and ions are pumped out into the medulla by active transport. This creates a high solute concentration in the medulla, and also dilutes the filtrate.
      The descending loop is permeable to water and impermeable to salt ions. As a result of the hypertonic environment of the medulla, water flows out of the descending limb by osmosis.

Collecting ducts
      The collecting ducts have a role in osmoregulation. They are differentially permeable to water. This depends on the presence or absence of antidiuretic hormone (ADH), which is secreted by the prosterior pituitary.
      When water content in the blood is low, ADH is secreted and this causes aquaporins (channels) to form in the membranes of the collecting ducts, making it more permeable to water. The hypertonic environment of the medulla causes water to be re-absorbed. This produces a small volume of concentrated urine.
      When water content in bloods is high, ADH is not secreted, aquaporins break down and the collecting duct becomes less permeable to water. A large volume of dilute urine is produced.
      As a result, water content in the blood is maintained at a constant level.

11.3.8 Explain the differences in the concentration of proteins, glucose and urea between blood
plasma, glomerular filtrate and urine.

 Content (mg per 100mL of blood)

blood plasma
glomerular filtrate

      Glucose: does become part of the filtrate because it is small enough to undergo ultrafiltration at the glomerulus, but does not become part of the urine because 100% of the glucose should be reabsorbed by active transport at the proximal convuluted tubule.
      Proteins: do not become a part of the filtrate or urine because they are too large to fit through the basement membrane preceding the Bowman’s capsule.
      Urea: is a waste product and its concentration is magnified in the urine because of the re-absorption of water.

11.3.9 Explain the presence of glucose in the urine of untreated diabetic patients.

      Glucose is often present in the urine of untreated diabetic patients. This is because glucose concentration in the blood is typically much higher than the normal 90 mg per 100mL, so the pumps in the proximal convoluted tubules are unable to reabsorb all the glucose that is filtered by the glomerulus.


11.4.1 Annotate a light micrograph of testis tissue to show the location and function of interstitial cells (Leydig cells), germinal epithelium cells, developing spermatozoa and Sertoli cells.

11.4.2 Outline the processes involved in spermatogenesis within the testis, including mitosis, cell growth, the two divisions of meiosis and cell differentiation.

Inside the seminiferous tubules, an outer layer called germinal epithelial cells (2n) continuously divide by mitosis so that there is a large reserve of diploid cells. Diploid cells undergo cell growth and become larger, and at this stage they become primary spermatocytes (2n). Primary spermatocytes undergo the first division of meiosis to form two secondary spermatocytes (n). Each secondary spermatocyte undergoes the second division of meiosis to form two spermatids (n). The spermatids become associated with Sertoli cells, which nourish them and help them develop into spermatozoa by differentiating. Differentiation includes the development of flagella and the acrosome layer. Ultimately spermatozoa detach from Sertoli cells and are carried out of the testis by the fluid from the centre of the seminiferous tubule.

11.4.3 State the role of LH, testosterone and FSH in spermatogenesis.
     LH: produced at the anterior pituitary; responsible for stimulating the production of testosterone within the interstitial cells.
     FSH: produced at the anterior pituitary; stimulates spermatocytes to undergo the first division of meiosis to form secondary spermatocytes; the target is Sertoli cells.
     testosterone: produced by interstitial cells in the testis; stimulates the development of secondary spermatocytes into mature cells.

11.4.4 Annotate a diagram of the ovary to show the location and function of germinal epithelium, primary follicles mature follicle and secondary oocyte.

11.4.5 Outline the processes involved in oogenesis within the ovary, including mitosis, cell growth, the two divisions of meiosis, the unequal division of cytoplasm and the degeneration of polar body.

In the ovaries of a female fetus, germinal epithelial cells (2n) divide by mitosis to create a large reserve of diploid cells. Diploid cells undergo cell growth and become larger cells called primary oocytes (2n). Primary oocytes begin the first division of meiosis, but stop at prophase I. A primary ooctye  with a single layer of follicle cells is called a primary follicle, and when a baby girl is born her ovaries have approximately 400 000 primary follicles. During each menstruation cycle, FSH causes a few primary follicles to begin development. The primary oocyte completes the first division of meiosis, producing two haploid nuclei. The cytoplasm of the primary oocyte divides unequally, resulting in a large secondary oocyte (n) and a smaller polar body (n). The secondary oocyte begins the second division of meiosis but halts at prophase II. The follicle cells however  continue to proliferate and follicular fluid forms. Once ovulation is triggered by LH, the ovarian follicle bursts open the secondary oocyte releases into the oviducts. After fertilization, the secondary oocyte completes the second division of meiosis to form an ovum (with a sperm nucleus inside it) and a smaller polar body (n). The first and second polar bodies do not develop and eventually degenerate.

11.4.6 Draw and label a diagram of a mature sperm and egg.

11.4.7 Outline the role of the epididymis, seminal vesicle and prostate gland in the production of semen.
     The epididymis acts as a storage structure for sperm arriving from the tesis. Sperm develops here and becomes motile.
     The seminal vesicles produce the seminal fluid, a component of semen. It includes: nutrients like fructose as an energy source for sperm; mucus to protect sperm from the harsh conditions of the vagina; and prostoglandins, hormones that stimulate contractions in the female reproductive tract which facilitate movement by the sperm.
     The prostate gland secretes prostate fluid, another component of semen. It is highly alkaline, and helps to neutralize the acidity of the vagina.

11.4.8 Compare the processes of spermatogenesis and oogenesis, including the number of gametes and the timing of the formation and release of gametes.

     Both begin with the proliferation of cells by mitosis.
     Both involve cell growth before meiosis.
     Both involve two divisions of meiosis.
     Both require LH and FSH.
     Both involve differentiation of cells: sperm requires flagella, mid-piece, acrosome, etc.; egg requires cortical granule, etc.

     Millions of sperm produced daily by spermatogenesis; one secondary oocyte produced every 28 days in oogenesis.
     Sperm are released during ejaculation in spermatogenesis; one secondary oocyte is released on the 14th day of the menstrual cycle by ovulation in oogenesis.
     Sperm formation starts at puberty for males under spermatogenesis; the early stages of oogenesis occur during fetal development in females.
     Sperm production continues throughout the entire lifetime of men for spermatogenesis; egg production stops after menopause for women in oogenesis.
     Four sperm are produced per meiotic division in spermatogenesis; one egg is produced per meiotic division in oogenesis.
     Meiosis I and II go to completion in spermatogenesis; meiosis II reaches prophase in the ovarian follicle in the menstrual cycle, then halts until a male nucleus fertilizes it, which triggers the completion of the second meiotic division.

11.4.9 Describe the process of fertilization, including the acrosome reaction, penetration of the egg membrane by a sperm and the cortical reaction.

Movement of the sperm towards the fertilization site is facilitated by contractions in the uterus and oviducts. Several sperm break through the follicle layer and reach the zona pellucia, where capacitation occurs. The hydrolytic enzymes of the acrosome are released from the head of the sperm and these digest a pathway for the sperm to reach the plasma membrane of the oocyte. The first sperm to reach the plasma membrane of the oocyte has its head engulfed and its nucleus is released into the oocyte. This triggers the cortical reaction, and cortical granules within the cytoplasm of the oocyte fuse to the plasma membrane and release their enzymatic content by exocytosis. The enzymes cause a structural change in the zona pellucia affecting its glycoproteins, making it hard and prevent other sperm from penetrating. The nucleus of the secondary oocyte is stimulated to complete meiosis II (resulting in one polar body), then both male and female nuclei undergo mitosis to form a two-cell embryo.

11.4.10 Outline the role of HCG in early pregnancy.

HCG is produced by the blastocyst cells and appears about 7 days after conception. HCG maintains the corpus luteum and this is necessary because it secretes progesterone and (to a lesser degree) estrogen, which are used to maintain the endometrium for pregnancy.

11.4.11 Outline early embryo development up to the implantation of the blastocyst.

As the embryo moves down the oviduct following fertilization, it is undergoing cleavage--mitotic division of the embryo into a mass of daughter cells. When it reaches the uterus, it is a solid mass of blastomere cells. Cell division continues and the blastomeres organize into a fluid-filled structure called a blastocyst. The implantation process begins at about day 7 and is complete by day 14, where the blastocyst becomes embedded into the endometrium to develop and be nourished.

11.4.12 Explain how the structure and functions of the placenta, including its hormonal role in secretion of estrogen and progesterone, maintain pregnancy.

      Estrogen and progesterone are secreted by the placenta after disintegrateion of the corpus luteum (approx. 4 months). They are used to maintain the endometrium.
      Placental villi - Small projections that provide a large surface area for gas exchange and exchange of other materials. Fetal blood flows through capillaries in the villi.
      Intervillus spaces (lacuna) - Maternal blood flows through theses spaces, brought by uterine arteries and carried away by uterine veins.
      Endometrium - Lining of the uterus, into which the placenta grows.
      Umbilical arteries - Carries deoxygenated fetal blood away from the fetus and towards the placenta for gas exchange.
      Umbilical veins - Carried oxygenated fetal blood towards the fetus from the placenta after gas exchange.
      Myometrium - Muscular walls of uterus used for contractions during childbirth.

Gas exchange
      Mitochondria in the chorion provide ATP for active transport.
      Chorion forms a placental barrier, controlling what enters and exits in each direction.
      There is a small distance separating maternal and fetal blood in the chorion, allowing for rapid diffusion.

11.4.13 State that the fetus is supported and protected by the amniotic sac and amniotic fluid.

11.4.14 State that materials are exchanged between the maternal and fetal blood in the placenta.

11.4.15 Outline the process of birth and its hormonal control, including the changes in progesterone and oxytocin levels and positive feedback.

      Immediately before birth, progesterone levels decline sharply.
      Progesterone-driven inhibition of muscle contractions in the uterine wall is now stopped.
      At the same time, the posterior pituitary releases oxytocin.
      This relaxes elastic muscle fibres that join the bones of the pelvic girdle, which helps dilation of the  cervix.
      Also stimulates rhythmic contractions of the muscles of the uterus wall.
      There is a positive feedback loop: uterine contractions stimulate secretion of oxytocin, and therefore contractions become progressively more powerful during labour.
      After the offspring is expelled, less powerful uterine contractions separate the placenta from the endometrium, and result in the discharge of the placenta and remains of the umbilical as afterbirth.

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