Gram-positive rods

Describe the basic classification of Gram positive rods based on relationship to oxygen, spore formation and morphology. Place the clinically important genera into this classification scheme.

Gram-positive rods can mainly be classified based on several factors:

• Relationship to oxygen- Bacteria may be obligate aerobes (need oxygen to survive), obligate anaerobes (need an absence of oxygen in order to survive), or facultative anaerobes (can survive with or without oxygen).
• Spore formation- Some bacteria form spores that help them survive in harsh environmental conditions for many years. Such spores may also be infective.
• Morphology- Not all rod-shaped bacteria are created equally. Some rods look pretty normal, whereas others might be curved, branched, and so on.

There are two main endospore-forming bacteria: Bacillus and Clostridium. Bacillus is aerobic, whereas Clostridium is anaerobic.

In terms of regular-shaped non-endospore forming bacteria, Listeria and Erysipelothrix are aerobic and Lactobacillus is facultatively anaerobic.

In terms of irregular-shaped non-endospore forming bacteria, Corynebacterium is aerobic whereas Propionibacterium is anaerobic.

In terms of branching non-endospore forming bacteria, Nocardia, Actinomadura, and Streptomyces are aerobic, whereas Actinomyces is facultatively anaerobic.

Name the clinically important species within these genera and describe diseases they typically produce

Bacillus

There are several different groups of Bacillus. The group that we will be focusing on is the Bacillus cereus group.

The main member of the Bacillus cereus group is Bacillus cereus. It can cause food poisoning via enterotoxins. You are most likely to acquire Bacillus cereus from reheated rice dishes that have been contaminated.

Bacillus thuringiensis is another member of the Bacillus cereus group. B. thuringiensis is interesting in that it does not affect humans, but is very useful to us. You see, B. thuringiensis has cry genes that produce toxic crystals within spores. These toxic crystals can be used to kill insects. Thus B. thuringiensis can be used as an insecticide.

Bacillus anthracis, which causes anthrax, is another important member of the Bacillus cereus group. It lives in the soil and affects animals, particularly herbivores. It can be found worldwide, but in Australia cases are rather sporadic and mainly occur in the "Anthrax Belt" in central New South Wales. Anthrax can be acquired via the cutaneous, inhalational, or ingestional (gastrointestinal) routes.

Cutaneous anthrax is the most common form of anthrax and usually forms lesions called eschars. It has a mortality rate of 10-40% if left untreated. Inhalational anthrax survives in macrophages and is carried to lymphatics in the mediastinum, resulting in widening of the mediastinum. It is almost 100% fatal if untreated. Finally, gastrointestinal anthrax is the least common form of anthrax. It can cause inflammation, swelling, and haemorrhage of the gastrointestinal tract, with a mortality of around 50%.

Clostridium

Clostridium, like Bacillus, produces spores. Clostridium species generally produce toxins.

One important type of Clostridium is C. perfringens, which can be broken down into five types depending on which toxins are produced. The most important types in human disease are A and C. Type A C. perfringens can cause gas gangrene, in which spores rapidly invade and cause liquefactive necrosis and gas production in the tissue. Type A C. perfringens can also cause food poisoning via the ingestion of contaminated meat. Type C C. perfringens causes a condition called necrotising bowel disease, or enteritis necroticans if you want to be fancy about it. Type C is relatively uncommon but may occur when contaminated food is eaten in conjunction with food that is rich in trypsin inhibitors, as trypsin inhibitors prevent the breakdown of the bacterial toxins.

C. tetani is a species of Clostridium that is found in soil. It can release tetanospasmin, which is a powerful neurotoxin that blocks inhibitory impulses. Since inhibitory impulses are blocked, patients have increased muscle tone and spasms, resulting in trismus (lockjaw), risus sardonicus ("sardonic grin"- teeth clenched and lips pulled back), opisthotonus (arched back), and so on. Tetanus is thankfully rare due to vaccination. If contracted, it has a mortality rate of 40% or more.

C. botulinum releases botulinum toxin, causing botulism. Botulinum toxin prevents the release of ACh at the neuromuscular junction, resulting in paralysis. C. botulinum may be found in aged or preserved foods.

C. difficile is a common nosocomial (hospital-derived) infection that may be spread between patients via the hands of staff. Strains of C. difficile that produce enterotoxins can cause "antibiotic-associated diarrhoea," which is severe, intractable diarrhoea during or after antibiotic treatment. This occurs because there isn't enough commensal bacteria to compete for resources. C. difficile may also cause pseudomembranous colitis, which is a severe inflammatory condition of the colon.

Lactobacillus

Lactobacillus is part of the commensal flora of the vagina and gastrointestinal tract and is rarely pathogenic. It can ferment carbohydrates to lactic acid, maintaining vaginal pH between 3.8-4.5. A lack of Lactobacillus may result in an increase in pH.

Listeria

Listeria is a cause of food poisoning. Listeriosis is often asymptomatic, except in people who are immunocompromised in some way. However, when listeriosis hits, it hits pretty hard, causing septicaemia (bacteria multiplying in the bloodstream) and/or meningitis. If a pregnant woman is infected, her fetus may be infected too, resulting in miscarriage or stillbirth. If the fetus manages to survive to term, the baby may be severely ill. Since Listeria is often carried by certain high-risk foods (e.g. soft cheeses), pregnant women are often advised to avoid these foods.

Erysipelothrix

Erysipelothrix rhusiopathiae causes erysipeloid, which consists of painful, raised areas of inflammation of the skin. It is found in meat, poultry, fish, and so on, and enters the skin via abrasions.

Corynebacterium

Corynebacteria are small, irregular, Gram-positive rods that are often commensals in humans and animals. Corynebacteria are often found contaminating blood cultures, but sometimes they might actually be the pathogen causing the infection. The most common Corynebacterium is Corynebacterium diphtheriae, which causes diphtheria. In diphtheria, exotoxin-producing strains of C. diphtheriae infect the nose and throat, causing formation of a pseudomembrane in the nasopharynx. Fortunately, diphtheria is quite rare in the developed world due to vaccination.

Propionibacterium

Propionibacterium is mostly commensal and non-pathogenic, but can cause annoying stuff like acne (in the case of P. acnes). It can also infect foreign devices such as prosthetic heart valves and joints.

Actinomycetes

Actinomycetes are a diverse group of bacteria that can be found in soil and rotting vegetation. There are many different genera of actinomycetes, too many to list here, but they are mostly branching/filamentous Gram-positive rods.

One condition caused by actinomycetes is actinomycotic mycetoma, which is usually caused by the genera Nocardia, Actinomadura, and Streptomyces. Actinomycetes enter the skin and take years to form a swelling. (Plenty of gross pictures on Google if you want a better idea of what this looks like.)

Nocardia can also cause other illnesses. In immunocompromised hosts, it can cause a range of horrible problems, such as respiratory infections and abscesses in various organs. Even immunocompetent hosts aren't safe: Nocardia can implant in the skin and cause lesions in a "sporotrichoid" appearance (so-called because sporotrichosis, caused by a fungus, looks similar).

Finally, actinomycosis, characterised by hard swellings, is caused by the genus Actinomyces.

Gram-positive cocci

Name the three important pathogenic genera of Gram positive cocci.

Staphylococcus, Streptococcus, Enterococcus.

Describe the role of the catalase and coagulase tests in distinguishing staphylococci and streptococci 

The catalase test can be used to distinguish Staphylococcus from other Gram-positive cocci. Staphylococcus is catalase-positive, whereas Streptococcus and Enterococcus are catalase-negative.

The coagulase test can be used to distinguish Staphylococcus aureus from other types of Staphylococcus. Staphylococcus aureus is coagulase-positive, whereas most other strains of Staphylococcus (at least out of those that are involved in human disease) are coagulase-negative.

Name clinically important species within these genera and describe diseases they typically produce

Staphylococcus

One of the most important Staphylococcus species is the coagulase-positive S. aureus. It is often carried in the nasal area and can cause a range of infections, ranging from minor wound infections to serious, fatal illnesses. S. aureus is a common cause of a range of skin lesions, ranging from boils, to cellulitis (subcutaneous infection in which the skin is inflamed), to hidradenitis suppurativa (recurrent boils in the axillary region). It can cause pyogenic (pus-forming) infections in almost any organ and is also the commonest cause of osteomyelitis (bone infection) and septic arthritis (joint infection). Some strains of S. aureus can also release toxins, which can cause conditions such as Staphylococcal scalded skin syndrome (SSSS), Staphylococcal toxic shock syndrome (STSS), and Staphylococcal food poisoning.

There are also several important coagulase-negative Staphylococcus species. The most common coagulase-negative Staphylococcus is S. epidermidis, which typically lives on the skin as part of the commensal flora. It is low-virulence, but is associated with infections related to foreign devices, such as prosthetic heart valves and prosthetic joints. Its main virulence factor is an extracellular polysaccharide ("slime"), which can cause biofilms on foreign devices.

Staphylococcus saprophyticus is another common coagulase-negative Staphylococcus. It is the second-most common cause of urinary tract infections in healthy, sexually-active, young females. (The most common cause is E. coli).

Streptococcus

Streptococcus species are usually classified according to how they break down blood agar. α-haemolytic Streptococci leave a greenish tinge, whereas β-haemolytic Streptococci completely break down the blood agar, leaving a clear area. Sreptococcus can also be classified based on the Lancefield grouping system, which looks at antigenic carbohydrates in the bacterial cell wall and assigns a letter accordingly (group A, group B, etc.).

α-haemolytic Streptococci can be further broken down into species groups. The main species groups are Streptococcus bovis, Streptococcus anginosis, Streptococcus mitis, Streptococcus mutans, and Streptococcus salivarius. α-haemolytic Streptococci can get into the blood and cause infective endocarditis as well as abscesses. S. bovis is also associated with colonic malignancy. S. mutans is important in dentistry, as it can cause dental caries. S. mutans has glucosyltransferases, which converts sucrose into glucans, which are insoluble and adhere to dental enamel, forming a plaque (an example of a biofilm).

Another important α-haemolytic Streptococcus is S. pneumoniae. Around 5-10% of the population is a carrier for S. pneumoniae, which can cause pneumonia and/or meningitis. There are over 80 distinct serotypes of S. pneumoniae, some of which can be vaccinated against.

The most important Lancefield groupings for β-haemolytic Streptococci are Lancefield group A and Lancefield group B. First, we will talk about Lancefield group A β-haemolytic Streptococci, particularly S. pyogenes. S. pyogenes usually causes a primary infection with suppurative (pus-forming) or non-suppurative complications. Non-suppurative complications are usually caused by toxins or the immune response.

S. pyogenes is the most common cause of pharyngitis and tonsillitis. Suppurative complications of S. pyogenes pharyngo-tonsillitis include abscesses and mastoiditis (inflammation within the mastoid process). Non-suppurative complications include scarlet fever, rheumatic fever, and post-streptococcal glomerulonephritis, though those complications will only occur if the strain of S. pyogenes has the toxin required to cause the complication. S. pyogenes can also cause a range of skin conditions, including impetigo (school sores), erysipelas (a raised reddish-orange rash with sharp borders), and cellulitis. Some of these skin infections may have further complications, such as necrotising fasciitis ("flesh-eating disease").

Enterococcus

Enterococci are usually commensals in the human bowel, but can cause infection. Enterococci are Lancefield group D. The main species are E. faecalis and, to a lesser extent, E. faecium. They can cause a range of infections in the abdomen, urinary tract, soft tissues, and so on.

Inheritance

Define the terms: gene, allele, loci, genotype, phenotype (trait), dominant, recessive, autosome, sex chromosome, homozygous, heterozygous, monogenic, wild-type, mutant, haploid, diploid, zygote.

• Gene- A section of DNA that encodes for protein or RNA. It can be passed down through the generations.
• Allele- Variants of a gene that can be found in the population.
• Loci- The area of the DNA where a particular gene can be found.
• Genotype- The set of alleles that a person has.
• Phenotype- The appearance or traits that a person has.
• Dominant- An allele that is expressed either alone or in a pair.
• Recessive- An allele that is only expressed if there are no dominant alleles.
• Autosome- One of the 22 non-sex chromosomes.
• Sex chromosome- The X or Y chromosome.
• Homozygous- Both alleles for that trait are the same.
• Heterozygous- The alleles for that trait are different.
• Monogenic- Only one gene codes for that trait.
• Wild-type- A trait or gene that is of the typical form found in nature.
• Mutant- A form of a trait or gene that is not typically found in nature.
• Haploid- A cell with half of the normal number of chromosomes (23 in humans)
• Diploid- A cell with the normal number of chromosomes (46 in humans)
• Zygote- The cell that forms when the egg and sperm meet for the first time.

Have a basic understanding of Mendelian inheritance and segregation.

Mendelian inheritance stipulates that each individual has two copies of each gene: one from each parent. During the formation of germ cells, the copies of each gene are segregated out, so each germ cell will only have one copy of a given gene. The copy that is inherited by a particular germ cell is random. When the sperm and egg meet, the randomly-assorted gene copies in the sperm and the randomly-assorted gene copies in the egg come together to form the genetic makeup of the zygote. The genotype of the zygote thus depends on which genes it inherits from the sperm and which genes it inherits from the egg, and the phenotype of the zygote depends on which genes get expressed.

Often, when talking about Mendelian inheritance, we are normally only looking at a specific gene for a specific disorder or trait that we are interested in. For example, cystic fibrosis is an autosomal recessive disorder, meaning that it is inherited on an autosome (non-sex chromosome) and will only be expressed if both copies of the gene have the recessive allele. If you know the genotype of the parents, you can guess the likely genotypes and phenotypes of the children. Let's say that the dominant allele on the CFTR gene (the gene involved in cystic fibrosis) is C, and the recessive allele is called c. Hence, if you have two parents that are both Cc, these are the combinations that could result:

	C	c
C	CC	Cc
c	Cc	cc

Note that in this particular example, there is a 1/4 chance that the genotype of the child is CC, 2/4 = 1/2 chance that the genotype is Cc, and a 1/4 chance that the genotype is cc. Since cystic fibrosis is a recessive trait, the child will only have the cystic fibrosis phenotype if they have two recessive alleles (i.e. a genotype of cc).

Also note that some genetic traits are sex-linked, meaning that they are passed down on one of the sex chromosomes (usually the X chromosome). If this is the case, you will also need to keep track of a) which chromosome is getting passed down and b) if it is the chromosome of interest, whether it is carrying the dominant or recessive allele for that trait. You can do this by using subscripts or superscripts (e.g. X^aY).

Recognise pedigree symbols & be able to determine modes of inheritance in pedigree charts.
Understand the possible genotypes within pedigree charts; label & explain genotypes & phenotypes.

A pedigree chart is a useful way of tracking how characteristics are inherited within families. Pedigree charts basically just look like family trees. The shape of the "leaves" on the tree represent sex- usually squares are males, circles are females, and diamonds are unspecified. The colour of the "leaves" represent whether or not the person in question has been affected by that trait- black means that they have the trait, whereas white means that they do not have that trait. Some pedigrees might even shade half the box if the person is a carrier (has a recessive allele that is not being expressed), but not all. Therefore, it is usually really easy to tell what phenotype a person of interest has (by the colour of their "leaf"), but it is not always easy to tell the genotype as someone could be either heterozygous or homozygous for a dominant allele.

Have an understanding of how human disorders are associated with single genes.

I've already mentioned cystic fibrosis as an example of a disorder that is associated with a single gene, but it is not the only monogenic disorder out there. Huntington's Disease is autosomal dominant, haemophilia is X-linked recessive, and vitamin D-resistant rickets (i.e. rickets that doesn't get fixed by simply supplementing vitamin D) is X-linked dominant. This is by no means an exhaustive list- this is just to give you an idea.

Cell Cycle Control

Appreciate the consequences of nondisjunction and gene balance

Nondisjunction occurs when too many or too few chromosomes make it into the daughter cells following meiosis. Nondisjunction occurs due to incorrect separation of chromosomes during either anaphase I or II: sometimes both chromosomes of a pair, or both chromatids of a chromosome, might make it into one of the daughter cells.

Nondisjunction is problematic because of gene balance, in which you need the right number of genes to function normally. This is due to the gene-dosage effect, in which more copies of a gene result in more transcripts and more proteins made. If too many or too few proteins are made, there may be deleterious results. For instance, nearly all monosomic disorders (disorders where one of the chromosomes is missing from one of the pairs) are fatal. The only monosomic disorder that is not fatal is Turner's syndrome, in which the only sex chromosome present is the X chromosome. There are more viable trisomic disorders (disorders with an extra chromosome in one of the pairs), each with an identifiable phenotype. The most well-known trisomic disorder is Down Syndrome, which is usually caused by an extra chromosome 21.

Usually? you might be asking. Well, there are actually ways in which someone can get Down Syndrome without an extra chromosome 21. Someone can also get Down Syndrome if a part of chromosome 21 translocates onto part of another chromosome, and the new fusion chromosome that results is passed on. One translocation that can cause Down Syndrome is the Robertsonian translocation, in which part of chromosome 21 is translocated onto part of chromosome 14. If one parent passed on the Robertsonian chromosome 14 as well as a regular chromosome 21, and the other parent passed on a normal chromosome 21 and a normal chromosome 14, the child would then have Down syndrome as they would then have three copies of many of the genes on chromosome 21: two copies from the two normal chromosome 21s, and another copy from the Robertsonian chromosome.

Translocations such as the Robertsonian chromosome, where two different chromosomes exchange parts of their DNA, are also known as reciprocal translocations.

Understand the basics of the process of apoptosis
Understand the cell cycle phases & checkpoints

• Cell Cycle and Apoptosis

Understand how Cdk-cyclin complexes help regulate cell cycle progression, that cyclin levels oscillate and how Cdk activity is controlled

• Cell Cycle Control

Have a basic understanding of the need for communication between cells to control cell cycling and apoptosis.

Cells need to communicate between each other to figure out when they should and shouldn't divide. For instance, if a cell is packed in by other cells, there would be no need for it to divide and produce yet more cells. Cells send survival, proliferation, death, and growth-inhibiting cues to each other. If cells lose their sensitivity to these cues, they may grow out of control.

Blood Transport and Acid-Base Balance I and II

List the different components of blood

• Blood

Outline the mechanisms and molecules used for transport of blood-borne substances

Many water-soluble molecules can travel while dissolved in the blood. Other molecules, such as steroid hormones, often need to be bound to a carrier molecule to be transported through the blood. The most common carrier protein is albumin, but there are other carriers that transport particular hormones: for example, sex-hormone binding globulin transports sex hormones around the blood.

Describe the different classes of lipoproteins
Outline lipoprotein metabolism and the functions of apoproteins

• Lipid and Lipoproteins: Structure, Function and Metabolism
• Plasma Lipoproteins

Describe the structure & function of haemoglobin
Understand the Hb-O2 dissociation curve
Outline CO2 transport

• Gas Exchange and Transport

Understand the importance of acid-base homeostasis in the body
Describe acid-base homeostatic regulatory systems
Describe pulmonary (respiratory) regulation of blood pH
Describe renal regulation of blood pH

• CO2 Transport and Acid/Base Balance

Understand the Henderson-Hasselbalch equation

• Amino Acids- Acid Base Chemistry

I don't think we need to know the Henderson-Hasselbalch equation in much detail. The main take-aways are that buffers work best when the pH is similar to the pKa and when there are roughly equal amounts of the two main components of the buffer (the weak acid/base and the salt of the weak acid/base).

Outline the principal buffers and know their strengths & weaknesses

The main buffers are as follows:

• Bicarbonate- pKa of roughly 6.37. Most common buffer in the extracellular fluid.
• Ammonia- pKa of roughly 9.25. Also found in the extracellular fluid, particularly in the renal tubules.
• Phosphate- pKa of roughly 7.21. A common buffer within cells.
• Proteins- pKa varies depending on the protein, but many have a pKa close to 7.4 (optimum pH for arterial blood. Haemoglobin has a pKa of 6.8. Perhaps the most important buffering system within cells.

Describe acid-base disorders and homeostatic compensation

The optimum pH for arterial blood is 7.4. If the pH falls below 7.35, that is called acidosis. If the pH rises above 7.45, that is called alkalosis.

Since pH is so important to the normal functioning of the body, there are many systems that can help to maintain pH (see here for more information). The most important systems are the respiratory system and the renal system. If we enter acidosis, our body may compensate by blowing off more carbon dioxide or reabsorbing more bicarbonate ions. If we enter alkalosis, our body may compensate by blowing off less carbon dioxide or secreting more bicarbonate ions. This is important to be aware of, because you don't want to mistake someone's hyperventilation for respiratory alkalosis when it might actually be a compensatory response for metabolic acidosis.

Interpret blood chemistry of acid-base disorders

When the kidneys and/or lungs fail to maintain blood pH, we can go into acidosis or alkalosis. If the acidosis or alkalosis is due to a problem with the kidneys, this is called metabolic acidosis or metabolic alkalosis. If the acidosis or alkalosis is due to a problem with the lungs, this is called respiratory acidosis or respiratory alkalosis.

In cases of acidosis or alkalosis, it is important to determine which organ is affected and if there are any compensatory effects. Firstly, look at the pH: is it acidic or alkaline? Next, look at the CO₂ and HCO₃^- values, and determine which one of those is reflective of the pH seen in the patient. For instance, if you have measured acidosis, and you have high CO₂ and high HCO₃^-, you are dealing with respiratory acidosis (since high CO₂ results in acidosis whereas high HCO₃^- would normally be associated with alkalosis). Finally, determine if there are any compensatory responses. For example, in the example I just mentioned, there would be metabolic compensation as can be determined by the high HCO₃^- levels which would not otherwise be associated with acidosis.

Sensation and Sensory Processing

Understand stimulus features encoded by the sensory system
List the classification of somatic senses and discuss the somatosensory receptor types

The stimulus features encoded by the sensory system include modality (i.e. the type of sensation), spatial information (where it is), intensity (how strong the stimulus is) and quality (other characteristics, such as the pitch of sound or the sharpness of pain). The types of stimuli that we have receptors for include mechanical, chemical, photic (visual), thermal, and noxious (pain).

There are many different types of receptors for touch that you might need to know about. Free nerve endings are slowly-adapting, unencapsulated receptors that can detect a range of stimuli, such as temperature and pain. Merkel's disks are also slowly-adapting, unencapsulated receptors that sense continuous light touch. There are three main types of nerve endings that are encapsulated (wrapped in glial cells or connective tissue). Meissner's corpuscles are superficial, rapidly-adapting nerve endings that respond to altered touch and spatial characteristics. Ruffini's corpuscles are deep, slowly-adapting nerve endings that respond to heavy touch and stretch of joints. Finally, Pacinian corpuscles are deep, rapidly-adapting nerve endings that respond to deep pressure and vibration. Mechanosensitive receptors all have stretch-gated ion channels that might be excitatory or inhibitory, depending on which ions they let through.

As well as receptors for touch, there are also receptors for temperature. The main ones you need to know about are TRPM8, which detects cold, and TRPV1/3 and TREK1, which detect heat.

Understand detection and transmission of sensory stimuli

Stimuli are detected by specialised cells. Each type of stimulus has a special type of cell- for instance, mechanoreceptors detect mechanical stimuli. Some receptor cells are nerves, whereas others are special cells that can communicate with a neuron. When sensory neurons are activated, they transmit action potentials to the central nervous system (brain and spinal cord). You can read about how action potentials work here.

Some neurons are rapidly-adapting, or phasic. These neurons respond better to dynamic stimuli (i.e. stimuli that are rapidly changing), rather than continuous stimuli. Slowly-adapting (tonic) neurons are the opposite- they respond much better to continuous stimuli than to dynamic stimuli.

Another important aspect of sensation is stimulus acuity, which allows for fine discrimination between two sensations that occur close together. Stimulus acuity depends on the number of receptors and the size of their receptor fields, as well as some other factors. Central convergence, in which multiple receptors can synapse onto the same second-order neuron, can decrease stimulus acuity, whereas lateral inhibition, in which a strongly-activated neuron inhibits surrounding neurons, can increase stimulus acuity.

Discuss the ‘labelled line’ concept of sensory transmission

The "labelled line" principle states that sensory nerve fibres transmit only one modality of sensation to a specific location. Hence, if a pain fibre is stimulated, you will feel pain, no matter what stimulus caused the pain or which receptors picked it up. All the brain cares is that a pain fibre was stimulated.

Understand encoding of sensory stimulus intensity

The more intense a stimulus is, the more rapidly the sensory neurons fire. The higher rate of firing is then picked up by the brain as being a more intense stimulus.

Describe the ascending sensory pathways, the somatosensory cortex and topographic maps

• Nervous System II

Describe nociceptors & nociception

Nociception is the sensation of pain. Nociceptors are receptors that respond to noxious stimuli and give the perception of pain. Some nociceptors are simply normal receptors but with a high threshold. For example, light pressure might activate only the mechanoreceptors that let you sense that you are experiencing pressure. However, as the pressure increases, nociceptors responsible for pain may then reach their threshold, so you are now experiencing pain. There are also chemicals that are able to stimulate nociceptors directly, such as histamine.

Autonomic Nervous System, again

This is a topic that I've mostly blogged about before- see here.

Discuss autonomic control
Describe the role of the ANS in vegetative functions
Describe the neurotransmitter & synaptic physiology of the ANS
Discuss the function of the adrenal medulla in the ‘Alarm’ or ‘Stress’ response 

• Autonomic Nervous System

Name some drugs that can be used to manipulate the function of the ANS

Many drugs can manipulate the function of the ANS by either activating or blocking receptors involved in the ANS. Some examples (note some drugs might be able to block multiple receptors):

	Activating (Agonist)	Blocking (Antagonist)
α1-adrenoceptor	Phenylephrine	Phentolamine
α2-adrenoceptor	Clonidine	Phentolamine
β1-adrenoceptor	Dobutamine	Propranolol
β2-adrenoceptor	Salbutamol	Propranolol
Nicotinic receptor	Nicotine	Hexamethonium
Muscarinic receptor	Muscarine	Atropine

Define NANC neurotransmitters

NANC neurotransmitters are "non-adrenergic, non-cholinergic." Examples of NANC neurotransmitters include ATP, nitric oxide, VIP (vasoactive intestinal polypeptide), and so on.

Muscles I and II

Another lecture that is likely going to just be a list of links to my undergrad posts...

Describe the structure and function of skeletal, cardiac and smooth muscle

	Cell structure	Cell function
Skeletal muscle	Long, cylindrical, multiple nuclei on the outside. Striated (stripy)	Voluntary movements, moving the skeleton etc.
Cardiac muscle	Branching, one nucleus in the centre, striated	Pumping blood
Smooth muscle	Not striated (smooth-looking!)	Many involuntary movements (e.g. digesting food)

Describe the mechanism of contractility in muscle and the generation of force
Explain the Ca2+ regulation of contraction
Describe the length tension relationship
Understand how Ca2+ regulation can result in wave summation and tetanus
Outline the physiological properties of motor units

• A Review of Basic Muscle Physiology
• Excitation-Contraction Coupling in Skeletal Muscle

Understand the organisation and function of the neuromuscular junction

I'm not really sure what I'm supposed to explain here. Basically, a motor neuron synapses onto an area of the muscle called the motor end plate. It is a cholinergic synapse, meaning that acetylcholine is released from the presynaptic neuron. That acetylcholine then binds to nicotinic ACh receptors on the target muscle cell. Nicotinic ACh receptors are sodium channels that always have an excitatory effect when opened. Each muscle cell only has one neuromuscular junction (there are more during development, but they get pruned away so that the muscles don't get conflicting and confusing input).

Describe how the nervous system (including reflexes) controls muscle contraction

• Nervous System II

It is also worth noting that spinal reflexes can be either monosynaptic or polysnaptic. In a monosynaptic reflex, the sensory neuron synapses directly onto a motor neuron. In a polysynaptic reflex, the sensory neuron synapses onto one or more interneurons, which synapse onto a motor neuron. Polysynaptic reflexes allow for the possibility of modulation of reflexes. For instance, in the inverse myotactic reflex (the "drop" reflex), an inhibitory interneuron secretes glycine (an inhibitory neurotransmitter), causing muscle relaxation. (This is the reflex that makes you instinctively drop something that would be too heavy to catch.)

Identify the muscle receptors and explain their role in spinal reflexes in skeletal muscle control.

There are several different muscle receptors that respond to tension and length of the muscle. These are the sorts of receptors that play a role in reflexes such as the knee-jerk reflex. The main receptors are Golgi tendon organs and muscle spindles. Golgi tendon organs are found in the tendon and are sensitive to tension and change of tension in the tendon. Muscle spindles are found in the belly of the muscle and are sensitive to length and change of length in the muscle. Both types of receptors can be either static (receptive to constant tension or length) or dynamic (responsive to changes in tension or length).

Describe different muscle fibre types & their properties

• Exercise Metabolism

Describe the recruitment patterns of motor units in relation to the nervous system control of force generation.

• Motor Control- see the end of the third section where I talk about Henneman's size principle.

Pharmacokinetics I and II

I have a feeling that I covered a lot of this at the start of PHAR2210, but oh well.

Explain the term “pharmacokinetics” and why it matters during drug use in patients
Identify the 4 processes that control the fate of drugs in the body
Understand drug absorption, the organs at which it occurs, and the factors that govern drug uptake at absorption sites.
Understand the concept of a “prodrug.”
Explain what is meant by the term “bioavailability”.
Show an awareness of the distribution of drugs within the body, and the tendency for particular drugs to accumulate in specific tissues.

• Drug Absorption and Distribution (you'll notice that the learning outcomes covered in that post are pretty much identical, word for word!)

Identify the main routes of human drug metabolism and the enzyme catalysts of these processes
Show basic understanding of the consequences of the induction and inhibition of drug metabolism pathways during drug treatment.
Show a basic appreciation of the role of inherited mutations in influencing CYP450 phenotypes.
Identify the organs and tissues which play the greatest role in removing drugs from the body.
Identify three key processes controlling renal drug excretion as well as the major classes of transporters involved in these pathways.

• Drug Metabolism
• Drug Excretion (more detail than you need to know)

Huh. So it turns out that I indeed did cover pretty much everything from this lecture back in PHAR2210...

Pharmacodynamics 1 and 2

These lecture had summary slides, not "learning outcomes" slides, but the first lecture had "key concepts" on the title slide so that's what I'll be basing this post on :)

Affinity & efficacy

Affinity is the ability of a drug to bind to its target. Affinity is determined by how well the shape of the drug fits the binding site, and how strong the bonds are between drug and binding site. The higher the affinity, the more readily the drug binds, and the less drug you need to have an effect. The K_A is the concentration of drug at which 50% of receptors are bound. The lower the K_A, the higher the affinity. Sometimes a drug might have a higher affinity (lower K_A) for one receptor than for another- for instance, adrenaline has a higher affinity for beta-receptors than for alpha-receptors.

Efficacy is the ability of a drug to have an effect once bound. The higher the efficacy, the greater the effect.

Agonism & antagonism

Agonists are drugs that have an effect by binding to the target. As such, agonists have both affinity and efficacy. A full agonist has high efficacy, while a partial agonist has lower efficacy. An example of an agonist is salbutamol (Ventolin), which binds to and activates beta-2 adrenoceptors.

Antagonists are drugs that have an effect by blocking a target. As such, antagonists have affinity, but no efficacy. An example of an antagonist is metoprolol, which blocks beta-1 adrenoceptors.

Selectivity

Selectivity refers to the ability of a drug to bind to only specific targets. Selectivity occurs because a drug has a higher affinity for one receptors or a set of receptors than for other receptors. It is desirable to have a highly-selective drug, as that means that there will be fewer unwanted effects due to binding at other sites. All drugs lose their selectivity at high doses because a higher concentration of a drug means that there will be more binding to receptors that a drug would otherwise have a low affinity for.

Potency & effectiveness

Potency refers to the concentration of a drug that is needed to have an effect. A less potent drug needs a higher dose to achieve the same effect as a more potent drug. Usually, the potency of a drug is not very important, unless you are administering the drug in such a way that the amount of a drug matters (e.g. transdermal patches).

Effectiveness refers to the maximum effect that a drug can have. A more effective drug has a greater maximum effect than a less effective drug. For example, morphine is better at reducing pain than paracetamol. Effectiveness is much more important than potency in deciding which drug to give a patient.

Dose-response relationship

The dose-response relationship shows the level of effect that you can get for a specific dose of a drug. Generally, the dose-response curve is S-shaped ("sigmoidal")- the drug has little effect at low doses, then as you increase the dose the level of response rapidly increases up to a point before tapering off again.

Adverse effects

Adverse effects are unwanted effects from a drug. Adverse effects usually happen when the dose is too high. This may be due to a loss of selectivity at high doses (off-target side effects), or from an effect that is stronger than you actually need (on-target side effects). For instance, if you have low blood pressure, you might take a drug that increases your blood pressure, but if you take too much of that drug, then you'll end up with high blood pressure, which also isn't good.

What Are Drugs and Where Do They Come From?

Define the terms “drugs,” “pharmacology,” “receptors” and “xenobiotics”

• Drug- A chemical substance that is given to prevent or cure disease or to enhance the mental or physical state of a human or animal. As the term "drugs" is often associated with illicit drugs, many people prefer to use the term "medicine," which only refers to drugs used to prevent or cure disease.
• Pharmacology- The study of how drugs work.
• Receptor- A molecule that a drug can bind to in order to produce a change in the body.
• Xenobiotic- A chemical that enters the human body. Includes not only drugs, but also other kinds of chemicals that might enter the body.

Appreciate the scope of pharmacology as a scientific discipline.

• What is Pharmacology?

Understand how 3 types of names are assigned to drugs.

The three main types of names are the chemical name, generic name, and brand name. See here for more information.

Show a basic awareness of 6 identifiable routes to finding new medicines.

“Bioprospecting”-Based Exploration

Some drugs are derived from useful substances in nature. For instance, penicillin comes from the Penicillum fungus.

Disease-Model Screening

Sometimes medications can be screened in animal models to give an indication if they might work in humans. An example of this is prontosil, a sulfonamide antibiotic.

“Me-Too” Drug Optimisation

Some drugs have been created by improving on previous drugs. For instance, captopril is an ACE inhibitor that can be taken orally- an improvement over earlier ACE inhibitors that could only be taken by injection.

Astute Clinical Observation

Sometimes drugs that were created for a different purpose might have useful unexpected effects. Sildenafil (Viagra) was not originally made to treat erectile dysfunction, but it was found to have "unexpected effects" in middle-aged males.

Rational Design

Rational drug design is basically the "gold standard" of drug discovery. Basically, chemists try and find a molecule that will fit a particular target. An example of a drug that was discovered this way is dorzolamide, a carbonic anhydrase inhibitor used to treat glaucoma (destruction of the optic nerve).

Irrational High-Throughput Discovery

Irrational high-throughput discovery makes use of our ability to test lots of chemicals simultaneously in vitro. One drug that has been found this way is sorafenib, which is primarily used to treat liver cancer.

Introduction to Immunology

The learning outcomes of this lecture were more like a summary, but oh well. Also, a lot of this stuff has been covered in previous posts, so enjoy this list of links :P

Contact with microorganisms rarely causes disease
Humans are colonised with normal microbiota that is usually harmless
To cause disease a pathogen much achieve several objectives: gain access to host through a portal of entry, adhere to the host, increase in number, cause damage, leave the host through a portal of exit

• Commensal Flora and Pathogenesis

Likelihood of disease is dependent on both the effect of the pathogen on the host, and the host response to the pathogen

• Commensal Flora and Pathogenesis- virulence factors make it easier for pathogens to hang out and make you sick.
• Infections in the Immunocompromised- more detail than you need to know, but is somewhat relevant.

Barriers to entry may prevent infection before it occurs
If barriers fail, the pathogen is confronted by the cells and molecules of innate immunity
Adaptive responses are activated if innate mechanisms fail to eliminate an infection

• Innate and Adaptive Immunity

Immune memory is the basis for vaccination

• Vaccines and Immunotherapy

Introduction to Microbial Pathogens

Define the meaning of “pathogen”.

A pathogen is a microorganism that is able to cause disease in a host.

Define disease and explain the difference between disease and infection.

Disease is a disorder of structure or function that produces symptoms and/or signs in the host and is not a result of physical injury. Infection is the invasion of the body by pathogens, but since infection doesn't always result in the production of symptoms and/or signs, infection is not always the same as disease.

Explain what is meant by a commensal, giving examples.

Commensal bacteria are bacteria that live in or on the body. See Commensal Flora and Pathogenesis.

Explain the difference between colonised and sterile body sites and recognise which body sites belong to each category.

Not all sites of the body have commensal bacteria. Some body sites are sterile, meaning that they don't even have commensal bacteria. Therefore, if you see bacteria in these sites, there's almost certainly something bad going on. These sites include the blood, cerebrospinal fluid, bladder, peritoneal cavity, and joint cavity. Nearly everywhere else in the body will have commensal bacteria.

Give examples of exogenous and endogenous infectious diseases.

An exogenous infectious disease is one that comes from an external source. For instance, you may catch a cold or flu from another person. On the other hand, an endogenous infectious disease comes from commensal flora. This usually happens when bacteria get into a place where they normally shouldn't be (e.g. a ruptured bowel may allow gut bacteria to enter the peritoneal cavity) or when the host is immunosuppressed.

Define “carriage”, giving examples.

"Carriage," or the "carrier state," is where someone is infected but doesn't have the disease. People who are carriers can infect others or develop disease themselves. For example, many people are carriers of meningococcal disease at some point, but not everyone develops the disease.

Define “opportunistic infection”, giving examples.

An "opportunistic infection" is an infection that doesn't usually cause disease in a healthy person, but can cause disease if someone is immunosuppressed in some way. An example of an opportunistic infection is C. difficile, which is usually only a problem if our commensal flora has been wiped out by antibiotics.

Define “virulence factor”, giving an example.

A "virulence factor" is something that can allow a pathogen to cause disease. These factors might include toxins (e.g. cholera toxin) or capsules that protect from phagocytosis. More info at Commensal Flora and Pathogenesis.

Explain why, in the clinical setting of infectious diseases, knowing the genus and species name of a causative microorganism is relevant.

Knowing the causative microorganism is relevant as it helps to guide specific treatments. As mentioned in my last post, not all antibiotics target the same species of bacteria, so it is important to pick the right drug for the job. Knowing the causative microorganism might also help you to figure out the likely progression of the disease.

Outline the differences between prokaryotic and eukaryotic cells.

• Cell Biology- Introduction and Energy Production

Outline briefly the structural components of the typical bacterial cell and the functions of these components.

Bacterial cells are simpler than eukaryotic cells, as they lack organelles. However, they still have a lot of important structures.

• Cell membrane- Since bacteria don't have organelles, the membrane performs many of the functions that organelles would otherwise do, such as protein secretion, lipid synthesis, and so on. Some bacteria only have one cell membrane, but some bacteria have two cell membranes (an outer membrane and an inner membrane). The outer membrane contains many crucial proteins, including porins, which control the influx of antibiotics and other molecules. Lipopolysaccharide (LPS), a component of the outer membrane, can also function as an endotoxin.
• Nucleoid- A single molecule of double-stranded DNA that holds most of the genetic information.
• Plasmids- Circular double-stranded DNA molecules that can be transferred between bacteria. Some plasmids may encode genes for bacterial resistance, so they are pretty crucial to know about.
• Ribosomes- Perform the same functions as in eukaryotic cells. However, bacterial ribosomes are made up of different subunits as compared to eukaryotic ribosomes (30S and 50S in bacterial ribosomes, 40S and 60S in eukaryotic ribosomes).
• Cell wall- Surrounds the cell membrane. Makes the cell rigid and protects it from bursting. The cell wall is made up of peptidoglycan, which is cross-linked by enzymes called transpeptidases. As the cell wall is found in bacteria and not human cells, the cell wall is a popular target for antibiotics.
• Capsule- Also known as the "slime layer," the capsule is a polysaccharide layer present in some bacteria. It protects from phagocytosis and helps with adhesion.
• Fimbriae- Little hair-like projections of the bacteria that help with attachment. Some fimbriae, called pili, are involved in transfer of DNA.
• Flagella- Longer hair-like structures that whip back and forth and help to move the cells.

Describe the differences between the Gram positive and Gram negative cell envelopes (= cytoplasmic membrane, cell wall, ± outer membrane) and how the Gram stain functions to distinguish these two.

Gram-positive bacteria have a single cell membrane, surrounded by a thick cell wall. Gram-negative bacteria have two cell membranes, with a thin cell wall in between them. Under the Gram stain, Gram-positive bacteria appear purple, whereas Gram-negative bacteria appear pink.

The Gram stain has four main steps:

• Addition of crystal violet, which stains the cell wall purple.
• Addition of Lugol's iodine, which helps to "fix" the crystal violet to the peptidoglycan of the cell wall.
• Washing with ethanol, which removes the crystal violet from the thin Gram-negative cell wall. (Gram-positive cell walls have much more peptidoglycan, so they hold on to the crystal violet much more strongly.)
• Addition of carbol fuchsin, which is a "counter-stain" that stains all of the Gram-negative cells that had the crystal violet washed out of them. Carbol fuchsin is pink, which is why Gram-negative cells stain pink.

Explain why it is important for the clinician to know the Gram stain and morphological appearance of the main pathogens encountered in practice.

The Gram stain is very useful, but it only distinguishes between two main groups: Gram-positive and Gram-negative. In order to narrow down the genus and/or species, you also need to have a look at other factors, such as shape and how the bacteria cluster together. Here are some examples:

• Gram-positive (stain purple)
• Cocci (round bacteria)
• Clusters- e.g. Staphylococcus
• Chains- e.g. Streptococcus
• Pairs (diplococci)- e.g. Streptococcus pneumoniae
• Bacilli (rod-shaped bacteria)
• Basic rod shape (not really sure how to describe them)- e.g. Clostridium
• Small and irregular- e.g. Corynebacterium
• Filamentous or branching- e.g. Nocardia
• Gram-negative (stain pink)
• Cocci
• Pairs- likely Neisseria meningitidis
• Bacilli
• Basic rod shape- e.g. Escherichia, Proteus, Salmonella, etc.
• Curved or comma-shaped- e.g. Vibrio
• Helical- e.g. Campylobacter

There are also many bacteria that do not take up the Gram stain and may need to be visualised in a different way, such as using a different stain or by using microscopy. Spirochaetes (e.g. Treponema, Borrelia, Leptospira) do not take up the Gram stain but can be recognised by their spiral-shaped appearance under the microscope. Mycobacteria, which have mycolic acid in their cell walls, need an acid-fast stain such as the Ziehl-Neelsen stain in order to be visualised.

Introduction to antibiotics

Explain the difference between antibiotics and anti-infective drugs.

"Anti-infective drug" (a.k.a. "antimicrobial") is a broad term that includes antibiotics, antivirals, antifungals, and so on. The term "antibiotic" has a much stricter definition. The strict definition of an antibiotic is a chemical produced by a microorganism that kills or inhibits other microorganisms, but in clinical practice, most people just use "antibiotic" to mean any kind of substance that kills or inhibits bacteria (with the exception of antiseptics and disinfectants).

Describe the sources of antibiotics.

Antibiotics can be naturally-derived, semisynthetic, or fully synthetic. Some antibiotics are derived from natural sources- for instance, penicillin is derived from the Penicillum fungus. Semisynthetic antibiotics are essentially these natural antibiotics with a few modifications to make them better, whereas synthetic antibiotics (which are relatively uncommon) are synthesised in the lab.

Describe the different mechanisms of action of antibiotics, and for each give an example of an antibiotic utilising the mechanism.

• Chemotherapy II: Antibacterial Drugs

Examples of antibiotics of each class:

• Beta-lactam (cell wall synthesis inhibitors acting on transpeptidase)
• Penicillins- e.g. penicillin, ampicillin, amoxicillin (and many other drugs ending in -cillin)
• Cephalosporins- e.g. cephalexin, cefazolin (and many other drugs beginning with ceph- or cef-)
• Monobactams- e.g. aztreonam
• Carbapenems- e.g. imipenem, meropenem (and many other drugs ending in -penem)
• Glycopeptides (cell wall synthesis inhibitors binding to the D-ala-D-ala end of precursor side chains)- e.g. vancomycin
• Rifamycins (inhibits the enzyme that produces mRNA)- e.g. rifampin (and many other drugs beginning with rif-)
• 50S inhibitors (prevent protein elongation)
• Macrolides- e.g. azithromycin, erythromycin (and many other drugs ending in -mycin, but note that not all drugs ending in -mycin are macrolides)
• Clindamycin (surprise! A drug ending in -mycin that isn't a macrolide- Google says that it's a lincosamide)
• Streptogramins- e.g. quinupristin-dalfopristin
• Oxazolidinones- e.g. linezolid
• Aminoglycosides (bind to the 30S ribosomal subunit and cause misreading of the genetic code)- e.g. gentamicin, amikacin
• Tetracyclics (bind to the 30S subunit and block binding of tRNA)- e.g. doxycycline, minocycline
• Folate synthesis inhibitors (basically what it says on the box)
• Sulfonamides- e.g. sulfamethoxazole
• Trimethoprim- often co-administered with sulfamethoxazole to form co-trimoxazole
• Quinolones (inhibit DNA gyrase and topoisomerase)- e.g. ciprofloxacin (technically a fluoroquinolone, but close enough :P)
• Lipopeptides (insert into the lipid membrane, disrupting it)- e.g. daptomycin

Define “spectrum of activity” and give an example of a broad spectrum and narrow spectrum antibiotic.

"Spectrum of activity" refers to whether an antibiotic is broad-spectrum (affects a wide range of bacteria) or narrow-spectrum (affects only a select few types of bacteria). An example of a broad-spectrum antibiotic is ampicillin, which can be used against a lot of gram-positive and gram-negative bacteria, and has some resistance to beta-lactamases (an enzyme that often threatens to break down beta-lactams like ampicillin). An example of a narrow spectrum antibiotic is isoniazid, which pretty much only works against mycobacteria species, such as M. tuberculosis.

Explain the difference between empirical and targeted antibiotic therapy.

Empirical antibiotic therapy involves treatment based on symptoms and likely causes of those symptoms. Since you often don't know for sure what the causative agent is, empirical therapy tends to be more broad-spectrum. Targeted antibiotic therapy involves treatment based on information from laboratory tests, and as such can be more narrow-spectrum and targeted towards the specific organism. Often, you would start with empirical therapy (as it can take days to get a result from the lab). Then, once the causative agent is known, you would switch to targeted therapy.

Define the term Minimum Inhibitory Concentration.

The Minimum Inhibitory Concentration (MIC) is the minimum concentration of an antibiotic needed to inhibit growth of bacteria in vitro. There are different types of tests for determining MIC, which I have written about here.

Outline the four broad mechanisms by which bacteria can be resistant to antibiotics.

• Antibiotic Resistance

Describe in detail the resistance mechanisms of S. aureus to beta-lactam antibiotics.

As mentioned earlier, the main target of beta-lactams is the transpeptidase enzyme, which is involved in cell wall formation. If the transpeptidase is modified in a way that beta-lactams cannot bind, then that bacteria will become resistant to beta-lactams. In fact, this is how Staphylococcus aureus can develop a resistance to beta-lactams.

Usually, the transpeptidase (a.k.a. Penicillin Binding Protein, or PBP) in S. aureus is PBP2, encoded by the gene pbpB. However, if S. aureus acquires the mecA gene, it can create a new transpeptidase, called PBP2a. Beta-lactams cannot bind to and inhibit PBP2a, so S. aureus is now resistant to beta-lactams. Such strains of S. aureus are also known as Methicillin-resistant S. aureus, or MRSA for short.

Regional Anatomy II: Head and Neck

Describe the functional matrix theory

The functional matrix theory essentially states that structure reflects function. For instance, the neural skull, which houses the brain, needs to be big and hollow in order to be able to fit the brain, but strong enough to protect it.

Explain the pharyngeal arches and their role in head and neck development

Pharyngeal arches are basically the head and neck's answer to somites (see here if you don't know what a somite is). There are six pharyngeal arches, though one disappears during development, so normally we only talk about five (1, 2, 3, 4, and 6). Each pharyngeal arch is associated with a particular nerve, as well as a bunch of muscles. For instance, the first pharyngeal arch is associated with cranial nerve V (trigeminal) and is associated with the muscles of mastication (though there are exceptions). The second pharyngeal arch is associated with cranial nerve VII (facial) and is associated with the muscles of facial expression (though again there are exceptions).

Explain the interaction of somites and arches in the structures of the head and neck

Myotome-derived muscles (i.e. muscles derived from the myotomes, a type of somite), make up most of the muscles of the neck. However, there are a couple of myotome-derived muscles in the head: the extra-ocular muscles that move the eye, and the tongue muscles. All other muscles in the head are derived from pharyngeal arches.

Have a basic knowledge of the supply and drainage of the head and neck

• The Heart and Major Blood Vessels

Visceral structures

This wasn't listed as a learning outcome, but it seemed kind of important when I flicked through the slides. Essentially, most of the visceral structures of the head and neck (nasal cavity, oral cavity, oesophagus, trachea, associated glands) are derived from the foregut. Yay I guess?

Regional Anatomy I: Thorax, Abdomen, and Pelvis

Recall the location and identify the major organs, vessels and nerves of the thorax, abdomen, and pelvis.
Recall the function of the major organs, vessels and nerves of the thorax, abdomen, and pelvis.

I covered a lot of this stuff in a lot of detail in my posts for ANHB2212. However, rest assured that we do not need to go into that level of detail for now.

Thorax

Things we have in the thorax:

• The Heart and Major Blood Vessels
• Lungs and bronchi (The Respiratory System)
• Oesophagus. Has skeletal muscle at the top (acts as a sphincter to stop us from swallowing anything we don't want), a mix of skeletal and smooth muscle for the middle third, and smooth muscle at the bottom. The inner muscular layer is circular and the outer layer is longitudinal.
• Thoracic duct: the main duct that carries lymph back to the circulatory system.
• Phrenic nerve: arises from C3, C4, and C5 and keeps the diaphragm alive. It also innervates the fibrous pericardium.
• Vagus nerve (Cranial Nerve X): travels behind the lungs and wraps around the oesophagus. Also travels down through the diaphragm to the abdomen. Innervates damn near everything.

All of the organs in the thorax are surrounded by the rib cage, made up of 12 ribs, most of which are attached to the sternum (breastbone).

Abdomen

Things we have in the abdomen:

• The stomach (Digestion and Absorption of Food- Part 1)
• The spleen: found in the upper left part of the abdomen, it filters the blood and protects against blood-borne pathogens. In fetal life, and in certain disease states, it is involved in haematopoiesis.
• The pancreas: has exocrine and endocrine functions. Exocrine functions: secretes digestive enzymes. Endocrine functions: secrete insulin and glucagon. Its head is encircled by the duodenum and its tail points to the spleen.
• Liver: receives some oxygenated blood from the hepatic artery, as well as a ton of deoxygenated blood from the GI tract. Filters blood and produces bile.
• Gallbladder: stores and concentrates bile received from the liver (does not produce bile). Bile helps to break down fats. Note that while the gallbladder looks green in cadavers, it is only green because formalin makes it green.
• Small intestine: made up of the duodenum, jejunum, and ileum. The main site of absorption. Has folds (plicae circularis), villi, and microvilli, all of which increase the absorptive area. The ileum also has lymphoid tissue known as Peyer's patches.
• Large intestine: made up of caecum, ascending colon, transverse colon, descending colon, and sigmoid colon. Absorbs water and makes poo.
• Kidneys: filters blood to make urine. Has ureters that deliver said urine to bladder.
• Suprarenal (adrenal) glands: sit on top of the kidneys and secrete a bunch of important hormones.

Pelvis

The pelvis is made up of three main bones: ilium, ischium, and pelvis. Here are the things that we have in the pelvis:

• Pelvic diaphragm muscles (a.k.a. levator ani): puborectalis, pubococcygeus, iliococcygeus. Act as sphincters and stop the contents of the abdomen from falling out the bottom.
• Rectum and anus: has two sphincters- internal smooth, external skeletal.
• Urinary bladder: stores the urine produced by the kidneys. The urethra connects the bladder to the outside world.
• Male and female reproductive organs.

The Heart and Major Blood Vessels

Identify the major features of the heart

• Heart and Mediastinum

Describe the anatomical pathway of blood through the heart

Superior/Inferior vena cava (from body) --> right atrium --> tricuspid valve --> right ventricle --> pulmonary valve --> pulmonary artery --> lungs --> pulmonary veins --> left atrium --> mitral (bicuspid) valve --> left ventricle --> aortic valve --> aorta (to body)

Identify the major blood vessels of the head, heart, abdomen, and upper and lower limbs

The first thing you need to know in identifying blood vessels is how to tell an artery and a vein apart. Both arteries and veins have three main layers: a tunica intima (simple squamous endothelial lining), tunica media (elastic tissue and smooth muscle), and tunica externa (elastic tissue and collagen), though the relative thickness of each depends on the type of vessel. Arteries carry blood away from the heart and since it is usually at a high pressure, the muscular tunica media is quite thick in order to help withstand the pressure. Veins carry blood back to the heart and has a much thinner tunica media, plus a higher ratio of collagen to elastin. Since the pressure is much lower in veins, they have valves to prevent backflow.

Major vessels of the head

The major vessels supplying the head are the carotid arteries. There are two common carotid arteries (left and right). The left common carotid branches directly off the ascending aorta, whereas the right common carotid branches off the brachiocephalic trunk. Each of the common carotid arteries branches into an internal carotid and an external carotid. The internal carotid supplies the brain, whereas the external carotid supplies the face.

The major vessels draining the head are the jugular veins. The external jugular veins drain the back of the head, whereas the internal jugular veins drain the face. The jugular veins drain into the subclavian veins, uniting to form the brachiocephalic veins. The brachiocephalic veins (left and right) drain into the superior vena cava, which goes to the right atrium.

Major vessels of the heart

The major vessels supplying the heart are the coronary arteries, which are the first arteries to come off the ascending aorta. The pattern of arteries supplying the heart can be very variable, but there are some that are pretty common to most people. Most people have a left and right coronary artery, and the left usually branches off into the anterior interventricular artery (a.k.a. left anterior descending artery) and left circumflex artery.

Major vessels of the abdomen

The major vessels supplying the abdomen are the branches of the descending aorta. There are three sets of paired arteries, as well as three unpaired arteries. The three paired arteries are the suprarenal arteries (supplying the adrenal glands), the renal arteries (supplying the kidneys), and the gonadal arteries (supplying the ovaries or testes). The three unpaired arteries are the coeliac artery, superior mesenteric artery, and inferior mesenteric artery.

The venous system has similar paired veins, but there's also something interesting going on: the hepatic portal system. The mesenteric veins, which drain the intestines, take the food that we've just absorbed to the liver via the hepatic portal vein. From there, the liver is drained by the hepatic veins. In the liver, we have veins going to capillaries which are going to veins, rather than arteries going to capillaries which are going to veins.

Major vessels of the upper limb

Some of the vessels of the upper limb are really just one big vessel joined together, but named different things depending on which region you're looking at. At the top of the upper limb, where the clavicle is, the arteries are called subclavian arteries. The subclavian arteries become the axillary and then the brachial arteries as they go down. The brachial arteries then divide into the radial and ulnar arteries, depending on which bone they are next to. Veins are named similarly, though there are some superficial veins as well.

Major vessels of the lower limb

The lower limb vessels are similar to the upper limb vessels, in that they run into each other: you have iliac arteries that become femoral arteries that branch into anterior and posterior tibial and fibular arteries. Once again, veins are kind of similar, plus a few superficial veins.

Nervous System II

Understand the organisation of the Nervous System

The nervous systems is divided into two main divisions: the central nervous system and the peripheral nervous system. The central nervous system consists of the brain, spinal cord, and cranial nerves I and II (olfactory and optic, respectively), whereas the peripheral nervous system consists of everything else. Both parts of the nervous system consist of nerves as well as other supporting cells.

Another term that you might hear is "autonomic nervous system." The autonomic system refers to the bits of the nervous system that take care of most functions that we don't generally think about but keep us alive- stuff like breathing and pumping blood. The autonomic nervous system encompasses parts of the central and peripheral nervous system, but mostly the peripheral nervous system.

Nerves come in many shapes, but have a few main components. Firstly, they have dendrites, which receive information from surrounding cells. Dendrites are connected to a cell body, where most of the organelles are. The cell body then leads into one or more axons, which carry action potentials away from the cell body. Some nerves might be myelinated- that is, they have a fatty sheath wrapping around the axon, allowing for faster conduction. (You can read about that here.)

Recognise the components of a simple reflex

Pretty much every control pathway in our body has three main components: something to pick up a signal from the environment, somewhere to process the information, and something to cause a change. Simple reflexes are no different. For instance, in the knee jerk reflex, various proprioceptors in the muscle and muscle tendon respond to the sudden lengthening of the muscle by sending a signal to the spinal cord. Information is processed in the spinal cord and output to the muscle, which responds by shortening the muscle.

Be able to explain the spinothalamic, proprioceptive, and corticospinal pathways

Spinothalamic / Anterolateral

The spinothalamic or anterolateral pathway is the main pathway for detecting pain, temperature, and touch. It is a slow pathway that consists of mostly thin, unmyelinated neurons that give poorly-defined sensations. There are three nerves involved in the spinothalamic pathway: one to go from the area of the sensation to the spinal cord, another to go from the spinal cord to the thalamus for integration, and a third to go from the thalamus to the sensory cortex. In the spinal cord, the second nerve crosses over from one side of the spinal cord to the other, so any kind of pain or touch felt on the left side of the body is processed by the sensory cortex in the right side of the brain.

The CNS has a similar system to the spinothalamic system: the trigemino-thalamic system that picks up sensations from the trigeminal nerve. It is also a three-neuron relay that crosses over and sends its output to the thalamus, and then the sensory cortex. (I *think* this pathway also sends proprioceptive input a la the next system that we're going to discuss, just to make things extra confusing.)

Proprioceptive / Dorsal Column-Medial Lemniscal (DC-ML)

The proprioceptive or DCML pathway is the main pathway for detecting proprioception and joint position. In contrast to the spinothalamic pathway, the DCML pathway consists mainly of large, myelinated neurons that are fast and give precise sensations. Once again, there are three nerves involved, but this time the nerves don't cross over until they get to the brainstem.

Corticospinal

The corticospinal pathway is the main pathway for motor output. In contrast to the previous two pathways, which had three-neuron relays, the corticospinal pathway is a two-neuron relay: an upper motor nerve in the motor cortex synapses with a lower-motor nerve located either in the spinal cord or brainstem. The corticospinal pathway crosses over in the base of the brainstem.

Nervous system I- Nervous system development

Notochord- Formation and Function

The notochord is a hollow tube made out of mesoderm cells that acts as a signalling centre for the early embryo. The notochord induces other cells, particularly in the overlying ectoderm, to proliferate and differentiate. You can read more about the notochord here.

Neural Tube Formation and Derivatives
Neural Crest Formation and Derivatives
Central Nervous System Elements
Peripheral Nervous System Elements

I have covered neural tube and neural crest formation here.

The neural tube is largely responsible for the formation of the brain and spinal cord (i.e. the central nervous system), as well as many motor neurons in the peripheral nervous system. Towards the head, the walls of the neural tube thicken and become folded, forming the brain. In the brain region, the inside of the neural tube becomes the ventricular system, where cerebrospinal fluid circulates. In the spinal cord, the inside of the neural tube becomes the central canal.

The neural crest covers the neural tube during development and is responsible for the formation of many sensory neurons. It is also responsible for the formation of some other structures, such as the adrenal medulla.

Skin

Understand the functions of the skin

There are lots of functions of the skin, most of which you are likely already familiar with. Firstly, skin protects you from all kinds of things, like harmful bacteria and abrasion. Secondly, there are many blood vessels underlying the skin that can be dilated or constricted to help regulate body temperature. There are also receptors in the skin that can help us sense the world. Synthesis of some stuff, like vitamin D, also occurs in the skin.

Identify the basic layers in skin
Describe the structure of the different layers in skin

There are three main layers of skin: epidermis, dermis, and hypodermis (a.k.a. "subcutaneous layer").

The epidermis is keratinised stratified squamous epithelium that can be divided up into four layers (or five, if you're talking about the thick skin on the palms of your hands and soles of your feet). The deepest layer, the stratum basale, is where stem cells divide, but there are also melanocytes (which secrete melanin) and Merkel cells (cells that sense light touch). Next up is the stratum spinosum, consisting of keratinocytes joined together by desmosomes. The next layer is the stratum granulosum, made up of layers of flattened cells and granules. The next layer, the stratum lucidum, is only present in thick skin. Finally, the most superficial layer is the stratum corneum, where all the cells are full of keratin and have died due to being too far away from blood vessels.

The layer below the epidermis is called the dermis. It is made up of connective tissue, often dense irregular connective tissue. It also contains blood vessels, nerves, and cells, such as fibroblasts and macrophages. The dermis also contains "epidermal derivatives" (structures that were derived from the epidermis but moved downwards), including receptors and glands, as well as hair follicles. Most of these structures have basement membranes to separate ectodermal-derived and mesoderm-derived tissues. Here are some more details about these structures that you should know:

• Hair- Associated with sebaceous glands (secrete sebum, an oily substance), erector pili muscles (smooth muscle that raises the hairs), and sensory nerves. The number of hairs are about the same for everybody, but hair can differ in terms of thickness and colour.
• Sebaceous glands- Glands that secrete an oily substance called sebum. Tend to associate with hair follicles.
• Ceruminous glands- Special sebaceous glands that are found in the ear canal. Secrete cerumen (ear wax).
• Sweat glands- Secrete sweat. Look like little knots.

Finally, below the dermis is the hypodermis, which is mostly fat. Beneath the fat, there is connective tissue, which connects the fat to tissues beneath it, allowing the skin to move freely.

Discuss the difference in skin between different areas

As I mentioned earlier, the skin on the palms of your hands and soles of your feet is thick, and thick skin also has a stratum lucidum layer in the epidermis. The rest of the body is covered in thin skin, which lacks this stratum lucidum layer.

Muscles

These learning outcomes are quite broad, so this post will probably end up being a bit vague. Oh well...

Understand the key concepts of muscle action.

The main thing to understand is that muscles never push- they always pull. So, wherever you have a prime mover muscle to perform one action, you will need an antagonist muscle pulling in the other direction to perform the opposite action. Prime movers and antagonists are usually located on opposite side of a joint. Sometimes, other muscles might be needed to help out by stabilising joints or adding force. Muscles that help out are called synergists, and synergists that immobilise bones to provide stability are called fixators.

Another thing to understand is that muscles attach to things (e.g. bones) and they produce movement by contracting and pulling those attachment points closer to each other. Muscles can be attached directly (the layer of connective tissue surrounding muscle can become fused to the layer of connective tissue surrounding bone) or indirectly (the connective tissue of the muscle can extend past the muscle as a rope-like tendon or sheet-like aponeurosis).

Yet another thing to understand is that skeletal muscles generally attach to two bones, and only one of those bones moves. The attachment that remains fixed is called the origin, whereas the attachment that moves is the insertion. When the muscle contracts, the insertion is pulled towards the origin.

Identify superficial muscles of the human body.

I'm not really sure why this is listed as a learning outcome, given that I'm fairly sure that at this stage we're still at the "learn the broad concepts of what muscles are made of" stage and not the "learn every single muscle and what it does" stage. If you want to learn more about muscles, head on over to TeachMeAnatomy.info- never used it myself, but I've heard good things about it.

Describe the actions of muscles.

Muscles have lots of useful actions within the body. As well as being able to help us move, they also help us maintain our posture. They also have many other functions within the body, such as heat generation, pumping blood, moving food through the intestines, and so on.

Understand the naming conventions of skeletal muscle.

Skeletal muscle is what we often think of when someone says the word "muscle." Simply put, it is muscle that is associated with moving the skeleton. It is striated, that is, it has a stripy appearance under the microscope due to the arrangement of its contractile proteins. Each muscle fibre is surrounded by a thin sheet of connective tissue called endomysium. Multiple muscle fibres are grouped together into fascicles, which are surrounded by another layer of connective tissue called perimysium. Finally, dense regular connective tissue surrounding the whole muscle is called epimysium.

Skeletal muscle is often named after various characteristics including location, shape, size, number of origins, action, and so on. For instance, the gluteus maximus is named after location (gluteal region) and size (maximus = large). Understanding what the different parts of a muscle name mean might help you to remember the muscles more easily.

Arrangement of fascicles

This wasn't listed as a learning outcome, but since so many slides are devoted to this, I thought I'd write about it here.

Fascicles can be arranged in many different ways, and there are names for the different arrangements:

• Circular- Fascicles are arranged in concentric rings, forming sphincters. Examples include orbicularis oris and orbicularis oculi.
• Convergent- Fascicles converge towards a single tendon, allowing for the generation of a lot of force at a single point. An example is pectoralis major.
• Parallel- Fascicles are arranged parallel to the long axis of the muscle. Examples include sartorius and rectus abdominis.
• Pennate- Fascicles are short and oblique and attach to a central tendon. In unipennate muscles, fascicles insert on one side of the tendon. In bipennate muscles, fascicles insert on opposite sides of the tendon. Finally, in multipennate muscles, there are many fascicles inserting onto different tendons. Examples include extensor digitorum longus (unipennate), rectus femoris (bipennate), and deltoid (multipennate).

Bone

Describe the categories of bone and give examples of each

There are several different categories of bone, often classified based on shape. Flat bones are flat (!)- examples include the sternum and the bones of the skull. Long bones are long (!!) and include bones such as the femur and humerus. Short bones are short (!!!!!!!!!!!!!!!!!!!), and by that I mean they are about as wide as they are long, and include the carpals and tarsals. Irregular bones have weird, irregular shapes (!?!?!?!?!??!!!!!) and include the vertebrae. Finally, there are sesamoid bones, which are bones that are found within tendons. An example of a sesamoid bone is the patella.

Describe the general features of a long bone and a flat bone

Long and flat bones have several features in common. Both bones are made out of several types of bone cells as well as non-cellular components, such as collagen and ground substance. The basic building block of bone is the osteone, or Haversian canal, which is made up of concentric rings of bone around a central canal containing an artery. Osteocytes (mature bone cells) can be found in lacunae, which are little spaces between the concentric rings of the osteone. Cells can communicate with each other via small passages known as canaliculi.

Both long and flat bones have two main regions: cortical bone and cancellous (spongy) bone. In cortical bone, the osteones make up a solid sheet. In cancellous bone, the osteones are arranged in web-like structures called spicules. Cancellous bone also contains the bone marrow, which comes in two flavours: red (blood-forming) and yellow (contains a higher number of fat cells). When we are young, we have more red marrow, but we get more yellow marrow as we get older.

The outer surface of bones is lined by a thin layer of connective tissue called periosteum. Long bones also have a medullary cavity within them. This cavity is lined by a thin layer of tissue called the endosteum.

Describe the four cell types in bone tissue; their function, origins, and locations in the tissue

The main cell types in bone tissue are osteogenic cells, osteoblasts, osteocytes, and osteoclasts.

Osteogenic cells are found in the inner layer of the periosteum, as well as in the endosteum. Osteogenic cells are stem cells that are able to divide to produce osteoblasts.

Osteoblasts are bone cells that primarily function to build up bone in a process known as osteogenesis. They are found in a single layer of bone underneath the endosteum.

Osteocytes are bone cells that are found in the lacunae of Haversian canals, as mentioned earlier. They contribute to maintaining bone. Osteocytes are formed from osteoblasts that are trapped in the matrix of bone.

Osteoclasts are found in pits called resorption bays. They have the opposite function to osteoblasts: osteoclasts function to break down bone. Osteoclasts are quite large and have multiple nuclei. As opposed to osteoblasts and osteocytes, osteoclasts do not arise from osteogenic cells. Instead, osteoclasts arise from monocytes and macrophages.

Describe the two mechanisms of bone formation

There are two main methods of bone formation: intramembranous ossification and endochondral ossification.

Intramembranous ossification can occur in areas where bones are not subjected to stress. In intramembranous ossification, bone forms within membranes. Bones of the cranium are formed in this way.

Endochondral ossification occurs in bones that are under load or stress during development. In endochondral ossification, there is a cartilaginous growth plate to absorb some of the stress. Over time, the cartilage becomes replaced by bone. Note that bone does not grow from cartilage- it simply replaces it!

Describe bone growth and remodelling

I don't think we need to know too much about this for now, other than that bone is continually being broken down by osteoclasts and built up again by osteoblasts. Bone growth and remodelling takes place according to where stresses are placed on bones.

Describe the structural and functional classification of joints

• The Articular System

Growth Disorders

When I saw this lecture on the schedule, I thought we were going to be learning about gigantism, dwarfism, and so on. However, it turns out that "growth disorder" also means an abnormal proliferation of cells and tissue. What are these abnormal proliferations of cells and tissue? Read on...

Understand terminology of the common growth disorders and how this relates to biological behavior (reactive vs benign vs malignant processes)

• Mass- An aggregate of tissue that normally has a name ending in -oma (e.g. lipoma, haematoma, etc.)
• Tumour- A solid proliferation of cells. May or may not be a neoplasm- hernias and abscesses can be tumours, but they are not neoplasms.
• Neoplasia/neoplasm- Abnormal and excessive tissue growth from proliferating abnormal cells, due to underlying cellular and genetic alterations. Can be benign or malignant. Note that not all neoplasms are tumours: a leukaemia is a neoplasm, but since it is made of circulating cells and not a solid proliferation of cells, it is not a tumour.
• Hamartoma- A mass formed of cells that are native to the tissue, but are found in a disorganised arrangement. NOT a neoplasm.
• Ectopia- Normal tissue that is found at the wrong site. NOT a neoplasm.
• Benign- A "well-formed" neoplasm made up of specific cell types with an abnormal architecture. Benign tumours are not cancer and are generally not fatal, but they can be incredibly harmful if they press against vital structures (e.g. the brain stem). Benign neoplasms may or may not progress to malignancy.
• Malignant- A neoplasm that is able to invade other tissues, able to metastasise (spread to other sites in the body), and has unconstrained proliferation.
• Cancer- Proliferation of a malignant neoplasm.
• Dysplasia- A lesion with atypical features. May or may not progress to malignancy.
• Metastasis- Spread of a malignant neoplasm to another site in the body.

In addition to the above, make sure that you are familiar with the terms described at the end of the post on Cell Injury and Adaptations.

Understand principles of how neoplastic tumours are recognised and classified based on macroscopic, microscopic and genetic features

As mentioned in the definitions above, neoplasms can be benign or malignant. A benign neoplasm is more "well-formed" and tends to stay put whereas a malignant neoplasm can invade, metastasise, and/or proliferate uncontrollably. Many neoplasms are named after their tissue type, with a suffix of -oma for most benign neoplasms, a suffix of -carcinoma for malignant neoplasms that are epithelial-derived, and a suffix of -sarcoma for malignant neoplasms that are mesenchymal-derived. There are, however, exceptions: melanoma and myeloma (plasma cell malignancy) may both end in -oma, but they are both malignant tumours. Leukaemia is another malignant neoplasm that doesn't fit standard naming conventions.

Understand the basic principles behind development of neoplastic disease, including interactions between genetic and environmental factors

Cancer is thought to arise from an interaction between genetic susceptibility and exposure to initiating factors, such as carcinogens (something that can increase the risk of cancer). Note that exposure to a carcinogen doesn't mean that you will definitely get cancer- it just increases the risk. That is why some people like to say, "I smoked for XX years and I didn't get cancer!!!!"

Cancer also generally doesn't develop all at once. The Knudson hypothesis states that cancer is a multi-step process. At each step, there are mutations that affect important functions of the cell, such as cell growth, cell division, etc. As these mutations accumulate, cell growth and proliferation can get out of control.

There are four broad phases for the development of cancer. In the initiation phase, there are changes in a single cell. In the promotion phase, this cell proliferates in a process known as clonal expansion. As it divides and expands, some of the daughter cells acquire new mutations of their own. Eventually, during the conversion phase, there are critical new mutations that transform these abnormal cells into an invasive malignancy. Finally, during the progression phase, there are further mutations that may confer treatment resistance, metastastis, and loads of other fun things.

List the intrinsic barriers that exist to prevent cancer development and the capabilities that cancer cells acquire to overcome these barriers

Part of the reason why cancer doesn't happen all at once is because cells and tissues have ways to prevent cancer development. For instance, DNA repair mechanisms can prevent mutations from taking hold. Cancer eventually takes off when the cells have acquired mechanisms to bypass these barriers to development and proliferation. For instance, cancer cells can acquire the ability to survive without external growth signals, insensitivity to growth inhibition, resistance to apoptosis, increased activity of telomerases (enzymes that keep our telomeres from shrinking, thus preventing cellular aging), ensure their own nutrient supply by promoting angiogenesis (growth of new blood vessels), and so on.

Metastasis itself requires many mechanisms to bypass defences that would otherwise prevent spread of cells. Tumour cells might have proteinases that can degrade physical barriers or can gain the ability to attach to extracellular matrix proteins. There are many ways in which tumours can spread: directly, haematogenous (via blood), lymphatic (via lymph), or transcoelomic (via body cavities such as the peritoneum).

Understand the local and systemic effects of neoplastic disease

As mentioned earlier, even benign neoplasms can cause problems by pressing against other structures. Aside from this, there are many ways in which neoplasms can be problematic: they can result in weight loss, unexplained symptoms such as fever and night sweats, an increased risk of thrombosis, and so on. There are also paraneoplastic syndromes, which are basically the result of hormone-like substances being produced by tumour cells. For instance, a neoplasm that secretes renin (part of the system involved in regulating blood pressure) might cause hypertension. Note that neoplastic disease can manifest differently in different individuals, according to individual characteristics such as age. Furthermore, neoplasms in different locations (i.e. liver vs. lung) can manifest very differently.

Understand general principles of diagnosis and treatment of neoplasms

Ultimately, we want to be able to identify neoplastic disease earlier as that usually results in better treatment outcomes. This may be done through screening the population and/or identifying individuals at high risk. In terms of treatment, curative treatment is obviously ideal, but where that is not possible, treatment aims to slow the progression of the illness and/or alleviate symptoms.

There are several features of cells that can suggest malignancy. Malignant cells may have dark nuclei with irregular outlines and large nucleoli. The cytoplasm may have more mitochondria, glycogen, or other substances in it. Tissues may also show features of malignancy, such as necrosis, infarction (as the tumour outgrows the blood supply), invasion of other tissues, or abnormal architecture. There may also be symptoms that can be detected, such as weight loss, shortness of breath, or the paraneoplastic syndromes as mentioned earlier. Finally, genetic sequencing might be able to detect mutations that are common to particular tumours.

The severity of a neoplastic disease can be assessed by either grading or staging. Grading is a subjective assessment of how much the tumour cells look like normal cells (differentiation). (A complete loss of differentiation is called anaplasia.) Unfortunately, since grading is quite subjective, it only has a fair correlation with the outcome. Staging is a more objective assessment as it assesses how far a tumour has spread from the original site. Since it is more objective, it is good for research purposes and for ensuring consistency of care.