Foundations Cheat Sheet

Anatomy 1 The Human Body

Synovial joints have fibrous (articular) capsule, and articular (hyaline)
cartilage lining joint surface, include:
Gliding/plane carpals at base of thumb
Hinge elbow
Pivot radioulnar
Condyloid metacarpophalangeal (proper knuckles)
Saddle 1st carpometacarpal
Ball & Socket hip/shoulder
Skeletal muscles make up 40-50% body weight, have limited ability to
repair themselves. Fibres (cells) are bundled (with endomysium in between) into
fascicles (wrapped in perimysium), together forming a muscle wrapped in
epimysium. They can be flat with an aponeurosis (abs), pennate (uni-, bi-,
multi-), fusiform (typical muscle, e.g. biceps), quadrate (flat, lots of fibres so
strong) or sphincteral.
Deep fascia = dense connective tissue, separating compartments and
surrounding neurovascular elements. Superficial fascia = areolar connective
tissue + fat.
Physiology 1 The Body Compartments
Intracellular Compartment [K+]>[Na+]
Fluid inside cells (incl. in RBC and WBC) 25L
Extracellular Compartment [Na+]>[K+] except transcellular variable
Plasma fluid of blood (excl. in RBC and WBC) 3L
Interstitial Space environment of most cells 13L
Transcellular pools (aqueous humour, synovial fluid, CSF, urine in
bladder) 1L
BUT, total osmoles of intracellular=interstitial=plasma=301mOsm/L (milli
osmoles per litre; 1om=6.021023 particles; note dissociating ions like NaCl will
count double the osmoles; pure water is 55.5mol/L, osmolarity=0 Osm/L)
Gradients across membrane to store energy in readily accessible form, for
cellular respiration, update or excretion of metabolites, and fast signalling
(neuron action potential, prevent multiple sperm fertilising egg).
Phospholipid = 2 fatty acids glycerol phosphate ethanolamine
Tight junctions (sutures of transmembrane proteins) control permeability
for fluid movement (e.g. from plasma of capillary to extracellular fluid) between
cells (more tight junctions=less leaky).
Diffusion and (osmotic pressure) is based on Brownian motion, following t
x2/D (D=diffusion coefficient=size, shape, temp.). 100m takes 2s, whilst 1cm
takes 7hr, and 1m takes 8yr.
Molecules may not diffuse as they may be charged/polar, too big, or the
conc. gradient is against them. To overcome this, cells have pores & channels,
pumps for ions, carriers to facilitate diffusion of larger molecules, and pinocytosis
and phagocytosis for really big molecules.
Osmosis = flow by diffusion of solvent across a semipermeable
membrane. Osmotic pressure can interact with hydrostatic pressure (a difference
of 1mOsm/L exerts a pressure20mmHg).
In arteries and capillaries, hydrostatic pressure (due to heart) > osmotic
pressure (higher conc. in plasma as more protein which cannot diffuse), hence
net filtration out (in capillaries). In veins, osmotic>hydrostatic (pressure lost), so

net absorption in. Almost all fluid (20L/day) that leaves capillaries by osmosis is
drawn back in (rest in lymphatics).
Histology 1 Histology of Basic Tissues
Mesothelium = lining of peritoneal, pleural and pericardial cavities
Endothelium = lining of cardiovascular and lymph passageways
Epithelium includes glandular and membranous tissues. Epithelium are
held together by attachment points (junctional complexes), also stabilises cell
shape. Rest on basement membrane separating from underlying CT. Avascular,
rely on nutrition by diffusion across basement membrane. Classified by number
of cell layers, shape, and surface specialisations (cilia, microvilli, keratin).
Functions:
Absorption lipids in small intestine, selective re-absorption of Na +
in kidney tubules
Gas Diffusion endothelium of capillaries in lungs
Secretion

glandular
epithelial
cells
(thyroid
follicle
hormonesblood, pancreatic enzymesducts, sweat glandsskin)
Excretion kidney tubules, sweat glands
Lubrication into GIT; mesothelial make serious fluid into body
cavities to prevent organ friction/rubbing
Protection injury, dehydration, bacterial invasion
Regeneration and replacement: epidermal (28 days), GIT lining
(4-6 days)
Connective Tissue = support framework (anchor/bind organs, provide
packing tissue); consists of intercellular matrix composed of an amorphous
ground substance in which there are cells (fibroblasts that make fibres, mast,
plasma cells, leukocytes, macrophages) and extracellular fibres (elastic,
collagen, reticular (thin, delicate spider web); in blood it is fibrin used for
clotting). Includes fibrous loose (subcutaneous, adipose), dense irregular
(collagen of dermis), dense regular (ligaments, tendons), as well as rigid and
flexible (cartilage: hyaline, fibrocartilage, elastic), rigid and inflexible (bone:
compact, cancellous), and circulating blood and lymph. Functions:
Transport blood
Support ligaments, tendons, bone, cartilage
Repair granulation tissue
Defence phagocytosis (macrophages), antibodies (plasma cells),
inflammatory response (histamine from mast cells)
Storage lipids in adipose/subcutaneous, lipids, mineral, calcium in
bone
Packing space between epithelium, muscle and glands
Contractile elements of muscles are myofibrils, composed of the
myofilaments actin and myosin.
Skeletal multinucleated, cylindrical (diam: 10-100m), parallel
arrangement of actin (light) and myosin (dark) lead to striations
Cardiac single, central nucleus; same banding as skeletal;
intercalating disks to ensure contracts at once
Smooth single, central nucleus, spindle-shaped (diam: 5-6m);
walls of blood vessels and hollow organs
(Involuntaries have single, central nucleus)
Nervous tissue: excitability, conductivity. Terminals of neuron are called
terminal boutons (end bulbs). Cell body also called soma. Myelinated fibres/cells
(1-20m diam, compared to unmyelinateds <2m) have Schwann cells with

flattened nuclei and make myelin (lipid-based). Further wrapped in CT sheaths

(collagen). In CNS, same function achieved by oligodendrocytes. 12 billion
neurons (structural and functional units) in body.
Biochemistry 1 Molecules of Life
Macromolecule = large organic molecule (polymers=covalent linkages of
monomers of similar or identical structure) formed by joining of small molecules,
usually by dehydration reaction. They are:
Carbohydrates (polysaccharides=monosaccharides with glyosidic
bonds) - energy storage and transport, structure
Lipids (hydrophobic fatty acids with ester bonds; some arent
polymers) energy storage and transport (TAGs three fatty acids
+ 1 glycerol), structure (phospholipids, sterols), chemical
messengers
(steroids
like
cholesterol),
photoreceptors
(carotenoids), coverings (waxes)
Proteins (amino acids: -carbons+H, NH 3+ (amino), COO- (carboxyl),
variable side chain determines properties; peptide bonds between
amino and carboxyl group) functions related to shape and
chemical properties of monomer; energy storage, structural
support, transport, protection and defence, regulation of metabolic
activities (insulin), movement, growth and development (muscle
fibres), enzymes
Variable Side Chain (R) determines classification:
charged hydrophilic, polar (OH, NH), nonpolar
hydrophobic; Cysteine had sulfhydrl (-SH) which can
form disulphide bridges (-S-S-) with other cysteines;
Proline has a modified amino group that covalently
bonds with the R group to form a ring
Denaturation = loss of proteins normal 3D structure
(hence function); due to high temp., mechanical forces,
chemical treatment
Structural Classification
Fibrous elongated, water-insoluble structural
proteins (keratin, muscle, fibrin, collagen)
Globular protein backbone folds in on itself to
produce spherical, compact, water-soluble
protein (enzymes, globins)
o Immunoglobulins/antibodies (e.g. IgG)
have 2 heavy chains, 2 light chains, hold
together by disulphide bonds; N-terminal
is hypervariable (therefore, lots of binding
sides for target antigens)
Functional Classification
Structural collagen
Contractile muscle
Blood albumin, haemoglobin, fibrinogen
Hormones insulin
Enzymes
o Primary = amino acid sequence
o Secondary = folding/coiling in repeating configuration(helix, -pleated sheet)

Tertiary = overall 3D shape due to amino acid interaction (Hbonding,

dispersion/van
der Waals
forces
between
hydrophobic chains, disulphide bridges, ionic bonds)
o Quaternary = aggregation of two or more polypeptide
subunits
Nuclei acids (nucleotides: one phosphate group 5C
pentose sugar 1C nitrogenous base) DNA or RNA
o

Cell Biology 1 Cells, Organelles and Cell Boundaries

Eukaryotic (nucleus, organelle and other compartments for
separation/specialisation) vs. Prokaryotic (bacteria and archaea = all unicellular).
Humans have 1013 cells with 210+ cell types, with 500-1000 bacterial species in
the gut (1014 in total), and flora (bacteria, fungi and archaea) on all surfaces
exposed to environment (skin, eyes, mouth, nose, small intestine). Typical
somatic cells are 20m, whilst bacteria are 21m, arose 3.5bya, biochemically
diverse, some have a cytoskeleton (different to eukaryotes), and some are highly
motile.
Gram-positive lack outer membranes and have thick cell walls, gramnegative have an outer and inner membrane and thin cell wall. Antibiotics inhibit
either bacterial protein or cell wall synthesis (thus targeting the type).
Prokaryotic mycoplasms are the smallest self-replicating organisms (5001000 genes), with no cell wall, spherical to filamentous shape, and are parasitic
in respiratory and urogenital tracts.
Viruses have a single compartment (no membranes), classified by RNA or
DNA. Virion = infective agent/virus particle (containing genetic material within
capsid (protective coat)). Prions are also not alive.
Human cell membranes are 7nm thick. Have a nuclear compartment:
nuclear
matrix
(intermediate
filaments/lamins),
nucleolus
(functional
compartment localised transcription), chromosomes (DNA and associated
proteins); cytoplasmic compartment, with cytoskeleton (3 filaments). Both
have functional compartments (no membrane visible) for signalling, metabolic
reactions, processing genetic info., in addition to the physical compartments.
Membranes contain phospholipids, proteins and cholesterol. A liposome
(lipid vesicle) is a small aqueous compartment surrounded by a lipid bilayer.
Membrane proteins, 20-30% of the genome, are used as transport channels,
enzyme reactions, cytoskeleton links, cell adhesion and cell identity. Membrane
gylcoproteins are proteins attached to carbohydrates. Membrane cholesterol
(small) regulates lipid mobility (rafts) and membrane protein activity (not in
bacteria). Membranes demonstrate high fluidity and fixed domains (experiments
with 2 cells, FRAP zap one, colours come back).
Pathology 1 Introduction to Pathology
Lesion = abnormality in structure/function, caused by injury or disease.
The pathological process (responses of cells and tissues to injury) involve
inflammation, healing and repair, thrombosis, embolism and infarction (death of
tissue by lack of O2), and disorded growth including neoplasia.
Framework of knowledge in pathology:
Definition
Epidemiology pattern within population (incidence, prevalence,
gender, race, SES)
Aetiology causes of disease: Chemical (acid, alkali, drugs, toxin),
Hypoxia, Infection, Nutritional (incl. hormonal, metabolic), Physical

(trauma, radiation, heat, cold), Immunologic (autoimmune disease),

Genetic; if unknown: idiopathic, essential, cryptogenic
Pathogenesis mechanism by which agent is changing
structure/function
Morphology change in structure (lesion)
o Macoscopic (gross) focal, multifocal, diffuse (everything is
abnormal)
o Microscopic (histopathology)
Clinical Manifestations
o Symptoms subjective experience
o Signs objective/observable evidence of disease
Disease Outcomes
o Complications lesions which develop as a result of another
lesion
o Prognosis likely outcome for individual
o Natural History course of untreated disease
Can investigate using imaging (X-ray, CT, ultrasound, MRI), haemotology,
biochemistry, microbiology, immunology, or procedures (endoscopy).
Quality of Medical Practice
QMP = EBM (evidence-based medicine) + Q&S (quality and safety);
integration of best research evidence, clinical expertise and patient values. 16%
of patients suffered adverse hospital events, leading to 50, 000 being disabled
and 18, 000 dying/year. Clinical questions include:
Magnitude size of health problem (prevalence, incidence), risk
for population/individual, costs of treatment; when looking at risk
Aetiology cause of disease; when looking at risk factors
Diagnosis interpret results of tests; diagnostic moments (patient
history, physical examination, deciding which test)
Therapy interventions (most benefit, least harm); looking for
therapy
Prognosis likely progress of resolution, likelihood of
complications; patient wants to know
PNO questions (not about treatment but question of magnitude; verifying
if something is a problem): Population (all male Australians 20-25 years old),
Number of people (No. that are obese, BMI>30 ), Outcome (there is or isnt an
obesity epidemic).
PICO questions (determining best treatment): Population/Patient (incl.
age, disease, stage of disease, care setting), Intervention (type of treatment
(drug, procedure, therapy), intervention level (dosage, frequency), stage of
intervention (preventative, early, late, palliative), delivery (by whom, where)),
Control/Comparison (alternative intervention: standard treatment, placebo,
different intervention, control), Outcome (improvements in symptoms, pain,
function and quality of life, cure, side-effects, cost-effectiveness).
Cell Biology 2 DNA and Information Flow
Genetic material must be accurately copied and passed onto progeny and
readily accessible for the information it contains. Hershey and Chase (1953),
grew phage in either radioactive sulphur or phosphorus, and found after
centrifuging, the phosphorus had been injected in the bacteria, hence it was
DNA. Also 1953, Watson and Crick used X-ray crystallography to show it was a
double-helix (naturally forms this in solution; 1962 Nobel Prize with Wilkins). Two

DNA strands are antiparallel. Each cell has 2m (310 9 bp). Complexed with
histones to form chromatin to maintain chromosome
structure and help regulate gene activity.
Immunology 1 Overview of the Immune System
Self = molecular makeup of host; dont normally
mount an immune response against ourselves (selftolerance). Non-self = molecular makeup of anything
foreign (particularly microbial invaders).
Antigen = foreign macromolecules that immune
system responds to by targeting it. Antibodies
(immunoglobulin, Ig) = produced by B cells in response
to antigen, and can bind to it to induce their formation.
Mucosal immunity = special defences found at
mucosal
surfaces
(respiratory,
gastrointestinal,
genitourinary
tracts).
Systemic
immunity
=
everything else (all other tissues, mostly by blood via
leukocytes=WBC).
Innate/Natural/Non-Specific
Immunity
=
broadly-directed (not a specific species, but can be a
type) protection resulting from the genetic constitution of the host (just how we
are), not improved by repeated encounters with same invader. First line of
defence (usually sufficient to prevent infection), includes:
physical barriers skin
mechanical processes reflexes like blinking, coughing, urination,
mucus and cilia
biochemical defences lysozyme in tears, sebum, spermine in
sperm, commensals in gut and vagina, acid in stomach
cellular defences phagocytes (neutrophils, macrophages; after
migration, attachment, engulfment, destruction and recruitment of
additional defences), natural killer cells (lymphocyte) that kills
infected host cells
acute inflammatory response blood capillaries dilate, blood flow
increases (redness, heat), plasma leakage into tissue space
(swelling, pain), increased output of phagocytic cells from bone
marrow, cells migrate from blood to tissue
Adaptive/Acquired/Specific Immunity = specific invader, marked by
an enhanced, faster and more prolonged response on repeated encounters
(immunological memory). Lymphocytes (2mi/mL of blood; 1/3 B cells, 2/3 T cells),
uses antigens of massive diversity (explained by MacFarlanes Clonal Selection
Theory of Antibody Production). Cytotoxic T cells kill cells that have been taken
over by viruses, whilst Helper T cells regulate the immune response. Each B cell
has just one specificity, but we have millions of different B cells generated
randomly at the birth of the cell from stem cells in the bone marrow (Clonal
Selection). Around 250, 000 antibody molecules expressed on B cell surface
(antigen receptors), and binding activates the cell, followed by cell division and
the formation of a clone of specific cells. Most mature into plasma cells, pumping
out free antibody, whilst others become memory cells with antibodies on their
surface. Antibody flags antigen, which helps by either triggers the complement
cascade, opsonisation for phagocyte, or by steric hindrance (e.g. antibody binds
to toxin, which stops it from binding to the receptor of a cell, being endocytosed
into the cell, then the active chain being released from the toxin and poisoning
the cell.

Virulence factor = factors contributing to ability of organism to evade

defences and cause disease.
Public Health 1 Healthcare
Healthcare = preservation, maintenance and restoration of health by
treatment and prevention of illness and disease through the services of health
professionals. A health system is the sum total of all organisations, institutions
and resources whose primary purpose is to improve health; it should improve
health status, defend against health threats, protect against financial burden,
provide equitable access, and allow people to make their own decisions. Whilst
policy is under federal control, public hospitals are run by state, and aspects of
public health like food safety and road maintenance are local. Even adjusted for
differences in cost of living, the average healthcare expenditure per capita has
increased in all developed nations. Australia is 2nd to France in avoiding
premature deaths that could be avoided with effective and timely care, whilst the
US is worst.
Cell Biology 3 Cell Division
DNA replication commences at the origin of replication, and in binary
fission, these origins attach separately to the plasma membrane and then the
plasma membrane grows inwards and a new cell wall is deposited.
The cell cycle must be regulated (otherwise cancer). It has two phases:
interphase (growth and replication of cellular component) and a mitotic phase
(nucleus divides, chromosomes distributed to daughter cells (mitosis), cytoplasm
divides into two (cytokinesis)). This occurs in sync in an embryo. After
duplication, sister chromatids are held together at a centromere by proteins
called a chromosome (2 chromatids). During cell division, each sister chromatid
moves to a new cell and is then called a chromosome (but now only 1
chromatid).
G1 growth with checkpoint not long before end: cell doesnt begin
dividing until signalled (e.g. repair required), nutrients available
S DNA replication
G2 with checkpoint at end: did all DNA replicate, enough organelles
replicated
Prophase chromosomes condense, centrosomes (with centriole pairs)
begin to move to opposite ends (mitotic spindle protruding)
Prometaphase further condensing, spindle fibres fully extended,
nuclear membrane breaks down
Metaphase final condensing (when we look at them), one spindle fibre
from each pole attaches to each chromosome, equal pressure causes lining up
across metaphase plate
M checkpoint right before separation, check everything connected
Anaphase protease cleaves protein, sister chromatids separate (if
problem, monosomy or trisomy)
Telophase complete separation, spindle fibres break down, nuclear
membrane begins to form
Cytokinesis cleavage furrow (contracting ring of filaments)
Meiosis in interphase I involves doubling chromosomes (2n4n) into
sister chromatids, then in Meiosis I homologous chromosomes separate (so
double of one set of alleles, not the other; 2n), and then Meiosis 2 is these
splitting so theres one of each (n). Genetic variability is increased by random
segregation (which pairs they go with) and crossing over (produces recombinant
chromosomes).

Histology 2 Cells of the Blood

REVISE DOCUMENT tabulate with prac info (see if can do it off-by-heart)
Scenario Plenary Johnnys Knee
The scenario depicts a child with infected cut living in poor social
circumstances: Johnny is a 10 year old boy living in public housing with his
mother, who is paraplegic. He is taken to the local hospital with a large cut on his
leg that has become infected after playing in an open space that is often used as
a tip by people living outside the estate. Johnny is sent home with oral antibiotics
and follow-up with a community nurse.
Health is a state of complete physical, mental and social well-being and
not merely the absence of disease or infirmity. Barriers in access to care include
distance, physical access, language, culture, and cost. Life expectancy decreases
as you move from major cities to very remote,
particularly with indigenous individuals.
Pathology 2 Responses of Cells to Injury
Injurious agents (most common to least
common):
Hypoxia
Chemical agents
Physical agents
Infective Agents
Nutritional abnormalities
Immunological Abnormalities
Genetic Abnormalities
The underlying biochemical lesions are inhibition of aerobic respiration,
loss of membrane integrity, alterations in structural or enzymatic proteins, or
interference with DNA synthesis or repair.
Revise pictures of lecture
Apoptosis = expending energy for regulated breakdown (parts packages
into vesicles absorbed by other cells)

Necrosis = intracellular enzymes activated (due to drop in pH from

anaerobic respiration producing lactic acid), eating nucleus then everything else
and poor recycling; if all nuclei missing, then coagulative necrosis (accidental cell
death due to ischemia or infarction; but structure preserved for several days);
liquefactive necrosis = everything breaks down really quickly and turns to goop
(e.g. cerebral); caesous (cheese-like) necrosis in TB-infected lungs
Acute Inflammation 1 Events and Mechanisms
Cardinal signs of inflammation: heat, redness, swelling, pain, loss of
function.
Acute inflammation is the process by which cells (mostly leukocytes) and
exudate (proteinaceous fluid due to increased vascular permeability; different to
transudate: non-proteinaceous fluid due to hydrostatic forces; both make tissue
more pale due to excess fluid: oedema) accumulate in irritated tissues and
usually protect from further injury.
Increased permeability of microvasculature occurs primarily in venules,
due to histamine-induced (released by mast cells near injury) contraction of
endothelial cells (otherwise tight junctions stop spread). Severe irritants (burns)
may directly injury endothelial cells (apoptosis, necrosis), causing larger gaps.
This eventually leads to stasis (slowing of blood flow).
Exudate benefits: dilutes the irritant, allows for extravasation
(bloodtissue) of plasma proteins (immunoglobulins, complement, coagulation
proteins including fibrinogen (fibrin, an eosinophilic, adherent protein made from
fibrinogen by coagulation cascade, walls off the irritant, preventing
dissemination, and provides a scaffold for repair; macroscopically: strand, offwhite), and provides nutrition for tissue cells and leukocytes.
Exudate harms: swelling (pain from stretching, blocked airways (glottis),
in bone (fixed compartment) leads to high tissue pressure, therefore ischaemia,
in meninges (fixed cranial compartment) raises intracranial pressure), could
spread microbe, stasis and endothelial injury may lead to thrombosis and
ischaemia.
After stasis (due to exudation of plasma causing increased viscosity of
blood), cellular emigration of neutrophils (PMNs: polymorphonuclear leukocytes;
multilobed
nuclei,
10-12m
diam,
in
acute
inflammation)
and
monocytes/macrophages (12-20m diam, vesicular, ovoid or kidney-shaped
nucleus, latter acute, chronic, healing) by:
Margination leukocytes move to sides of vessels (erythrocytes
remain in middle where they are usually with leukocytes, but
leukocytes have been moving to perimeter of blood column then to
sides of blood vessels, plasma around edges; when leukocytes
cover endothelium of vessel called pavementing)
Adherence stick to epithelium
Emigration between two adjacent epithelia (vesseltissue; via
rearrangement of leukocyte cytoskeleton under influence of
chemotaxis)
Chemotaxis moving along chemical gradient; draw neutrophils
first due to specific chemotactic molecules (PMNs dominate first
24h, then apoptosis, monocytes dominate at 24-48h, unless
continuing recruitment of neutrophils)
o N-formylated peptides (in bacterial cell wall; often referred to
as pyogenic (pus-inducing) microbes)
o IL-8 (interleukin-8)
o LTB4 (Leukotriene B4)

o Lysosomal Enzymes
Also lymphocytes (round to oval nucleus, thin rim of basophilic cytoplasm,
chronic, viral acute).
The morphology (appearance) of the exudate depends on the nature and
dose of the irritant, tissue involved, and nature of host response. Examples
include:
Serous watery and low in protein (e.g. allergy, mild inflammation)
Mucous/Catarrhal common cold, rejected mucus comes to nose
Fibrinous rich in fibrin
Purulent/Suppurative pus forming, with pyogenic bacteria
Pseudomembranous dipetheria toxin injure tracheal epithelial
cells, the necrotic debris combines with fibrin to form tenacious
psuedomembrane (obstructs airway)
Ulcerative destruction of epithelium
Haemorrhagic leakage of RBC
Phagocytosis involves three stages:
1) Recognition and attachment opsonins (IgG, the complement
fragment C3b; recognised by receptors on leukocyte membranes)
2) Engulfment phagosome (formed by cytoplasmic pseudopods,
hence membrane bound)
3) Killing/degradation of ingested material phagolysosome
(phagosome fuses with lysosomal granule, discharging lysosomal
enzymes and oxygen radicals (bleach-like ClO -))
Exudation is paralleled by increased lymphatic drainage (limiting swelling,
so good), and if antigen is drained to a lymph node an immune response may be
initiated. Bacteria can also spread via lymphatics, causing inflammation of
vessels (lymphangitis) and nodes (lymphadenitis), and if reaches thoracic duct,
gets to blood (bacteraemia; if rapid/continuous bacterial or bacterial toxin entry
to circulation, then sepsis).
REVISE INFLAMMATION 1 [FLOWCHART] EVENTS AND
MECHANISMS
Inflammation 2 Mediators and Outcomes
Mediators are either plasma-derived (present in plasma as precursors to
be activated; for complement pathway (assists or complements antibodies) or
Factor XII activated) or cell-derived (preformed in intracellular granules to be
secreted (histamine) OR newly synthesised in response to inflammatory stimulus
(prostaglandins, leukotrienes, cytokines, O2 radicals). Major cellular sources are
neutrophils, monocytes/macrophages, mast cells and platelets, and epithelial
and mesenchymal cells (e.g. endothelium) can be activated to produce
inflammatory mediators.
Most mediators bind to specific receptors (except lysosomal enzymes and
reactive oxygen species) on multiple types of target cells (different effects
depending on type), often stimulating the release of secondary mediators (either
amplifying or inhibiting the response). Most are short-lived (as you dont want it
to continue on; by decay (arachidonic acid metabolites), scavenging (O 2
metabolites by antioxidants), or inhibition (complement by complement
inhibitors)), and have the potential to harm the host.
Plasma-derived: (slightly more detail on pg6)
Factor XII-activated pathways (Factor XII contacts basement
membrane or interstitial collagen; therefore, exudate must have
gone bloodtissue)
o Coagulation Cascade for blood clotting

Fibrinolytic System prevents blood clotting becoming

problematic (fibrin lysis)
o Kinin Cascade bradykinin is a vasodilator
Complement System cascade of proteolytic enzymes (C1-9;
circulate in inactive form), resulting in the formation of the MAC
(membrane attack complex: C5b-9; lyses microbes); additionally,
complement fragments aid inflammation: C3a and C5a
(anaphylotoxins) cause vasodilatation and vascular permeability by
releasing histamine from mast cells, C5a mediates chemotaxis and
leukocyte activation, and C3b is an opsonin
o Classic Pathway activated by antigen-antibody complexes
o Alternative Pathway activated by microbial surfaces,
lysosomal proteases, aggregation Igs, plasmin (local
environment by microbial surfaces)
o Lecithin Pathway mannose-binding lecithin binds to
pathogen surface
Cell-derived:
Histamine mast cells, basophils, platelets; pre-formed in
granules, released by stimuli that cause degranulation (trauma,
cold, heat, allergic reactions (IgE-mediated), inflammatory
mediators
(complement
fragments));
principal
arteriolar
vasodilation and venular permeability mediator (but 15-30mins as
receptors get saturated quickly)
Prostaglandins all leukocytes, platelets, endothelium; from COX
pathway; vasodilation, potentiate pain
Leukotrienes all leukocytes; from lipoxygenase pathway;
neutrophil chemotaxis, vascular permeability, smooth muscle
contraction
o BOTH PGs & LTs derivatives of arachidonic acid (from
damaged cell membrane phospholipids); rapidly synthesised,
short-lived, local effects
Platelet-activating factor (PAF) derived from membrane
phospholipids of activated leukocytes, endothelial cells and
platelets; increase venular permeability (highly potent), leukocyte
adhesion, chemotaxis and activation, boosts PG and LK synthesis
Nitric Oxide macrophages; short-lived soluble gas, local effects;
made by endothelial cells via eNOS (vasodilatation), neurons in
nNOS; Cytokine-activated macrophages produce iNOS; proinflammatory: microbicidal activity (reactive N), potential tissue
damage, role in septic shock; anti-inflammatory: inhibits leukocyte
recruitment
Cytokines (incl. chemokines) primarily activated macrophages,
lymphocytes, endothelium more detail on pg13
o Interleukin-1 (IL-1) and Tumour Necrosis Factor-
(TNF-) major cytokine mediators; local effects:
induces adhesion molecules on endothelium
induces chemokines (IL-8), PGs, NO
activates leukocytes
o systemic effects:
acute-phase response fever, anorexia, neutrophil
leukocytosis (neutrophilia), hepatic protein synthesis
principal mediators of septic shock
o

The system effects of acute inflammation (or acute-phase response)

includes:
Fever IL-1 and TNF- induce PGE2 in hypothalamus
o Stimulation of vasomotor centre in brainstem
o Vasoconstriction in skin
Hepatic synthesis of acute-phase proteins - acute-phase
proteins (listed below) synthesised in liver in response to IL-1, IL-6,
TNF-
o C-reactive protein (CRP; marker of inflammation) opsonin,
binding complement (used as marker for acute inflammation
as serum conc. raises several hundred fold)
o Fibrinogen, complement
Leukocytosis (increase in WBC count) due to IL-1 and TNF-
o Initial release of neutrophils from bone marrow reserves
o Later induction of colony stimulating factors (G-CSF)
Acute complications include harmful effects of the irritant, ischaema
(made worse by stasis of vascular tissues, particularly in fixed spaces like bone),
and toxic products of inflammatory cells (superoxide radicals, neutrophil
lysosomal enzymes (collagenase, plasmin (fibrin breakdown), elastase; leads to
liquefactive necrosis: pus (living and dead neutrophils, cellular debris, exudate).
Abscess is a localised collection of pus in an organ/tissue, caused by
infection of pyogenic bacteria (N-formylated peptides recruit large numbers of
neutrophils; golden staph) OR obstructed drainage of infective material.
Complications include sinus/fistula (connecting two places that should be
separate; will move to nearest external or internal surface), pyaemia (pusforming bacteria entering blood stream), or sepsis/septic shock. Basophilic
collection of pus typically bordered by eosinophilic fibrin barrier, with possibly
ongoing inflammation around.
Onset of recovery occurs when irritant falls below critical level due to
dilution/neutralisation by exudate, phagocytosis/destruction by leukocytes,
drainage via lymphatics, or medical treatment (e.g. antibiotics).
Resolution will occur if tissue architecture is intact (no abscess), exudate
has been removed, and organ/tissue has capacity to regenerate (not neural or
myocardial). Otherwise repair by granulation tissue (thin-walled, leaky blood
vessels, fibroblasts producing collagen, macrophages and other mononuclear
inflammatory cells), regulated by macrophage-derived cytokines. Note: fibrin is
in exudate for stopping spread of infection. Fibrous means collagen made by
fibroblasts.
Failure to remove irritant may result from:
Nature of irritant resistant to
phagocytosis/destruction (inorganic
particles like silica, TB)
Overwhelming dose of irritant
Inadequate/inappropriate host =
immunodeficiency, autoimmunity
Nature of host tissue (bone)

Physiology 2 Cells and Communication

The nerve Action Potential controls the entire body (including cilia
movement via cell potential), going from -80mV, spiking up to +30mV, and then
back down in about 10ms.

Ion channels (a selective facilitated diffusion) allows K + to move out

whilst Na+ comes in, to counteract any depolarisation of the action potential.
Another method of movement is bulk movement (lipid vesicle exo- and
endocytosis, phagocytosis and pinocytosis).
The Na+ pump (a primary active transport, uses ATP; additionally, some
facilitated) is essential for life, as it establishes the Na + and K+ gradients (pushes
3Na+ out and 2K+ into the cell), providing energy for secondary active transport
(the same energy is used to pull other things out) and electrical signalling. As a
result of pumps, there is more K+ in a cell, whilst more Na+, Mg2+, Ca2+ and Cloutside a cell.
Ions move according to chemical (diffusion: highlow conc.) and electrical
(opposite charges attract, like repel) forces, resulting in the electrochemical
equilibrium when the two forces are balanced (thus resulting in a slight conc.
imbalance and difference in cell potential; ion permeability also determining
factor). Selective efflux of K + down the gradient and out of the cell causes charge
separation and a negative potential in the cell. If only permeable to K +, then K+
leaves until Vm=EK+=-98mV, whilst if only permeable to Na + then Na+ enters until
Vm=ENa+=+67mV.
Membrane potential is a different charge distribution across the
membrane due to different numbers of ions (moving by leak or gated channels),
leading to a polarized membrane; negative values mean inside is more negative.
The resting membrane potential in all excitable cells is usually -60 to -80mV
(hyperpolarised; usually due to K+ leaving through resting/leak channels).
Depolarisation (inside becomes more positive) means the membrane is
less polarised (Vm less negative, moves in positive direction as more cations
inside or less anions outside (Na + influx, K+ efflux, Cl- efflux).
Hyperpolarisation (inside more negative) means the membrane potential
moves in a negative direction (K+ efflux, Cl- influx). Hyperpolarisation after

depolarisation
=
repolarisation.
Membrane potential types:
Resting Membrane Potential
all excitable cells, usually -60 to -80mV
Action
Potential

rapid
response of 100mV, Vm temporarily
positive (+30mv), for nerve impulses
and initiating muscle contraction
Synaptic
Potential

nerve
response to neurotransmitter, causing either depolarisation or hyperpolarisation
Receptor Potential response to sensory stimuli in specialised sensory
receptors (photoreceptors, skin nerves)
Graded Potential depolarisation proportional to stimulus (like receptor
potential): graded muscle contraction
Public Health 2 Social Determinants of Health
Define and discuss key concepts of social determinants of health, health
equity, inequality and related terms
Describe common patterns of health inequality in western industrialised
countries.
Identify and describe common theoretical frameworks to explain health
inequalities.
-Age
-Gender
-Marital Status
-Occupation/employment status
-Culture
-Income/socioeconomics
-Education
-Place of residence
Health is determined by genetics (20-30%), healthcare (10%) and social
and environmental conditions and behaviour (60-70%).
In Australia, the richest fifth are 7 times richer than the poorest fifth (4 th
worst in world). Greater income quality correlates with the index of health and
social problems (life expectancy, math and literacy, child wellbeing, etc.). In
Australia, money for basic needs like housing, clothing and food. 15% of
Australian children live in jobless homes, and a millio11% of adults and 12% of
children live in poverty (and growing), with 2.2mi not having enough n children
dont get enough food to eat, relying on food relief. The number of adverse
childhood experiences also increases adult heart disease risk. The inverse care
law is exemplified by the inverse proportionality of length of GP consultations in
each socioeconomic quintile and the prevalence of diabetes. Additionally, the
gap in life expectancy is widening (lower quintile dying sooner, higher living
longer, middle constant).
To explain health inequalities, there are several frameworks:
Divine Order Gods will results in acceptance, prayer and
charity to easy disadvantageds suffering, but not change to basic
order
Artefact statistics are incorrect due to probability results in
ignoring problem, possibly collecting better data
Natural Selection survival of the fittest results in acceptance,
welfare to relieve suffering, genetic manipulation

Social Drift the sick become poor results in welfare, equal

employment opportunities and non-discrimination policies
Culture different values and way of life results in blame, group
responsibility and health promotion
Behavioural bad habits cause bad health results in blame,
individual responsibility and health promotion
Materialist cant afford the basics results in welfare, living
wage, improved opportunities and access, economic equity
Psychosocial identifies social hierarchy results in redistribution
of power and resources, social equity

Microbiology 1 Introduction to Microbiology

Few bacteria are always harmful, some are potentially harmful, but most
are not harmful.
Eukaryotic organisms include algae (photosynthesise, some uniceullar and
microscopie), protozoa (unicellular, many free living, some intracellular
parasites), fungi (mushrooms, yeast, moulds: unicellular or multicellular, non-photosynthetic).
Prokaryotes have a single, circular chromosomes and
plasmids (circular, double-stranded DNA that replicates within a
cell independently of chromosomal DNA; generally <30 genes).
Prokaryotic misfits:
Mycoplasma are the simplest life form
capable of independent growth, free-living, have no cell wall
(primary atypical pneumonia), Rickettsia are obligate intracellular
parasites, usually arthropod (e.g. flea) borne, and bacteria-like
(Typhus fever), and Chlamydia are obligate intracellular parasites dependent
upon host cells for energy (trachoma and STI).
Viruses arent living as they are unable to reproduce
independently or carry out metabolic processes (obligate
intracellular parasites). Prions are small proteinaceous infectious
particles (100nm) with no nucleic acid and extremely resistant to
killing (heat, disinfectants, irradiation, but susceptible to phenol),
with slow replications (up to 35 years) and cannot be cultured in
vitro (glass) with no immune response. They cause bovine
spongiform
encepthalitis
in
animals/Kuru/Creutzfeldt-Jakob
disease in humans. Prion protein (PrP c) is found on the plasma membrane of
most mammalian cells (highest conc. in brain) to bind copper ions and help the
cell resist effects of toxic oxygen radicals. If folded into different form, become
prion (PrPSc; not broken down by proteases), leading to amyloid plaques and
neurodegeneration.
Bacteriology=bacteria,
parasitology=parasites,
virology=viruses, mycology=fungi.
Gram staining (Hans Christian Gram in 1884) is used for bacterial
identification (colour and shape can be seen) and is important for diagnosing
infection. The bacteria are first fixed, then crystal violet, then iodine are added,
to form a crystal violet-iodine complex, then it is watched with ethanol to
dehydrate the cell wall and decolourise it, and if gram positive, the thicker
peptidoglycan cell wall stops the stain from leaving making it blue-purple, whilst
the gram negative are given a counter stain (safranin) to make it pink/red.
Healing
The process by which the body replaces damaged tissue with living tissue.
Regeneration is replacement of parenchymal cells (function tissue of
organ, not connective or supporting) by replication of similar surviving cells.

Requires particular types of parenchymal cells, 3D organisation of cells with

respect to each other, and extracellular matrix intact. Types of parenchymal
cells:
Labile continually renewing (surface epithelia)
Stable conditionally renewing, proliferate in response to stimuli
(liver, renal tubules, secretory cells of most glands, smooth muscle)
Permanent non-renewing, little ability to divide (nerve cells,
skeletal muscle; but we can use stem cells for tissue engineering via
transdifferentiation)
Otherwise, healing by repair involves a variable amount of replacement of
parenchymal cells by connective tissue called granulation tissue (except in
specialised tissue like bone and CNS):
Newly-formed blood vessels with markedly increased
permeability, make skin red
Activated Contractile Fibroblastic Cells properly-designated
myofibroblasts which synthesise matrix proteins, proteoglycans and
glycosaminoglycans
Inflammatory Cells especially macrophages, which phagocytose
cellular and protein debris AND coordinate the secretion of
cytokines
Tissue injury can cause haemorrhage, leading to haemostasis and then an
acute inflammatory response, then healing.
Restoration of the epithelial layer involves migration of adjacent
epithelial uninjured cells, yielding a thin continuous epithelial surface, and then
cellular proliferation to normal thickness (some excess/damaged epidermal
cells may flake off). As inflammation becomes dominated by macrophages (24h),
endothelial cells sprout from existing vessels to form new capillaries, whilst
fibroblasts make matrix components, particular collagen. Overtime there is
vascular regression, scar remodelling (degradation by collagenases and
further collagen deposition to make it slightly more parallel/ordered), and scar
contraction (wrinkly appearance).
Healing in an apposed (close to) incised wound heals by primary
intention, with limited inflammation, rapid restoration of epithelium, and
relatively little granulation tissue/scarring. With substantial tissue loss, it is
secondary intention, with marked inflammation, ingrowth of granulation tissue
under the defect to ensure it is pushed out, varying degrees of wound
contraction, delayed re-epithelialisation and significant scarring (no surface
specialisations like sebaceous glands or hair roots). If in parenchymal cells,
healing with scarring = fibrosis.
Healing mediated by locally-acting cytokines (those in healing called
growth factors) from platelets, macrophages, mast cells, by autocrine (same cell
type) or paracrine action. Most have multiple effect (pleiotropy), and may
overlap with other cytokines (redundancy).
Factors affecting healing include local factors: vascularity, infection,
mechanical trauma, chemical injury (incl. irritant dressings), foreign bodies,
irradiation and neoplasia; systemic factors: age, nutritional status (protein,
Vitamin C, Vitamin D or zinc deficient), coexisting systemic diseases (diabetes,
neoplasia) and hormonal status (steroid therapy).
Biochemistry 2 Enzymes
Amylase=starch, protease=protein, lipase=lipid, cellulase=cellulose.
Enzymes are highly specific, with respect to both the reactions they
catalyse and choice of substrates, and have great catalytic power (increase rate

by >106; otherwise life unsustainable) by decreasing the activation energy (E A)

by providing an alternate reaction pathway to the transition state, but dont
change an equilibrium (or free energy G; same amount of product made for
given substrate)/allow for thermodynamically unfavourable reactions to occur.
They do this by orienting the two substrates correctly, straining the chemical
bonds, or adding charges to the substrates. Many require other components for
activity, like cofactors (small molecules like Mg 2+) or coenzymes (larger like
Vitamin B12). They use an induced fit (conformation change) model at their
active sites (part of the active site is the substrate binding site). A single enzyme
catalyses thousands of reactions per second. In a ribbon model (as opposed to
space-filling or CPK) alpha helices are shown as helices, beta-sheets as shown as
arrows in the amino-carboxyl direction.
Factors influencing enzyme activity:
Enzyme concentration [E] rate is directly proportional (as small
amount of enzyme used, so like initial part of substrate graph)
Substrate concentration [S] reaches maximum due to saturation
of enzymes
Temperature each has optimal range, otherwise denatures; higher
increases metabolic rate (human=37oC, thermophilic=78oC)
pH each has optimal range, otherwise denatures (pepsin low,
tripsin high)
Cofactor Requirements non-protein component (metal ion or
complex organic molecule=coenzyme; water-soluble Vitamins (Bs
and C) are either coenzymes or are converted into coenzymes)
Inhibitors commonly reversible (as with substrate binding), but if
covalent bond formed then irreversible; competitive mimics
substrate, binds at active site (may bind more strongly); noncompetitive bind at separate site; this is the basis of many
pharmaceuticals:
o Methotrexate similar to the substrate folic acid (B 9), used for
leukaemia as the enzyme is important in rapidly dividing cells
o Penicillin irreversibly binds to enzyme for bacterial cell-wall
synthesis
o Crixivan inhibits HIV protease (which would otherwise
breakdown a polyprotein which they would use to make
different proteins)
Anatomy 2 Gross Anatomy
Nervous system monitors and regulates all body activities via direct and
indirect (endocrine system) body tissues, organs and systems. SomNS=skin,
bone, joints, skeletal muscle, sense organs (touch, temp, pain in skin,
proprioceptors in muscles and joints). ANS=viscera (incl. stretch, pain and other
receptors), cardiac and smooth muscle, glands (PSNS&SNS).
Endocrine (slower and more sustained than NS; linked via hypothalamus
and ANS) glands secrete hormones that activate specific target tissues. Includes
pineal gland, hypothalamus, pituitary (under hypothalamus), thyroid,
parathyroid, thymus (behind sternum), adrenal glands, pancreas, and gonads
(ovaries and testes). Stimuli for hormonal release:
Humoral (blood) low Ca levels in blood stimulates parathyroid
hormone secretion to increase blood Ca levels
Hormonal hypothalamus can secrete hormones so the pituitary
secretes hormones that act on other endocrine glands (thyroid,
adrenal, gonads) to secrete hormones

Neural sympathetic neurons stimulate adrenal medulla to secrete

adrenaline OR release of hormones itself (anterior pituitary lobe
releases hormones to control endocrine cells, posterior pituitary
lobe bypasses endocrine systems to secrete hormones acting
directly on target organs)
Blood carries gases, nutrients, wastes, minerals and hormones.
Heart has pericardium (covers top of diaphragm), lungs have parietal
pleura. Heart surfaces: base (posterior), sternocostal (anterior), pulmonary (left),
diaphragmatic (inferior), apex. Four chambers separated externally by coronary
(runs along atrioventricular border) and interventricular (anterior and posterior;
interventricular septum underneath; end at coronary) sulci, all containing
coronary and cardiac vessels. Atria have pectinate muscles, ventricles have
trabeculae carneae. The inner layer is endocardium, then myocardium, then
epicardium (visceral parietal, outside is serous parietal and fibrous pericardium).
Ascending aortaarch of aortadescending aorta (thoracic and
abdominal). Arteries and veins consist of (inout) a tunica intima (endothelium,
subendothelial layer, internal elastic membrane artery only), tunica media
(smooth muscle, external elastic membrane artery only), and tunic externa
(collagen). Capillaries only have endothelial cells sitting on a basement
membrane.
Gondadal artery = halfway between the renal arteries and inferior
mesenteric artery, on side of abdominal aorta. Arcuate at feet.

Lymphatics consist of fine lymphatic vessels (drain excess tissue fluid via
veins), lymph nodes (monitor and destroy foreign protein and microbes), and
specialised organs such as the spleen and thymus.
Respiration for gas exchanges, olfaction (smell) and speech. Carina of
trachea is bifurcation into right main bronchus (short, horizontal) and left main
bronchus (bronchi have smooth muscle). Split into lobar bronchi (upper, middle,
lower lobes in right, with horizontal then oblique fissue; only oblique for upper
and low on left), then segmental, branching 23 times to terminal and then
respiratory bronchioles, into an alveolar duct to an alveolar sac with alveoli (have
elastic fibres and capillaries).

Digestive system (gut tube and glands: liver, pancreas, salivary: parotid,
sublingual, submandibular) is for ingestion, digestion (breakdown), absorption of
nutrients, and waste elimination.

Celiac Trunk: (left gastric artery), bifurcates into splenic and common
hepatic (right gastric, loops to left, covers stomachs lesser curvature),
(gastroduodenalright gastroepiploic, loops to left, connects to splenic),
becomes hepatic artery proper
Superior Mesenteric: middle colic, intestinal (for vasa recti and vascular
arcades not included), right colic, ileocolic
Inferior Mesenteric: left colic, sigmoidal, superior rectal
Into IVC, renal veins, common iliac veins, hepatic vein from hepatic portal
vein: (gastric veins), splenic vein (inferior mesenteric), (right gastroepiploic vein),
superior mesenteric
Urinary system for removing nitrogenous waste, controlling pH, fluids and
electrolyte balance
Integumentary (skin 16% body weight, 1-2m 2): protection (physical,
chemical, pathogens), waterproofing, thermoregulation (sweating, vasodilatation,
piloerection), Vitamin D production, excretion (sweat), sensory (touch, temp,
pain), cover for underlying soft tissues.
Histology 3 Skin and Associated Structures
Thick skin = palms and soles, 400-600m thick, no hair follicles, arrector
pili muscles or sebaceous glands, but still sweat glands, stratum lucidum and
thicker stratum corneum
Thin skin = most of rest of body, 75-150m thick, hair follicles, arrector
pili muscles, sebaceous and sweat glands, but no stratum lucidum and thinner
stratum corneum
Epidermis has 4 types of cells: keratinocytes (skin), melanocytes, Merkel,
and Langerhans. Keratinocytes in 5 layers, stratum:
Basale single layer of mitotically, active cuboidal cells (cells
moving up takes 20-30 days)
o Melanocytes melanosomes (organelle) containing melanin
are produced and transferred via maloncyte dendritic
processes to keratinocyte cytoplasm
o Merkel Cells mechano- and pressure receptors, especially
numerous in fingertips
Spinosum thickest layer, cells begin to flatten, connected to each
other by desmosomes (hooks attached to cell by tonofilaments)
giving them a prickly/spiny appearance
o Langerhans (mostly here, scattered elsewhere) originate
and continually replaced from precursors in bone marrow via
blood stream; antigen-present cells that migrate to lymph

nodes in the cavity, where they present epitopes (part of

antigen where antibody binds)
Granulosum 3-5 flattened layers, as moving up enzymes
(released by lyososomes) digest organelles and nucleus (most
superficial layer with nucleus)
Lucidum (only in thick) clear, contain eleidin (from ketohyalin)
which are converted to keratin filaments (found in lucidum)
orientated parallel to skin surface
Corneum most superficial, have keratin filaments embedded in
an amorphous matrix (nonliving tough shells), eventually shed
Dermis:
Papillary Layer (superficial) papillae interdigitate with epidermal
pegs. Has loose CT with thin type III collagen (reticular) fibres and
elastic fibres. Contains cells (fibroblasts, macrophages, mast cells)
and many capillary loops that extend to the epidermis/dermis
interface to regulate body temperature and nourish cells of the
avascular epidermis.
o Meissner corpuscles (spring) discriminative touch
mechanoreceptors, common in regions of high sensitivity:
lips, external genitalia, nipples; in some dermal papillae
Reticular Layer (deep) dense, irregular collagenous CT with
elastic fibres in large bundles parallel to surface
o Ground Substance extracellular matrix that fills spaces of
reticular layer, rich in dermatan sulfate (glycosaminoglycans);
cells (fibroblasts, mast cells, lymphocytes, macrophages, fat
cells) more sparse; also have sweat glands, sebaceous glands
and hair follicles
o Pacinian Corpuscles (cabbage) coarse pressure and
vibrations
o Ruffini Corpuscles tension in collagen
Hypodermis is not part of skin, superficial fascia covering whole body,
contains adipose, adipocytes, blood vessels, nerves, collagen and fibroblasts.
Glands:
Eccrine Sweat Glands 0.4mm diam, coiled tubular glands deep
in dermis or hypodermis
Apocrine Sweat Glands axilla (armpit), nipple areola, eyelids,
anal region; up to 3mm diam, produce pheromones, controlled by
hormones, doesnt begin until puberty
Sebaceous Glands thin skin (mostly face, scalp, forehead),
produce sebum (wax mixture of cholesterol and triglycerides),
assists in skin texture, hair flexibility, bactericidal and fungicidal
agents; controlled by sex hormones, active after puberty
Mammary Gland modified, specialised sweat gland
Skin appendages:
Hair hard, keratinised over most of body except vermillion zone of
lips, palms, soles, glans penis, glans clitoris, labia minor and the
vestibular aspect of labia majora
Hair Follicles organs from which hairs develop; invaginations of
(and surrounded by) epidermis into dermis, hypodermis or both;
hair bulb = surrounding dense, fibrous CT + expanded part of the
hair follicle, the hair root, which conforms to the shape of the

dermal papilla pushing into it; have melanocytes around, giving

colour
Arrector Pili smooth muscle from dermal sheath and inserting
into hair follicles, under sympathetic nervous stimulation (pull hair
up if cold or frightened)
Nails modified corneum over tips of distal digits, lying on nail
bed (epidermis); beneath proximal nail fold is the nail matrix
where cells proliferate and become keratinised; distal end is
continuous with skin of finger or toe, and the accumulation of
corneum near this junction is the hyponychium; extending from the
nail for 0.5-1mm is the eponychium (cuticle)

QMP Measuring Health

5 Steps of EMB:
1) Asking questions
2) Acquiring information
3) Appraising (is it something you can use?)
4) Applying (testing)
5) Assessing (does it work?)
a. Adjusting (changing until it does work)
To measure health outcomes, we use death, disability and disease. Data
can be qualitative (textual; e.g. perceptions of health, local descriptive accounts)
vs. quantitative (statistical), national or local, and routine (can give idea of
effectiveness of care, looks at socio-demographics and morbidity no. of people
with a disease/mortality) or ad hoc (specially collected).
Descriptive Study (survey) taking a snapshot; measuring a health
characteristic of interest in a representative sample (sometimes compare to
previous time: time factor)
Incidence = no. of people developing the disease over time = number of
new cases/(population at risk time when cases were ascertained); requires
routine data
Prevalence = total no. of people with the disease; Point Prevalence =
at one point in time; Period Prevalence = over a specific (short, e.g. month)
length of time
Study designs:
Randomised Controlled Trial (RCT) (prospective) assign study
factor (smoking or not) and placebo randomly, compare to
determine outcome factor (did those that smoked develop lung
cancer); minimises bias that cohort may have (e.g. smokers may all
be alcoholics and that causes lung cancer)
Cohort (prospective) categorise by exposure to study factor (e.g.
smoking or not), then compare outcomes (if develop lung cancer)
Case Control (retrospective) start with outcome (case vs.
controls; if they have lung cancer), then go back and see if exposed
to study factor
Cross-Sectional Analytical Study (snapshot) looking at study
factor and outcome factor at the same time (no waiting to develop
or starting at a particular spot)

The quality of the data is dependent

upon validity (relevant, defined, avoids bias, recent, applicable/generalizable),
technical quality (appraising original source methodology; recording,
completeness, bias, groupings chosen), quality of analytical methods (do you
need to adjust to apply to your population, are there summary measures that are
useful, is it statistically significant), and practical questions (confidentiality issues
in using the data, cost, what form are the data available in). Quality can be
assessed using CRAAP (currency, relevance, authority, accuracy, purpose) or
CART (completeness, accuracy, relevance/representativeness, timeliness).
Pharmacology 1 Sites of Drug Action
Drug = an agent that interacts with specific target molecules in the body
and produces a physiological effect.
Pharmacodynamics = mechanism by which drugs exert their effect on
the body in order for a therapeutic action to occur (incl. drug-receptor
interactions,
general
principle
of
drug
action,
dose
response).
Pharmacokinetics = what body does to the drug (absorption, distribution,
elimination).
Two types of drugs: activity at high conc. causing physical changes (little
structural specificity; general anaesthetics) vs. activity at low conc. causing
chemical changes (structural specificity; isoprenaline).
Agonists mimic endogenous ligands, binding to receptors and causing a
secondary effect, whilst an antagonist binds to a receptor to prevent the action
of an agonist. Majority of drug receptors (the site at which a ligand (agonist or
antagonist) can attach) are proteins, and the ligand may be neurotransmitters,
hormones or local factors. Selectivity is when a drug acts preferentially with one
receptor (avoiding side effects). Types of receptors include:
Ligand-gated ion channels
G-protein coupled receptors
Kinase-linked receptors
Nuclear Receptors
Agonists directly open/close ion channels, or indirectly (transduction
mechanisms) activate/inhibit enzymes, modulate ion channels, or control DNA
transcription.
Receptors within a given family occur in several subtypes (e.g. cholinergic
have muscarinic and nicotinic; adrenergic have 1 (blood vessels), 1 (heart), 2
(lungs)) so drugs are developed to target one subtype. Side effects are due to
affecting several tissues AND non-specificity of drugs (particularly high dose).
Affinity = binding of drug to receptor; Efficacy = response to binding
(intrinsic activity).

Potency = measure of drug dosage needed to produce a particular

therapeutic effect, determined by receptor affinity. Efficacy = measure of
effectiveness of drug in producing a maximum response (full
agonists=high efficacy, antagonists=no efficacy).
Assumptions about drug-receptor interactions (not
always true): effect of drug is proportional to fractions of
receptors occupied AND maximal effects when all receptors are
occupied and adding more drug wont change anything (but
some drugs are highly efficacious and produce responses at
50%; unneeded receptors are called spare receptors). If true,
KD (equilibrium/binding/dissociation constant) = ED 50 (median
effective dose (or EC50; concentration) = dose that produces
50% effect). The lower the ED50, the greater potency (smaller
dose for stronger response). Measurement of a response can be
done in an organ bath or whole animals (e.g. recording blood pressure) after
addition of a known dose of drug. However, drug concentration at a receptor side
is not known (e.g. Ach may be metabolised by AChE), and hence cannot be used
to calculate affinity.
Pharmacology 2 Agonists and Antagonists
Antagonist = has affinity for a receptor but no efficacy, types:
Competitive (Surmountable) compete for same receptor site, but
maximal effect unchanged (with enough agonist can be
surmounted), so just parallel shift to the right
Non-Competitive (Irreversible) bind irreversibly/cause change in
receptor so agonist can no longer bind, and hence the maximum
effect is no longer produced (tail of graph brought down) unless new
receptors are made OR there are spare receptors (the assumption
doesnt hold true)
Physiological (Functional) when two agonists act on different
receptors to produce opposite effects (e.g. bronchoconstriction from
histamine counteracted by adrenaline cause vasodilation)
The effect of an antagonist relies on blocking the action of an agonist, and
hence they control the tone produced by the agonist (e.g. if agonist slows heart
rate, antagonist increases heart rate, but if no agonist present wont increase
heart rate).
Partial agonists are less efficacious, and never achieve maximum effect,
but act as competitive antagonists against full agonists. Adding a partial agonist
will pull the graph down (as maximum effect isnt achieved), but
again surmountable (unless irreversible).
Some receptors are constitutively active (produce a basal
response) without the presence of any agonist, but inverse
agonists can restore to inactive state with negative efficacy (not an
antagonist as doesnt require another agonist to function).
Agonists dont remain bound to receptors and become
inactivated by metabolic processes, and potentiation is decreasing
this level of inactivation so the drug can stay around longer (e.g. acetylcholine in
presence of acetylcholinesterase, but stopped by anticholinesterases like
neostigmine and physostigmine; similarly noradrenaline saved by uptake
blockers like cocaine and tricyclic anti-depressants). However, they do NOT
enhance the effect.
Quantitative Response = measured in gradual steps (e.g. fall in blood
pressure, tells us ED50 and maximal response). Quantal Response = all or none

(i.e. responded, didnt (often set min level); eliminates biological variation).
Quantal response is good for finding the sum total amongst a population.
LD50 = lethal dose, and you want as large a gap as possible between this
and ED50. As LD50 should be larger, a larger therapeutic ratio is better. Issues with
this measurement are ethics (dont kill hundreds
of animals), differences in animals and humans,
and dont see side-effects.
Therapeutic Ratio =
Digoxin=2,
Barbiturate=10, Valium=almost infinite
TD50 = toxic dose, looking at occurrence of
a particular side-effect (and forewarns of
lethality). Issues with TD50 include the fact it
doesnt account for multiple side-effects.
Toxic Ratio =
Tolerance = with same drug dose on repeated administration, less effect
produced. Tachyphylaxis = rapidly developing tolerance. Desensitisation =
less effect is produced the longer the agonist remains in contact with the
receptor, due to:
Change in receptors (phosphorylation, but not change in no. so
quick recovery)
Down-regulation of receptors (internalisation=receptor
damaged/reduced expression; takes longer to recover as new ones
must be made)
Depleted mediators (amphetamine releases noradrenaline, must
wait for more to be made if run out)
Increased metabolic breakdown (drugs can speed up or slow down
own metabolism; e.g. alcohol increases alcohol metabolism, so
more required at higher stages for effect)
Immunology 2 Immunology of Antibodies
Antiserum = serum (cell-free fluid prepared from clotted
blood) that contains antibodies that account for 20% of serum
proteins (discovered by Behring)
Each antibody is made of at least four polypeptide
chains, two IDENTICAL heavy chains and two IDENTICAL light
chains. Each chain has a variable region (millions of types due
to clonal selection theory; determines specificity) and a
constant region. In the heavy chain, the constant region
(specifically from the Fc region) has five major types creating
classes or isotypes: IgG (4 subclasses), IgM, IgA (2 subclasses),
IgE, IgD. Thus the Fc region determines the antibodies class and
function, which include complement fixation (interaction
between Fc regions of aggregated Igs and complement protein)
an acting as Fc receptors. There are 2 binding sites per
antibody (each Y top), and multiple binding sites per antigen,
resulting in an immune complex formation (or aggregation of
Igs) that allow better grip on the antigen.
Connections at Fc region also allow for better
grip, and hence IgM is secreted as a pentamer.
Monomeric (Y-shaped) IgM is found on the B cell surface. It activates
complement well, is a good agglutinator of antigen (due to the
multiple binding sites), and prominent in the primary response.
IgG1 is abundant in serum and body fluids, having the longest half-life (30
days), but being prominent in the secondary response (in primary, but not as

much). It is a good activator of complement, binds to Fc (the same

as the constant region of the heavy chain) receptors on many cells,
and crosses the placenta to provide protection for the newborn. The
function of other IgGs is unknown.
As maternal IgG drops and
newborn IgG develops, just before 4 months there is
a particular low point where they are prone to
infection.
IgA is abundant in secretions (milk, tears,
saliva, respiratory, genito-urinary, GIT) and serum,
and exported by plasma cells as dimers. They are
actively transported across epithelium to function
within the mucosal barrier. Secreted IgA includes a
secretory component which confers resistance to
proteolysis, as bacteria in the gut may break down
IgA using special proteases.
IgDs function is uncertain, but is found on the surface of nave B cells
(mature B cells that havent encountered antigen; in addition to IgM).
IgE is produced in very small quantities, but is very powerful, and
responsible for allergic reactions and responding to parasitic infections.
Comparing the variable regions, there are three hypervariable regions
(due to more changing in genes; clonal selection) in the light chain and three
hypervariable regions in the heavy chain that together make the antigen binding
site (complementarity determining regions), and thus specificity. Antigen selects
a specific B cell by binding to cell surface antibody, resulting in cell activation,
division and the formation of clone specific cells. Some become plasma cells and
pump out free antibody, others memory cells with the same antibodies acting as
receptors on the cell surface. Downstream of these variable genes are a constant
region of genes that determine the isotype, and genes of a particular specificity
can be associated with different constant region genes (which determine
function).
After clonal selection, if T cell help is provided, B cells will switch from IgD
and IgM to production of IgA, IgG or IgE. These antibodies have the same
variable region genes, and ONLY the constant region genes
change (hence specificity remains, function changes).
Vaccination is uses chemically-modified infectious agents
or toxoids (modified toxin) to encourage a secondary response
when you actually get it, as repeated encounters are faster,
greater and more prolonged. However, many vaccinations (e.g.
tetanus toxoid) just continue producing antibodies but at a
decreasing rate, so a booster is required.
IgM is measured to detect recent infection (IgG persists long after
infection).
Immunology 3 Immune Response to infectious Diseases
Anti-Viral
Lymphocytes: B cells, T cells, Natural Killer cells (large, granular
lymphocytes). Innate defences include NK cells, which lyse virallyinfected cells. Virally-infected cells produce the cytokines IFN-, IFN-
and IL-12, leading to the recruitment of NK cells, and if necessary T
cells.

Adaptive antiviral responses include antibodies, which can neutralise

viruses when out of the cell, preventing attachment and
colonisation/endocytosis by steric hindrance, or interfering with viral
processes in uncoating their capsid and fusing RNA into cell, but more
commonly through cytotoxic T cells (but results in cell death/tissue
injury). They express CD8 (cluster of differentiation, a transmembrane
glycoprotein co-receptor) with T cell receptors (TCR). Other T cells
express CD4. These have the same structure as one side of the FAB region of an
antibody, but sit in the membrane and are not secreted.
Antibodies bind to epitopes displayed on the surface of antigens, but those
recognised by T-cells are often buried so the antigen must be broken down first,
and then an MHC (Major Histocompatibility Complex) in ER will grab it and
present it on the cell surface for the TCR to bind to and thus the cytotoxic T cell
to kill. MHC Class I are used for viruses (epitope from protein produced by virus),
which all cell express. Cytotoxic T Cells are better killers than NK cells, and as
they are derived from memory T cells (which also split into others like helper T
cells to produce cytokines), will have stronger and faster responses in
subsequent exposures (adaptive).
All lymphocytes are generally activated in the lymph nodes (sampling
stations) when antigen comes from the site of invasion and lymphocytes come to
the lymph nodes to meet them (from Thymus or Bone marrow via bloodlymph).
Lymphatics drain fluid from tissues into circulation (via thoracic duct), transport
macromolecules (incl. antigens) from tissues to lymph nodes, and provide a
pathway for the migration of cells. Immature dendritic (antigen-presenting) live
in peripheral tissues, and once in contact with antigen become mature and travel
to lymph nodes via lymphatic vessels where they activate nave T cells.
Anti-Bacterial
To identify bacteria, innate defences recognise Pathogen-Associated
Molecular Patterns (PAMPs) using Pattern Recognition Receptors (PRRs), with
different PAMPs triggering different responses. PAMPs include:
Cell Wall Constituents
o Peptidoglycan
o Lipopolysaccharide (LPS) can target this to break it down
o Mannan
Formylmethionine/N-formylated terminus
o First amino acid added during prokaryotic protein synthesis
PRRs include Toll-Like Receptors (TLR; highly conserved across species),
mannose receptors and LPS receptors, expressed on macrophages.

Adaptive: Both T cells and B cells are

used to fight bacteria (T helps B).
Antibodies are good for:
Steric
Hindrance/Neutralisation
stop toxins and bacterial
virulence
factors
(e.g.
enzymes
that
act
as
spreading factors), which can
then
be
ingest
by
macrophages
Opsonisation increases
ingestion by macrophage
Activate
Complement
Cascade

increases
ingestion by macrophage AND
lysis (by perforating cell
membranes)
Complement system is a cascade
between 20 complement proteins, with
three triggers that lead to a common pathway. It aids antibody response
resulting in lower bacterial survival. Perforation of cell membranes results in
lysis.
Microbiology II Bacterial Structure and Growth
Bacterial capsules are made from complex polysaccharides,
and are used to mediate adherence, protect from phagocytosis and
drying, and act as a carbohydrate reserve. In Streptococcus
pneumoniae, there are 75 different types of capsule (for different
strains, based on sugar content, changes immune recognition).
Flagella are responsible for motility (water is viscous, so important
for colonisation and nutrient acquisition). They move by rotation
like a boat propeller. Pili/fimbriae are surface filaments used for
adhesion (e.g. E. coli in urinary tract and intestines).
Bacterial spores, or endospores, are often seen in gram-positive rods like
Bacillus and Clostridium, allowing the bacteria to survive for long periods under
adverse conditions by turning into a hibernating seed. They have an exosporium
(outer
membrane),
spore
coat
(proteins
for
protection),
cortex
(peptidoglycan=like cell wall), and core (genetic material, ribosomes, organelles
required for growing again). Dipicolinic acid is 10-15% of the dry weight of
spores, and is important in resistance to heat/radiation, stability (dehydrates to
protect from denaturing DNA and proteins), and protects it from damage. The
spore develops inside a bacteria and then escape. In better
conditions, a full rod will germinate out within minutes. Some
notable spores include Bacillus: antracis (anthrax) and cereus
(food poisoning); Clostridium: tetani (tetanus), botulinum
(botulism), difficle (infect after hospital antibiotic treatment,
inflame colon).
Bacterial growth is exponential. There are four phase:
Lag Phase bacteria adapting to new
environment, find nutrients (no growth); first
few hours

Log Phase population enters active growth, mass of each cell

increases rapidly (linear on log graph); when symptoms occur
Stationary Phase reproductive rate=death rate (due to lack of
nutrients, formation of toxic metabolites which change pH, immune
response); less susceptible to antibiotics as not taking in many
nutrients
Death/Decline Phase death rate > reproductive rate
Factors affecting bacterial growth:
Temperature psychrophiles (0-20oC), mesophiles (20=40oC),
thermophiles (40-90oC)
Oxygen
o Aerobic require O2
o Anaerobic cannot grow in O2
o Facultative can grow with (and use) or without O2
o Microaerophilic require low O2 conc. (<20% atmospheric)
o Aerotolerant anaerobe unaffected by O2
pH most best a 7 (blood and tissues 7.2-7.4), but some
acidophiles
Nutrients - Liquid media = increasing bacterial numbers, solid
media = growing colonies (from single bacterium) for identification
(agar + nutrient broth).
Skin infections (impetigo) = Step. Pyogenes
Lung infection (pneuomia) = Strep. Pneumoniae
Nervous system (meningitis) = Haemophilus influenzae
UTI (cystitis, pyelonephritis) = E. coli
Genital tract infection (Gonorrhoea) = Neisseria gonorhoeae
Stomach (peptic ulcers) = Helicobacter pylori
Intestine (typhoid fever) = Salmonella tyhpi
Viruses cause hepatitis, HPV (warts), influence, HIV/AIDS (rash), chicken
pox and measles.
Archaea do not have peptidoglycan cell walls, have a different lipid
composition in their membranes, and have unique nucleotide sequences in the
RNA of their ribosomes, but havent conclusively been shown to produce disease.
Fungi include mushrooms, yeast, and mold like peniccilium and aspergillus
with hyphae, and fungal spores (for reproduction) aid in identification. Include
tinea capitis (scalp), tinea versicolor (chest), ringworm (tinea corporis),
onychomycosis (nails), tinea pedia (athletes foot) and orgal and vaginal thrush
from candida albicans.
Protozoa are the largest microbe, with no chlorophyll and single and
multicellular forms, obtaining food by phagocytosis (incl. bacteria), and
reproduce asexually. Produce ameobiases, giardiasis, trichomoniasis (STI),
toxoplasmids, and malaria.
Parasites include roundworms and pinworms (lead to anaemia, protein
loss, obstruct intestine).
Microbiology 3 Diagnosis of Infection
Clinician must collect (before antibiotic therapy unless life-threatening like
meningitis or septicaemia; avoid normal flora), store and transport specimen.
Microbiologist must process and identify specimen (microbes, their products, or
serology for antibodies), and determine antibiotic susceptibility if relevant.
Clinicians use:
Aseptic technique antibacterial agent on skin, dont touch
swabbed area, needle/cannula, top of bottle where inoculation

occurs; urine is collected midstream (MSU) as initial urine washes

out normal flora (in bladder actual no. of bacteria is important, not
just their presence)
Sterile swabs and containers
Correct transport conditions blood culture bottles (BCB) with
enrichment broth; problems include desiccation (drying out, so use
semi-solid agar), toxicity (kill itself in own waste, so contains
charcoal to inactivate toxins) and overgrowth of normal flora (taken
straight from pus or lesion); depending on pathogen, may be room
temp. (e.g. CSF, as bacteria that cause meningitis are fragile and
die easily) or 4oC (used in bladder, as stops normal flora or
pathogen from multiplying as no./L is critical for diagnosis)
Label specimens date, time of collection, name, sex, D.O.B., type
of specimen
Complete request form
Observations can be macroscopic (urine cloudy or RBC, CSF turbid or
bloody, sputum mucoid), direct microscopy (with gram staining) if obtained from
sterile site (blood, CSF, bladder, serous fluids, tissues, lower respiratory tract
(lungs)) as opposed to those with normal flora (mouth, nose, skin, upper
respiratory tract, female genital tract, urethra, intestinal tract) that will need
selective media. Rapid testing can be done by antigen detection, toxin detection
or PCR. For viruses, use electron microscopy or PCR (more readily available).
Clinical notes guide microbiology testing, which includes choice of media
(horse blood, chocolate blood (heated and lysed), selective (only one type
grows), addition of antibiotics, or differential (different colours; e.g. lactose, as
some can ferment)), incubation temp (usually 37oC), pH requirements (6.5-7 for
most bacteria, 5-6 for moulds and yeasts, <4 for some bacteria), gaseous
requirements, length of incubation (afterwards may start new ones or a
subculture to obtain a pure culture), and other tests (gram-reaction, cell
morphology, cultural characteristics, biochemical characteristics (catalase,
oxidase, urease), antigenic differences, motility test, carbohydrate breakdown),
and antibody detection (titre=how many times can dilute and it still reacts; IgM
indicates active infection).
Psychiatry Introduction to Human Behaviour
Id = need to survive and reproduce
Super-Ego = societal influence (conflicts with ID=shame, guilt)
Ego = reality and reason
Biochemistry 3 Carbohydrates and Lipids
Carbohydrates = aldehydes (carbonyl C=O on end) or ketones (carbonyl in
middle) with multiple hydroxyl groups, or polymers yielding these upon
hydrolysis (e.g. Starch n(Glucose) under acidic conditions). Carbohydrates
uses:
Storage of metabolic fuel (glycogen in animals, starch in plants)
Structural materials (connective tissue, plant cell wall=cellulose)
Molecular recognition (A, B and O antigens determined by single
genetic locus with 2 alleles, encoding glycosyltransferases
controlling synthesis of oligosaccarides)
Can be monosaccharides (glucose, fructose), oligosaccharides (2-20
monomers; sucrose, lactose) or polysaccharides (glycogen, cellulose). Only Dseries (dextro, not levo) as enzymes can only do D. Includes ribose in ATP, RNA,
DNA, FAD, NADH, NADPH and Coenzyme A. Polymers have glycosidic bonds, and

synthesis and breakdown are catalysed by enzymes. Sucrose=glucose+fructose,

lactose=galactose+glucose, maltose=glucose+glucose. Cellulose () and starch
() are both glucose polymers, but isomers. Amylopectin is branched at every
25th glucose, whilst glycogen is branched at every 10 th (enables you to take out
multiple strands, efficient).
Lipids are insoluble in water, and have three important groups:
Triacylglycerols/Triglycerides margarine; storage of metabolic fuel
(TAGs in adipose), twice as much as carbohydrate/gram, and
anhydrous
Phospholipids (membranes=6nm thick) lecithin; two fatty acidsglycerol-phosphate-alcohol (often choline)
o When damaged, phosphtidylcholine (lecithin) is converted to
arachidonic acid by phospholipase A2 to produce
eiconsanoids: thromboxane, prostaglandins, leukotrienes
o Integral proteins are free to diffuse in sea of phospholipid,
and unsaturated lipids make it more fluid (H, C=C, kinks,
weaker IMF, fluidity), whilst cholesterol make it more gellike (rafts)
Steroids cholesterol (hormone and in membranes; just one
hydrophilic OH, rest hydrophobic)
Sphingomyelin is the primary component of myelin sheaths, and
intertwining of hydrocarbon chains strengthen the sheath.
Skin A Clinical Approach
Fitzpatrick Classification
1) Pale, red hair, blue eyes, freckles, always burn, never tan
2) White, fair, burn easily, tan little
3) Light brown, burns moderately, tans uniformly
4) Olive, can burn, tans easily
5) Dark brown, doesnt burn, dark tan
6) Black, doesnt burn
Barrier functions
Defence against pathogens
o Anatomical barrier
o Langerhans cells (antigen-presenting)
Thermoregulation (main function of superficial venous system)
o Hot vasodilatation and sweat production
o Cold vasoconstriction, anterio-venous shunts open to return
warm blood to core circulation, erector pili muscles contract
Barrier and Protection
o Semi-permeable barrier to fluid loss (and therefore nutrient)
o Sensory (heat, pressure, pain, touch)
o Melanocytes (melanin to protect from UV)
Skin Condition Causes
Structural
o Congenital hereditary or mutation
o Acquired venous lake due to loss of elastic fibre, trauma,
physical or chemical
Inflammatory
o Infection
o Infiltrate (e.g. autoimmune)
Neoplastic benign or malignant

Basic classification of skin conditions PERHAPS REVISE IMAGES,

INSERT DISEASES I KNOW
Lesion area of altered skin
Rash widespread eruption of multiple lesions
Dermatosis skin disease
Primary Descriptions
Infiltrates
Macule <1.5cm, non-palpable discolouration (like macula lutea)
Papule <0.5cm, palpable
Nodule large, palpable (lump)
Patch large discolouration, smooth surface
Plaque - >0.5cm, palpable but flat (may be elevated or thickened,
but not visibly)
Disruption
Vesicle <0.5cm, fluid-filled blister
Bulla >0.5cm, fluid-filled blister
Cyst fluid filled space (not necessarily infective)
Pustule papule/vesicle containing pus (often sterile)
Abscess nodule containing pus
Destruction
Erosion discontinuity of skin (incomplete epidermal loss)
Ulceration complete epidermal loss, often portion of dermis and
subcutaneous fat
Secondary Descriptions
Texture
Palpable can feel it
Excoriated scratched
Scaly implies epidermal change
Lichenified thickened (often excessive scratching)
Verrucous wart-like
Crusting plasma exudation
Size
o Hypertrophic enlarged
o Atrophic depressed (epidermal or dermal)
o Dystrophic degeneration or abnormal function (e.g.
calcification)
Colour
Blanchable (pale) non-occlusive (not due to blockage)
Pallor (pale) implies ischaemia (lack of blood flow)
Erythematous (red) implies vascularity
Violaceous (violet) implies vascularity
Purpuric (purple) implies prior haemorrhage
Pigmentary pigmented, hyperpigmented, hypopigments,
apigmented, depigmented
Distribution
Generalised vs localised
Unilateral vs bilateral
Acral extremities, distal phalanges, toes, ear, nose, penis
Extensors (psoarsis) vs Flexors (atopic eczema)
Follicular based on hair follicles

 Photo-distributed areas exposed to sun

Seborrheic follows distribution of sebaceous glands
Configuration
Discoid/nummular like disk/coil
Linear/striate (often from plants)
Targetoid concentric rings
Gyrate whirling
Annular ring
Patterns
Linear
Blashkoid spotty line pattern
Dermatomal corresponding to dermatomes
Stellate star-like
Reticulate follows blood vessels, implies vascular origin
Physiology 3 Cardiovascular System
Cardiovascular system for transporting gases, nutrients, fluids,
electrolytes, wastes, hormones, defence against infection, delivery of platelets to
stop bleeding, and thermoregulation.
Valve closure sounds: S1 (lub: AV valves closing) and S2 (dub: semilunar
valves closing). Aortic pressure=85mmHg, pulmonary=15, central venous=0.
Arteries=conduit vessels (transport blood under high pressure),
arterioles=resistance vessels (hydraulic filter that controls flow to individual
tissue beds), capillaries=exchange vessels, venules/veins=capacitance vessels
(store most of blood; 60-68% in supine (lying down) person). All vessels have
simple endothelium, the aorta has more elastic tissue to cope with high pressure
(venules none, veins some), arteries and arterioles have more smooth muscle for
control (venules none, but veins some), and larger vessels have more fibrous
tissue than smaller ones.
Ventricular
systole=contraction (arteries store
blood), diastole=relax and fill
(arteries smooth muscle contracts
to cope).
Microcirculation
have
precapillary sphincter to stop loss
of heat, and blood returns to vein
through a bypass (non-nutrient
flow).
Above the heart, pressure is lost (less volume), with negative pressure in
the sagittal sinus (although arteries arent negative), whilst pressure is gained
below the heart. When walking, lower leg pressure drops as it creates a muscle
pump (in conjunction with valves) to push blood up.
CO=SVHR. Cardiac Output (L/min: 5L/min) = Stroke Volume (L/beat:
70mL/min, usually 120mL in ventricle, so ejection fraction of 60%, increases with
adrenaline) Heart Rate (beat/min: 70mL/min). At rest, most blood flow is at
abdominal organs, then muscle and kidney. During exercise, far more in muscle,
skin (to dissipate heat), and less in abdominal organs.

Blood flow follows: Conductance Diameter 4, with

blood in the centre of a vessel moving faster than that on
the outside. Resistance (impediment to blood flow in a
vessel)=1/conductance, but cannot be measured directly
and is thus found by P=FR (change in pressure=flow IN
SECONDSresistance in PRU (peripheral resistance units).
Pulmonary circulation has a resistance 1/7 that of system
(thus much easier and requires less pressure). Crosssectional area is most in capillaries (as many more) than
arteries or veins. Velocity is inversely proportional to crosssectional area (the tighter the gap, the harder theyre
pushed through).
Note: flow is cm3/s=mL/s, and the same across vessels, whilst velocity is
cm/s.
Blood flow is controlled acutely by factors that are local (metabolites (O 2,
CO2, H+, K+, adenosine all increases blood flow), autoregulation, substances
released by endothelium), neural, or humoral (hormones like adrenaline,
noradrenaline are vasoconstrictors, bradykinin and histamine are vasodilators).
Neural predominates gut (via splanchnic) and skin circulation (PSNS vs SNS),
whilst local predominate vital tissues (brain, heart) and exercising muscle as they
require a constant supply. Long term involves altering size and number of
vessels.
A blood pressure cuff is done to higher than blood pressure, then slowly let
down. Sounds only heard when equal to blood pressure (as too high stops blood
flow, too low doesnt cause constriction); first sound is systolic pressure (at
maximum), last is diastolic pressure (at minimum) as slowly lowering pressure.
Mean pressure = DP + 1/3 PP (Pulse Pressure = SP-DP; difference). Baroreceptors
detect pressure by measuring vessel stretching, this information is processed in
the brain stem, then changes in HR, SV, vessel diameter, and thus blood
pressure. They regulate arterials lowering the pressure.
Pharmacology 3 - Receptors
Drugs target receptors, enzymes, transporters, and some proteins and
ligands. Major types:
Ligand-Gated Ion Channels binding domain near N-terminus, 45 transmembrane helices (subunits, 2 always s), milliseconds,
long loop joining two; e.g. in nicotinic receptor, acetylcholine binds,
causes conformational changes in -Helices, opens
G-Protein Coupled Receptors 7 transmembrane helices,
binding domains near N-terminus or across 2-3 TH, G-protein
coupling domain across long loop and C-terminus, seconds; when
drug binds, activates G protein; one of largest protein families (3%
of genome, with 850 GPCRs in human genome, 250 identified as
known ligands, the rest orphan receptors (unknown function), thus
most abundant drug targets)
Catalytic Receptors binding domain near N-terminus, 1
transmembrane helix, catalytic domain at C-terminus, hours; need
at least two (sometimes 4) as when a ligand binds, they dimerise,
often phosphorylating the proteins below by twisting further; protein
phosphorylation leads to transcription
o Receptor Tyrosine Kinase (RTK) puts phosphates on
tyrosines of other proteins

Tyrosine-Kinase Associated Receptors receptors that

associate with proteins that have tyrosine kinase activity
(cytokine receptors; no catalytic domain, require JAKs to
phosphorylate)
o Receptor Serine/Threonine Kinase phosphorylates
serine and threonine
o Receptor Guanylyl Cyclases modify cyclic GMP
Nuclear Receptors binding domain near C-terminus, halfway
across DNA-binding domain (zinc fingers), in nucleus or cytoplasm,
soluble (not in membrane), hours; ligand must cross membrane to
receptor, receptor dimerises, crosses to nucleus, binds to
responsive elements of DNA it specifically recognises, cofactors
bind, then transcription, translation, new protein
o Class I in cytoplasm, homodimers (two identical), mainly
endocrine ligands, high affinity
o Class II in nucleus, heterodimes (RXR + something else),
mainly lipid ligands, low affinity
Channel blockers will block permeation, whilst modulators will increase or
decrease opening probability. A false substrate in an enzyme can produce an
abnormal metabolite, whilst in a transporter can result in an abnormal compound
accumulation.
o

Anatomy 3 Overview of the Nervous System

Nervous tissue = neurons (transmit and process information) and
supporting cells. Spinal cord cross-section: grey matter in middle (mostly cell
bodies),
white
matter
around
(myelinated
axons).
Association
neuron=interneuron. Spinal cord in vertebral canal of vertebral column. Conus
medullaris (end of spinal cord) is L1/L2, after that cauda equina. Reflex arcs:
withdrawal (pinprick) reflex has interneuron, stretch does not.
ANS includes sensory neurons that carry impulses from sensory receptors
in body organs (similar to other sensory neurons), whilst motor neurons carry
impulses to smooth muscle, cardiac muscle and glands (preganglionic and
postganglionic/ganglionic neuron). Most SNS synapse in sympathetic trunk, but
some go straight out to form splanchnic nerves which synapse on ganglia in the
abdomen (to sympathetically supply the GIT and abdominal organs). PSNS
mostly comes from brainstem via cranial nerves (vagus supplies organs of thorax
and abdomen).
Near termination, an axon branches into telodendria, ending in small
swellings called axon terminals. Synaptic cleft=20nm, neurotransmitters (most
common: GABA (inhibitory), acetylcholine and glutamate (excitatory)) released
by exocytosis. Typical neurons (including motor) are multipolar, having multiple
dendrites and an axon that branches further away. Pseudounipolar neurons have
one large dendritic process, and one central process (axon). Spinal nerves exit
through intervertebral foramina.
Embryology Introduction to Human Development
The first trimester (8 weeks) is embryonic (organogenesis, placentation),
the following two foetal. Fertilisation (used scientifically) typically occurs two
weeks after the last menstrual period (LMP; gestation age, used clinically).
GA=FA+2 weeks. Ultrasound are used to determine age, and the primipara (1 st
pregnancy)=274 days, then multipara (subsequent pregnancies)=269 days. The
haploid gametes are spermatozoa (sperm) and oocytes (egg).

The menstrual cycle is endocrine-controlled by the hypothalamus, pituitary

and gonads (ovaries), involving a negative feedback loop in which progesterone
and oestrogen control luteinising hormone and follicle stimulating hormone. The
two weeks before ovulation is the follicular phase (6 days of menses: uterine
lining shed, then proliferative when lining is replaced), whilst the two week after
is the luteal phase (secretory; uterine glands release hormones just in case of
pregnancy, like a pseudo-pregnancy). Ovaries sit in abdominal cavity. Male
puberty is later than females, and they produce 2000sperm/s, releasing millions
(but requiring activation and capacitation).
Fertilisation is the process of 2 haploid gametes fusing in the far uterine
tubes and combining genetic material to make a conceptus (entire product of
fertilisation; every cell from zygote onwards, including foetus and foetal
component of placenta). The spermatozoa bind to the zona pellucida (jelly-like
extracellular matrix), to produce a zygote (fertilised oocyte), then all other
blocked from entering. By mitosis, forms a solid ball (morula), then inflates and
collapses with fluid to stretch the zona pellucida until blastocyst hatches out.
During this time, it moves along the uterine by cilia, and in early Week 2 will
implant into the uterine wall anywhere in the uterine body (implantation),
telling the body to stop the next menstrual cycle by releasing hormones. HCG
(hormone) levels are used to detect pregnancies. Ectopic sites are the external
uterus surface, ovary, bowel, GIT, mesentery, peritoneal wall or uterine tubes.
In Week 3, three key processes:
Gastrulation formation of trilaminar (3 layer) embryo:
o Ectoderm epithelium of skin, NS
o Mesoderm connective tissue, muscle
o Endoderm - epithelium of GIT, GIT organs and respiratory
tract
Somitogenesis segmentation of mesoderm into somites (body
segments), forms axial body plan
Neurulation segment skin from NS in ectoderm
By Week 4, cardiogenesis (first functioning organ). For 4-8 remaining
organs, tissues and limbs.
The placenta has maternal and foetal cells, but no blood crosses. By week
12, the uterine cavity is lost. The uterus lining is instead called the Decidua,
having three distinct regions by week 3:
Decidua Basalis implantation site
Decidua Capsularis encloses conceptus
Decidua Parietalis remainder of uterus
In the 2nd and 3rd Trimesters, there is continuing growth and differentiations
of these organs, and some continue developing after birth (neural, genital,
respiratory, bones). The Second Trimester is a growth in size and length, whilst
the Third is a growth in weight (enough energy and structures to survive without
mother). Birth (or parturition) is believed to be initiated by the foetus, having the
stages dilatation, expulsion, placental and recovery. The newborn then activates
several systems:
Lung function fluid drainage, gas exchange, muscular activity
(begins practising in uterus)
Circulatory changes closure of 3 vascular shunts
Thermoregulation metabolic rate, fat metabolism
Nutrition GIT function, peristalsis
Waste kidney function (before through placenta via maternal
kidneys)

 Endocrine function loss of placenta, maternal hormones

Abnormal development can be genetic, environmental (teratogen), or
unknown. The system affected depends on time of development, neural being
first and most prolonged. The first trimester is major abnormalities, whilst the
remaining two are functional and minor abnormalities.
Biochemistry 4 Energy and Metabolism
Phototroph
(light
energy)
Autotroph (CO2)
Photo-Autotroph
Photosynthestic
bacteria,
plants,
some protists (algae)
Heterotroph (organic, e.g. Photo-Heterotroph
glucose)
Some bacteria

Chemotroph (chemical
energy)
Chemo-Autotroph
Some bacteria

Chemo-heterotroph
Animals, parasitic plants,
many
bacteria
and
protists
Metabolism = totality of organisms chemical reactions to manage
material and energy resources, consisting of:
Catabolic Pathways breakdown to release energy (e.g. cellular
respiration); exergonic (energy-releasing); generally oxidation (the
electrons are collected by a coenzyme/cofactor)
Anabolic Pathways build complex molecules by consuming
energy (e.g. protein synthesis); endergonic (energy-consuming);
generally reduction
The energy for this is passed around as ATP (adenosine triphosphate),
consisting of the nitrogenous base adenine, a ribose sugar, and three phosphate
groups, whose high energy bonds are broken by hydrolysis and release energy to
leave an inorganic phosphate. In animals, catabolic processes require oxygen,
whilst many protists and bacteria are anaerobic). Respiration will produce H 2O
and CO2 with 36ATP, whilst fermentation will produce organic products (ethanol
or lactate-) and 2ATP for the same glucose molecule. Fats, carbohydrates and
amino acids can be broken down by aerobic catabolic pathways to convert to CO 2
and H2O, however in skeletal muscle during intense exercise, carbohydrate
catabolism involves fermentation (conversion to lactate, which is why cells die if
O2 supply is interrupted).
Reduction: NAD+ NADH
(so if given these, can work out what
other stuff must
Oxidation: NADH NAD+
be doing; note still broken down/built up)
Metabolism is controlled by feedback inhibition, in which products bind
to an allosteric site (not active site) on an earlier enzyme and inhibit or
stimulate function. ATP inhibits catabolism but activates anabolism (dont make
more, use it up), whilst ADP/AMP activate catabolism and inhibit anabolism
(make energy before we use it). In general, activated by reactants, inhibited by
products.
Cells are compartmentalised to bring order to metabolic pathways. For
example, some enzymes reside in specific organelles. Enzymes for glycolysis are
located in the cytosol, whilst those for the TCA cycle are in the mitochondria (the
final stage oxidative phosphorylation, or the electron transport chain). The
stages of catabolism are:
1) Digestion to yield basic monomers in GIT (extracellular)
2) Update, breakdown into 2C-units (intracellular)
3) Citric
Acid
Cycle
produces
reduced
coenzymes/cofactors
(intracellular)

4) ATP formed in mitochondria (intracellular)

The brain, nervous tissue and RBCs cannot use fat or amino acid and are
glucose-dependent, whereas all other tissues can use any (although active
skeletal muscle generates ATP fast when breaking down carbohydrates
comparted to fat or amino acid).
Pharmacology 4 Anti-Inflammatory Drugs
The eicosanoids (derivatives of arachidonic acid) include:
Prostanoids
Prostaglandins (D2, E2, F2) vasodilatation, vascular permeability,
oedema, potentiate pain
Thromboxane A2 vasoconstriction and platelet aggregation
Prostacylin I2 vasodilatation and inhibits platelet aggregation
(opposite to TX)
Leukotrienes
LTB4, LTC4 increase vascular permeability, promote leukocyte
chemotaxis, contraction of bronchial smooth muscle
NSAIDs (non-steroidal anti-inflammatory drugs):
Anti-Inflammatory modify effects of inflammation reaction;
inhibit prostaglandin synthesis and thus inflammation (without
affecting other mediators; high doses can inhibit expression of
adhesions molecules and cytokines (IL-1 and TNF-))
Analgesic reduce pain; PGs sensitise nociceptive nerve endings
to other inflammatory mediators like bradykinin and histamine
Antipyretic lower raised temperature, but only in fever; PGEs (in
response to IL-1 made by macrophages reacting to bacterial
endotoxins) in hypothalamus elevate temperature (fever), so block
this
They work by inhibiting cyclooxygenase (can lead to a small increase in
leukotrienes, which are potent bronchoconstrictors, particularly for asthamtics).
However, they do not halt the progression of arthritis. COX1 inhibitors have
unwanted side-effects, whilst COX2 inhibitors have therapeutic anti-inflammatory
effects. As the COX2 receptor is larger, drugs can be made so they are bulkier
and cannot fit in COX1, producing COX2-selective drugs (others are COX-1
selective or non-selective). Aspirin is an irreversible inhibitor, paracetamol a
reversible non-competitive inhibitor, but most NSAIDs are competitive inhibitors.
Side effects include ulcer formation and haemorrhage risk (as PGs normally
protect gastric muscosa, inhibit acid secretion and increase muscosal blood
flow), renal damage (as PGs vasodilate the renal medulla and glomeruli), and if
allergic can cause bronchospasm and skin rashes.
Aspirin is a non-selective, irreversible COX inhibitor of both isoforms, and
inhibits platelet aggregation. It is used to manage mild to moderate pain and
CVD for anti-platelet properties, but just 2 aspirins can cause internal bleeding,
and it can cause brain swelling (not for children under 16). Other non-selective
NSAIDS are generally reversible, treat mild-moderate pain and inflammation, and
have GIT, kidney and breathing side effects.
COX-2 selective inhibitors (coxibs) have fewer GIT side effects, but no
cardioprotective effects and thus have higher cardiovascular thrombotic events.
Paracetamol is analgesic and antipyretic, but not very anti-inflammatory,
and preferred for COX-2 as no GIT or CVD effects but hepatotoxicity (metabolises
a toxic metabolite).

Topic ophthalmic (eye drops) NSAIDs include diclofenac and ketorolac, and
is used for corneal abrasians, decreasing postoperative ocular inflammation,
allergies and photophobia.
Glucocorticoids (or corticosteroids) are steroidal anti-inflammatory drugs
and immunosuppressants, used for rheumatoid arthritis, inflammatory bowel
conditions, bronchial astha and inflammatory skin conditions. They inhibit both
phospholipase A2 AND COX-2, and thus both prostaglandins and leukotrienes
(thus inflammation). As an immunosuppressant,
they inhibit accumulation of neutrophils and
monocytes and decrease antigen processing by
macrophages,
T-helper
cell
function,
phagocytosis,
antibody
production,
and
production of IL-2. They act by binding to
receptors on cell membranes, being transferring
to the nucleus and alter mRNA transcription,
inhibiting cytokines (thus less inflammatory cell
recruitment) and COX-2 (less PGs, TXA 2), and
expressing annexin/lipocortin-1 which inhibits
phospholipase A2 from producing arachidonic
acid. Side effects include immune system suppression, osteoporosis, impaired
wound healing, diabetes, peptic ulcers, and growth suppression.
DMARDs (disease-modifying anti-rhematic drugs) actually slow bone
destruction in arthritis, but take a month to work.
Anti-cytokines target the action of TNF- (which is at the top of the
inflammation cascade), such as infliximab or etanercept. Monoclonal
antibodies can be used against the IL-2 receptor, including basiliximab and
daclizumab. These can halt progression of arthritis.
Anti-histamines are H1 receptor agonists, used in allergic reactions,
motion sickness and sedation (a side-effect but also use). These include
mequitazine, fexofenadine and cetirizine.
COX-1
Selective
(non-selective) Ketorolac topical ophthalmic
NSAIDs
Flurbiprofen
Suprofen
Ketoptofen
Indometacin
Aspirin
Naproxen
Tolmetin
Ibuprofen
Amyprone
Fenoprofen
<5-fold COX-2 Selective NSAIDs
Zomepirac
Niflumic acid
Sodium salicylate
Diflunisal
Proxicam
Tomoxiprol
Melcofenamate
Sulundac
Diclofenac topical opthalmic
5-5-fold COX-2 Selective NSAIDs
Nimesulide
Celecoxib
Meloxicam
Etodolac

>50 fold COX-2 Selective NSAIDs

Corticosteroids (increasing potency)

DMARDs

Anti-cytokines
Monoclonal antibodies
Anti-histamines

Rofecoxib
Cortisone
Hydrocortisone
Prednisone
Prednisolone
Triamcinolone
Methyprednisolone
Dexamethasone
Betamethasone
Gold salts
Penicillamine
Chloroquinine
Sulfasalzine
Immunosuppressents
methotrexate
Infliximab
Etanercept
Basixilimab
Daclizumab
Mequitazine
Fexofendaine
Cetirizine

like

Microbiology 4 Introduction to Viruses

Virus = 80nm (20-350nm) cellular organism whose genome consists of
nucleic acid (one strand of DNA or RNA), which replicates inside host cells and
uses host metabolic machinery (not growth and division) to form a pool of
components into particles called virions (protect and transfer genome to other
cells; insert carriers). Virions may be regarded as the extracellular phase of the
virus.
Virions can be spherical (normally icosahedron: 20 equilateral triangles, 12
verticies) or helix (cylindrical; all have a lipid envelope).
Virions acquire an envelope during maturation stolen from the hosts
plasma membrane as it leaves (budding or cell lysis dont always kill cell).
However, a naked without an envelope is hydrophilic and thus protected from
organic solvents (as the capsid protects, whilst those with the additional
membrane are subject to the environment like acid, detergent, desiccation,
heat). Those with an envelope are hidden from the immune system. Proteins in
the envelope are virally-encoded, including:
Glycoproteins projections known as spikes
Matrix Proteins on inside of enveloped, adding rigidity (only in
helical)
Viruses are classified based on type of nucleic acid, DNA or RNA, shape,
polarity (transcription first=negative-stranded, genome acts as mRNA=positivestranded), replication strategy, nucleocapsid symmetry, envelope or not.
Viruses enter via skin/wounds, mucosal surfaces (eyes, mouth, nose,
respiratory, genital, GI tracts), directly into blood (drug injections, insect vectors),
vertical transmission (motherchild). Subclinical disease are infections you
cannot see. They cause disease by cell death, interference with functions of
essential cells (hepatitis), bodys response, local immune responses (rash),
systemic immune response (fever), autoimmune responses (cause at least 25%
of cancers).

Pathogenesis: Viral replication within a cell produces visible effects called

cytopathic effects, including cell lysis, cell fusion (syncytia), and
transformation.
Patterns of infections can be acute with rapid recover (influenza) or rapid
death (rabies), or persistence, with symptom free periods then reactivation
(herpes), long symptom free periods then illness/death (HIV), or chronic disease
(HPV).
Microbiology 5 When Humans and Microbes Come Together
Infection = successful multiplication of microorganism within a host.
Colonisation = persistence in particular body site of microorganisms that do not
cause disease. Infection = produces signs (objective) and symptoms (subjective).
Infection causes 24% of deaths/year, being three of the top 10 causes of diease
(lower respiratory infections, HIV/AIDS, diarrhoeal disease). Only first in high
income countries, also malaria and tuberculosis in low income (5/10).
TB is the leading killer of HIV-positive people (1/3), with 1.2million dying of
AIDS-related diseases and 36.9mi suffering, only 15mi of those receiving
antiretroviral treatment.
In 2014, 9.6mi developed TB, 1.5mi died (>95 in low and middle income
countries).
1.7bi cases of diarrhoeal disease/year, and 2 nd leading cause of death in
children under 5, and easily prevented with safe drinking water, adequate
sanitation and good hygiene.
Lower in developed countries as we have clean water (filtration and
chlorination decreases typhoid fever incidence), improved sanitation, low density
of living, food handling laws, insecticides and vaccination.
However certain diseases have increased. People living near forests get
tick bites with lyme disease (bacterial), legionnaires disease is transported via
aircons (as aerosol), and hospital acquired infections affect 1/11.
Pathogen = microbe with capacity to cause disease. Principle pathogen =
regularly causes disease, opportunistic pathogen= rarely causes disease
(depends on strain, state of host). They can enter through conjunctiva, skin,
insect vectors, mouth, respiratory tract, urinogenital tract, anus, but have to
fight host defences:
Skin relatively impermeable, dry, acidic, falls off
Mucus Membranes GIT, RT, UGT, goblet cells and ciliated cells,
traps bacteria, antibacterial action (lysozyme to kill Gram+,
lactoferrin removes source of iron), antibodies (secretory IgA leads
to phagocytosis)
Blinking, tears (lysozyme, sIgA)
Nasal hairs traps
Cough response expels
Saliva flushes from mouth, lysozyme
GIT stomach acidic, bile salts in small intestine, normal flora in
large (competes for nutrients and space, metabolic processes
change pH, produce toxic metabolites and bacteriocins)
Phagocytosis and adaptive immune response
Virulence = measure of pathogenicity, ability to cause disease. Virulence
factor = a microbial factor/strategy that contributes to virulence, includes:
Adherence pili/fimbriae
Motility/chemotaxis use flagella to move to mucosal surface

Engulfment change host cell cytoskeleton to be engulfed by nonphagocytic cells (escapes host immune system)
Capsules prevents binding of complement
Enzyme production sIgA protease, catalase breaks down H 2O2
produced by neutrophils
Toxin attack specific host cells (e.g. neurotoxin, hepatotoxin)

Extra
-haemolytic (green) oxidise iron in haemoglobin
-haemolytic (clear) rupture red blood cells
-haemolytic (no change; red) dont cause haemolysis (rarely disease)

Introduction to Autonomic Pharmacology

NS
Supplies
First Synapse
Second Synapse
Parasympatheti Cardiac/smooth
Ach N
Ach M
c
muscle, gland
LongShort
cells, nerve
(excitatory
terminals
except)
Sympathetic
Sweat Glands
Ach N
Ach M
ShortLong
Cardiac/smooth
Ach N
Ne ,
(inhibitory except muscle, gland
heart rate and
cells, nerve
cardiac output)
terminals
Renal vascular
Ach N
D D1
smooth muscle
Adrenal medulla
Ach N (makes Epi, NE hormones)
Somatic
Skeletal muscle
Ach N
Dual innervation = most organs receive both sympathetic and
parasympathetic motor neurons; physiological antagonists (organs said to be
under antagonistic control) leading to homeostasis; sweat glands, adrenal
medullar and most blood vessels only innervated by sympathetic branch and rely
on tonic (up and down) control
Cholinergic neurotransmission: nerves that release acetylcholine, a
positively charged quaternary (4 C around) ammonium group and a partially
negatively charged ester group that is easily hydrolysed. It is virtually of no
therapeutic use because it is very quickly hydrolysed (metabolised by
acetylcholinesterase, hence must be dispensed right into synaptic cleft), and is
non-selective. Cholinergic receptors respond to Ach, and include (bolded
important for drugs):
Nicotinic (ion channel) cation permeability=faster excitatory
synaptic transmission
o NM neuromuscular junction
o NN autonomic ganglia, adrenal medulla, CNS
Muscarinic (GPCR) secondary messenger (IP3 and cAMP)
o M1 CNS, glands
o M2 heart, smooth muscle
o M3 smooth muscle, glands
o M4 nerve cells
o M5 - unknown

Adrenergic
neurotransmission:
nerves
that
release
norepinephrine=noradrenaline at a synapse when a nerve impulse passes
(reuptake rather than broken down). Epinephrine is made from norepinephrine,
which is made from dopamine (all catecholamines). Adrenoceptors respond to
catecholamines, and include:
-adrenoreceptors (GPCR)
o 1 smooth muscle
o 2 presynaptic nerves
-adrenoreceptors (GPCR)
o 1 heart
o 2 smooth muscle
o 3 fat, bladder
Introduction to Endocrine Physiology
Primary endocrine organs (main purpose): hypothalamus, pituitary,
thyroid, parathyroid, adrenal, pancreas (insulin, glucagon), gonads (ovaries and
testes). Secondary (other function): heart (blood volume and pressure), liver
(regulates glucose, growth and metabolism), stomach (appetite, digestion,
enzyme secretion), kidney (activates Vitamin D, blood pressure), small intestine
(appetite, digestions), skin (Vitamin D which regulates Ca 2+ levels) and placenta
(hormones for foetal development and maternal metabolism).
Endocrine system function: Integration and Control, coordinating function
of cells and tissues in body. Work as a slower and more sustained version of the
nervous system. It is used for growth (including epithelial replacement),
development, reproduction, and homeostasis. Secretory cells are arranged in
groupings around a lumen, with good vascularity (fenestrated capillaries) so
hormones can be directly secreted into blood. A hormone is a chemical
messenger that acts at target tissues via specific receptors.
Types of hormones:
Amines derived from amino acid tyrosine (hydrophilic except
thyroid hormone)
Peptides translated from mRNA (hydrophilic); synthesised in
advance so fast release, stored in vesicles that are released by
exocytosis, metabolised fast (last minutes)
Steroids synthesised from cholesterol (hydrophobic); synthesised
on demand so slow release, not stored, metabolised slowly (lasts
hours-days)
Transport: Hydrophilic hormones dissolve in the blood, hydrophobic
hormones bind to carrier proteins, and a small proportion are free (as it is an
equilibrium).
Autocrine chemical messengers that act on the same cell type they
were released from (e.g. secretion regulation of oestrogen). Paracrine act on
other types of cells by simple diffusion (e.g. histamine from mast cells).
Endocrine secreted by endocrine glands into blood to get to target cells with
specific receptors. Neurohormones secreted by neurosecretory neurons
(mostly from hypothalamus secreting releasing hormone for pituitary to secret
other hormone).
Hormone sections is in response to particular stimuli:
Hormonal Stimuli in response to another hormone
Humoral Stimuli internal environment change (blood glucose
levels, osmolarity)
Neuronal Stimuli emotional or physical stress

Hormone release is regulated by endocrine axis-driven negative feedback

(a hormone produced later can inhibit previous secretory cells) and responsedriven negative feedback loops (a physiological effect or response to stimulus
changes secretion).
Each hormone has a specific receptor, and can be on the surface
membrane (if hydrophilic as cant cross membrane) or inside the cell
(hydrophobic).