ICS Flashcards
what are the 2 types of autopsies?
- hospital
- medico-legal (coronial and forensic)
what are the 2 types of medico-legal autopsies?
- coronial (lawful death)
- forensic (non-lawful death)
which type of autopsy is most common?
medico-legal: coronial
what does a hospital autopsy require?
MCCD (medical certificate of cause of death?)
what are hospital autopsies used for?
- teaching
- research
- governance
when are coronial autopsies conducted?
when death is lawful
when are forensic autopsies conducted?
when there’s a non lawful death
what are the 4 questions of the coroner?
- who was the deceased?
- when did they die?
- where did they die?
- how did they come about their death?
what does an autopsic pathologist have the same role as?
the coroner
what are 3 types of deaths referred to a coroner?
- presumed natural
- presumed iatrogenic
- presumed unnatural
what does iatrogenic mean?
caused by medical exam/treatment
what is the no. of days where if not seen by a doctor, a presumed natural death is referred to a coroner?
14
what is the most common referral reason for autopsy?
presumed natural death - not seen doc in last 14d
what are examples of iatrogenic deaths? (4)
- peri/post-op deaths
- anaesthetic deaths
- illegal abortion
- complications of therapy (even if recognised)
name some examples of presumed unnatural deaths (4)
- industrial deaths eg asbestos
- suicide
- unlawful killing
- custody deaths
do docs have a statutory duty to refer deaths to coroners?
no
who has a statutory duty to refer deaths?
registrar of BDM (births, deaths n marriages)
who else can make referrals for autopsy?
relatives, police etc
who performs coronial autopsies?
forensic pathologists
who performs majority of autopsies (hospital)????
histopathologists
what are the 5 steps to an autopsy?
- history/scene
- external examination (formal identifiers etc)
- evisceration (removal of external organs)
- internal examination
- reconstruction
what happened in oct 2016 relating to autopsies?
digital - full body CT scan reported by consultant radiologist
define coronial autopsy
systematic scientific exam that helps coroner determine who the deceased was, when and where did they die and how they came about their death?
define acute inflammation
the initial and often transient series of tissue reactions to injury
how long does acute inflammation often last?
few hours to a few days
what is an example of acute inflammation?
appendicitis
what is inflammation?
(hard to define): local physiological response to tissue injury [often involves cells eg neutrophils n macrophages]
is inflammation a disease?
no, but usually a manifestation of disease
what are the benefit(s) of inflammation? (2ish)
- destruction of invading microorganisms and wailing off of an abscess cavity
- PREVENTING infection spread
what are the negatives of inflammation? (3)
- autoimmunity eg rheumatoid arthiritis
- when it’s an over-reaction to the stimulus
- fibrosis resulting from chronic inflammation may distort tissues and alter their function
list 6 causes of inflammation :/
- microbian infections
- hypersensitivity reactions
- physical agents
- chemicals
- acids/alkalis
- tissue necrosis
list 4 macroscopic (n essential) appearances of acute inflammation
- redness [rubor]
- heat [calor]
- swelling [tumor]
- pain [dolor]
what is rubor?
redness
1 of the 4 classical signs of acute inflammation
what is calor?
heat,
1 of the 4 classical signs of acute inflammation
what is tumor?
swelling,
1 of the 4 classical signs of acute inflammation
what is dolor?
pain,
1 of the 4 classical signs of acute inflammation
why is there heat/calor in acute inflammation?
increased blood flow (AKA hyperaemia) –> vascular dilation
what is hyperaemia?
increased blood flow
why is there swelling/tumor in acute inflammation?
- swelling is from oedema/physical mass of inflammatory cells
- formation of new connective tissue also contributes to swelling
why is there pain/dolor in acute inflammation?
- stretching/tissue distortion due to inflammatory oedema
- AND pus under pressure in abscess cavity
- (also some chemical mediators eg bradykinin, prostaglandins are known to induce pain)
what are 3 features of chronic inflammation?
- slow onset/sequel to acute
- long duration
- may never resolve
what are 3 features of acute inflammation?
- sudden onset 2. short duration 3. usually resolves
list 6 cells involved in inflammation
- neutrophil polymorphs
- macrophages
- lymphocytes
- endothelial cells
- fibroblasts
discuss neutrophil polymorphs (5)
- short-lived cells
- first on scene of acute inflammation
- cytoplasmic granules full of bacteria-killing enzymes
- usually die at scene of inflammation
- release chemicals that attract other inflammatory cells eg macrophages
which wbc is short lived?
neutrophils
which cells are first on scene at acute inflammation?
neutrophils
do neutrophils die at scene of inflammation?
usually
what do neutrophils release?
chemicals that attract other inflammatory cells eg macrophages
what is the life span of macrophages?
long lived compared to neutrophils - weeks to months
what do macrophages do?
- ingest bacteria n debris
- may carry debris away
- may present antigen of lymphocytes
what are kupffer cells an example of?
macrophages
what is the lifespan of lymphocytes?
years
what do lymphocytes do? (2)
- produce chemicals which attract other inflammatory cells
- have an immunological memory for past infections and antigens
what do endothelial cells do? (4)
- line capillary blood vessels in areas of inflammation
- become sticky in areas of inflammation so inflammatory cells adhere to theme
- become porous to allow inflammatory cells to pass into tissues
- grow into areas of damage to form new capillary vessels
what do fibroblasts do and what is their lifespan like?
- form collagen in areas of chronic inflammation and repair - they are long-lived cells
where are inflammatory cells?
in bone marrow, released into blood
what is the best known chemical mediator in acute inflammation?
histamine
name an example of chronic inflammation
tuberculosis
discuss tuberculosis (5)
- no initial acute inflammation
- mycobacteria ingested by macrophages
- macrophages often fail to kill the mycobacteria
- lymphocytes and macrophages appear
- fibrosis occurs
what are granulomas?
- collection of macrophages - surrounded by lymphocytes?
list 3 medications for inflammation
- aspirin
- ibuprofen
- steroids
what is resolution? (2)
- initiating factor removed
- tissue undamaged or able to regenerate
what is repair? (2)
- initiating factor still present
- tissue damaged and unable to regenerate
which organ is a good example for resolution?
liver
what can a paracetamol OD result in?
liver failure
how does alcoholism impact regeneration?
bc of ongoing damage which results in abnormal architecture (cirrhosis)
can pneumocytes that line the alveoli regenerate?
yh
what are the most superficial skin wounds & an example?
abrasion eg road rash from cycling
what happens during abrasion?
only top cell layer is removed, leaving the bottom layer/follicles/glands for scab to form and for the epidermis to eventually be regenerated
what are the 2 types of skin would healing?
healing by 1st n 2nd intention
what is healing by 1st intention?
- edge to edge healing (heals w/ reasonable scar)
- both ends are sealed together, the slight gap is filled w blood, fibrin etc which holds together a little w stitches
- epidermis regrows, fibroblasts produce collagen
- scar line is stronger than surrounding tissue as more blood vessels are grown
do scars along skin creases heal better or worse?
better
what does healing by 2nd intention usually involve?
traumatic wound where u can’t bring 2 edges together
what forms initially during healing by 2nd intention?
granulation –> epithelium slowly grows in from edges (depending on wound size)
define repair
replacement of damaged tissue by fibrous tissue
what is damaged tissue replaced by?
fibrous tissue
what is collagen prod by?
fibroblasts
after a MI, what is there where dead heart tissue was?
a fibrous scar
what does MF stand for?
myocardial fibrosis
what type of scar does MF (myocardial fibrosis) result in?
a dense white fibrous scar (patient may live for a few months but may die after)
which type of healing is preferred?
healing by 1st intention
if healing by 2nd intention, we don’t want infection… what may be done to reduce this?
artificial skin dressings to keep the skin moist so it doesn’t dry out - sometimes may have growth factors in them
what is fibrosis in the brain called?
gliosis
what is gliosis?
fibrosis in the brain
is gliosis contagious?
not as much as usual fibrosis
how does stroke recovery happen?
only the injured (not dead tissue) around the edge of the infarct gets better, with plasticity involved
list some cells that regenerate (5)
- hepatocytes
- pneumocytes
- all blood cells
- gut and skin epithelium
- osteocytes
what are some cells that don’t regenerate?
- myocardial cells
- neurones
what can venous thrombosis potentially cause?
pulmonary embolism
what is clotting within an intact vascular system aka
thrombosis
what is thrombosis within the arterial system usually due to?
damage to the vessel wall (which is often due to the formation of atherosclerotic plaques)
how does platelet aggregation happen?
when atherocsclerotic plaques rupture, then connective tissue collagen is exposed to the blood leading to platelets attaching to it
what can platelet aggregation activate?
the blood clotting system leading to an occlusion of the vessel
what does occlusion of a coronary artery result in?
death of heart muscle due to lack of blood flow (MI)
what does occlusion of a cerebral artery result in?
death of brain tissue due to a lack of blood flow (CI)
what is a stroke aka?
cerebral infarction (CI)
why does thrombosis in the veins most commonly occur?
due to slow blood flow within those veins eg when a patient is lying in bed for long periods of time after a major op
list some preventions of DVT in hosp (3)
- early mobilisation
- use of small doses of anti-coagulants eg heparin
- venous stocking to prevent leg veins being full of blood
what is heparin?
an anti coagulant
what are the 2 reasons why clots are rare?
- laminar flow
- endothelial cells not sticky when healthy
what is laminar flow? and why is it important?
cells travel in the centre of arterial vessels and don’t touch arteries - this is important in reducing risk of blood clots
define thrombosis
the formation of a solid mass from blood constituents in an intact vessel in a living person
what is the first stage of thrombosis?
platelet aggregation
how do platelets cause other platelets to stick to them? (which also starts clotting cascade off)
they release chemicals
why is platelet aggregation and clotting cascade difficult to stop?
both pos feedback loops
what is the name of the large protein molecule formed once the clotting cascade has begun?
fibrin
what does fibrin do?
makes a mesh in which rbc can become entrapped
define embolism
the process of a solid mass in the blood being carried through the circulation to a place where it gets stuck and blocks the vessel (most commonly a thrombus)
could also be a bubble of air/fat/foreign etc
what are some less common causes of embolus? (4)
- air (pressurised systems of IV fluids/blood in infants n kids esp)
- tumour
- amniotic fluid
- fat
if an embolus enters the venous system, where will it lodge?
it will travel to the vena cava –> through RHS of heart –> &will lodge in pulmonary arteries
why can’t an embolus in the venous system get through to arterial circulation?
bc the blood vessels in the lung split down to capillary size so lung acts as a filter for any venous emboli
what acts as a filter for venous emboli?
lungs
what happens if an embolus enters the arterial system?
it can travel anywhere downstream of its entry point eg a mural thrombus overlying a myocardial infarct in LV can go anywhere in systemic circulation
define ischaemia
a reduction in blood flow to a tissue without any other implications
define infarction
reduction in blood flow to a tissue that is so reduced it cannot even support mere maintenance of the cells in that tissue so they die
what is infarction usually caused by?
thrombosis of an artery eg thrombosis in LAD coronary artery causing infarction of anterior wall of LV
what is the triad of factors impacting thrombosis?
Virchow’s triad
- change in vessel wall (endothelial injury)
- change in blood flow (stasis of blood flow)
- change in blood constituents (hypercoagulability)
what does end arterial supply mean?
most organs only have a single artery supplying them so they are very susceptible to infarction if this supply is interrupted
name some organs which don’t have end arterial supply (3)
- liver: portal venous and hepatic artery supplies
- lung: pulmonary venous and bronchial artery supplies
- brain: around COW w multiple arterial supplies
what do endothelial cells act as?
a teflon coating
what can injury lead to exposure of?
collagen
what does fibrinogen get activated by?
chemicals the platelets release
an LAD CA thrombus can led to an MI. how will this present on ecg?
ST elevation on chest leads
how does cigarette smoke change vessel walls?
kills endothhelial cells
why does CO inhalation result in an increased risk of thrombosis?
- inhaling lots of CO
- –> more rbc production
- –> more cells
- = blood more turgid
- –> can thrombus more easily
how does atherosclerosis disrupt laminar flow?
makes artery walls sticky
what is aspirin in low doses daily good for?
inhibits platelet aggregation
what is the most common cause of an embolus?
broken off thrombus travelling in blood stream
what is significant about IV drug abusers?
- street heroin is often cut with talcum powder which isn’t v soluble
- –> injected emboli into veins
- –> usually filtered in lungs, sometimes liver
above what ml of air can cause an embolus?
150
what is infarction a subset of?
ischaemia
what is the diff btwn ischaemia and infarction?
- ischaemia = any red in blood flow
- infarction = death of cells due to lack of blood cells(?)
what causes atherosclerosis?
atheromas
define atheroma
pathology of arteries in which there is deposition of lipids in the arterial wall with surrounding fibrosis and chronic inflammation
what is the predominant cause of M/CI?
atherosclerotic plaques
list 3 risk factors for atheromas
- raised serum lipids
- hypertension
- diabetes mellitus
what is the linkage between high serum lipids and atherosclerosis?
lipids cause endothelial damage
what is the major process after endothelial damage (and with which cells)?
chronic inflammation - with macrophages/fibroblasts
name 3 factors that can reduce endothelial damage
- reduced lipids
- lowered BP
- stopping smoking
which drug can reduce the amount of platelet aggregation at the site of endothelial damage?
taking low dose aspirin
define atherosclerosis
narrowing of arteries due to plaque formation
what is the diff btwn atherosclerosis and arteriosclerosis?
- athero = narrowing of arteries due to plaque formation
- arterio = hardening of arteries
define arteriosclerosis
hardening of the arteries
can u have a genetic predisposition to atherosclerosis?
yes
when is complicated atherosclerosis usually seen?
later in life
what is significant about atherosclerosis?
it is mostly based on incremental episodes of endothelial cell damage over a LONG period of time eg decades
what is in a plaque? (3)
- quite a lot of fibrous tissue
- lipids
- lymphocytes (maybe also inflammation)
name 4 risk factors for atherosclerosis
- smoking
- hypertension
- diabetes
- increased deprivation :(
why does vaping have adv over smoking?
free radicals in cig smoke/CO/nicotine kills endothelial cells, vaping has fewer free rads and no CO
list the journey from smoking –> chest pain
- smoking
- endothelial cell damage
- thrombus
- heals bc endothelial cell layer grows over
- small bump
- not much impact
- repeated endothelial damage
- cycle continues w/o symptoms
- symptoms may finally begin after years eg slight chest pain OR still asymptomatic
what are the symptoms of atherosclerosis in coronary arteries?
- vomiting
- anxiety
- angina
- coughing
- feeling faint
what can atherosclerosis in coronary arteries result in?
ischaemia of cardiac muscle cells
list some symptoms of atherosclerosis in carotid arteries
- weakness
- dyspnea
- facial numbness
- paralysis
what is dyspnea?
shortness of breath
wich disease can atherosclerotic plaque also cause?
peripheral vascular disease
what are some symptoms of peripheral vascular disease?
- hair loss
- erectile dysfunction
- weakening of area
what are some symptoms of atherosclerosis in renal arteries?
- reduced appetite
- hand swelling
- renin release can be increased –> BP may be sig increased
high or low amounts of circulating LDL can lead to endothelial dysfunction?
high
plaque formation steps?
?
define apoptosis
programmed cell death of a single cell
define necrosis
unprogrammed death of a large number of cells due to an adverse event
list some examples of adverse events that could result in necrosis?
- infarction
- burns
- frostbite
- etc
which type of cell death is important in the normal function of the human body?
apoptosis?
why is apoptosis important in embryogenesis?
apoptosis removes cells that are no longer needed as organs develop eg tissue btwn fingers/toes so we dot s so that we dont end up w webbed feet n hands
what 2 things is apoptosis implemented by?
caspases and BCl2 protein
what can an aging or ill cell do besides apoptose?
- autophagy
- closing down protein synthesis
- cell cycle arrest
when can abomal apoptosis occur?
in a variety of situations inc:
- drugs
- graft vs host disease after bone marrow transplantation
- neurodegeneration
thermal injury of a burn that physically causes the death of many cells is by what?
necrosis
what are condensed bodies in apoptosis aka
apoptic bodies
is apoptosis a well-coordinated process?
yes
are there any accompanying inflammatory reactions with apoptosis?
no
what does p53 protein detect?
dna damage in dividing cells
why do cancers get bigger?
bc apoptosis is lacking (often bc of a mutation in p53 gene so dna damage is not recognised)
why is apoptosis switched off in HIV?
as p53 is switched on to kill myphocytes?
what happens to the contents of cells in necrosis?
swelling and disintegration of small bodies of cell
list some examples of necrosis
- frostbite
- CI
- avascular necrosis of bone
- pancreatitis
where do congenital and acquired diseases tend to predominate?
congenital = paeds acquired = geriatric
where do autosomal diseases occur?
non-sex chromosomes
what is a congenital disease?
a disease that someone is born with (mostly genetic but can be acquired)
what is an acquired disease?
one that occurs after birth (often due to env, can be genetic)
name 2 prenatal factors, other than genetic abnormalities that can contribute to disease risk?
- transplacental transmission of env agents eg FA
- nutritional deprivation
what is a genetic disease?
1 that occurs primarily from a genetic abnormality
what is caused by a point mutation in the beta-globin chain of Hb?
sickle cell anaemia
in sickle cell anaemia, when do the RBC deform/sickle?
when oxygen sat is low
single gene disorders are typically classified into what?
dominant or recessive
an single gene disorders be further classified?
autosomal (non-sex chromosomes)
sex-linked (parts of x chromosome that dont have a corresponding region on y chromosome)
what type of disorder is breast cancer an example of?
polygenic disorders (bc BRCA1/BRCA2 do have a large individual efffect but mostly risk is composed of incremental rises in risks by 100s of unrelated genes)
what is the E4 apoprotein associated with?
high risk of ischaemic heart disease due to atheroma
3x higher in pop of papa new guinea than caucasians
what is spina bifida occulta?
malformation of 1+ vertebrae
GH excess is usually due to what?
pituitary tumour - adenoma
define adenoma
benign tumour formed from glandular structures in epithelial tissue
what does hungtington’s disease result in?
death of brain cells
early symptoms - subtle with mood/mental abilities
general lack of coordination and unsteady gait often follow
what type of disorder is huntingtons?
inherited - autosomal dominant - gene called huntingtin (HTT) on chromosome 4… ≥36
increased cell growth is caused by which 2 processes?
hypertrophy and hyperplasia
define hypertrophy
when the SIZE of an individual cell/tissue/organ is increased by an increase in the SIZE OF THE CELLS without the increase number of cells
define hyperplasia
increased growth of cell/tissue/organ because of an INCREASE IN NUMBER OF CELLS. often accompanied by increase in cell size
bodybuilders prefer what? hypertrophy or hyperplasia
hypertrophy - increase in size of cells (appearance)
athletes prefer what? hypertrophy or hyperplasia?
hyperplasia - increased number of cells (or myofibrils in each cell, strength)
which 2 factors contribute to hypertrophy?
sarcoplasmic hypertrophy - focuses more on increased muscle glycogen storage
myofibrillar hypertrophy - focuses more on increased myofibril size
how does hypertrophy/hyperplasia present in pregnancy?
hyperplasia - breast epithelial cells respond to increased demands
uterus - both hypertrophy and hyperplasia
define atrophy
decrease in the size of cells caused by a decrease in NUMBER of cells OR decrease in SIZE
why might pathological atrophy happen?
bc of loss of blood supply, loss of innervation, pressure, lack of nutrition, lack of hormonal stimulation or bc of hormonal stimulation
define metaplasia
reversible transofrmation of 1 mature cell type in another fully differentiated cell type
what is an example of metaplasia in smokers?
transofmration of normal pseudostratified columnar ciliated epithelium of bronchi into squamous epithelium after repeated exposure to cig smoke
what is dysplasia?
an imprecise term forthe morphological changes seen in cells in the progression to becoming cancer
it’s a premalignant condition characterised by increased growth, cellular atypia and decreased differentiation
why does hearing loss occur in older age?
hair cells in the cochlear don’t regenerate
list some examples of illnesses associated w/ ageing
osteoporosis
cataracts
dementia
sarcopaenia (lack of muscle)
deafness
what is the generic term for a malignant tumour?
cancer
how does basal cell carcinoma of the skin act?
only invades localy - can be locally excised and cured !
most carcinomas spread to where?
lymph nodes that drain the site of the carcinoma
what are 5 common tumours that spread to bone?
breast
prostate
lung
thyroid
kidney
what is the easiest way to confirm breast cancer?
small needle biopsy
what is a lumpectomy?
breast conserving surgery / partial masectomy / wide excision
what is the most widely used cancer staging system and what does it mean?
TMN system
T = extent of tumoour
M = presence of metastases
N = spread to lymph nodes
what is the TNM staging converted to?
0 = carcinoma in situ
1-3 = size of cancer/nearby spread
4 = metastatic disease
define carcinogenesis
process which results in the transformation of normal cells to neopalstic cells due to permanent genetic alterations (mutations)
what does carcinogenesis only strictly apply to?
malignant tumours
what are carcinogens?
agents known/suspected to participate in the causation of tumours
how may env carcinogens be identified?
from epidemiological studies
assessment of occupational risks
direct accidental exposure
experiemntal observations
what type of process is carcinogenesis? and why?
multistep - may require initiating and promoting agents - often resulting in a latent period btwn exposure to carcinogen and clinical recognition of a tumour
what is the diff btwn carcinogenic and ongogenic?
carcinogenic = cancer causing
oncogenic = tumour causing
list some classes of carcinogens
- chemical
- viral
- ionising and non-ionising radiation
- hormones, parasites and mycotoxins
- miscellaneous
what are some host factors for carcinogens?
race
diet
constitutional factors eg age/gender
premalignant lesions
transplacental exposure
what is a neoplasm?
a lesion resulting from the autonomous growth of cells which persists after the initiating stimulus has been removed
what are benign neoplasms like ?
generally slow growign
closely resemble parent tissue
remain localised
what are malignant neoplasms like?
have the capacity to invade surrounding tissues
grow more rapidly
show variable resemblance to parent tissue
all neoplasma are designated by which suffix?
“-oma”
benign connective tissue neoplasms have a prefix denoting what?
cell of orgin
eg lipoma - benign neoplasm arising from adipocyte
malignant epithelial tumours = carcinomas
malignant connective tissue neoplasms = ?
sarcomas
what are neoplasms made up of?
neoplastic cells and stroma
what is a stroma?
supporting networking cells
define angiogenesis
recruiting blood vessels to help and grow
how can neoplasms be classified behaviourally?
benign, borderline, malignant
why should we worry about “benign” neoplasms?
they cause morbidity and mortality through:
- pressure on adjacent structures
- obstruct flow
- produce hormones
- transform to malignant neoplasms
- anxiety
how can neoplasms be classified histogenetically?
- specific cell of origin of a tumour
- histopathological exam
- specifieis tumout type
what is a papilloma?
benign tumour of non-glandular, non-secretory epithelium
prefix with cell type of origin eg squamous cell papilloma
what is an adenoma?
benign tumour of glandular/secretory epithelium
prefix with cell type of origin eg thyroid adenoma
name 2 benign epithelial neoplasms
papilloma
adenoma
name 2 malignant epithelial neoplasms
carcinoma
adenocarcinoma
what is the diff btwn carcinoma and adenocarcinoma?
carcinoma - malignant tumour of epithelial cells
adenocarcinoma - carcinomas of glandular epithelum
all carcinomas are caused by malignancies of what?
epithelium
all sarcomas are malignancies of what?
connective tissue
what is invasion of tumours dependent upon?
decreased cellular adehesion
abnormal (increased) cellular motility
prod of enzymes w/ lytic effect on surrounding tissues
what is metastasis?
process by which a malignant tumour spreads from its primary site to prod secondary tumours at distant sites?
metastasis is dependent upon what?
a chain of events known as metastatic cascade (detachment, invasion, intravasion, evasion of host defences, arrest, extravasation, vascularisation)
what is the diff btwn carcinoma in situ and invasive carcinoma?
carcinoma in situ = can’t metastasise, can be locally removed
invasive carcinoma = worry of spreading
breast cancer is a malignant tumour arising from what?
the epithelial cells lining the ducts and lobules of the breast
name a popular anti-oestrogen drug?
tamoxifen
what are 2 ways of increasing tumour size?
cell division
lack of cell death (apoptosis)
T cells originate from what and mature where?
originate from stem cells in bone marrow
mature in the thymus
travel to blood and lymph
does innate immunity depend on lymphocytes?
no, adaptive does
draw out the graph thing of what a multipotent stem cell differentiates into :)
polymorphonuclear leucocytes are mainly involved in what?
allergic reactions
when are neutrophils important and what for?
innate immunity
phagocytosis
what are eosinophils mainly associated w?
parasitic infections and allergic reactions
what are basophils similar to? what are they mainly involved in?
mast cells
immunity to parasitic infections/allergic reactions
when are monocytes important n what for ?
innate and adaptive immunity
phagocytosis
how are monocytes and macrophages linked?
monocytes –> macrophages
once a monocyte leaves blood, it matures into a wandering/fixed macrophage
what do T cells expresss
CD3 - T cell receptor complex
what are complements?
group of ≈20 serum proteins that need to be ‘activated’ to be functional
what is epitope?
part of the antigen that binds to the antibody/receptor binding site
what is the most common Ig?
IgG
what are cytokines?
proteins secreted by immune and non-immune cells
what are interferons? (IFN)
induce a state of antiviral resistance in uninfected cells
limit spread of viral infection
IFNa&b - prod by virus infected cells
what are interleukins? (IL)
produced by many cells
can be pro-inflammaotry (IL1) or anti-inflammatory (IL-10)
can cause cells to divide, differentiate and secrete factors
what are tumour necrosis factors (TNF)
mediate inflammation and cytotoxic reactions
potent
list examples of cytokines
IFN
IL
TNF
what 3 things does innate immunity include?
- physical/chemical barriers
- phagocytic cells (neutrophils and macrophages)
- serum proteins (complement, acute phase)
what is inflammation?
a series of reactions that brings cells/molcules of immune system to sites of infection or damage
how is bacteria/funghi generally responded to?
phagocytosis
killing
how are viruses generally handled?
cellular shut-down
self-sacrifice
cellular resistance
what is pattern recognition
recognition of microbes/viruses depends on seeing ancient, conserved features of them
families of receptors exist to detect these in fluids, cell surfaces and compartments and intracellularly
what is an adjuvant?
a substane which enhances the body’s immune response to an antigen
what are the 3 types of drug interaction?
synergy
antagonism
other
what are some risk factors for drug interaction?
patient wise:
- polypharmacy
- old age
- genetics
- hepatic/renal disease
drug wise:
- narrow therapeutic index
- steep dose/response curve
- saturable metabolism
what is the diff btwn pharmacodynamics and pharmacokinetics?
pharmacodynamics - what the drug does to the BODY eg falling asleep, slower HR etc
pharmacokinetics - what the body does to the DRUG
the pharmacokinetics model of drug interaction looks at which 4 factors?
A - absorption
D - distribution
M - metabolism
E - excretion
what is the biggest cause of OD in the world?
aspirin !
name a drug that causes LOTS of drug ineractiosn
warfarin !!!!!
what are the 3 traditional forms of vaccines?
live attenuated
whole killed
toxoids
what is passive immunisation?
transfer of preformed antibodies
define natural immunity
transfer of maternal antibodies across placenta to the developing foetus or via breast milk
what is artificial immunity?
treatment with pooled normal human IgG OR treatment with immunoserum against pathogens/toxins
what is inoculation?
introduction of viable microorganisms into the subject but basically
inoculation = vaccination = immunisation
what are some advantages and disadvantages of whole live attenuated pathogen vaccines?
advantages
- sets up transient infection
- activation of full natural immune response
- memory response (t/b cells)
disadvantages
- immunocompromsied
- complications
what are some adv/disadv of whole killed, inactivated pathogens?
advantages
- no risk of infection
- storage less critical
disadvantages
- tend to just acivate humoral response (lack of t cell)
- immune response may be weak w/o transient infection
- repeated booster vaccinations required
- patient compliance can be an issue
what are some advantages and disadvantages of subunit vaccines?
advantages
- safe - only parts of pathogen used
- no risk of infection
- easy to store n preserve
disadvantages
- immune response less powerful
- repeated vaccines
what is a drug?
chemical substance of known sturcture (other than nutrient/essential vitamin) which, when administered to an organism, produces a biological effect
what is the diff btwn pharmacodynamics and pharmacokinetics again?
dynamics - effect of drug on body. dynamic effects that a drug may have !
kinetics - effect of body on the drug - kinetically, the drug may behave in many diff ways
what is a drug receptor?
biological term for recognition proteins of endogenous mediators
a drug which binds to a receptor is termed what?
ligand
what are the diff types of ligands?
agonists - initiate bio response
antagonists - don’t initiate bio response but prevent naturally occuring mediators from binding
what does efficacy refer to in drug use?
maximum response “drug required to prod 50% of max)
what are some types of ligands?
exogenous (drugs)
endogenous (hormones, neurotransmitters etc)
what are some types of receptors? n what are receptors?
principal means by which chemicals communicate
neurotransmitters, autacoids (local) eg cytokines/histamine, hormones
what are some types of receptors?
- ligand-gated ion channel
- g protein coupled receptors
- kinase-linked receptors
- cytosolic/nuclear receptors
what is an example of a ligand-gated ion channel
nicotinic ACh receptor
which receptor is beta-adrenoceptors an example of?
g protein coupled receptors
name a kinase-linked receptor
receptors for growth factors
name a cytosolic/nuclear receptor
steroid receptor
what is diff btwn affinity and efficacy?
affinity is how well a ligand BINDS to the receptor
efficacy is how well the ligand ACTIVATES the receptor
what are some receptor-related factors governing drug action?
affinity
efficacy
what are some tissue-related factors governing drug action?
receptor number
signal amplification
what is EC50?
conc required for half maximal response
sodium channels can be inhibited by afferent nerve fibres by local anaesthetics to what? (3))
to prevent pain
in the heart to treat arrhythmia
in the brai to treat epilepsy
which channels may be inhibited in vascular smooth muscle to treat hypertension?
calcium
potassium channels can be inhibited to treat what? (2)
arrhythmia
diabetes
what are 3 main types of protein ports in cell membranes?
uniporters: use energy from ATP to pull molec in
symporters: use movement in of 1 molec to pull in another molec against conc grad
antiporters: 1 substance moves against grad using energy from 2nd substrance moving down its grad)
what are xenobioitcs?
compounds foreign to an organism’s normal biochem, such as any drug or poison
what are the 2 key beliefs influencing patient adherence to med?
necessity beliefs: perceptions abt personal need for treatment
concerns abt a range of potential adverse consequences
what are the 4 impacts of good doc-patient communication?
- better health outcomes
- higher adherence to therapeutic regimens
- higher pt and clinician satisfaction
- decrease in malpractice risk
what are the key principles of improving patient adherence?
- improve communication
- increase pt involvement
- understand pt’s perspective
- provide info
- assess adherence
- review meds
what does drug elimination refer to?
the removal of a drug from the plasma compartment towards its eventual excretion from the body
what is pharmacology?
action of drugs in the body inc: absorption, distribution, metabolism, excretion
list 10 routes of drug admin
- oral
- IV
- IA
- IM
- SC
- inhalational
- topical
- SL
- rectal
- intrathecal (injection into spinal canal)
what is pinocytosis?
aka fluid endocytosis
ingestion of liquid into a cell by the budding of small vesicles from the membrane
what is pKA of a drug?
pH at which half of substance is ionised n half unionised
what is the easiest and most convenient route for many drugs?
oral - large SA/high blood flow of S intestine –> rapid.complete absorption
drug needs to be _____ soluble to be absorbed from the gut
lipid
what is 1st pass metabolism?
drug taken orally have to pass 4 major metablic barriers to reach circulation:
- intestinal wall
- intestinal lumen
- liver
- lungs
how do u avoid hepatic 1st pass metabolism
by giving drug to region of gut not drained by splanchnic eg mouth or rectum (GTN)
what is the fastest route for admin?
IV - 20-60 secs
what is the slowest route for drug admin?
transdermal (topical) - variable, mins to hrs!
what is cytochrome p450?
fam of membrane bound isoenzymes
present in smooth ER, largely in liver tissue
smoking/alcohol can induce p450 enzymes - more rapid drug metabolism
what are some naturally occuring opioids?
morphine
codeine (weak)
how do opioids work?
- inhibit the release of pain transmitters at SC (sup colliculus? idk)/mid brain
- modulate pain perception in higher centres
- euphoria (changes emotional perception of pain)
what is potency?
whether a drug is strong/weak - relate sto how well the drug binds to receptor
what is tolerance?
down regulation of receptors with prolonged use
need higher doses to achieve the same effect
what is the potential with opioid use?
respiratory depression
addiction - esp when used for chronic stuff
what are the 2 main neurotransmitters?
ACh
NAd
where are M1/M2 (muscarinic receptors) mainly found?
in the heart
- their activation slows heart, so we can block these
where are M3 muscarinic receptors found
glandular and smooth muscle
- cause bronchoconstriction, sweating,s salivary gland secretion
where are M4/5/ muscarinic receptors found?
CNS
how do u treat bronchoconstriction?
block M3 receptor - anti-cholinergics or anti-muscarinics
short-acting: ipratropium bromide
long-acting: LAMAs eg tiotropium
ACh is a major transmitter innervating what?
skeletal muscle
what are some side effects of anti-cholinergics?
in the brain - worsen memory, may cause confusion
peripherally - constipation, mouth drying, vision blurring etc
what are inotropes?
group of drugs that alter contractility of the heart
positive inotropes - incr FORCE OF CONTRACTION of the heart
negative inotropes - weaken it
how do chronotropic drugs change the heart rate n rhythm?
affecting the electrical conduction system of heart n nerves that influence it eg by changing rhythm prod by SA node
pos chronotropes INCR HEART RATE
neg chronotropes DECR HEART RATE
what does alpha 1 activation cause?
vasoconstriction particularly in skin and splanchnic (abdo) beds
good for septic shock treatment
beta 1 activation will do what to the heart?
incr HR
chronotropic effects
may incr risk of arrhythmias
when may beta blockers be used?
angina
MI prevention
high BP
anxiety
arrhythmias
heart failure
what does propranolol do and what group of drugs does it belong to?
beta blockers
blocks beta 1 n beta 2
- will slow HR, reduce tremor, may cause wheeze
what does atenolol do n what class of drugs does it belond to?
beta 1 selective
main efects on heart
beta blocker
what is eclampsia?
a cond in which 1+ convulsions occur in a pregnant woman suffering from high BP, often followed by coma
what is pre-eclampsia?
disorder of pregnancy - high BP and either large amts of protein in urine or other organ dysfunction
what is an allergic reaction?
an inappropriate immune response to an otherwise harmless substance
what are some skin clinical indications related to allergy?
eczema
itching
reddening
what are some airway clinical indications related to allergy?
excessive mucus production
bronchoconstriction
what are some GI clinical indications related to allergy?
abdo bloating
vomiting
diarrhoea
what is anaphylaxis?
acute allergic reaction to an antigen EG bee sting, to which the body has become hypersensitive
what is atopy?
tendency to develop allergies
what is allergic rhinitis?
hayfever
how can anaphylaxis be treated?
adrenaline !
what is an adverse drug reaction?
unwanted/harmful reaction following admin of a drug under normal cond of use .. n its suspected to be related to the drug
when should an adverse drug reaction be suspected?
- symptoms soon after new drug started
- symptoms after dosage increase
- symptoms disappear when drug is stopped
- symptoms reappear when drug is restarted
what are the most common drugs to have adverse reactions?
ABs
anti-neoplastics
CV drugs
NSAIDs
what are some common ADR’s?
confusion
nausea
balance issues
diarrhoea/constipation
what are the 4 types of hypersensitivity?
t1 - igE mediated drug hypersensitivity
t2 - IgG mediated cytotoxicity
t3 - immune complex deposition
t4 - t cell mediated
what happens in anaphylaxis?
occurs within mins, lasts 1-2hrs
rash
swelling of lips, face
wheeze/SOB
hypotension
cardiac arrest
vasodilation
incr vascular permeability
bronchoconstriction
angio-oedema
what are some common drugs for anaphylaxis?
penicillin
aspirin
NSAIDs
how does adrenaline affect the heart?
vasoconstriction - incr peripheral vascular resistance, incr BP, incr coronary perfusion (alpha1-adrenoceptors)
stimulation of beta1-adrenoceptors - positive inotropic and chronotropic effects
reduces oedema/bronchodilates via beta2adrenoceptors
what do u do to a patient with suspected anaphylaxis?
immediately: lie flat, raise legs (if breathing not impaired)
when skills/equipment available:
- establish airway
- high flow oxygen
- IV fluid challenge
monitor: pulse ox, ECG, BP
what does helminth mean?
parasitic worm
what is the pre-patent period in a worm infection?
interval btwn infection n appearance of eggs in stool
what are the 3 groups of worms (helminths)?
- roundworms (nematodes)
- flatworms, flukes (trematodes)
- tapeworms (cestodes)
what is ascaris lumbricoides?
large roundworms
found worldwide, mainly tropics
children particularly prone
what is the only common helminth infestation in the UK
pinworm/threadworm
what is trichus trichirua?
the whipworm
what is schistosomiasis?
aka bilharzia - an infection caused by a parasitic worm that lives in fresh water in subtropical/tropical regions
what is mycobacteria?
a bacterium of a group which includes the causative agents of leprosy and tuberculosis
what happens in leprosy?
causes lots of deformation
damages nerves
loss of sensation: ppl get injured, may lose ends of digits/limbs etc
what is acid fast bacilli?
mycobacteria!
what can mycobacteria cause?
tuberculosis, leprosy
is mycobacteria easy to culture?
no, bc they are slow growing
name some viruses that can cause rashes
rubella
measles
parovirus
list 5 basic properties of viruses
- grow only inside living cells
- possess only 1 type of nucleic acid: RNA or DNA
- no cell wall struc but have an outer protein coat
- essentially inet outside the host cell
- protein receptors on surface allow attachment to susceptible host cells
what are the 6 stages of virus replication?
- attachment
- cell entry
- interaction w/ host cells
- replication
- assembly
- release
list 5 ways in which viruses can cause disease
- damage by direct destruction of host cells (influenza)
- damage by modification of host cell structure/function (HIV)
- damage involving over-reactivity of host as a response to infection (hep B/C)
- damage through cell proliferation/immortalisation (HPV)
- evasion of both EX/IC host defences (measles, Hep B/C etc)
what are the medically important pathogens?
streptococci
staphylococci
what are the 3 structures of bacteria?
spherical - COCCUS
rod-shaped - BACILLUS
SPIRAL
what are 3 types of microorganism
bacteria
viruses
eukaryotic organisms
what colour is gram positive?
purple
what colour is gram negative bacteria?
pink / (red)
define pathogen
organism that is capable of causing disease
define comensal
organism which colonises the host but causes no disease in normal circumstances
what is an opportunist pathogen?
microbe that only causes disease if host defence are compromised
what is virulence/pathogenicity?
the degree to which a given organism is pathogenic
what is asymptomatic carriage?
when a pathogen is carried harmlessly at a tissue site where it causes no disease
what is haemolysis?
the ability of bacteria to break down RBC in blood agar
what is coagulase?
enzyme produced by bacteria that clots blood plasma
how can steph aureus be spread?
by aerosol (coughs/sneezes) and touch
eg MRSA !
what are some infections caused by s.pyogenes?
wound infections
tonsilitis/pharyngitis
impetigo
scarlet fever
rheumatic fever
what can s.pneumoniae cause?
it’s a normal commensal in oro-pharynx that can cause:
pneumonia
sinusitis
meningitis
list some important gram-pos bacteria
s. aureus
s. epidermidis
s. pyogenes
s. pneumoniaeviridans streptococci
c. diptheriae
how can gram positive bacteria be spread?
aerosols
surface-to-surface contact
colonisation of prostheses
how can gram positive bacteria be managed?
antimicrobials
vaccination
what is source of bacteraemia often?
infection of abdo organ
also wounds, cystitis etc
what is the pathogenesis of salmonellosis
ingestion of contaminated food/water
invasion of gut epithelium - s intestine
intestinal secretory/inflammatory response
etc
list some important gram negative bacteria
haemophilus influenzae
h. influenzae
bordetella pertussis (whooping cough)
n. meningitidis (meningococcus)
n. gonorrhoea (gonococcus)
campylobacter (c. jejuni, c. coli)
helicobacter pylori
chlamydiae
what is the diff btwn yeast and mould?
yeast - small single celled organisms, divide by budding
moulds - form multicellular hyphae and spores
define funghus
group of spore-producing organisms feeding on organic matter, inc moulds, yeast, mushrooms
what is a spore?
unit of sexual/asexual reproduction - may be adapted for dispersal/survival, often for extende dperiods of time, in unfavourable cond
spores form part of life cycles of many plants, algae, fungi and protozoa
what is mucosal candidiasis?
thrush
the prodution of what, by t cells/macrophages, is important in controlling the spread of virus from 1 cell to another?
gamma-interferon
how are worms in the body killed?
eg schistosomes coated with IgG/IgE - recognised by eosinophils - release toxic substances to kill them
what are key attributes of pathogens?
infectivity
virulence
invasiveness
what is antigenic drift n what can it result in?
viral spontaneous mutations, occur gradually, giving minor changes - epidemics
what is antigenic shift n what can it result in?
sudden emergence of new subtype diff to that of preceding virus - pandemics
what do adhesins do
help bacteria bind to mucosal surfaces
what do pattern recognition receptors do (PRR)
recognise PAMPs (pathogen associated molecular patterns) but also damage associated molecular patterns from host cells
what is a protozoa?
single-celled eukaryote that commonly show characteristics usually associated with animals, most notably mobility/heterotrophy
what is african trpanosmiasis aka
sleeping sickness !
what is a chancre?
painless genital ulcer
what is american trypanosomiasis aka?
chagas disease
discuss faecal-oral transmission
occurs when bacteria/viruses found in stool of 1 child/animal are swallowed by another child
what can amoebiasis result in
dysentry
colitis
liver and lung abscesses
what is myalgia
muscle pains
what is a fancy word for high temp?
pyrexia
if there’s fever and recent travel, question WHAT?
malarrrrrrrrrIA!
how is malaria transmitted?
bite of female anopheles mosquito
which plasmodium of malaria has the most severe disease?
plasmodium falciparum
what kind of infection is malaria?
protozoan - can have up to 1 yr incubatiionperiod
how do u diagnose malaria
blood film
what are malaria symptoms?
FEVER
FEVER
FEVER
also: chills, headache, myalgia, fatigue, D&V, abdo pain
what are some signs of malaria?
anaemia
jaundice
hepatosplenomegaly (lack water fever)
what are some complications of malaria?
acute resp distress syndrome
renal failure
bleeding
shock
what is hypovolaemic shock?
clinical state in which loss of blood/plasma causes inadequate tissue perfusion
what is clostrium difficile?
bacterium - can infect bowel n cause diarrhoea
how might bacteria resist ABs
mutations
destroy ABs
antigenic variation
what does MRSA stand for
methicillin resistant stapylococcus aureus
which factors should be considered when determining if ABs are safe for patient use?
- intolerance, allergy and anaphylaxis
- side effects
- age
- renal and liver function
- pregnancy n breast feeding
- drug interactions
what are beta lactams?
cell wall (peptidoglycan) killers
name some causative organisms for hosp acquired infectiosn
staphyloccocus aureus (inc MRSA)
streptococcus pyogenes (group A streptococcus)
what are key components of infection prevention n control?
infection prevention n control team
ward teams
microbio/virology labs
etc
what is the major means of HIV transmission worldwide?
heterosexual intercourse
other risk factors include: homosexual intercourse, IVDU, blood transfusions
when is HIV untransmittable?
when it’s undetectable
(so if ur HIV+, take treatment, maintain undetectable viral load - can have sex knowing u won’t pass it on)
what treatment is there for HIV?
HAART - highly active antiretroviral treatment
in HIV how do u measure how well the immune system is doing?
CD4 count
what are some methods of HIV prevention?
circumcision
PEP
STI control
vaccines
diagnosis/partner notif
HAART treatment as prevention
screen blood prods/needle exchange
maintain a high index of HIV suspicion if what?
prolonged episodes of herpes simplex
persistent thrush
oral thrush
recent/worsening skin conditions
unexplained weight loss
what is HIV caused by?
HIV-1 or HIV-2
what happens in HIV?
decrease in number of CD4 t-lymphocytes by a number of related mechanisms including cell death by apoptis sand increased trapping of cells in lymphoidal tissue
after a HIV infection, there is a variable period of _-_ months before the antibody test is positive
3-6
what is the approx HIV clinically latent period before ppl start getting unwell?
≈ 7 years
on presentation of antigen, CD4 cells mature in 2 types of helper cells… waht do these then prod?
Th1 - prod specific interleukins (IL4, 5, 10, 13)
Th2 - prod IFN alpha and TNF
what are the 9 steps of HIV replication?
- attachment
- entry
- uncoating
- reverse transcription
- genome integration
- transcription of viral RNA
- splicing of mRNA and translation into proteins
- assembly of new virions
- budding
how does the immune system respond to HIV? (draw the graph LOL)
what is shingle in HIV patients like?
usually more severe
can be multidermatomal
usually occurs in elderly
when is a HIV patient said to have AIDS?
when CD4 count < 200
or
when “AIDS defining illness” is present
what are the 3 stages of a HIV/AIDS epidemic?
- nascent: HIV prevalence less than 5%
- concentrated: prevalence has surpassed 5% in 1+ high risk populations, but prevalence among women attending urban antenatal clinics still less than 5%
- generalised: HIV has spread far beyond original subpopulations - prevalence among women attending urban atenatal clinics is 5%+
why does circumcision lower the risk of HIV?
- reduced ability of HIV to penetrate due to keratinisation of inner aspect of remaining foreskin
- inner part of foreskin contains langerhan cells: prime targets for hiv. these are removed w/ foreskin
- ulcers (characteristics of some STI’s that ca facilitate HIV transmission) often occur on foreskin
- foreskin may suffer abrasions/inflammation during sex that could facilitate the passage of HIV
