Block 9 Flashcards
What are the main ‘AIDS indicator diseases’?
Pneumocystis jiroverci = fungal pneumonia Candida albicans = fungal candidiasis Cytomegalovirus = viral chorioenteritis TB Cryptococcus Varicella zoster virus = herpes shingles Herpes virus 8 = Karposi's sarcoma EBV = Burkitt's lymphoma HPV = cervical and oral cancer
How can partial thickness burns be distinguished from full thickness burns.
Partial = red, painful and blistered
Full = painless, white, no blistering
What are the 3 most important aspects of a burn to assess?
Size
Site
Depth
What are the 5 layers of the epidermis?
Stratum basale = basement membrane and germinal layer of stem cells which provide new keratinocytes.
Stratum spinosum = Growing keratinocytes which are starting to produce keratin.
Stratum granulosum = formation of intracellular granules which contribute to the keratinisation of the cells. Secretion of lamellar bodies which form a water resistant oil.
Stratum lucidum = Thin layer of keratinocytes
Stratum corneum = the final layer where the keratinocytes have fused, flattened and died to produce a protective layer.
What are the advantages of liquid medication over tablets?
Drug is immediately available for absorption
Easy to give flexible dosing
Lots of different absorption methods (injection, oral, enema, topical)
Much easier to swallow
What are the disadvantages of liquid medication over tablets?
The drug stability is reduced due to hydrolysis and oxidation of the drug in question
Can taste very unpleasant
Bulky, hard to transport and easy to break
Hard to measure exact dosing
Measuring equipment is required for administration
What are the organs imbedded into the skin?
Hair follicles
Sebaceous glands
Sweat glands
Arrector pili muscles
What is the dermis?
The dense bed of vascular connective tissue, supplying the epidermis.
Two layers:
papillary = vascular bed
reticular = dense connective tissue for strength
What is the process of plaque formation in atherosclerosis?
Damage to vascular endothelium
LDL invades the endothelium and is oxidised causing an inflammatory response and the endothelial cells ‘calling’ for monocytes by increased expression of adhesion molecules.
Monocytes enter the intima of the artery and become macrophages which then express LDL absorption molecules, ingesting lipids to become foam cells.
Foam cells form visible fatty streaks on the arterial lumen.
Proliferation of surrounding tissue builds up to form a plaque.
Plaque becomes calcified through calcium deposition causing hardening of the artery.
What is the rule of 9 for burns?
Each main area of the body is worth around 9% of total surface area, the legs are 18% and the groin in 1%.
Why are plaques within arteries dangerous?
They can occlude the arterial lumen,
they are rough so can form thrombi,
they can easily rupture, generating a thrombus themselves.
What are the main risk factor catagories for atherosclerosis?
High blood cholesterol / LDL levels
Increased likelyhood of arterial damage
Fixed
Non-fixed
What are the causes of arterial endothelial damage?
Diabetes mellitus Hyertension Smoking Being male Excess blood iron Some genetic conditions
What are the main functions of the skin?
Protection: (mechanical, thermal, water, chemical, immunological, UV light)
Sensation: (touch, pressure, pain, temperature)
Thermoregulation: (Insulation, sweating)
Metabolic functions: (Vit. D, lipid store)
What are the 3 zones of burns?
Zone of coagulation = tissue loss due to protein coagulation
Zone of stasis = low perfusion which can be saved
Zone of hyperaemia = tissue with high perfusion to facilitate normal functioning
What is the importance of large areas of burn?
Burns larger than 30% of bosy surface area (rule of 9) can lead to hypovolaemic shock due to hypotension.
Increased capillary permeability, blistering, peripheral vasoconstriction, bronchoconstriction.
All due to cytokines etc. released from the dead and damages cells.
What is the basic process of burn healing for all degrees?
1st degree = cellular repair from the stratum basale as it has not been damaged
2nd degree = initial fibrous repair of the dermal layers by fibroblasts and then repopulation of the stratum basale from the invaginations around accessory organs in the skin such as hair follicles.
3rd degree = scar formation from fibroblast activity in the demal layers. No natural repair as conplete loss of all stem cells. Requires skin grafting for seeding of new skin.
Define ischaemia.
When the blood supply to an tissue is too low to meet that tissues metabolic demands. Can lead to necrosis of the tissue (if accute) or hypotrophy (if chronic).
What are the 3 broad causes of ischaemia?
Vascular insufficiency (atherosclerosis etc.) Hypotension (shock etc.) Increased demand (hypertrophy etc.)
How long does tissue necrosis take?
Depends on the tissue.
Neurones = 4 minutes
Kidney = 20 minutes
Cardiac muscle, liver, = 40-80 minutes
Skeletal muscle = hours
Define infarction.
An area of ischaemic necrosis caused by the occlusion of the blood supply to that tissue (usually acute).
What are the two types of infarction?
White = arterial occlusion of normal organ parenchyma.
Red = venous occlusion, organs with dual or colateral blood supply.
What is the ischaemic cascade?
The cellular processes (due to ischaemia) that cause damage or death.
Reduced oxidative phosphorylation –> reduced ATP production –> Na+ pump not working, anaerobic respiration and detachment of ribosomes from RER
pumps not working = influx of Ca2+ and Na+ = cellular swelling and activation of enzymes
anaerobic respiration = lactic acid, reduced pH and protein denaturing
Detachment of ribosomes = low protein synthesis and reduced cellular functioning.
Why is an influx of Ca2+ bad for a cell
Main cause of IRREVERSIBLE cellular injury. Causes the activation of enzymes that damage the ultrastructure of the cell.
Phospholipases and proteases = reduced membrane permeability.
Endonucleases = nuclear damage
ATPases = reduced cellular ATP
What is quorum sensing?
The ability of bacteria to behave as a multicellular organism by secreting and sensing different amounts of chemicals.
E.g. autoinducer peptides which only take effect when concentrations reach high levels. Enables bacterial colonies to lie dormant.
What are bacterial adhesins?
Bacterial surface molecules (techoic acid/protein F) which allow bacteria to adhere onto host cells.
What are bacterial pili?
Small protein fillaments which vary between bacterial species and allow bacterial adherence to SPECIFIC cells of the host’s body.
What are the two types of bacterial toxin?
Endotoxin = toxins imbedded into the becterial cell wall (lipopolysaccharide on gram -ve)
Exotoxins = toxins that are secreted by the bacteria into the host body. (enzymes, neurotoxins, superantigens etc.)
What are the 4 main types of pneumonia?
Community acquired
Hospital acquired
Aspiration
Chronic
What are the main organisms responsible for community acquired pneumonia?
S. pneumoniae H. influenzae M. catarrhalis S. aureus Enterobacteriaceae
What are the main organisms responsible for hospital acquired pneumonia?
Enterobacteriaceae
S. aureus
What are the main causes of chronic pneumonia?
Fungal infections:
Nocardia, Actinomyces etc.
M. tuberculosis
Why is a bacterial pneumonia more likely after a viral respiratory infection?
Viral respiratory infections cause a build up of mucus (consolidation) and damage to the mucocillary system within the lungs. This creates a prefect environment to harbor the growth of bacterial pathogens.
What are the two main forms of bacterial pneumonia?
Lobar = Consolidation of a large part/lobe of the lung
Lobular bronchopneumonia = Patchy consolidation of the lung.
What are the 4 inflamatory stages of lobar pneumonia?
Congestion = (vascular enlargement, intra-alveolar fluid and LOTS of bacteria)
Red Hepatization = leekage of erythrocytes causing the lung to become red and airless (like the liver)
Gray Hepatization = degredation of the erythrocyte, lung still consolidated
Resolution = Digestion of the consolidated exudate, lung can become scared or permenantly recover.
What are the symptoms of pneumonia?
Fever (hypothalamic changes) Cough (mucosal irritants) Rigors (to raise temperature) Fatigue Headache (vascular constriction) Decreased appetite Nausea and vomiting Chest pains on breathing (hypersensitivity of nociceptors) Shortness of breath (consolidation)
What are the risk factors for hospital acquired pneumonia?
Immunosuppressed vulnerable state
Mechanical ventilation
Prolonged antibiotic use
Describe the microbiology of S. pneumoniae
Gram +ve cocci in chains
Most common cause of community acquired pneumonia, diagnosis via sputum culture although false positives due to normal flora
Describe the microbiology of K. pneumoniae
Capsulated gram -ve bacillus.
Most common cause of gram -ve pneumonia. Creates a very sticky mucus due to the large polysaccharide capsule.
Give some examples of mechanisms of bacterial resistance.
Reduced cell wall permeability Eflux of the drug from the cell Alteration of the target site Enzymes which inactivate the drug Development of a new metabolic pathway
What are the methods of genetic exchange in bacteria?
Transformation = free DNA taken up by the cell
Transduction = DNA transferred by bacteriophage
Conjugation = Purpousful transmission of a PLASMID between 2 bacteria
Transposons = jumping genes that can change position within the bacterial genome.
What are the health implications of bacterial resistance?
Increase in hospital acquired infections which are harder to treat
Delayed response for propper treatment
Increased mortality and morbidity
Increased complications
Increased patient worry
What are the economic implications for bacterial resistance?
Longer hospital stay
More expensive drugs (last line) required
Screening costs
Isolation costs
(the estimated cost of MRSA to the NHS is £3.2-£4 billion p/y)
What are the implications of bacterial resistance to medical practice?
More prudent prescribing
Education
Infection control
Need to increase the development of new drugs
What are the 3 main types of meningitis?
Acute pyogenic (bacterial) meningitis
Acute aseptic (viral) meningitis
Chronic meningitis
What are the symptoms of meningitis?
Fever
Headache
Stiff Neck
Irritibility
Photophobia
Coluding of consciousness
Purpuric rash (only with neisseria meningitidis)
Why does neisseria meningitidis cause a purpuric rash?
When the bacteria dies it produces an endotoxin which causes activation of clotting factor XII and results in abnormal intravesicular clotting
What are the common causes of bacterial (pyogenic) meningitis in all 3 at risk groups:
Neonates
Adolescents
Geriatric
Nonatal = H. influenzae, group B strep, E.coli
Teenage = Neisseria meningitidis
Geriatric = S. pneumoniae, L. monocytogenes
Describe the presentation and treatment of viral meningitis.
Presentation = reduced symptoms to bacterial meningitis
Signs = no sign of meningococcal organisms in blood/CSF
Treatment = symptomatic, the disease is self managing.
What are two of the major complications of meningitis?
Hydrocephalus = increased intracranial pressure due to water
Endarteritis = inflamation of arterial tunica intima and resulting necrosis of the underlying brain tissue.
Describe the microbiology of:
N. meningitidis E. coli Group B strep H. influenzae S. pneumonea L. monocytogenes
N. meningitidis = gram -ve diplococci
E.coli = gram -ve bacillus
B Strep = gram +ve cocci on chains
H. influenzae = gram -ve coccobacillus
S. pneumoneae = gram +ve cocci in chains
L.monocytogenes = gram +ve bacillus
What is the mechanism of antibiotic allergy?
Both type 1 and type 2 allergies.
Hapten = a joining of the antibiotic and a host molecule as normally antibiotics are too small to elicit host immune responses.
E.G. penicillin forms haptens with RBC proteins due to highly reactive beta-lactem rings
Type 1 = IgE hypersensitivity to the antibiotic hapten during re-exposure.
Type 2 = Antibody mediated attack of the bodies own cells as the hapten remains attached to the cell. E.G. penicillin can cause a type 2 hypersensitive haemolytic anaemia.
Describe the cell wall of a gram positive bacteria.
The outer surface has teichoic acid on the outer surface with a thick layer of peptidoglycan underneath.
What are basket cells?
They surround the base of the hair follicle and sense pressure.
What are commensals? How are they beneficial?
this is the normal flora of the body.
Stimulate the immune system
Competition for pathogen colonisation
Produce beneficial nutrients
What are desmosomes?
They connect neighbouring cells together to provide structural support.
What are keratinocytes?
They are maturing cells from the basal layer that produce keratin they mature and adhere together.
What are merkel cells?
They are found in the basal layer of the epidermis and act as sensory receptors.
What are the 4 main routes for infection to enter the CNS?
Haematogenous spread
Direct implantation
Local extension
Transport along CNS
What is a virulence factor?
A factor that facilitates colonisation, growth and spread in the host. It is only a virulence factor if it is no longer a pathogen without it. e.g. adhesins, flagella, toxins and capsule.
What is bacterial pathogenesis is dependent on?
Adherence of bacteria to host cells
Ability to invade host cells
Ability to deliver toxins to tissues
What is MIC in terms of antibiotic use?
Minimum Inhibitory concentration
It is the minimum concentration of the antibiotic required to inhibit bacterial growth
Who is given prophylaxis after a case of meningitis?
Those with prolonged contact in a household setting in the 7 days prior to the case.
Transient close contact if exposed to infected droplets.
Describe the cell wall of gram +ve bacteria.
1 phospholipid bilayer
thick peptidoglycan layer
Adhesins in peptidoglycan (Teichoic acid, protein F)
What are the 4 main types of necrosis and the main tissues in which they occur?
Coagulative necrosis = normal organ parenchyma
Liquefactive necrosis = CNS tissue
Gangrenous necrosis = coagulative necrosis of the peripheral limbs
Fat necrosis = necrosis of adipose tissue. Most commonly in the abdoman as a result of acute pancreatitis.
Describe the cell wall of gram -ve bacteria.
2 phospholipid bilayers enclosing a thin lipopolysaccharide layer
Lots of antigenic (toxic) lipopolysaccharides imbedded in the wall.
What are the two main methods for genetic testing of bacteria?
16s RNA = identifying pary of the bacterial ribosome = good at SPECIES identification
Full genome sequencing = very detailed, can find different bacterial serotypes.
What are the 4 stages of bacterial growth? (GRAPH)
Lag phase
Exponential growth phase
Stasis phase (limitation of nutrients)
Death
What are the 2 broad methods for the development of bacterial resistance?
DNA mutation
Genetic exchange (Conjugation, transformation, transduction, transposons)
What are the 4 stages of bacterial infection, leading to the cause of disease?
Exposure Adherence Colonisation Toxin production and invasiveness Disease
Name 5 different bacterial virulence factors.
Flagella Pili Adhesins Toxins Capsules
Name some different methods of bacterial evasion of the immune system.
Hiding within cells
Antigenic variation (can cause resistance due to a single point mutation)
Molecular mimicary
Modification or blockage of the immune system
What is the importance of bacterial serotypes (using E.coli as an example)?
It can determine if a bacterium is pathogenic or not.
E.coli K12 = non-pathogenic
E.coli 0157 = food poisoning or haemolytic anaemia
E.coli K1 = neonatal meningitis
What is Koch’s postulate?
That a bacteria can be said to cause a disease if it can be isolated from a diseased animal and induces the same disease if introduced into a helathy animal.
How does a blister form?
It is due to the mechanical fatigue of the epidermis. A split occurs in the stratum spinosum. As they separate the hydrostatic pressure allows fluid to form in the space. New cells in the basal regenerate to form the new skin layer.
What are the 2 main morphological types of virus?
Encapsulated = contained in a phospholipid bilayer that it broke off during endocytosis
Naked = just a capsid containing bacterial genetic information
In which direction is DNA/RNA read?
5’ –> 3’
What are the advantages of naked vs encapsulated viruses?
Naked = spreads more easily and more stable
Encapsulated = must stay wet, sensitive to detergents, does not need to lyse cell to reproduce.
What are the 6 types of viral genome?
RNA (double and single stranded)
What are the major complications of chicken pox?
Varicella pneumonia Varicella hepatitis Varicella encephalitis (vasculitis of vasa nervosum) Thrombocytopaenia (reduced platelets) Adrenal necrosis
What is the basic timeframe for a chickenpox infection?
Exopsure –> 14-21 day incubation –> symptoms –> systemic rash
What are the 4 stages of rash in chickenpox?
Macules = change of skin colour Papules = raised skin lesions Vesicles = small blisters w/ clear fluid Pustules = small purulent blisters
Describe the Varicella Zoster Virus
Encapsulated
Double stranded DNA
Cell associated replication
HIghly temperature sensitive (50-60 oC)
Describe the basic pathology of primary infection with varicella zoster virus.
Initial transmission = respiratory droplet.
After infection, virus has a 2-3 w incubatory peroid (in the mononuclear phagocyte system) where the patient is infectious just before the onset of symptoms
The rash is caused by the viral replication inside the epithelium of the respiratory mucosa.
Complications result from infalmmation of other organ epithelium
Rash = macular papular –> vesicular –> pustular –> crusting
Describe the recurrent infection of the varicella zoster virus
SHINGLES (zoster)
After primary infection with the VZV it lays dormant in the dorsal roots of nerve ganglia.
Here it consistently reactivates but usually subclinically. Sometimes (rarely 3/1000) the virus causes a clinical infection of the nerve resulting neuropathic pain and a vesicular rash localsed within the borders of the neurological dermatome.
Recurrence of the infection is common in immunocompromised patients (chemotherapy, steroid therapy, HIV, etc…)
What is the prophylaxis for Varicella Zoster?
High levels of passive immunity (IgG antibodies) given within 72 hours of the contact with infectious individual.
Preganant women
Immunocompromised patients
Newborns
What are the main infectious agents pregnant women have to avoid? (TORCHS)
T = toxoplasmosis O = other vertical infections R = Rubella C = Cytomegalovirus H = Herpes viruses S = syphilis
What are the 4 main areas of limitation with antiviral therapy?
Adherence to treatment Resistance Cost Interactions Side effects
Describe the difficulty of adherence with antiviral therapy.
Complex regime Poor Dr. - patient interaction Other druge use Severe side effects Mental illness Lack of patient education
Very important becuase effectiveness is strongly correlated to adherence to treatment
complex regimes are not as important now. Antiretroviral theray was 21 p/d in 1996, now 2/d
Describe the difficulty of resistance with antiviral therapy.
Some viruses (HIV) are very good at resisting antivirals through their VERY high mutation and replication rates.
This requires the use of multiple drug therapy but that comes back to more complex treatments.
Difficulty is keeping doses high enough to prevent resistance but low enough to prevent serious side effects (sin curve).
What are the main methods of heat loss and gain within the body?
Gain: Basal metabolic rate Extra metabolism (shivering, exercise) Digestion of food Fat acts as insulation (1/3 normal conduction)
Loss: Peripheral vasodilation Sweating (Evaporation) Conduction and convection Radiation
Both also have behavioural changes
What area in the brain is responsible for temperature regulation?
Preoptic and anterior hypothalamic nuclei.
Where are temperature receptors within the body?
Cold receptors:
Mainly in the periphal skin and some central arteries
The hypothalamic nuclei
To prevent hypothermia
Heat receptors:
Mainy in the hypothalamic nuclei
The vast majority of temperature sensation comes from temperature sensors directly within the hypothalamus itself.
Describe the basic physology of fever.
There are many substances (pyrogens) which can raise the hypothalamic temperature set point = PYROGENS!
Two types of pyrogen.
Exogenous = pathogen breakdown products and gram -ve LPS. These act on phgocytic cells to produce interleukin 1.
Endogenous = interleukin 1. This acts on the hypothalamus to cause the creation of prostaglandin E2 which, whilst present in the hypothalamus causes a rise of the set point.
How do NSAIDS (particularly aspirin) work to reduce fever?
They incativate the COX enzymes (importantly 2) which catalyse the formation of prostaglandins from arachnodonic acid. PgE2 is the main regulator of the temperature set point that acts on the hypothalamus to cause pyrexia.
What are the main types of fever?
Continuous = constant with change of 1ºC - 5ºC<
[typhoid, infective endocarditis]
Septic = fever with changes > 5ºC
[some septicaemias]
Pel Ebstein = continuous recurrence of fever with days between changes
[Hodgkins lymphoma]
Low grade = slight rise in temperature
[possible TB]
What is the meaning of +ve and -ve sense in regard to viral RNA and DNA?
+ve sense RNA = same direction of mRNA so can be directly converted to protein
-ve sense RNA = must be converted to +ve sense RNA (RNA polymerase) before use to form proteins.
DNA -ve sense strand is used to form mRNA, therefore, opposite.
Describe the pathogeneis and pathophysiology of Infectious Mononucleosis.
EBV is present in 95% of pop.
Clinical symptoms in 50% of adolescents infected.
Transmission = oral
Initial site of infection = oropharyngeal membrane
Invades B-cells
Latent within B-cells
Infection –> 30-40 d incubation –> symptoms (1-4 w)
The virus can re-activate from B-cell latency, causing proliferation, leading to IM / Burkitt lymphoma with specific gene translocation. (RARELY immunocompromised)
What are the tests for infectious mononucleosis?
Monspot test (70% sensitive 99% specific) = agglutination of horse RBC's due to production of specific antibodies from B-cell proliferation
Atypical lymphocytes in peripheral blod
Presence of antibodies for EBV envelope and nuleceocapsid
Who are the at risk groups for HIV infection?
Homosexual and bisexual men
IV drug users
Haemophiliacs
Sexual contacts of high risk groups (particularly if other STI’s are present)
Children of HIV +ve mothers
