ICS Flashcards
ACUTE INFLAMMATION
Acute inflammation is the initial and often transient series of tissue reactions to
injury - may last from a few hours to a few days
Causes of acute inflammation:
6
- Microbial infections e.g pyogenic (pus causing) bacteria, viruses
- Hypersensitivity reactions e.g parasites, tubercle bacilli
- Physical agents e.g trauma, ionising radiation, heat, cold (frost-bite)
- Chemicals e.g corrosives, acids, alkalis, reducing agents
- Bacterial toxins
- Tissue necrosis e.g ischaemic infarction
Essential macroscopic appearances of acute inflammation:
5
- Redness - rubor
- Heat - calor
- Swelling - tumor
- Pain - dolor
- Loss of function is also characteristic
Acute inflammatory response process:
3
- Changes in vessel calibre (gets wider) and consequently increased vessel flow
- Increased vascular permeability and formation of the fluid exudate
- Formation of the cellular exudate - emigration of the neutrophil polymorphs into the extravascular space
THE diagnostic histological feature of acute inflammation is …
… the accumulation of neutrophil polymorphs within the extracellular space
Stages in neutrophil polymorph emigration
- Margination of neutrophils
- Adhesion of neutrophils
- Neutrophil emigration
- Diapedesis
Endogenous chemical mediators of acute inflammation cause:
5
• Vasodilation
• Emigration of neutrophils
• Chemotaxis (the attraction of neutrophil polymorphs towards certain
chemicals e.g at the site of inflammation)
• Increased vascular permeability
• Itching & pain
CHRONIC INFLAMMATION
• The subsequent and often prolonged tissue reactions to injury following the initial
response
• Can be defined as an inflammatory process in which lymphocytes, plasma cells and macrophages predominate
Characteristic microscopic features of chronic inflammation:
3
- The cellular infiltrate consists characteristically of lymphocytes, plasma cells &
macrophages
A granuloma is …
… an aggregate of epithelioid histiocytes
ORGANISATION IS …
The repair of specialised tissue by …
… the formation of a fibrous scar
Cells that regenerate:
6
- Hepatocytes
- Pneumocytes
- All blood cells
- Gut epithelium
- Skin epithelium
- Osteocytes
Cells that do not regenerate:
2
- Myocardial cells
- Neurones
THROMBOSIS
why is it different from a clot?
- The solidification of blood contents that forms within the vascular system
during life
Blood coagulated outside of the vascular system or after death
Aspirin can … ?
Warfarin … ?
INHIBIT PLATELET AGGREGATION thus a low dose can help prevent thrombosis. In severe cases, warfarin can be used (inhibits vitamin K (clotting factor) - thereby preventing clotting)
EMBOLISM
An embolus is a mass of material in the vascular system able to lodge in a
vessel and block its lumen
ISCHAEMIA
A reduction in blood flow to a tissue or part of the body caused by constriction
or blockage of the blood vessels supplying it
INFARCTION
The death (necrosis) of part or the whole of an organ that occurs when the artery supplying it becomes obstructed
GANGRENE
When whole areas of a limb or a region of the gut have their arterial
supply cut off and large areas of mixed tissue die in bulk
ATHEROSCLEROSIS
Disease characterised by the formation of atherosclerotic plaques in the intima of
large (aorta) and medium-sized arteries, such as the coronary arteries
Atherosclerosis can cause …
6
- Cerebral infarction
- Carotid atheroma - emboli causing transient
ischaemic attacks or cerebral infarcts - Myocardial infarction
- Aortic aneurysm - rupture causes certain
death - Peripheral vascular disease
- Gangrene
Risk factors for Atherosclerosis risk factors …
6
- Hypercholesterolaemia: • Essentially high cholesterol levels • MOST IMPORTANT RISK FACTOR • It can cause plaque formation and growth in the absence of other known risk factors • Lipids directly damage endothelial cells - Smoking: • Increases blood pressure • Damages endothelial cells - Hypertension - Diabetes - Male gender - Increasing age
Preventive and therapeutic measures to atherosclerosis:
5
- Smoking cessation
- Control of blood pressure
- Weigh reduction
- Low dose aspirin - inhibits the aggregation of platelets, advised for people
with clinical evidence of atheromatous disease - Statins - cholesterol reducing drug
ANEURYSMS
A localised permanent dilation of part of the vascular tree
APOPTOSIS
A physiological cellular process in which a defined and programmed
sequence of intracellular events leads to the removal of a cell WITHOUT the
release of products harmful to surrounding cells
Inhibitors of apoptosis
4
- Growth factors
- Extracellular cell matrix
- Sex steroids
- Some viral proteins
Inducers of apoptosis
8
- Growth factor withdrawal
- Loss of matrix attachment
- Glucocorticoids
- Some viruses
- Free radicals
- Ionising radiation
- DNA damage
- Ligand-binding at ‘death receptors’
Apoptosis intrinsic pathway …
2
Uses the pro- and anti-apoptotic members of the Bcl-2 family:
• Bcl-2 can inhibit many factors that induce apoptosis
• Bax forms Bax-Bax dimers which enhance apoptotic stimuli
CONGENITAL DISEASE
• Simply a disease that is present at birth
INHERITED
Disease caused by an inherited genetic abnormality
IS GENETIC
doesn’t need to be present at birth
SPONTANEOUS
Disease caused by a spontaneous mutation
IS GENETIC
ENVIRONMENTAL
Acquired by environmental factors
NON-GENETIC
ACQUIRED DISEASE
• Disease caused by non-genetic environmental factors
HYPERTROPHY
• Increase in cell size without cell division (SAME NUMBER)
HYPERPLASIA
Increase in cell number by mitosis
ATROPHY
The decrease in size of an organ or cell by reduction in cell size and/or
reduction in cell numbers, often by a mechanism involving apoptosis
NECROSIS
Traumatic cell death which induces inflammation and repair
METAPLASIA
The change in differentiation of a cell from one fully-differentiated cell type to
a different fully-differentiated cell type
DYSPLASIA
Imprecise term for the morphological changes seen in cells in the progression
to becoming cancer
CARCINOGENESIS
The transformation of normal cells to neoplastic cells through permanent
genetic alterations or mutations
NEOPLASIA IS …
4
-Autonomous
• Abnormal
• Persistent
• New growth
NEOPLASM
A lesion resulting from the autonomous or relatively autonomous abnormal
growth of cells which persists after the initiating stimulus has been removed - a
new growth
TUMOURS
Any abnormal swelling
Tumours include:
4
- Neoplasm
- Inflammation
- Hypertrophy
- Hyperplasia
Tumours can cause morbidity and mortality due to:
5
- Pressure on adjacent structures (e.g. benign meningeal tumour causing epilepsy)
- Obstruction to the flow of fluid (e.g. benign epithelial tumour blocking duct)
- Production of a hormone (e.g. benign thyroid tumour causing thyrotoxicosis (excessive thyroid hormone)
- Transformation into a malignant neoplasm
- Anxiety & stress since patient thinks the lesions may be something more sinister
Malignant neoplasms can cause morbidity and mortality due to:
(7)
• Pressure on and destruction of adjacent tissue
• Formation of secondary tumours (metastases)
• Blood loss from ulcerated surfaces
• Obstruction of flow (e.g. malignant tumour of the colon causing intestinal obstruction)
• Hormone production
• Paraneoplastic effects resulting in weight loss and debility
• Anxiety & pain - many cancer cause no pain until quite late
into the disease
HISTEOGENESIS
the specific cell or origin of a tumour
Histogenic classification major
categories of origin:
(3)
• Epithelial cells (forming carcinomas)
• Connective tissues (forming sarcomas)
• Lymphoid (ONLY GIVE RISE TO MALIGNANT NEOPLASMS) and/or
haemopoietic organs (forming lymphomas or leukaemias)
MALIGNANT TUMOUR GRADING
- Well differentiated - Grade 1
- Moderately differentiated - Grade 2
- Poorly differentiated - Grade 3
Nomenclature of Neoplasia of Connective tissue and other mesenchymal
tumours:
BENIGN (7)
named according to cell of origin and behavioural
classification
B- named after cell or tissue of origin suffixed by -oma:
- Lipoma: benign tumour of adipocytes
- Rhabdomyoma: benign tumour of striated muscle
- Leiomyoma: benign tumour of smooth muscle cells
- Chondroma: benign tumour of cartilage
- Osteoma: benign tumour of bone
- Angioma: benign vascular tumour
- Neuroma: benign tumour of the nerve
Nomenclature of Neoplasia of Connective tissue and other mesenchymal
tumours:
MALIGNANT (7)
M- always designated sarcoma, prefixed by the name that describes the cell or tissue of origin:
- Liposarcoma: malignant tumour of adipocytes
- Rhabdomyosarcoma: malignant tumour of striated muscle
- Leiomyosarcoma: malignant tumour of smooth muscle cells
- Chondrosarcoma: malignant tumour of cartilage
- Osteosarcoma: malignant tumour of bone
- Angiosarcoma: malignant vascular tumour
- Neurosarcoma: malignant tumour of the nerve
Exceptions to the rules of nomenclature:
- OMAS (3)
- MALIGNANT TUMOURS (3)
- NAMED (4)
- RANDOM (2)
• Not all -omas are neoplasms:
- Granuloma - chronic inflammation
- Mycetoma - fungus in body
- Tuberculoma - mass of TB
• Not all malignant tumours are carcinoma or sarcoma:
- Melanoma - malignant neoplasm of melanocytes
- Mesothelioma - malignant tumour of mesothelial cells (line body
cavities and outer surface of internal organs, secrete lubricating
fluid)
- Lymphoma - malignant neoplasm of lymphoid cells, all are
malignant
• Tumours named after the person who first discovered/described them:
- Burkitt’s lymphoma - B-cell lymphoma caused by Epstein Barr virus
- Ewing’s sarcoma - malignant tumour of bone
- Hodgkin’s lymphoma - malignant lymphoma characterised by the
presence of Reed-Sternberg cells
- Kaposi’s sarcoma - malignant neoplasm derived from vascular
endothelium, commonly associated with AIDs
• Teratoma - neoplasm of germ cell origin that forms cells representing all
three germ cell layers of the embryo; ectoderm, mesoderm & endoderm
• Carcinosarcomas - mixed malignant tumours showing characteristics of
epithelium & connective tissue
CARCINOGEN
An environmental agent participating in the causation of tumours
Classes of carcinogen
5
- Chemical
- Viruses
- Ionising & non-ionising radiation
- Hormones, parasites & mycotoxins
- Miscellaneous
Host factors that influence carcinogenesis:
5
Race
- Diet
- Constitutional factors - age, gender etc.
- Premalignant lesions
- Transplacental exposure
ONCOGENES
These are genes driving the neoplastic behaviour of cells
Three major families OF Proteinases and inhibitors OF INVASION:
- Interstitial collagenases; degrade types I,II & III collagen
- Gelatinases; degrade type IV collagen and gelatin
- Stromelysins; degrade type IV collagen and proteoglycans
Most important sole criterion for malignancy IS
INVASION
METASTASIS
The process whereby malignant tumours spread from their site of origin
(the primary tumour) to form other tumours (secondary tumours) at distant
sites
Metastasis sequence
6
- Detachment of tumour cells from their neighbours
- Invasion of the surrounding connective tissue to reach
conduits of metastasis i.e. blood & lymphatic vessels - Intravasation into the lumen of vessels
- Evasion of host defence mechanisms, such as natural killer
cells in the blood - Adherence to endothelium at a remote location
- Extravasation of the cells from the vessel lumen into the
surrounding tissue
Bone is a site favoured by haematogenous metastases
from five carcinomas:
- Lung
- Breast
- Kidney
- Thyroid
- Prostate
TUMOUR GRADE
This is an assessment of its degree of malignancy or aggressiveness (can be
inferred from its histology)
TUMOUR STAGE
This is the extent of a tumours spread
TUMOUR STAGE - how to classify
TNM system:
• T
- Refers to the primary tumour and is suffixed by a number that
denotes tumour size
- The number varies according to the organ harbouring the tumour
• N
- Refers to lymph node status and is suffixed by a number that
denotes the number of lymph nodes or groups of lymph nodes
containing metastases
• M
- Refers to the anatomical extent of distant metastases
UK screening programs
- Cervical cancer
- Breast cancer
- Colorectal cancer
Biases in screening programs
- Lead time bias:
• Earlier detection does not affect the inevitable fatal outcome, but
prolongs the apparent survival time - Length bias:
• Preferential detection of slow growing tumours with intrinsically better
prognosis - Overdiagnosis bias:
• Diagnosis of lesions that, although histologically malignant, are
clinically relatively harmless - Selection bias:
• Volunteers for screening are more at risk of good-prognosis tumours
COMPLEMENT
• A complex series of interacting plasma proteins which form a major
effector system for antibody-mediated immune reactions
The major purpose of the complement pathway is
to remove or destroy
antigen, either by direct lysis or by opsonisation
When activated by coming into contact with pathogen complement can:
(4)
- Lyse microbes directly (Membrane Attack Complex - when a group
of complement proteins make a hole in a pathogen which causes
an inrushing of fluids that results in lysis and thus the destruction
of the pathogen) - Increase chemotaxis (C3a & C5a)
- Enhance inflammation
- Induce opsonisation (C3b) - process by which an antigen becomes
coated with substances (i.e. complement) that make it more easily
engulfed by phagocytic cells since macrophages have special
receptors for specific complement proteins
ANTIBODIES AKA IMMUNOGLOBULINS
A protein produced in response to an antigen. It can only bind with the
antigen that induced its formation i.e. specificity
ANTIGEN
A molecule that reacts with preformed antibody and specific
receptors on T and B cells
EPITOPE
The part of the antigen that binds to the antibody/receptor binding
site
AFFINITY
A measure of binding strength between an epitope and an
antibody binding site - the higher the affinity the better
CYTOKINES
Soluble proteins secreted by lymphocytes or macrophages/monocytes
that act as stimulatory or inhibitory signals between cells
Adaptive immunity hallmarks:
7
** Cell mediated - T cells for intracellular microbes
** Antibodies - B cells for extracellular microbes
SPECIFIC
• Response specific to antigen
• Memory to specific antigen
• Quicker response
• Requires lymphocytes
Major Histocompatibility Complex (MHC):
cell surface glycoproteins of two basic types:
- MHC I:
• Intracellular i.e virus
• Found on the surface of virtually all cells of the body
except erythrocytes
• Cytotoxic T cells (CD8) require an antigen to be
associated with class I MHC proteins before they kill
the cell containing the intracellular pathogen - MHC II:
• Extracellular i.e. phagocytosis
• Found mainly on the surface of macrophages, B
cells & dendritic cells (i.e antigen presenting cells)
• Helper T cells (CD4) require class II MHC proteins
before they help B cells to make antibodies to the
extracellular pathogen
ALLERGY
Abnormal response to harmless foreign material
ATOPY
Inherited tendency for overproduction of IgE antibodies to common
environmental antigens
HYPERSENSISTIVITY REACTIONS:
GELL & COOMBS CLASSIFICATION:
- Type 1. IgE - ALLERGIC,ACUTE
• acute anaphylaxis, hay fever
• IMMEDIATE & ACUTE - Type 2. IgG bound to cell surface antigens/ IgM
• transfusion reactions, autoimmune disease
• FAIRLY QUICK - Type 3. Immune complexes, activation of complement/IgG
• SLE, Post-streptococcal GN - Type 4. T Cell Mediated Delayed Type Hypersensitivity (DTH)
• TB & Contact dermatitis
The ultimate goal of tumour immunology is …
… to induce clinical effective anti-
tumour immune responses that would discriminate between tumour cells
and normal cells in cancer patients
Natural passive immunity provides protection against:
6
- Diptheria
- Tetanus
- Streptococcus
- Rubella
- Mumps
- Polio virus
Aims of a “perfect” vaccine:
5
• To achieve long term protection (ideally from a small number of
immunisations)
• To stimulate both B cells and T cells
• To induce MEMORY B cells and T cells
• To stimulate protective high affinity IgG production (IgA too if possible
(can migrate through mucosal barriers useful some pathogens infect
primarily through mucous membranes))
• The importance the memory B cell response depends on the nature of
the pathogen
ADJUVANTS
Any substance that is added to a vaccine to stimulate the immune system
IMMUNODEFICIENCY
• Deficiency in the immune response, can either be acquired (HIV) or inherited
(defects in T cell function)
PHARMACOLOGY
the study of the effects of drugs
PHARMOKINETICS
how the body affects the drug; Absorption, Distribution,
Metabolism and Excretion (ADME)
PHARMOCODYNAMICS
how the drug affects the body - D in dynamic = drug!!
POTENCY
measure of how well a drug works
AGONIST
a compound that binds to a receptor and activates it
INTRINSIC ACTIVITY
Emax of partial agonist ÷ Emax of full agonist
ANTAGONIST
a compound that reduces the effect of an agonist
AFFINITY
describes how well a ligand BINDS to the receptor
EFFICACY
describes how well a ligand ACTIVATES the receptor
Three phases of plasma level
- Uptake into the plasma
- Distribution from the plasma
- Elimination from the plasma
Order of reactions for a dissolved drug (in the plasma)
- First order = rate is directly proportional to the concentration of
drug (rate ∝ [drug]) - Second order = rate is directly proportional to the square of the
concentration of the drug (rate ∝ [drug]2)
171
KP
All information is taken from lectures and textbooks, there may be mistakes!!
- Third order = rate is directly proportional to the cube of the
concentration of the drug (rate ∝ [drug]3)
- Zero order = rate is unrelated to the concentration of the drug
(rate ∝ [drug]0)
Basic components: compartments
Plasma (5 litres), Interstitial (15 litres) & Intracellular (45 litres)
Non ionic diffusion
When pH is INCREASED:
- Weak acid - MORE IONISED
- Weak base - LESS IONISED
Non ionic diffusion
When pH is DECREASED:
- Weak acid - LESS IONISED
- Weak base - MORE IONISED
BIOAVAILABILITY
amount of drug taken up as a proportion of the amount administered
Uptake of aspirin:
Gastric pH affects the amount of aspirin uptake
A raised GASTRIC pH results in …
… The reduced uptake of aspirin from the
stomach and thus a reduction in bioavailability
- Proteins/large molecules are only active
- Water soluble molecules are active in
- Lipid soluble molecules are only active
- A drug is distributed in the plasma according to
- Dissolved gases & small ionic molecules are found in
- Lipophilic drugs tend to adhere to
-in the plasma compartment (5L)
-plasma and interstitial compartment
(5L + 15L)
-in the intracellular fluid (45L)
-its chemical properties and
molecular size
-the aqueous phase
-hydrophobic areas of plasma proteins
Volume of distribution =
Total amount of drug in body ➗ Concentration of drug in plasma
VOLUME OF DISTRIBUTION (VD)
the volume (litres) that the drug would occupy if it was distributed through all the compartments as if they were all plasma
DRUGS found in each compartment:
–Interstitial:
- Aspirin/ other NSAIDs
• Antibiotics
• Muscle relaxants
– Intracellular:
• Steroids
• Local anaesthetics
• Opioids
• An CNS drugs
- Paracetamol
-Amiodarone (has a volume of distribution of 450L i.e. very
easily taken up by tissue)
The elimination of a drug is
from the plasma compartment
CLEARANCE
-The volume of plasma that can be completely cleared of drug per unit
time (mls minute-1 (ml/min))
-The rate at which plasma drug is eliminated per unit plasma
concentration (mls minute-1 (ml/min))
**= Rate of appearance in urine ➗ Plasma concentration
HOW UNITS ARE DERIVED
The rate at which plasma drug is eliminated = mg per minute
• Per unit plasma concentration = mg per ml
• Total = mg per minute ➗ mg per ml
• Cancel out the “mg”
• Results in = mls minute-1 (ml/min)
***** Thus the units of clearance are mls minute-1 (ml/min)
Adult renal clearance values:
- Renal blood flow is 18% of cardiac output = 1L/min
- Renal plasma flow is 60% of blood flow = 600mls/min
- Glomerular filtration is 12% of renal blood flow = 130mls/min
Hepatic blood flow is
24% of cardiac output (3/4 from portal vein and 1/4 from hepatic artery)
Hepatic extraction ratio (HER):
The proportion of drug removed by one passage through the liver
There is minimal effect on drug metabolism until at least
70% of functioning liver is lost
Drugs with active metabolites:
- Prednisone
- Isosorbide dinitrate
- Codeine
- Diamorphine
- L-dopa
- Cortisone
- Morphine
Steady state means that infusion dosage =
rate of elimination from plasma
Peripheral nervous system (PNS):
- Somatic (NMJ) = voluntary = Acetyl choline (ACh)
* Autonomic = involuntary = ACh & Noradrenaline (NAd)
Autonomic nervous system:
- Parasympathetic - ACh
* Sympathetic - NAd
Nicotinic ACh receptors (nAChR) are found …
… in the neuromuscular junction (NMJ)
Adverse effects of muscarinic agonists:
7
- Diarrhoea
- Urination
- Miosis (excessive pupil constriction)
- Bradycardia
- Emesis (vomiting)
- Lacrimation (tears)
- Salivation/sweating
- Remember by DUMBELS!
Parasympathetic nervous system:
10
- Acetyl choline
- Rest & digest
- Constricts pupils
- Stimulates tears
- Stimulates salivation
- Lowers heart rate
- Reduces respiration
- Constricts blood vessels
- Stimulates digestion
- Contracts bladder
Sympathetic nervous system:
12
- Noradrenaline
- Fight or flight
- Dilates pupil
- Inhibits tears
- Inhibits salivation
- Activates sweat glands
- Increases heart rate
- Increases respiration
- Inhibits digestion
- Release of adrenaline
- Relaxes bladder
- Ejaculation in males
TYROSINE >
DOPA > dopamine > noradrenaline > adrenaline
Effects of alpha-adrenoceptors:
• Alpha-1:
• Alpha-2:
• Alpha-1: - Vasoconstriction - Pupil dilation - Bladder contraction • Alpha-2: - Presynaptic inhibition of noradrenaline (negative feedback) i.e. when blood sugar is low then alpha-2 in pancreas will be stimulated to reduce noradrenaline release thereby reducing insulin levels being released from the pancreas
Effects of beta-adrenoceptors:
• Beta-1:
• Beta-2:
• Beta-3:
• Beta-1: - Increased force of heart contraction (positive inotropic effect) - Increased heart rate - Increased electrical conduction in heart - Increased renin release from kidney - Increased blood pressure • Beta-2: - Bronchodilation - Vasodilation - Reduced GI motility • Beta-3: - Increased lipolysis - Relaxation of bladder
Adrenergic agonists:
• Adrenaline (non-selective agonist):
Targets:
- Blood vessels (Alpha-1)
- Heart (Beta-1)
- Bronchial smooth muscle (Beta-2)
Adrenergic agonists:
• Adrenaline (non-selective agonist):
Effects:
- Vasoconstriction (Alpha-1)
- Positive inotropic effect (Beta-1)
- Bronchodilation (Beta-2)
Do NOT use Beta-blockers
in ASTHMATICS since most will already be on Beta-2 agonists
-Alpha-1 = • Alpha-2 = • Beta-1 = • Beta-2 = • Beta-3 =
-Alpha-1 = Vasoconstriction & Bladder contraction
• Alpha-2 = Presynaptic inhibition
• Beta-1 = Increased cardiac effects
• Beta-2 = Bronchodilation
• Beta-3 = Bladder relaxation & Increased lipolysis
The chirality of a molecule influences biological activity; D (S form) or L (R form):
- Biological systems use
L-amino acids (R form)
Pain:
- Unpleasant sensory and emotional experience associated with actual or potential tissue damage
Pain Positive role:
- Warning of tissue damage
- Immobilisation for healing
- Protection of the species: establishment of memory
Pain Physiological effects:
- Increased heart rate
- Increased blood pressure
- Increased respiratory rate
CHRONIC PAIN
Ongoing persistent pain greater than 3-6 months
ADVERSE DRUG REACTIONS
A response to a drug which is noxious and unintended
Types of adverse drug reactions (ADR’s) - ABCDE (Rawlins-Thompson)
- A - Augmented
- B - Bizarre
- C - Chronic
- D - Delayed
- E - End of Use
Drug history is important:
• To identify which type of ADR it is, ask yourself:
(5)
- Is there a history of allergy? - Type B (Bizarre)
- Is it predictable from the mechanism of action? Does it seem
dose-related? - Type A (Augmented) - Has the patient been using the medication for a long time? - Type
C (Chronic) - Is the patient withdrawing from a medicine? - Type E (End of
Use) - Has the patient uses a drug in the past that could be causing a
problem now? - Type D (Delayed)
Hypersensitivity:
TYPE EXPL
• Type 1: IgE-mediated drug hypersensitivity - ANAPHYLAXIS
• Type 2: IgG-mediated cytotoxicity - some drugs can cause renal failure
through this type
• Type 3: Immune-complex deposition - reacts with antibiotics
• Type 4: T-cell mediated - usually substance containing metals
Mast cell degranulation:
• Cross linking of IgE receptors releasing:
(3)
- Histamine
- Thromboxanes, prostaglandins
- Tumour Necrosis Factor (TNF)
Main features of anaphylaxis:
6
• Exposure to drug, immediate rapid onset • Rash withe characteristic blotches • Swelling of lips, face, oedema, central cyanosis (go blue/purple) • Wheeze • Hypotension (Anaphylactic shock) • Cardiac arrest
Alternative presentation of anaphylaxis:
2
- Cardiorespiratory arrest
* NO SKIN CHANGES!
Management of Anaphylaxis:
3
• Commence basic life support ; A (airway), B (breathing), C (circulation)
• Specific treatment:
- STOP DRUG if infusion
- Adrenaline 1mg (10mls of 1:10,000 (IV)) 1ml IV increments -
note: if cardiac arrest then may need to give cardiac massage in
order to get drugs circulating
- IV Anti histamine (Chlorphenamine 10mg)
- IV Hydrocortisone (100 to 200mg) - note: unlikely to cause harm
in excess so can’t really give too much
• Effect of adrenaline:
- Vasoconstriction, bronchodilation & increased cardiac output
If ADR is suspected:
Identify markers:
• Type A : Serum concentration - plasma monitoring
• Type B:
- Tryptase - released from only mast cells - BEST TEST TO CONFIRM ALLERGY BASED ADR
- Urine Methylhistamine - breakdown product of histamine
Drug interactions
Risk factors - Patient:
(5)
- Polypharmacy - on many different drugs
- Old age
- Genetics - e.g. slow/fast metabolism
- Hepatic disease
- Renal disease
Drug interactions
Risk factors - Drug:
(3)
- NARROW therapeutic index
- Steep dose/response curve
- Saturable metabolism - e.g. paracetamol and
alcohol are metabolised at a SET RATE
Renal excretion
Weak acids are … eg.
cleared faster if urine alkali. • Aspirin - try to alkalinise urine to help increase excretion with aspirin overdose • Ibuprofen • Paracetamol • Warfarin
Renal excretion
Weak bases are … eg.
cleared faster if urine acidic • Amphetamine • Atropine • Propranolol • Salbutamol
Whats required for a prescription:
8
- Patient name
- Dose
- Route
- Frequency
- Duration
- Total number of tablets
- Drug name
- Date & Signature
Drugs discontinued before surgery:
Nil by mouth policy for fluids is 2 hours - due to fear of aspiration under anaesthesia
Opioid induced respiratory depression:
Opioid antagonists:
• Naloxone - give to reverse overdose - IV is fastest route - 400 micrograms per ml
10mg of morphine orally is equivalent to
5mg parenterally (sub-cutaneous, intramuscular & IV)
Pathogen:
- Commensal:
- Opportunist pathogen:
- Virulence/Pathogenicity:
- Asymptomatic carriage:
– Organism that causes or is capable of causing disease
- Organism which colonises the host but causes no disease in normal circumstances
- Microbe that only causes disease if host defences are compromised
- The degree to which a given organism is pathogenic/ any strategy to achieve this
- When a pathogen is carried harmlessly at a tissue site where it causes no disease
- Gram positive:
* Gram negative:
- Gram positive: Purple
- Gram negative: Pink
- Can remember since pink has an n and so does negative
- Acid-fast bacilli:
- Non acid-fast bacilli:
- Acid-fast bacilli: Red e.g. Mycobacterium
- Non acid-fast bacilli: Blue e.g. E.coli
Catalase test:
• Staphylococci are …
• Streptococci are …
• Many GRAM NEGATIVE bacteria e.g. E.coli and fungi (aspergillus spp.) are catalase …
- catalase POSITIVE
- catalase NEGATIVE
- POSITIVE
Coagulase test:
Staphylococcus. aureus is coagulase …
Other staphylococci are coagulase …
- POSITIVE - clumping
- NEGATIVE - no clumping
Alpha haemolysis:
Beta haemolysis:
- green or brown - strep pneumoniae & strep viridans
- clear/colourless - strep pyogenes & staph aureus
Optochin test
- SENSITIVE:
- RESISTANT:
- Streptococci pneumoniae - clear zone of no growth around disc
- Viridans streptococci and other alpha haemolytic streptococci - there will be growth around the disc
Oxidase test
- Oxidase positive: Blue - bacteria is AEROBIC e.g. V. cholerae
- Oxidase negative: No colour change - bacteria may be aerobic or anaerobic
Monkey agar
• Gram-negative bacilli ONLY
• Will turn PINK/RED if lactose-fermenting bacteria e.g. E.coli
• Will turn WHITE/TRANSPARENT if non-lactose fermenting e.g.
Salmonella
XLD AGAR:
- Used to differentiate SALMONELLA and SHIGELLA mainly
- Salmonella: Red/pink colonies some with black spots
- Shigella: Red/pink colonies
Streptococci can be classified in three ways
- Haemolysis
- Lancefield typing
- Biochemical properties
Streptococci can be differentiated using haemolysis:
- Alpha haemolysis - greenish/brownish e.g Strep. intermedius
- Beta haemolysis - clear/colourless e.g. Strep. pyogenes
- Gamma haemolysis - no lysis e.g. Strep. mutans
Streptococci can be differentiated using lancefield typing:
Why?
• Important groupings:
• A method of grouping CATALASE NEGATIVE & COAGULASE NEGATIVE bacteria based on the bacterial carbohydrate cell surface antigens
- Group A - Strep. pyogenes; an important pathogen
- Group B - Strep. agalactiae; neonatal infections
GRAM-NEGATIVE BACTERIA:
Lipopolysaccharide (LPS) is an endotoxin and forms the outer leaflet of the outer
membrane of gram-negative bacteria and comprises:
LPS on on gram-negative bacteria is the main ….
- Lipid A - the toxic portion of LPS that is anchored in the outer leaflet of the
outer membrane - Core (R) antigen - short chain of sugars, some are unique to LPS
- Somatic (O) antigen - a highly antigenic repeating chain of oligosaccharides
difference between gram-negative and gram-positive bacteria.
MYCOBACTERIA…
Koch postulates:
(4)
- Bacteria should be found in all people with disease
- Bacteria should be isolated from the infected lesions in people with the disease
- A pure culture inoculated into a susceptible person should produce symptoms of the disease
- The same bacteria should be isolated from the intentionally infected individual
Principles of mycobacteria treatment:
4
- Slowly replicating bacteria so need prolonged treatment - 6 months of
antimicrobials - There are different populations of mycobacteria in particular locations
intracellularly and extracellularly or in environments of differing pH - Resistance may emerge on treatment so use multi-drug combinations to
ensure target all populations and mutants - Compliance is essential; directly observed treatment used for many patient
groups to ensure success
The highly immunogenic nature of mycobacterial lipids stimulate T-cell
responses 3-9 weeks after exposure to M.tuberculosis:
+ve & -ve effects
• Positive effects; macrophage killing of mycobacteria, containment of
infection, formation of a tissue granuloma
• Negative effects: hypersensitivity reactions (type 4) with skin
lesions, eye lesions and swelling of joints
PRE-PATENT PERIOD
the interval between infection and the
appearance of eggs in the stool
Presentation of toxoplasmosis:
- Recent HIV positive diagnosis: CD4 count: 70 (below
450= low & below 100= high risk of AIDs) - 2-week history of progressive left sided weakness
- Headaches & visual disturbances
- Commonly presents when people are
immunosuppressed e.g. HIV/AIDs or cancer on chemotherapy
4 species of malaria cause human disease:
3
- P. falciparum (most common)
- P. ovale
- P. vivax
- P. malariae
Malaria is transmitted by …
… the bite of the FEMALE ANOPHELES MOSQUITO
The malaria vector is …
- Female Anopheles mosquito - mainly bites at night
- Worldwide distribution
- Infection is acquired during feeding from infected human
Malaria Parasitology:
5
-Can remember by OVO - Ovale Vivax Overstay
-Each cycle of this process, which is called erythrocytic schizogony, takes about 48 hours in P. falciparum, P. vivax & P.ovale disease
• Whereas in P. malariae it takes 72 hours
• Summary of stages of parasite:
- Sporozoites > Merozoites > Trophozoites > Schizonts >
Merozoites
Anaemia due to anaemia is due to:
4
- Haemolysis of infected red cells
- Haemolysis of non-infected red cells (Blackwater fever - when
malaria is left to go untreated results in dark coloured urine) - Splenomegaly
- Folate depletion
Clinical features of malaria
7
• FEVER is common (BUT NOT ALWAYS PRESENT) • Other common features: - Chills & sweats - Headache - Myalgia - Fatigue - Nausea & vomiting - Diarrhoea
Stages of virus replication:
6
- Attachment:
- Viral and cell receptors e.g. HIV (gp120 on HIV and CD4 on T cell) - Cell entry:
- Only the viral ‘core’ which carries the nucleic acid and some associated proteins acting as enzymes for replication and negation of intracellular host defence factors are freed into the host cell cytoplasm
- Outer protein coat does not enter - Interaction with host cells:
- Virus uses cell materials (enzymes, amino acids, nucleotides) for their own replication
- Also needs to subvert host cell defences - Replication:
- Production of progeny viral nucleic acid and viral proteins in nucleus, cytoplasm or both - Assembly:
- Can occur in nucleus e.g. herpesvirus
- Can occur in cytoplasm e.g. polio virus
- Can occur in cell membrane e.g. influenza virus - Release:
- By bursting open (lysis) of cell e.g. rhinovirus
- By ‘leaking’ (exocytosis) from the cell overtime e.g. HIV & influenza virus (2-3 days from upper respiratory tract)
- Only a few virus particles will enter the host but millions will exit due to replication
The SINGLE MOST EFFECTIVE METHOD OF PREVENTING CROSS
INFECTION is …
• Hand hygiene:
Antibiotics can also be called
Antimicrobial
Clostridium difficile antibiotics:
- In general ANY antibiotic that begins with the letter C can result in clostridium difficile: • Ciprofloxacin • Clindamycin • Cephalosporins • Co-amoxiclav (augmentin) • Carbapanems e.g. meropenem
• Note: Flucloxacillin is used to treat Staphylococcus Aureus
Pathogens are …
… micro-organisms capable of causing disease
Bacteria Low number or virulence - High number or virulence - Extracellular bacteria - Intracellular bacteria -
The number of organisms and virulence as well as location determine the defence mechanism employed:
• Low number or virulence - phagocytes active
• High number or virulence - immune response
• Extracellular bacteria - antibody response
• Intracellular bacteria - cellular response
- Schistosomiasis:
process
Snail > larvae > human > liver > intestinal mesentery (bladder veins) > male + female (adult worms) > eggs > faeces/urine > snails
Worm evasion
Glycolipid/glycoprotein coat is host derived so not perceived as foreign to the immune system - utilises host self antigens
- HIV, bird flu or variant Creutzfeldt-Jakob (vCJD) disease (mad cow disease) are or are not notifiable
NOT NOTIFIABLE
Notifiable diseases
Acute encephalitis, acute infectious hepatitis, acute menigitus, acute poliomyelitis, anthrax, botulism, brucellosis, cholera, diptheria, enteric fever (typhoid or paratyphoid), food poisonising, haemolytic uraemic syndrome, infectious bloody diarrhoea, invasice group A Strp disease, Legionnaire disease, leprosy, malaria, measles, meningococcal septicaemia, mumps, plague, rabies, rubella, SARS, scarlet fever, smallpox, tetanus, tuberculosis, typhus, viral haemorrhagic fever, whooping cough.
Meningococcal infection is a … disease. Its seen as GRAM … under microscope
vaccine preventable
NEGATIVE PURPLE DIPLOCOCCI
Meningococcal infection
Complications:
(9)
- Brain abscess
- Brain damage
- Seizure disorders
- Hearing impairment
- Focal neurological disorders
- Organ failure
- Gangrene
- Auto-amputation due to arterial occlusions
- Death
MICROBIOLOGY CHEATS:
• Gram-positive bacteria:
- If gram positive then use PENICILLIN TYPE ANTIBIOTICS
Sexy - Streptococcus spp.
- Students - Staphylococcus spp.
- Can - Corynebacterium spp.
- Look - Listeria spp.
- Bad - Bacillus spp.
- Come morning - Clostridium spp.
MICROBIOLOGY CHEATS:
• Gram-negative bacteria:
- Huge - Helicobacter
- Vaginas - Vibrio cholera
- Can - Coliforms
- Never - Neisseria
- Provide - Parvobacteria
- Pleasure - Pseudomonas
MICROBIOLOGY CHEATS:
DNA viruses:
- H - Herpes viridae
- A - Adenovirus
- P - Parvovridae
- P - Papopviridae
- H - Hepaviridae
- Mneumonic - HAPPH
