What regulatory systems does the endocrine system control? (HINT: there's 5)
1. Regulation of cellular metabolism 2. Maintenance of homeostasis (e.g. Ca++) 3. Sexual development and reproduction 4. Growth and development from childhood to adult 5. Modulates long term behaviour (mood, sleep)
What is the difference between an endocrine and exocrine gland?
ENDOCRINE glands have no ducts they secrete and release hormones directly into the blood. (Endo = internal, crime = secretion.) EXOCRINE glands = Epithelial cells form ducts to carry secretions onto the surface of the epithelium (e.g. salivary, sebaceous and sweat glands open onto the skin, Pancreatic duct opens into the duodenum)
Describe paracrine secretion.
Paracrine factors (polypeptides) diffuse over short distances. Cell - cell communication: inducing changes in adjacent cells (e.g. peptide neurotransmitters). Important in embryogenesis where gradients of polypeptides influence developmental change: - Fibroblast growth factor (FGF) family - Hedgehog family (sonic hedgehog) - WnT family - TGF-β superfamily
Name, and distinguish between, the three classes of hormones.
1. PROTEINS = chains of aa's (usually injected) 2. STEROIDS = Synthesised from cholesterol (oral administration) 3. AMINO ACID DERIVATIVES = thyroid hormones, catecholamines (adrenalin, dopamine, noradrenalin)
Explain how the endocrine system is controlled including the concept of negative feedback loops.
1. EndocrineAxes/Cascades = the target tissue of one hormone is another endocrine gland - allows amplification and fine control 2. Hypothalamus secretes hormones that control the secretion and release of pituitary hormones, which stimulate/control many other endocrine glands E.g. hypothalamus releases GnRH, which stimulates secretion of FSH that stimulates gonad to secrete oestrogen/testosterone (which inhibits GnRH) CONCEPT OF -VE FEEDBACK = The final product of a cascade acts to inhibit a hormone higher up the cascade
What is the function of the hypothalamus?
1. Controls release of ANTERIOR pituitary hormones by RELEASING hormones ( NB prolactin is controlled by a hypothalamic inhibiting factor) 2. It also secretes hormones that are stored and released by the POSTERIOR lobe of the pituitary gland (oxytocin and Antidiuretic hormone (ADH) )
What hormones does the (i) Anterior pituitary (ii) posterior pituitary secrete? (HINT: there's 6 anterior and 2 posterior)
(i) Growth hormone Thyroid stimulating hormone Adrenocorticotropic hormone Follicle stimulating hormone Luteinising hormone Prolactin (ii) Antidiuretic hormone (ADH) and oxytocin
What are the anterior and posterior pituitary made up of?
ANTERIOR - develops from epithelium of the mouth POSTERIOR - a down growth of the hypothalamus (neural tissue)
Describe the THYROID GLAND, (i) Where is it? (ii) What hormones does it produce? (iii) What effect does the hormone (s) have?
(i) develops as a down growth of the epithelium of the tongue (leaves a pit at the back of the tongue - the foramen caecum). Lies ANTERIOR to the trachea in the neck (ii) Follicular cells secrete TRI-IODOTHYRONINE (T3) and THYROXINE (T4), both secretions require iodine. These are stored in colloid (thyroglobulin). Parafollicular (akaC) cells produce CALCITONIN (iii) T4 is a prohormone (must be converted by target cells into T3 to become active). Thyroxin regulates: – energy use by body cells = rate of metabolism – protein production = growth and development – Regulates sensitivity of cells to other hormones Calcitonin regulates calcium homeostasis, stimulates osteoblasts to lay down more bone and so reduce blood calcium levels.
Describe the PARATHYROID GLAND, (i) Where is it? (ii) What hormones does it produce? (iii) What effect does the hormone (s) have?
(i) Develops from the wall of the pharynx and forms two pairs of glands which are embedded in the posterior aspect of the thyroid (ii) Parathyroid hormone (iii) Regulates calcium homeostasis by stimulating osteoclasts to breakdown bone matrix and therefore increases blood calcium levels.
Describe the ADRENAL GLANDS, (i) Where is it? (ii) What hormones does it produce?
(i) Cortex develops from mesoderm of the posterior abdominal wall, has three layers of epithelial cells (zona glomerulosa, zona fasciculata, zona reticularis). Medulla is made up of natural crest cells (neuroectoderm). (ii) Cortex Produces STEROID hormones. Glomerulosa produces mineralocorticoids – e.g. Aldosterone. Fasciculata produces glucocorticoids – e.g. Cortisol. Reticularis produces sex steroids – Androgens Medulla contains chromaffin cells which produce catecholamines - epinephrine, dopamine, norepinephrine NOTE: the medulla has a direct connection with the SNS (controlling fight or flight response)
Describe the PANCREATIC ISLETS (Islets of langerhans), (i) Where is it? (ii) What hormones does it produce? (iii) What effect does the hormone (s) have?
(i) Develops as an out growth of the gut tube, closely associated with the development of the gall bladder. Ducts join before entering the duodenum. Composed of an exocrine component and an endocrine component. (ii) Exocrine PANCREATIC ACINI produce pancreatic amylase etc (disorder –pancreatitis) Endocrine ISLETS OF LANGERHANS produce hormones (disorder = Diabetes mellitus) – Alpha cells = glucagon – Beta cells = insulin
What are the 2 basic building blocks of the nervous system? Describe them.
1. NEURONES - Axon, dendrites and the cell body (powerhouse of the nervous system). Communicate via synapses 2. GLIA - in the central nervous system these are oligodendrocytes (from myelin), astrocytes (from radiological cells), and microglia (specialised macrophages of NS)
What does (i) gray matter (ii) white matter consist of?
(i) Cell bodies of neurons reside in the gray matter (CNS = ‘nuclei’, PNS = ‘ganglia’) (ii) Axons reside in white matter
What are the 2 anatomical divisions of the NS?
Peripheral NS - cranial and spinal nerves, and ganglia Central NS - brain and spinal cord
What does the Peripheral Nervous System consist of? Describe (i) Cranial nerves (ii) Spinal nerves.
Consists of sensory receptors, nerves conducting impulses to and from the CNS, their associated ganglia, and motor endings. (i) Twelve pairs of cranial nerves originate from the brain and travel through the skull to innervate the head and neck. (The Vagus Nerve (X) is the exception, extending into the thoracic and abdominal cavities.) (ii) The 31 pairs of spinal nerves (mixed nerves) are numbered successively according to the region of the spinal cord from which they originate. Spinal nerves are formed by the union of dorsal and ventral roots of the spinal cord and are short, confined to the intervertebral foramina.
What are the 2 major functional divisions of the nervous system? Describe what they do.
1. Sensory (afferent – impulses/info going towards the CNS) – responsible for acquiring and processing information from the environment 2. Motor (efferent – impulses/info from CNS going to effector organs) - responsible for generating movements and other behaviours The efferent division includes the somatic (voluntary) system, which serves skeletal muscles, and the autonomic (involuntary) system (ANS), which innervates smooth and cardiac muscles and glands, it is important for internal homeostasis
What are the 2 divisions of the ANS? Describe these divisions.
1. PARASYMPATHETIC - conserves body energy and maintains activities at basal levels (‘Rest-and-Digest’). Parasympathetic (Craniosacral) Division - Parasympathetic preganglionic neurons arise from the brain stem and from the sacral (S2-S4) region of the cord. 2. SYMPATHETIC - activates the body under conditions of emergency and is called the ‘Fight-or-Flight’ System. Sympathetic (Thoracolumbar) Division – Preganglionic sympathetic neurons arise from the lateral horn of the spinal cord from the level of T1 to L2.
Compare the somatic and autonomic nervous systems
In the somatic division, a single motor neuron forms the efferent pathway from the CNS to the effectors. The efferent pathway of the autonomic division consists of a two-neuron chain: the cell body of the preganglionic neurons in the CNS and the cell body of the postganglionic neuron in a ganglion.
What 4 things is the brain protected by?
Bone Meninges Cerebrospinal fluid (CSF) Blood-brain barrier
What are the meninges, from superficial to deep? What is their function?
Dura mater Arachnoid mater Pia mater Enclose the brain and SC and their BVs Inward fold of the dura mater secure the brain to the skull, dampening movement of the brain in the cranial cavity
The brain contains 4 ventricles filled with CSF, what are the names of these 4 ventricles and where are they located?
(a) 2 LATERAL ventricles in cerebral hemispheres (b) 3RD VENTRICLE in the diencephalon (c) 4TH VENTRICLE in the brain stem (connects with the central canal of the SC)
What 4 functions does the brain provide us with?
Voluntary movements Interpretation and integration of sensation Consciousness Cognitive function
What 4 parts does the brain consist of? What are they composed of?
Cerebral hemispheres Diencephalon Brain stem Cerebellum Cerebral hemispheres & diencephalon have internal grey matter nuclei surrounded by white matter and an outer cortex of grey matter. The diencephalon and brain stem lack an outer cortex of grey matter.
What does each cerebral hemisphere consist of? Describe how it receives sensory impulses & dispatches motor impulses.
Cerebral cortex, cerebral white matter and nuclei Receives sensory impulses from, and dispatches motor impulses to, the opposite side of the body. The body is represented in an upside down fashion in the sensory and motor cortices
What are the 4 functional areas of the cerebral cortex? Where are they located?
a. Motor areas: primary motor cortex and premotor of FRONTAL lobe b. Sensory areas: primary somatosensory cortex and somatosensory association cortex of PARIETAL lobe c. Visual areas in the OCCIPITAL lobe d. Auditory and Olfactory areas in the TEMPORAL lobe
The cerebral hemispheres show lateralization of cortical function. Describe this.
In most people, the left hemisphere is dominant (i.e., specialized for language and mathematical skills), the right hemisphere is specialized for visual-spatial skills and creativity
What does the diencephalon consist of?
Thalamus hypothalamus encloses the 3rd ventricle
What is the thalamus the major relay station for? What is the function of the hypothalamus?
a. sensory impulses ascending to the sensory cortex b. inputs from subcortical nuclei and the cerebellum travelling to the cerebral motor cortex HYPOTHALAMUS = an important autonomic nervous system (ANS) control centre. It maintains water balance and regulates thirst, eating behaviour, gastrointestinal activity, body temperature, and the activity of the anterior pituitary gland.
What 3 parts does the brain stem consist of? Describe each part.
MIDBRAIN contains Superior & inferior colliculi (visual & auditory reflex centres) • Red nucleus (subcortical motor centre) • Pyramidal tracts (on ventral surface of cerebral peduncles) • Substantia nigra • Motor nuclei of CN III, IV • Surrounds cerebral aqueduct The mid-brain surrounds the cerebral aqueduct. PONS is mainly a conduction area. Its nuclei contribute to regulation of respiration and cranial nerves V-VII. MEDULLA OBLONGATA has pyramids on its ventral surface (descending corticospinal tracts). The fibres cross-over at the decussation of the pyramids before entering the spinal cord. Important nuclei in the medulla oblongata regulate respiratory rhythm, heart rate, and blood pressure and serve cranial nerves VIII-XII. The cough, sneezing, swallowing, and vomiting centres are in the medulla.
Describe the cerebellum, (i) what does it consist of? (ii) How is it connected to the brainstem? (iii) What is its function?
(i) consists of two hemispheres marked by convolutions. (ii) connected to the brain stem by sup, middle, and inf cerebellar peduncles. (iii) processes and interprets impulses from the motor cortex and sensory pathways and coordinates motor activity so that smooth, well- timed movements can occur. It is also important in balance.
What is the spinal cord? Where is it located and where does it extend from and to? What is it protected by?
The spinal cord is a two-way impulse conduction pathway and reflex centre. It resides within the vertebral column and extends from foramen magnum to end of L1 vertebra. It is protected by meninges and CSF.
Where is the spinal cord enlarged? Why is this the case?
In cervical and lumbar regions - where spinal nerves serving the limbs arise
What do dorsal and ventral rami serve?
Dorsal rami serve the muscles and skin of posterior body trunk Ventral rami within the cervical and lumbar spinal cord form plexuses that serve the limbs. T1-T12 ventral rami give rise to intercostal nerves that serve the thorax wall and abdominal surface.
Describe the cross sectional anatomy of the spinal cord
The central grey matter of the cord is H shaped. Anterior horns mainly contain somatic motor neurons. Lateral horns contain visceral (autonomic) motor neurons. Axons of neurons of the lateral and anterior horns emerge from the cord via the ventral roots. Posterior horns contain interneurons. Axons of sensory neurons (with cell bodies located in the dorsal root ganglion – DRG) enter the posterior aspect of the cord and form dorsal roots. Each side of the white matter of the cord has posterior, lateral, and anterior columns, and each column contains ascending and descending tracts. All tracts are paired and most decussate.
What is a lipid? What are the 3 functions of a lipid?
Lipids have low solubility in water They include phospholipids, fats, sterols and some vitamins Sources of energy, forms membranes, participates in cell signalling
What are the 4 types of sterols?
bile acids steroid hormones vitamins cell membranes
What are 2 disorders inherited in lipid pathways? Explain, generally, how they come about. (including what they affect within the body)
Gaucher's (most common) Fabry disease Defects in enzymes which metabolise lipids leading to lipid accumulation Largely affect neurological system, liver, spleen and bone marrow Failure to thrive
Describe the lipid bilayer in terms of the 2 conflicting forces and how they are resolved.
it has a hydrophilic head which is attracted to water and a hydrophobic tail which dislikes water and looks to aggregate with other hydrophobic molecules Hydrophilic heads face water and hydrophobic tails are shielded from the water and lie next to each other
Why are membrane important? (HINT: there's 4 reasons)
1. compartmentalisation 2. organelles as well as plasma membrane 3. highly selective barriers 4. have sensors to respond to internal and external conditions
What is meant by the fluid mosaic model? What are the 2 classes of proteins involved in this model?
The phospholipid bilayer is a fluid matrix The bilayer is a two-dimensional solvent The lipids and proteins can undergo rotational and lateral movement Peripheral proteins (extrinsic proteins) Integral proteins (intrinsic proteins
What are the 2 lipid components of bilayers?
1. PHOSPHOLIPIDS - choline, ethanolamine, serin, inositol 2. GLYCOLIPIDS - have sphingosine core
How is a lipid bilayer and cell membrane formed?
Membrane synthesis occurs in the ER. The new membrane is then transported to other parts of the cell. This occurs through a series of vesicle budding and fusion. Bits of the membrane pinch off from the ER to form vesicles and then fuse with other membranes
How is asymmetry generated in the bilayer?
a new phospholipid is synthesised by enzymes at the ER facing the cytosol using fatty acids that are available in the cytosol. They release the new phospholipid into the outer leaflet of the ER bilayer Lipids are then transferred to the other side by flippases Some flippases are selective for particular phospholipids so different types may be concentrated in each monolayer
What is (i) exocytosis (ii) endocytosis?
(i) Delivery of lipids (and membrane proteins) to cell membrane. It allows movement of other molecules out of cell (ii) Movement of material into cells via membrane bound vesicles. It is especially important in the immune response. May be mediated by specific receptors
What are the 4 types of membrane proteins? Describe each of them.
1. TRANSMEMBRANE: they tend to have a number of hydrophobic amino acid residues which “shun” the aqueous environment on the inside and outside. Some proteins can have a range of these domains which come together. This can form a channel or pore where the groups are selective for a particular cargo. If the groups on the inside are hydrophilic this can be the structure of an aqua pore. 2. MEMBRANE ASSOCIATED: usually contain domains that selectively bind to phospholipids. Compartment-specific association E.g. pleckstrin homology domains (PH) Approx. 100 amino acid region found in many proteins that bind to certain types of phospholipid Removal of PH domain alters a protein’s membrane binding properties (e.g. Phospholipase C-n2) 3. LIPID-LINKED GPI (glycosylphosphatidylinositol) anchors 4. PROTEIN-ATTACHED especially important in signal transduction
What is the concept of cell communication? Whata re the 6 steps of cell-cell commuication?
Phospholipids not only make up the lipid bilayer, they participate in cell signalling mechanisms by giving rise to intracellular second messengers. They also serve as precursors for the compounds that are released from cells and act on other cell types, called eicosanoids - inflammatory mediators.
- Synthesis of signal
- Release of the signalling molecule by the signalling cell: exocytosis, diffusion, cell-cell contact.
- Transport of the signal to the target cell
- Detection of the signal by a specific receptor protein
- A change in cellular metabolism, function or development triggered by the receptor-signal complex
- Removal of the signal or desensitisation
Signals can act at short or long-ranges. In animals, signalling by extracellular molecules can be classified into different types/ Describe these 2 types.
LONG RANGE -
- ENDOCRINE = hormone released by endocrine cell and carried in bloodstream to distal target cells. E.g. FSH released from pituitary acts upon ovary
- NEUROTRANSMISSION e.g. Breathing – the phrenic and thoracic nerves send impulses from the brain to the diaphragm
- PARACRINE = signalling molecules only affect target cells in clsoe proximity to secreting cells e.g. somatostatin release by pancreas cells acts locally
- AUTOCRINE = cells respond to substances that they themselves release e.g. Some neurotransmitters and growth factors bind to the cells that release them.
- MEMBRANE BOUND PROTEINS = A signalling cell expresses specific molecules on the cell surface and an adjacent target cell has receptors for these and binds acting as a trigger for a cellular process e.g. signalling T cells in the immune system
Insulin released from β-cells act in an autocrine, a paracrine and an endocrine manner. Describe how and why this is the case?
Insulin acts on cells far away (endocrine) which regulate uptake of glucose
Acts in an autocrine manner after a certain amount of insulin is secreted it binds to receptors on the cell to stop insulin secretion.
It also acts in an paracrine way binding to alpha cells to prevent secretion of glucagon.
What is signal transduction?
Most things that affect cell activity or function do not actuallyenter cells. Instead, they act on membrane-bound receptors that control the production of intracellular chemicals (second messengers), these mediate cell activity.
What are the 4 main types of signalling receptors? Describe them.
1. LIGAND GATED ION CHANNELS (ionotropic)
- the receptor is also a channel and when the signalling molecule binds to receptor it allows ions to flow into the cell either depolarising or polarising the cell and causing a cellular effect.
2. G-PROTEIN COUPLED RECEPTORS (metabotropic)
- usually have 7 transmembrane domains and exist on the plasma membrane surface. When they bind to the signalling molecule a G-protein that is normally bound to the receptor is disengaged evoking a cellular effect. Common pathways caused by liberation of G-proteins are opening of ion channels, bind and activate enzymes to produce second messenger to release calcium or activate kinases. This is a fast type of signalling.
3. KINASE-LINKED RECEPTORS
- once the signalling molecule is recognised they phosphorylate a protein which often happens as part of a cascade, and eventually a transcription factor is switched on causing a protein to be synthesised. This is a slow form of signalling as it requires the synthesis of a new protein.
4. NUCLEAR RECEPTORS
- Lipid Soluble Molecules can pass through the plasma membrane and be recognised by intracellular receptors e.g. steroid hormones. The receptor-signal complex often switches on a family of transcription factors causing a slower form of signalling
What is the inositol phospholipid signalling pathway?
Phosphatidylinositol 4,5-bisphosphate (PIP2) is a phospholipid found in the lipid bilayer.
The enzyme phospholipase C (PLC), liberates two signalling molecules from PIP2; inositol 1,4,5 trisphosphate (IP3) and diacyglycerol (DAG).
PLC can be activated down stream from uncoupled G-protein receptors, this enzyme recognises PIP2 and cleaves it into IP3 and DAG. IP3 can bind to receptors such as ligand activated channels that reside in the endoplasmic reticulum allowing Ca2+ to move into the cytosol. At the same time DAG is recognised by protein kinase C (PKC) and this activates the kinase. Through the activation of the kinase and the change in the Ca2+ concentrations in the cytosol, cellular responses are evoked. Calcium can activate cellular pathways by binding to groups of proteins strongly at high concentration, and this calcium switches on these molecules. These proteins are responsible for exocytosis, contraction, metabolism and gene transcription. So for a short period of time these responses will be evoked but once the calcium levels fall the response ends.
What are the 3 ypes of PKC? What are the substrates for DAG-dependent PKC?
1. “Conventional” require DAG and Ca2+
2. “Novel” require DAG but not Ca2+
3. “Atypical” doesn’t require DAG or Ca2+
1. tumour suppressor p53 - prevents tumour formation through inducing apoptosis
2. CaV 1.2 calcium channel - heart muscle contraction
3. IKK𝛂 - B cell activation (immune function)
What are the 3 principle eicosanoids? What is the main source of eicosanoids?
prostaglandins, thromboxanes and leukotrienes
How are eicosanoids sythesised? Indicating the rate-limiting step. What are the 2 ways in which arachidonic acid can be metabolised?
The initial and rate-limiting step in eicosanoid synthesis is the liberation of arachidonic acid by phospholipase A2 (PLA2) - PLA2 is acitvated by a variety of receptor-mediated signals.
1. Cyclo-oxygenase and peroxidase to give thromboxanes and prostaglandins
2. Lipoxygenases to give leukotrienes
What 3 things are prostaglandins responsible for?
2. Inhibit/promote platelet aggregation
3. Inflammatory response and thermoregulatory (fever) and pain
Thromboxanes... (i) where are they synthesised? (ii) What is their 2 functions?
(ii) stimulate platelet aggregation
Leukotrienes...(i) where are they synthesised? (ii) What is their function?
(ii) immune response, they are heavily implicated in asthma and allergy
What is platelet activating factor? (PAF) Where is it sythesised? What 4 things does it cause?
A bi-product of arachidonic acid liberation
Synthesised in leukocytes (and also by injured tissue e.g. endothelial cells)
1. Platelet aggregation
4. Immune response (also anaphylaxis)
How does mRNA get from the nucleus to the cytoplasm? Once in the cytoplasm what initially happens to the mRNA?
Through the nuclear pore complex
= a basket on the inside of the nucleus and the cytosolic fibrils on the cytoplasmic side.
This process is tightly controlled, and is energy dependent which requires the reorganisation of the proteins at the core of the nuclear pore. Some small molecules can diffuse across the nuclear envelope but other molecules passage are controlled by the nuclear pores.
After mRNA passes through the nuclear pore the cap-binding protein is exchanged for an initiation factor which binds to 5’ cap.
The genetic information encoding proteins needs to be read from a specific starting point, without this the information could be read - in blocks of three - to give very different outcomes. What is the starting point and what is the ending point?
The starting point is defined by the initiation codon (AUG).
The ending point is defined by the stop codon (UGA) which defines the end of open reading frame
Translation occurs in 3 phases. Describe and explain each phase.
The 5’ cap structure of the mRNA is recognised by the cap-binding protein complex which then recruits ribosomes. The ribosomes ‘scan’ through the 5’non-coding region until the initiation codon is found. Requires initiation factors
the (correct) charged tRNAs then bind and a peptide bond is made between the amino acids. Once the peptide bond is formed, the ribosome moves along the mRNA one codon. The deacylated tRNA exits the complex and a new, charged, tRNA binds (specified by the next codon of the mRNA)........etc., etc., until
the termination codon is encountered at the end of the open reading frame and the bond between the protein and the (last) tRNA is broken to release the finished protein. The whole complex disassociates. Requires termination factors
What are the types of mutations? What do they result in?
1. DELETION or INSERTION (nonsense or frameshift)
- the reading frame is shifted as bases are either inserted or deleted
2. SUBSTITUTION (missence or point shift)
3. SILENT MUTATION
THE BIG RED ANT ATE ONE FAT BUG
THA BIG RED ANT ATE ONE FAT BUG
NOTE: a POLYMORPHISM is not a mutation, it is a minor change in DNA sequences that is present in >1% of the population
What 3 things can occur once translation is completed?
1. Translocation to relevant part of cell
2. Protein folding
3. Post-translational modification
What is translocation?
Translocation within the cell can happen co-translationally. As a protein is being made the amino acids encoded in the protein form a signal sequence that is recognised by other proteins and direct it to the endoplasmic reticulum membrane. There are channels in the ER membrane that recognise the protein and allow the protein and the ribosome with it, as it is still being synthesised, into the ER hence rough ER.
The signal sequences can code for movement to destinations such as the nucleus, ER, mitochondrion etc.
What is post-translation modification? Describe it, ensuring to mention what disease it can be associated with.
Signals can also dictate post-translation modifications such as glycosylation. N-linked glycosylation tends to start in the ER and occur in the Golgi. Too much as well as too little modification can be harmful, tau-hyperphosphorylation is associated with neurofibrillar tangles in dementia.
What are the 4 reasons that SSIs occur?
Damage to tissues
Damage to blood vessels
Presence of a foreign body (sutures)
Reduced efficacy of inflammatory response
What are the 4 origins of SSIs?
1. Acquisition during surgery
2. Acquisition post operatively
3. Endogenously (pts own microflora)
4. Exogenously (other pt or staff)
Surgical site infections can occur when the integrity of the skin is broken. What are the risks involved? (HINT: there's 4 risks)
- Dehiscence - reopening of a closed wound (can lead to evisceration)
- Abscess development
- Localised spread of infection
Systemic spread of infection
Systemic spread of infection
What factors influence the development of SSIs? (HINT: there's 10 so list as many as can - think logically!)
- Type of surgical wound(clean/dirtyetc.)
- Pre-, intra- and post operative care
- Surgical team
- Age and general health of pt
- Extent of tissue injury
- Infection prevention procedures
- Presence of prosthesis or foreign body
- Presence or absence of drain
- Duration of surgery
- Place in operation list
What are the 4 classifications for surgical wounds? Describe them.
Clean (class I)
– Elective surgery
– No acute inflammation
– Do not involve R, GI or GU tracts
Clean / contaminated (class II)
– Clean wounds with higher risk of infection
– Uncomplicated R, GI or GU tract surgery
Contaminated (class III)
– Outside object comes into contact with wound
– Large amounts of spillage from GI tract into wound
Dirty class (IV)
– Purulent inflammation
– Foreign object lodged in wound
– Traumatic or infected wounds
What are the microbial causes of SSIs in the skin and bowel? (HINT: there's 3 for skin and 5 for bowel)
What care is taken pre-operatively to reduce the chance of SSIs?
Do not remove hair
Give antibiotic prophylaxis before:
– Clean surgery (prosthesis or implant only)
– Clean-contaminated surgery
– Contaminated surgery
Do not routinely use nasal decontamination
Do not routinely use mechanical bowel preparation unless harvesting gut
WHY does shaving INCREASE the chance of SSIs?
Shaving inflicts microtrauma and increases susceptibility to colonization by bacteria
What are the 2 types of (i) conventional (ii) occlusive dressings used to prevent infection?
What 6 things ar edone to reduce the risk of post-operative infection?
- Keep pre-operative length of stay in hospital to a minimum
- Elective surgery should be postponed if evidence of infection pre-op
- Keep length of surgery as short as possible
- Maintain good operative technique
- Debridement of dead and necrotic skin - to bleeding tissue
- Ensure adequate vascularization - never close a dusky wound
What are the 5 roles of the surgical team?
- Skill of individual surgeon
- Quality of aseptic technique
- Adequacy of protective clothing
- Wearing of gloves
- Carriage of S. aureus
What 4 things are done to prevent catheter related infections?
- Always wash hands before procedure
- Wear gloves when handling catheter
- Use single use antiseptic wipe
- Cover insertion site with dressing
What are the 4 risk factors for prosthetic joint infections?
What diagnostic procedures are done to diagnose a prosthetic joint infection? (HINT: 6 points)
Collection of pus by needle aspiration
Raised ESR and CRP
What are the 5 causative agents of prosthetic joint infections?
Gram negative bacilli
How do you make a microbiological diagnosis? (HINT: there's 4 points)
Describe (i) smear diagnosis (ii) culture diagnosis (iii) Maldi a positive step , listing pros and cons.
Simple to perform
Not very sensitive OR specific
Requires considerable expertise
(ii) More sensitive than smear
Allows susceptibility testing
Allows rapid presumptive diagnosis
Allows detailed identification
Rendered negative by antibiotics
(iii) Rapid identification of bacteria
Does not provide susceptibilities
Delayed by slow growth
Of no value if antibiotics render cultures negative
What 3 things does microbiology do?
- Identify the infecting organism DIAGNOSTIC ADVICE
- Susceptibility testing TREATMENT ADVICE
- Identify clustered organisms over-represented in the community INFECTION CONTROL
What does serological diagnosis do? What are the various tehniques that can be used?
Detect high IgG concentration
Detect rising of falling titres
Measure avidity of binding
Examples = agglutination, precipitation, complement fixation, virus neutralisation etc
What are examples of molecular techniques?
- DNA hybridisation
- Nucleic acid amplification testing
- LCR (ligase chain reaction)
- Automated DNA amplification
- Real time PCR
- LCR (ligase chain reaction)
- Automated DNA amplification
- Real time PCR
What is the (i) sensitivity (ii) specificity of a test?
(i) The ability of a test to detect all of the true positives. It is equal to the number of positives obtained divided by the total number of positives
(ii) Ability to identify the number of true negatives. It is equal to the number of negatives obtained divided by the number of true negatives
What is the structural hierarchy of a multi-cellular animal?
Define (i) cells (ii) tissues (iii) organs (iv) organ systems.
(i) The basic and structural functional unit
(ii) an aggregate of a specialised cell type with a particular function e.g. muscles, epithelial, nervous
(iii) Sspecialised tissue organised by connective tissue and served by nerves, blood vessels and more depending on function e.g. kidney, liver, pancreas
(iv) A group if integrated organs that collectively perform a function .e.g. cardiovascular, urinary.
What is the importance of physiological control systems?
Fundamentally all cells remain viable using common basic cellular pathways controlled by housekeeping genes.
On top of this differentiated cells express genes that allow the cell to perform a special function(s).
E.g. muscle cells generate force and produce motion
nerve cells initiate and propogate electrical signals
epithelial cells form boundaries between different compartments
endothelium defines vessels e.g. blood vessels
connective tissue cells connect, anchor and support structures of the body
What do organ systems create?
the functional internal environment
What is the importance of extracellular fluid?
Bathes the cells and tissues and is the internal environment of the body
What are the 5 major features of homeostatic control systems?
- Primarily operate through a negative feedback mechanism
- Stability is achieved through balancing the inputs and outputs (irrespective of the absolute magnitude of change)
- Unable to maintain complete constancy of the internal environment (range of normal values)
- Unable to maintain every system constant (hierarchy of importance)
- The set point of some control systems can be reset
What is the meaning of homeostasis?
Physiological control systems maintain the internal environment in a relatively stable state. Homeostatic balance is the result of the regulated and integrated activity of tissues and organ systems.
Homeostatic regulation involves mechanisms that feedback, FEEDBACK can only occur in a system where the outputs are routed back in someway as inputs.
Define (i) negative feedback (ii) feed forward (iii) positive feedback.
(i) the feedback action reduces the effect of the circuit/pathway (most common in maintaining homeostasis) PROMOTES STABILITY
(ii) the system ANTICIPATES the need for change ANTICIPATES CHANGE
(iii) the feedback action produces a positive or heightened effect PROMOTES CHANGE IN ONE DIRECTION, INSTABILITY
What is the gain of a control system?
The effectiveness of a negative feedback system
What is the 4 questions to ask about the physiological control systems?
- What is the variable that is being maintained in the face of changing conditions?
- What are the receptors that detect change?
- Where is the integrating centre and what are the
afferent and efferent pathways?
4. What are the effectors and how do they alter their activities to maintain the set point?
Describe, using physiological examples, the process of homeostatic control. (thermo-regulation, baroreceptors)
Body temperature controlled at ~37oC
Ambient temp can be ;50oC ; +50oC
Main sensor = skin
Controller = hypothalamus
•Effectors = skin (sweating, hairs trap heat) and muscle.
BARORECEPTORS - see diagram
GLUCOSE - Fasting blood sugar tightly maintained at 3.5 to 8 mmolL-1
Glucose sensor = specialised pancreatic cells that receive blood via portal circulation
Controller = autonomic nervous system
Effectors = α Pancreatic cells in islets of Langerhans
(secrete glucagon for glucose release)
β Pancrea0c cells in islets of Langerhans (secrete insulin for glucose uptake by cells)