ABCDE Flashcards
What is SIRS?
Systemic Inflammatory Response Syndrome
- Hyper/hypothermic, tachycardia, tachypnoea, high or low WCC
Causes = sepsis, pancreatitis, trauma, burns
What is the pathophysiology of sepsis?
Get invading organisms => activation of macrophages - release pro-inflammatory molecules (cytokines, thrombin and NO) => combination of hyper coagulability and hypocoagulability, inflammation, endothelial dysfunction.
Why do we get sepsis?
Normally - needs to be a pro-inflammatory response to microorganisms and a counter-response by the body of anti-inflammatories to keep inflammation localised to the area it is needed.
In septic shock - the pro-inflammation molecules overwhelm the anti-inflammatory ones
What are micro-emboli called that end up the in small capillaries due to sepsis?
Purpura fulminans
What do pro-inflammatory cytokines cause?
Endothelium of BVs connected with tight junctions - infection - then these become less tight for migration of pro-inflammatory factors. Want the WBCs to get to the infection.
Vascular system becomes very permeable
Early stages of sepsis - they are already hypovolemic. When you add fluid - it doesn’t stay in the vasculature as a result.
P becomes hypotensive. Causes negative inotropy - reduces cardiac contractility
Has fever - high temp - body losing water and heat - generating massive amounts of energy and losing it. Diarrhoea as well = further fluid losses and electrolyes.
Initially - get hypercoagulability - can cause microemboli. Forming the clot - body uses up the coag factors - uses up the fibrin etc - cant keep up with the consumption of these ingredients - even though the body wants to coagulate, the body runs out of materials to form clots = hypocoaguable state.
Get increased WBCs - esp Ns - massive inc - get to site of infection, adhere.
Metabolic changes - see insulin resistance v quickly - because the body wants lots of glucose circulating in order to supply the energy needs. Body also quickly starts to consume proteins in order to meet energy demands to fight the infection and to rebuild after the infection
What cardiovascular changes occur in sepsis?
Initially warm and dry or warm and sweaty
Can get vasoconstriction at this point as the body tries to stop the loss. Still resuscitatable - bolus of fluid or leg raise will bring them round.
End - very cold, very shut down. Heart is very dysregulated - when you fill them with fluid, the venous system fills up. Its not going into the arterial system because the heart is not pumping to move the fluid into the arterial system = this is not fluid responsive.
What metabolic changes occur in sepsis?
Fundamentally - driven by evolution
Sepsis - body thinks we cant do anything - tries to reduce the amount of energy that it needs apart from fighting the infection - and self-cannibalises in order to do so.
In ITU - these mechanics act against interventions
Mitochondria function differently - in areas where there is no inflammation the mitochondria are downregulated. Ps to begin are hyperglycaemic.
Get circulatory changes - vasoconstriction and dilation in the appropriate areas - as it becomes dysregulated you get generalised vasodilation. Leads to tissue hypoxia in the areas where the mitochondria are not working. Instead you get anaerobic respiration and lactic acidosis.
How can you identify sepsis?
Suspected infection
+
An acute change in SOFA score of more than 2 points consequent to infection
How can you identify sceptic shock in Ps?
Persisting hypotension requiring vasopressors to maintain a MAP of 65mmHg
Serum lactate >2mmol/L
despite volume resuscitation
If a patient has problems breathing - how can you identify this?
What do you give a patient who has problems breathing in septic shock?
A 15L non-rebreather mask
What signs are concerning regarding circulation in a sceptic patient?
Cap refill > 2 seconds (very sensitive indicator)
Core v. peripheral temperature differences (cool peripheries = not good)
HR, BP
Oliguria
Confusion
Mottled, cold and dry = bad - person is about to die.
What is usually the first evidence of organ dysfunction in the CVS/Respiratory system?
The appearance of ALI or ARDS (acute lung injury or acute respiratory distress syndrome)
Not pneumonia - caused by sepsis. Get inflamed capillaries in the lungs - fluid is pouring out of the capillaries and into the air spaces in the lungs.
Do sequential CXRs
What is shock?
The body cannot provide enough glucose for its metabolic demands. Starts to shut down circulation to underperfusing parts of its circulation (evolutionary response).
= Massive cellular dysregulation. Lose K+ and Na+ = fluids in interstitium. Lysosomes release -> cell death.
Cell contents are released - these are pro-inflammatory = start to magnify the response => causes inflammatory cascade.
What is biofilm?
Is a community of microorganisms in which cells stick to each other and often also to a surface. These adherent cells become embedded within a slimy extracellular matrix that is composed of extracellular polymeric substances (EPSs)
What type of bacteria is Staph aureus?
Gram positive
Which is harder to treat - gram positive or gram negative bacteria?
Gram-Negative Bacteria
Their peptidoglycan layer (LPS) is much thinner than that of gram-positive bacilli. Gram-negative bacteria are harder to kill because of their harder cell wall. When their cell wall is disturbed, gram-negative bacteria release endotoxins that can make your symptoms worse.
What proportion of sceptic patients are a result of gram positive bacteria?
50% (mostly staph aureus)
How do macrophages recognise S aureus?
By their peptidoglycans and lipoteichoic acids - recognised on Macs TLRs -> inflammatory response
Why does TSS occur?
Certain bacteria produce toxins which function as super antigens = trigger responses in up to 20% of all T cells (rather than just the tiny proportions of resting T cells).
Superantigens are big molecules - locks a T cell into a pro-inflammatory position, no disassociation = massive and prolonged response.
Which inflammatory factors are released during TSS?
IL1
IL2
TNF
What does C Diff do?
Causes severe epithelial and mucosal damage - esp in the colon where it can cause massive sloughing of cells
What is the difference between sepsis, SIRS and septic shock?
What were the problems with the SIRS criteria?
How is sepsis now defined?
Life threatening organ dysfunction caused by a dysregulated host response to infection.
What NEWS score can indicate possible sepsis?
NEWS >7
What are the qSOFA score criteria?
SBP <100mmHg
RR >22
Altered mental status - GCS <15
What are the sepsis six?
What type of antibiotics should you use in sepsis?
Broad spectrum bacterio-cidal ABx
NOT bacteriostatic ones
Check local guidelines
What should you do before starting systemic Abx?
Send blood cultures!
How does normal glucose metabolism occur?
Glucose enters body and goes to the liver through the mesenteric circulation - enters metabolic pathways - brain, blood, muscle, fat, pancreas and liver.
What is the first phase of starvation?
What happens in this phase?
Simple starvation - occurs 4-6 hours after the last meal.
Involves adaptive metabolic responses -
- consumption of glycogen (glycogenolysis)
- gluconeogenesis (FAs and glycerol)
Lean tissue is conserved (i.e. protein)
What is the second phase of starvation?
What happens in this phase?
Phase 2 = catabolic weight loss (adipolysis)
Uses mainly stored fat for energy (occurs 12-18 hours after last meal)
Generates ketones form fat stores = ketotic state (mild ketosis)
Body starts to consume bicarb to balance out the acidosis from the ketones = bicarb levels fall
What is the third phase of starvation?
What happens in this phase?
Phase 3 = catabolic weight loss via proteolysis
Fat stores are gone - proteins used to produce AAs.
Not uniform loss - muscles, liver and spleen are catabolised first. Tries to maintain basal metabolism.
Poor wound healing, immune response, GI integrity etc common at this phase.
When is ketosis not pathological?
When conc is only mildly elevated (<3mmol) above baseline
Due to a normal response to low glucose availability.
What happens when the body is in a state of ketosis?
Machinery of glucose production shifts to the liver
Insulin inhibits lipolysis
Feedback mechanism - the more ketones you have, the more lipolysis is inhibited
What is ketoacidosis?
A metabolic state associated with metabolic acidosis and pathologically high serum and urine concs of ketone bodies.
What causes ketoacidosis?
- DKA
- Alcoholic ketoacidosis (AKA)
- Salicylate poisoning
- Isopropyl alcohol ingestion
- Starvation ketoacidiosis (>3 w of starvation)
What is the difference between starvation and injury?
In injury - metabolic rate is increased for repair whereas in starvation it is decreased to conserve calories.
In injury - protein is used for catabolism as the products from its breakdown are used for repair. In starvation - fats and ketones are used for catabolism as they are the least useful materials needed by the body and are therefore expendable.
What causes sepsis and septic shock?
An imbalance between the proinflamamtory and anti-inflammatory responses. Both pathways occur but should stay in balance. When they get out of balance and you get too much proinflammation - this causes sepsis and septic shock.
By how much do energy requirements increase in sepsis?
Energy requirements can go up by 30% in sepsis
How is the post-shock metabolic response categorised?
Into the ebb phase and flow phase.
Ebb phase - starts immediately and lasts for 24 hours as the body conserves energy.
Flow phase - the body expends energy and massive catabolic efforts take place.
What causes a huge rise in nitrogen excretion after stressful insults to the body?
Protein catabolism used for repair of the body
What do you need to beware when feeding sick Ps?
If you underfeed or overfeed a P - the mortality rates go up. Is a “goldilocks feeding point” = need to provide the right number of calories which is only a little bit more than the cumulative normal basal metabolic rate.
Why do Patients go off their food when they are unwell?
Stress mediators oppose the anabolic actions of insulin.
Get peripheral insulin resistance in these patients.
In times of illness, which places stress on the body, there are additional glucose requirements - how does the body obtain these?
What is the hypermetaboic response to injury?
The flow phase of recovery - HT, tachycardia, Nitrates in urine, mild pyrexia, albumin v high
Pro inflammatory condition.
Massively consumes lean body mass - muscle, bone, parenchyma (liver and spleen) - results in very high energy metabolites (lactate and Fas) being released - body floods itself in the absence of being able to take food in. Get hyperglycaemia, plus ketones and lactic acid create acidosis as well.
What is lactate used for in the body?
Used both in the cori cycle and the Krebs cycle to make energy
What can cause a high serum lactate?
Lots of things
- Exercise
- Critical illness
- Sepsis
- Cardiogenic shock
- Liver failure
- Open heart surgery
Why do you get hyperlactatemia in sickness?
Is not always due to tissue hypoperfusion (response to this is to increase tissue perfusion by increasing fluids). Fluid challenge is not always the right response to a raised lactate.
Initial problem of high lactate can be due to both overproduction from sickness OR inability of the body to clear the lactate it has.
Over production happens due to massive inflammation - accelerates glycolysis and proteolysis - catabolic state - mobilisation of substrates to increasing the production of pyruvate and lactate.
Happens in skeletal muscle - supply source that the body turns to when it has run out of glycogen.
Lactate is moved in the circulation from skeletal muscle to places like the liver where it can be utilised. High lactate - body is deliberately producing it as an energy source for increased demand. In sepsis - vast majority is oxidised = limited uptake by the Cori cycle - remainder is turned into glycogen by gluconeogenesis in the liver. Not efficient energy supply.
What is it called when you have 2+ altered organ functions in acutely ill patients -> homeostasis cannot be maintained without intervention.
Multiple Organ Dysfunction Syndrome
Where does MODS usually appear first?
Cardiovascular and respiratory systems - can manifest as acute lung injury ./ acute respiratory distress syndrome.
This leads to hepatic and renal dysfunction
Then disorders of haemostats, GI and CNS
Finally bone marrow failure and myocardial dysfunction are usually late manifestations.
How can you assess a P’s volume status?
What clinical signs can you use to monitor volume status?
Cap refill - really sensitive measure of fluid refill
If in bed for a long time - fluid can accumulate in flanks and sacrum - get pitting oedema
Are they warm, cold? Do they have swollen knees?
Breathless - because fluid overloaded or because they are hypovolaemic?
Arterial line - look for a swing in systolic pressure - does the systolic pressure move up and down in line with respiration - sign that someone needs fluid.
JVP - not useful in determining fluid balance
What does 0.9% saline contain?
154 mmol/L Na and Cl
What does 5% glucose contain?
50g of glucose/L
What does Hartman’s contain?
Na (131)
K (5)
Cl (111)
Ca (<0.5)
Lactate (5.16)
HCO3 (29)
What is the osmolality of the extracellular and intracellular spaces?
280-310
Which crystalloid fluids is the most similar to normal physiological fluids?
Haartman’s
Hartmann’s = Na, K, Cl - closer to physiological normal levels - small amount of Ca - isnt much Ca IC - so this amount of Ca maintains normal body levels. Is no glucose but there is lactate. Lactate - is a useful molecule for metabolism. Also has HCO3 in it - good for buffering and metabolism.
What fluids would you give in this case?
What do you want to do now?
Non-rebreathe mask @ 15L
High flow O2
Blood cultures taken now
Proper Abs - double check the Abs - are they bacteriacidal?
Needs a fluid challenge - 500ml bolus as fast as you can get it in - squeeze it in
Measure lactate - arterial sample.
Put catheter in and measure urine output
How much fluid should be given in resus?
500ml over 15-20mins, 250ml over 30mins if frail
Keep on giving until they dont need any more or if they stop responding (if they stop responding - they are getting worse).
When you give crystalloid fluids - how much stays in the intravascular space?
1/4
Why does dextrose distribute much further than normal fluids?
The glucose is taken up by all compartments - only 1/12 will remain intravascular.
Why is dextrose not used for resus?
Only 1/12 remains intravascualr
It can cause electrolyte dilution - esp hyponatremia
Will lyse cells as well due to hypotonic status - not good
What types of colloid fluids are there?
Colloid = fluid with big molecules in there
- Succinylated gelatin
- Albumin
- Blood products
When are colloids used?
In specific situations - when you need rapid volume expansion or when protein loss is high.
- Replacement (ascitic / pleural losses)
- Trauma resus if blood loss
- Balanced resus in severe sceptic shock ( in sepsis the tight junctions fail and even the big molecules can leak out. Give colloids for specific therapeutic indication - e.g. RBCs for anaemia or FFP for coagulopathy)
What do you need to complement giving 0.9% saline with?
5% dextrose
Otherwise P can develop acidosis and hypernatremia as saline does not contain K+
