Exposure (everything else) Flashcards
Define pH?
log^10 [H+]
Where does acid load come from in the body?
Predominantly generated via CO2 being turned into carbonic acid and in turn giving H+.
- Via enzyme carbonic anhydrase
Also via:
- Metabolism of sulphur containing amino acids
- Generation of lactic acid during anaerobic respiration
- Generating ketone bodies in DKA
Main acidic buffers?
HCO3-
Phosphate
Plasma proteins
globin of Hb
What is Henderson hasselbalch equation?
Describes relationship between dissociate and undissociated acids and bases.
Allowing us to identify pH of a buffer solution.
pH = pK + Log [HCO3-/CO2]
Means we can analyse what happens of CO2 changes for example
Which organs are involved inn acid base balance?
Respiratory:
- Controls PCO2 via ventilation.
- Increased PCO2 stimulates chemoreceptors in medulla by releasing H+ which crosses BBB
Renal:
Controls bicarb
Haematology:
Plasma proteins and globin chains buffer acids
GI:
Liver can generate bicarb and ammonia
In kidneys, ammonia secretion generates more bicarb
How do the kidneys regulate acid base balance?
• Tubular cells of nephron secrete H+, and in doing so facilitate the reabsorption of bicarbonate.
-80% of this is reabsorbed in the proximal tubule.
• Tubule cells can also generate de novo bicarbonate from glutamine, which it metabolises to 2 ammonia and 2 bicarb.
-Generally, bicarb returned to blood, and NH4 secreted into urine
• Kidney also excretes urinary buffers phosphate being the predominant buffer
-Phosphate is excreted, meaning more H+ can be excreted which also generates more bicarbonate to be reabsorbed.
-Acidosis stimulates increased PTH which causes increased phosphate excretion.
• Tubular cells in the collecting duct can also conversely excrete bicarbonate and reabsorb H+
Define base excess?
This is the amount of strong acid needed to return 1L of fully oxygenated blood to a normal pH at a PCO2 of 5.3kPA at 37 degrees.
What is metabolic acidosis?
low pH, with a fall in bicarbonate
How can bicarbonate ions be lost?
Excreted e.g. D+V, fistula
Depleted via buffering, if overwhelming H+
How can we classify the causes of metabolic acidosis?
Via anion gap.
Anion gap = (Na+K) - (Bicarb + Cl)
normal anion gap = hyperchloraemic metabolic acidosis, is due to loss of bicarb NOT GAIN OF ACID.
It is normal because with loss of bicarb, the body is very good at displacing a different. negative ion to extracellular space e.g. chloride, so it balances it out.
Raised anion gap = impaired H+ secretion / accumulated organic acids
In this case you will have an increase in UNMEASURED ions. So raised anion gap as chloride not raised.
Causes of normal anion gap vs raised anion gap?
Normal anion gap = bicarb loss:
GI loss e.g. D+V, fistula, stoma
Renal loss = Renal failure, RTA type 2 and 4
Raised anion gap: KUSMEL
Ketoacidosis Uraemia Salicylate poisoning Methanol Ethylene glycol poisoning Lactic acidosis
Physiological effects an acidosis has on the body?
- Shifts oxygen dissociation curve to the left = lower affinity to oxygen = readily available oxygen to perfuse tissues.
- Acids causes reduced myocardial contractility and risk of arrhythmias
- Acids cause pulmonary vasoconstriction = pulmonary hypertension
What is a metabolic alkalosis?
a pH >7.45, with bicarbonate >28.
Other ions implicated in a metabolic alkalosis?
- Loss of H+, e.g. by vomiting = relative increase in bicarb.
- Chloride ions lost, causes renal tubules to take up more bicarb.
- Loss of potassium, causes increased bicarbonate absorption in renal tubules
How can we classify metabolic alkalosis and its causes?
Chloride responsive with urinary chloride <10, due to:
- loss of hydrogen via the GI tract ,
- diuretic therapy
- post-hypercapnia syndrome
- Contraction alkalosis - diuresis or severe dehydration…. means reduced water, means RAAS activation = water and Na retention but at expense of H+
- Cystic fibrosis due to excess loss of NaCl in sweat
Chloride unresponsive with urinary chloride >40, due to:
- Retention of bicarbonate
- Intracellular shift of H+ e.g. in. hypokalaemia
- Hyperaldosteronism - aldosterone increase Na and Water retention but at expense of H+
- Barters and Gittlemans
Why does metabolic acidosis develop in pyloric stenosis?
Gastric acid is lost which contains protons and electrons
Reduction in pancreatic juice secretion due to reduced acid load at duodenum = retain bicarb
So currently we have lost H+, and retain bicarb.
Volume depletion maintains the alkalosis by leading to bicarbonate absorption over chloride e.g. contraction alkalosis
Also as we lose chloride, there is increased uptake of bicarb in renal tubules to maintain neutrality
Why alkaloid patients have poor oxygen perfusion?
Alkalotic means reduced H+, so oxygen dissociation curve shifts to the left = greater affinity = reduced perfusion
Also as part of compensatory mechanism = hypoventilation to increase PCO2.
Defining features of lactic acidosis?
pH <7.35
Lactate >2
How can you classify lactic acidosis?
Cohen and Woods classification:
Type A = due to inadequate tissue oxygenation:
1. Anaerobic metabolism e.g. sprinting, seizures. Lactate from pyruvate
2. Shock - poor tissue perfusion = cellular hypoxia = anaerobic
3. Reduced oxygenation e.g. Severe anaemia or carbon monoxide poisoning
Type B = No clinical evidence of poor tissue oxygenation
- Chronic disease = renal / liver / malignancy
- Drug induced e.g. paracetamol, salicylate, metformin
- Inborn errors of metabolism e.g. pyruvate dehydrogenase deficiency
Precautions in using therapeutic bicarbonate ?
- Need to carefully titrate - can overshoot and cause alkalosis
- Infuse slowly as can alter myocardial contractility
- Can get a respiratory acidosis as extra CO2 generated to balance equation
Distribution of calcium within the body?
99% in bone
1% readily exchangeable as calciums phosphate salts
State of calcium within the blood?
50% unbound and ionised
45% bound to plasma proteins
5% associated with anions such as citrate and lactate
Outline the hormonal control of calcium?
Parathyroid releases PTH:
- Increases calcium via increased bone resorption + increased synthesis of 1,25(OH)D2 which causes increased gut absorption
- Causes reduced phosphate via decreased renal absorption + reduces renal calcium loss
- 25(OH)D2:
- Increased plasma calcium and phosphate
- Increased renal absorption of both calcium and phosphate
- Increased gut absorption
- Increased bone resorption at high levels
CALCITONIN: from thyroid C cells
- Inhibits gut absorption of calcium
- Osteoclast activity inhibited
- Inhibits renal absorption
Features of hypercalcaemia?
Stones - renal, polyuria and polydipsia
Bones - Pain / cysts
Moans - depression / confusion
Groans - Pancreatitis, constipation and peptic ulcers (Ca causes increased gastric acid secretion)
Hypercalcaemia ECG changes?
Shortened QT
Increased PR
Flattened t-waves
Causes of hypercalcaemia?
Is PTH suppressed? YES = appropriate 1. Malignancy e.g. myeloma or bony mets 2. Small cell lung Ca producing PTH-rP 3. Sarcoidosis with exogenous vitamin D
No = inappropriate = primary hyperparathyroidism 80% = solitary adenoma 20% = MEN1
Differentials of abdominal pain with hypercalcaemia?
Peptic ulceration, could be perforated
Renal colic
Pancreatitis
Constipation
Emergency management of hypercalcaemia?
ABCDE
IVF usually 3-6L within 24 hours
- if worried about overload can give furosemide, which would also lower calcium
Meds:
Bisphosphonates
Steroids if malignancy
Features of hypocalcaemia?
Muscle spasms / cramp
Irritability
Chvosteks = tap facial nerve anterior to tragus
Trousseaus = Hand spasm when having BP taken
Causes of hypocalcaemia?
Is it PTH driven?
Yes = low PTH:
- Autoimmune hypothyroid
- DiGeorge syndrome
- Surgical removal parathyroids
No = PTH normal / raised
- Low vitamin D e.g. malabsorption, osteomalacia, rickets
- Chronic renal failure
Management of hypocalcaemia?
ABCDE
10ml 10% calcium gluconate
Treat any hypomagnaesaemia as well
normal magnesium level ?
0.7 - 1.0
What is magnesium distribution within the body?
Most abundant intracellular cation after potassium, so serum levels are poor indicator of total body store
65% located in bone
1% found in serum
Purpose of magnesium?
cofactor for number of enzymes
Relationship between magnesium and calcium?
High magnesium prevents calcium entering cells. For this reason low magnesium can lead to bradycardia and sluggish reflexes
Management of severe hypermagnesaemia is….
Calcium gluconate
Which organ largely responsible for magnesium homeostasis?
Kidney:
It is freely filtered at glomerulus
Reabsorbed at PCT and thick ascending limb
Causes of hypomagnesaemia?
- Low intake e.g. ETOH, malnutrition
- Increased excretion:
GI = diarrhoea, bowel resection, bypasses
Renal = any state of diuresis e.g. diuretics or acute renal failure
Endocrine e.g. diabetes mellitus, hyperPTH
Occurs in 60% of critically ill patients, often due to diuretics
Features of hypomagnesaemia?
Arrhythmias e.g. AF
ECG changes = prolonged PR and wide QRS
Muscular weakness
Confusion
Potassium distribution in the body?
98% intracellular
How is potassium regulated?
GI - dietary intake
Endocrine:
1. Aldosterone = Mineralocorticoid produced in zone glomerulosa of adrenal gland.
Causes K excretion in DCT and cortical collecting duct, to allow reabsorption of sodium
- Insulin = stimulates uptake into cells
Renal:
K and H+ are readily exchanged
So if acidotic K goes up
If alkalotic potassium lowered
Causes of hyperkalaemia?
Renal:
- reduced GFR = no filter
- Reduced renin in NSAID use
Drugs e.g. NSAIDS, ACEI, K-sparing diuretics
Low aldosterone = Addisons
Cellular release = rhabdomyolysis in burns/trauma, any acidosis or massive transfusion
Hyperkalaemia ECG changes?
Tall tented t-waves
Small p waves
Widened QRS
Eventually VF
Management of hyperkalaemia?
Calcium gluconate 10ml 10%
50ml 50% dextrose with 10iU of insulin over 30 mins
Treat underlying cause
How is potassium used in surgery?
Potassium rich cardioplegic fluid is used to arrest the heart in bypass surgery
Causes of low potassium?
Renal loss:
Loop diuretics / barters = NA/K/Cl transporter blocked, so no K or Na. But Na absorbed further downstream at sake of K
Thiazides / Gittlemans = Block Na/Cl transporter, so further downstream Na absorbed at expense of K
GI loss e.g. D+V
Excess aldosterone e.g. Conns
Cellular redistribution e.g. Alkalosis or insulin
ECG changes in hypokalaemia?
Flattened T waves, U-waves, prolonged PR.
Distribution of sodium within the body?
50% extracellular, 45% bone, 5% intracellular
Major physiological effects of sodium?
Osmotic force
Generating action potentials
Daily requirement?
1mmol/kg/day
Classifying hyponatraemia?
Hypovolaemic, euvolaemic and hypervolaemic
Hypovolaemic = lose Na+H20 = ADH = reabsorb water but not sodium
- Renal losses (Urinary sodium >20)
- Diuretics
- Salt losing nephropathy - Extra-renal loss (urinary sodium <20)
- Fistula / D+V / burns
Euvolaemic:
- SIADH e.g. lung Ca, meningitis
- Adrenal insufficiency = Addisons - low cortisol means low BP = ADH release
- Hypothyroid = reduced cardiac output = reduced BP = ADH release
Hypervolaemic:
- Cardiac failure = low BP = ADH release
- Cirrhosis = NO release = low BP = ADH
- Renal failure
- Excess dextrose / TURP syndrome
What is pseudohyponatraemia?
Falsely low sodium as serum volume is raised due to increased lipid/protein levels
TURP syndrome?
Following transurethral resection of prostate, use of hypotonic fluid for irrigation. Fluid s absorbed through inured vessels producing a dilutional hyponatraemia.
PC = haemodynamic instability, confusion and severe cases have convulsions and comas.
Features of low Na?
<135. = malaise <130 = headache and confused <125 = seizures and coma
Causes of hypernatraemia?
Unreplaced water loss e.g. GI losses
Diuresis in diabetes
Reduced ADH receptors in diabetes insipidus
What is diabetes insidious, tests and Mx?
Diabetes insipidus is polyuria ceasing severe thirst and dehydration, leading to hypernatraemia
Causes can be central = no vasopressin produced, or nephropgenic when kidneys cannot respond
Ix:
Fluid deprivation test - still will not concentrate urine
Then give Desmopressin - if responds means it is central, if does not means it is nephrogenic
Mx:
Central = desmopressin
Nephrogenic = thiazide diuretic
Why measure urine output?
- indicator of renal perfusion pressure = therefore cardiac output + ability to perfuse peripheral tissue
- Indicator of renal tubular function
- Indicator urinary tract is functional with no blockage
what is normal urine output?
0.5ml/kg/hour
Kids = 1ml
Common causes of post reduced urine output?
Physiological stress response
Poor renal perfusion:
- Dehydration
- Bleeding
- Low CO e.g. MI, PE, arrhythmia, excess IVF causing CCF
- Vasodilated
Renal tubular dysfunction
Renal tract blockage
Intra-abdominal HTN (>20mmHg) = compresses renal parenchyma
Most common cause of post op oliguria?
Physiological stress in first 36 hours
- Circulating glucocorticoids and MR’s inducing salt and. water retention
Clinical signs you would look for when examining oliguria patient?
A - nil
B - tachypnoeic, wet crackles
C:
Dry mouth, drains and fluid chart, drug chart
Cool peripheries, tachycardia, low BP / CVP
Acute tubular necrosis vs pre-renal AKI investigations?
ATN: Na = >20, urine osm <500, Urine:plasma osm <1.2
Pre-renal: Na <40, urine osm >350, Urine:plasma osm >1.2
Management of poor urine output?
Flush catheter
Fluid challenge and response to CVP
Inotropes if required - dopamine increase renal blood flow as well as being inotropic
Drug review
Renal support if severe
Definition of AKI?
abrupt reduction of kidney function inn <48 hours
Loosely biochemically defied as:
Oliguria <30ml/hour for >6 hours
Creatinine rise of 1.5x
what is acute tubular necrosis?
Renal failure due to injury of tubular epithelial cells
Can be ischaemic injury e.g. due to shock
Can be nephrogenic e.g. drugs, toxins, myoglobin
Major causes of AKI?
Renal = ATN, glomerulonephritis and tubulointerstitial nephritis
Post-renal = stones, obstruction secondary to tumour, renal tumours, iatrogenic injury, BPH
Which part of the kidney is most susceptible to injury?
cells of thick ascending limb for two reasons:
- Cells reside in medulla, which has less oxygenation vs cortex
- Active NA/K ATP-ase pump on the cell membranes has high oxygen demand
Pathogenesis of AKI?
- Vasoconstriction:
- Compensatory response to fall in renal perfusion pressure of efferent arteriole
- Maintains capillary filtration pressure, at expense of reduced blood supply to the tubules perfused by efferent arteriole - Obstruction:
- Tubular cell ischaemia and necrosis = shed cells = obstruction - Pressure changes:
- obstruction cases back weak of tubular fluid into parenchyma = increases interstitial hydrostatic pressure.
Drugs causing AKI?
Paracetamol = ATN
NSAIDS = reduces protective effect of PGE during ischaemia
Aminoglycosides
How to distinguish AKI vs CKD?
Historic blood results
CKD has features such as anaemia, nocturia, pruritus. As well as radiological features e.g. small scarred kidney
2 most life threatening complications of AKI?
Acute pulmonary oedema due to fluid retention form over hydration
Hyperkalaemia: Can lead to metabolic acidosis and arrhythmias
Definition of CKD?
Kidney. damage for > 3 months based on proven. structural / functional abnormality
Most commonly caused by diabetes and HTN
What is creatinine?
Creatine minus a water molecule
Formed in muscle by non-enzymatic and irreversible degradation of creatine phosphate
Why is serum creatinine better marker of kidney function than urea?
50% of serum urea that is filtered gets reabsorbed, which means you underestimate GFR
Classification of CKD?
Stage 1 = >90
Stage 2 = 89-60
Stage 3A = 59-45
Stage 3B = 44-30
Stage 4 = 29-15
Stage 5 <15
Causes of CKD?
Congenital - PCKD
Glomerular disease e.g. diabetes, glomerulonephritis
Renovascular e.g. vasculitis
Chronic outflow obstruction e.g. tumour / BPH
Tubular e.g. nephritis
Clinical features of CKD?
- HTN secondary to fluid retention
- Polyuria and nocturia due to osmotic diuresis caused by uraemia
- Oedema - due to fluid retention and proteinuria
- Features of uraemia e.g. skin pigmentation, anorexia, nausea, malaise and constipation
- Haematological = normocytic normochromic anaemia
- Renal osteodystrophy
- Neurological deficit
Acid base disturbances in CKD?
Low sodium and calcium
Raised phosphate and potassium
Produces a resistant metabolic acidosis with increased anion gap. Due to chronicity has a low bicarbonate and raised creatinine
What is renal osteodystrophy pathophysiology?
Kidneys that are damaged cannot produce 1-alpha hydroxylase = reduced 1,25(OH)D3
This causes secondary hyperparathyroidism
This increases bone resorption, cyst formation and osteitis fibrosa
Hyperphosphataemia develops as a direct result of renal dysfunction, cannot excrete it.
Why are uraemia patients anaemic?
- Deficiency of EPO from kidney
- Presence of circulating toxins
- Bone marrow fibrosis drone osteitis firbosa
- Increased. red cell fragility due to toxins
Clinical findings when examining a CKD patient?
- Tachypnoeic from :
- metabolic acidosis - kussmauls (deep and laboured breathing).
- Fluid overload
- Anaemia - Uraemia signs - pigmentation of skin, pruritic scratch. marks, anorexic
- Pitting oedema due to overload as well
- signs of renal therapy = May see fistula on arm or abdominals car from renal transplant
management of CKD?
Optimise electrolytes and fluid balance
Treat the cause
ESRF = RRT or transplant
How can we assess burns?
1. According to % SA = Wallace's Rule of 9's (-Each palm is 1%) - Head 9% - Each arm 9% - Each leg 18% - Ant/post torso each 18% - Genitalia 1%
- According to depth…
- Superficial = just epidermal layer, erythema and painful, blanche and blisters
- Partial thickness = mid dermal, skin pale and dry, adnexae remain, painful ++
- Deep partial = deep dermal layer, non-blanching, mottled red, NO PAIN
- Full thickness = Leathery and charred, NO PAIN
Why in burns are you susceptible to respiratory side effects?
- Thermal injury to airway
- Smoke = hypoxia + pulmonary oedema if ARDS
- Carbon monoxide
- Circumferential burns = respiratory restriction
- Aggressive IVF can cause pulmonary oedema
Why is carbon monoxide toxic?
Its affinity for Hb is 250x greater than oxygen
So oxygen dissociation curve to the left = poor oxygenation of tissue
ALSO binds to some respiratory chain enzymes, affecting oxygen utilisation
Whens do you suspect impending respiratory distress in burns patients?
- Fire in a confined space
- Soot at mouth / in sputum
- Burns on face / singed hair or eyebrows
- Vocal changes
- Serum carboxyhaem >10%
Why do you get AKI in burns?
- severe loss of fluid means reduced renal perfusion = ATN
2. Circulating myoglobin = rhabdomyolysis = ATN
Systemic complications of burns injuries?
Burns shock = hypovolaemia Hypothermia as no skin Gastric stress ulcers Coagulopathy secondary to DIC Haemolysis = haemoglobinuria
Management principles of burns?
A = any impending distress intubate B = High flow oxygen early C = IVF and CVP monitoring if necessary
Renal - catheter
Thermoreg = convection heaters
GI = stress ulcer prophylaxis such as sucralfate
Escharotomy if circumferential burns of torso
How much IVF in burns?
Parklands formula:
4ml x weight (kg) x % burns = IVF inn 24 hours, half within first 8 hours
nutritional requirements in burns?
Curreri formula:
Adult = 25kcal/kg + 40kcal/%BSA
Kids = 40-60kcal / kg / %BSA
How can we assess nutrition?
Anthropometrics:
Height, weight, BMI
Fat indices
Lean muscle indices
Biochemical markers:
Serum proteins e.g. albumin
Clinical markers:
Appearance
Grip strength
How much does each energy source supply?
Fats = 9.3 Kcal/g glucose = 4.1 Kcal/g Protein = 4.1 Kcal/g
Define the respiratory quotient…
Respiratory quotient is the ratio of CO2 produced to the volume of oxygen consumed for the oxidation of a given amount of nutrient
Carbs = 1 Fat = 0.7 Protein = 0.8
Disadvantages of using glucose as main source of energy?
- Glucose intolerance:
- As part of the stress response, critically unwell patients are often in a state of hyperglycaemia and glucose intolerance. - Fatty liver:
- Excess glucose is converted too lipids in the liver - Respiratory failure:
- Given its higher respiratory quotient means it produces more CO2, glucose use only may lead to respiratory failure
Recommended daily intake of nitrogen and protein?
Protein is 1g/kg
Nitrogen = 0.15g/kg/day
How much protein gives 1 g of nitrogen?
6.25g of protein yields 1g of nitrogen
What is an essential amino acid?
An amino acid that cannot be synthesised by. the body, it must be ingested
e.g. isoleucine, leucine, lysine
What are essential minerals (elements)?
Copper, calcium, iron
What are fat soluble vitamins and their function?
A = cell membrane stabilisation and retinal fucntion
D = Calcium homeostasis
E = Free radical scavenger
K = Involved in gamma carboxylation of glutamic acid residues of Factors 2,7,9,10
What are the names of each vitamin B, and the result of their deficiency?
B1 = Thiamine = wernickes encephalopathy and beri beri
B2 = riboflavin = Glossitis + stomatitis + cheilosis
B3 = niacin = Pellagra (3 D’s dementia, diarrhoea, dermatitis)
B5 = panthothenic acid = acne and paraesthesia
B6 = Pyridoxine = stomatitis and peripheral neuropathy
B7 = biotin = rarely in isolation, but immune deficiency
B9 = Folate = Macrocytic anaemia and neural tube defects
B12 = cobalamin = megaloblastic anaemia + peripheral neuropathy
functions of vitamin C?
- Hydroxylation of proline and lysine residues during collagen synthesis
- Iron absorption in gut
- Synthesis of adrenaline from tyrosine
- Antioxidant function
Indications for enteral feeding?
Functionally intact GI system, but. cannot meet daily requirements
Types of enteral feeding?
Oral supplements
NJ / NG
PEG / PEJ
Polymeric vs elemental diet?
Polymeric = if well functioning GI tract whole protein used, glucose and fat
Elemental if poorly functional GI tract:
Free amino acids
Glucose polymers
Long chain triglycerides
Other enteral diets?
Modular = enriched in particular nutrient
Specific formulation = made to requirement e.g. ventilated patients have diet rich in fat to reduce CO2
Why do gastrically fed patients receive break periods?
constant feeding encourages colonisation of stomach, so if aspirate = increased risk of nosocomial infection
Continuous feeding = induces secretory response from colon = DIARRHOEA
What happens in bowel to those not fed enterally ?
Atrophic changes of intestinal mucosa
Due to NO local hormonal release in response to food stimulus
What is the result of gastric mucosal atrophy?
Loss of cellular adhesion and development of cellular channels
Means bacteria can translocate across bowel into the sytemic circulation = sepsis
Complications of enteral feeding?
Tube displacement
Infection around PEG/PEJ
re-feeding syndrome = low phosphate, thrombocytopaenia and confusion
Hyperkalaemia if renal impairment
Hyperglycaemia if critically ill and reduced glucose tolerance
Indications for TPN?
Which is the. only one that is an absolute indication?
General critical illness:
- Severe malnourishment, multiple trauma, sepsis/multi-system failure, severe burns
Gut problems:
- Enterocutaneous fistula, Short bowel syndrome, IBD
ENTEROCUTANEOUS FISTULA
How do we administer TPN?
Via central line as high osmolality mixture will irritate small veins.
If given through PICC must be <900mOsm/L
Why monitor liver in TPN admin ?
Can cause derangement in LFT’s
secondary to enzyme induction due to amino acid imbalances
Can also cause fatty changes
Metabolic complications of TPN?
Hypo/hyperglycaemia
Hyperlipidaemia
Hyperchloraemic metabolic acidosis
Ventilatory problems if excess glucose
What is myoglobin and its function?
A respiratory pigment found in cardiac and skeletal muscles = single globin chain of 8 alpha-helical regions, with a single haem component
Ready source of oxygen during increased activity
How does oxygen dissociation curve differ for myoglobin?
Shape is hyperbolic
not affected by pH, CO2.
What is rhabdomyolysis?
Clinical syndrome caused by release of toxic muscle cell components into circulation
Causes = trauma, drugs, metabolic and congenital conditions
What kinds of trauma can trigger rhabdomyolysis?
Blunt trauma e.g. crush injury
Prolonged immobilisation on hard floor
massive burns
Acute ischaemic reperfusion injury
Complications of rhabdomyolysis?
AKI - ischaemic tubular injury due to myoglobin and its breakdown products accumulating in tubules
DIC due to pathological activation of cascade
Metabolic disturbance - due to haemolysis and AKI
Compartment syndrome
Hypovolaemia - can haemorrhage into necrotic muscle
electrolyte disturbances of rhabdomyolysis?
Hyperkalaemia
Hyperphosphataemia
Hyperuricaemia
Hypocalcaemia
How do we confirm diagnosis of rhabdomyolysis?
CK > 1000
Elevated LDH
Elevated creatinine
Positive blood dip urine, with absence of haemoglobinuria on microscopy
managing rhabdomyolysis?
IVF to ensure UO >30ml/hour
You can alkalinise using sodium bicarb
Manage any electrolyte disturbances
Clinical features of compartment syndrome?
Pain out of proportion to injury
Paraesthesia
Late sign = loss of pulses
What level of pressure may lead to compartment syndrome?
First clinical signs occur at pressures 20-30mmHg
Management of compartment syndrome?
Fasciotomy
Which four physiological systems are involved in stress response?
- Acute phase response = cytokines, PGE, leukotrienes, kinins
- Sympathetic nervous system:
- Noradrenaline released from symp nerves and adrenaline from adrenal medulla
- Stimulates catecholamine release = tachy and HTN
- as well as: Bronchodilation, reduced intestinal motility, increased glucagon and glycogenolysis - Vascular endothelium:
- NO produces vasodilation
- PGE induces vasodilation and platelet aggregation - Endocrine system:
INCREASE = GH, prolactin, ACTH, ADH, cortisol, renin, aldosterone, glucagon
DECREASE = Insulin, testosterone and oestrogen
No CHANGE = TSH, LH, FSH
Outline the key hormonal changes in stress response?
- Cortisol increase:
- Significant. within 4-6 hours
Usual negative feedback fails, and concentrations of ACTH and cortisol remain high
- Metabolic effects of cortisol are enhanced:
* Skeletal muscle breakdown
*lipolysis
*anti-insulin
* MR effects
* anti-inflamm - GH increase:
- Important for preventing muscle breakdown and promotes tissue repair via insulin GF’s - ADH increased:
- Vasopressor and enhances haemostasis
- Renin released causing angiotensin 1 to 2
- Causes aldosterone secretion = sodium reabsorption - Insulin decrease:
- Inhibition of pancreatic B cells by the alpha 2 inhibitory effects of catecholamines
what happens during the two phases of metabolic response?
Ebb phase = reduction in metabolic rate in 24 hours following stimulus
Flow phase = Increase in metabolic rate, with general catabolism / -ve nitrogen balance and glucose intolerance
Why is there fall I UO post surgery?
Activation of RAAS = release of ADH = sodium and water reabsorption
Post surgery why may metabolic alkalosis develop?
Increase in aldosterone and cortisol promote sodium retention and potassium excretion. Low potassium = excrete H+ to get K back
