Fluid Administration Flashcards
Describe the pharmaceutics of hypertonic saline
CVC only
Stable in storage
10ml contains 2g of salt, 20g per 100ml
pKa 3.09, good water solubility, osmolality 6840 mosm/kgh
What is the osmolality of hypertonic saline?
CVC only
Stable in storage
10ml contains 2g of salt, 20g per 100ml
pKa 3.09, good water solubility, osmolality 6840 mosm/kg
What ist he pKA of hypertonic saline
CVC only
Stable in storage
10ml contains 2g of salt, 20g per 100ml
pKa 3.09, good water solubility, osmolality 6840 mosm/kg
What is the osmolality of hypertonic saline
CVC only
Stable in storage
10ml contains 2g of salt, 20g per 100ml
pKa 3.09, good water solubility, osmolality 6840 mosm/kg
What additional organ action does hypertonic saline have aside from osmolality, circulating volume icnrease
Anti-inflammatory
What are the side effect of hypertonic saline?
Metabolic acidosis (NAGMA) – hyperchloraemia
Hypokalaemia
Seizures (sodium fluctuations)
Coagulopathy (apt/INR)
Altered platelet aggregation
What is the duration of action of hypertonic saline?
130 minutes of ICP effectO
Onset of hypertonic saline ffect
<1 minutes
Vd and distirbution of hypertonic saline?
Vd 0.2L/kg, confined to ECF – 25% intravascular 75% ISF
pH of 0.9% saline
9g NaCl; IV/SC/orally or as a neb. Clear colourless solution, non pyrogenic heat stable packaging
8.8g of NaCl added to water, pKa 3.1
pH 4.5-7
How many g of salt in 1 L of 0.9% saline?
9g NaCl; IV/SC/orally or as a neb. Clear colourless solution, non pyrogenic heat stable packaging
8.8g of NaCl added to water, pKa 3.1
pH 4.5-7
pka of saline
9g NaCl; IV/SC/orally or as a neb. Clear colourless solution, non pyrogenic heat stable packaging
8.8g of NaCl added to water, pKa 3.1
pH 4.5-7
What effect does 1L of saline have on volume
Volume expansion fo the IV by 25% of the infused volume after 25-30 minutes, below circulatory reflex activation threshold. Effect greater prior to redistribution.
What effect does 1L of saline have on Na
0.5-1mmol/L
What effect does 1L of saline have on Cl
3mmol/L rise
What effect does 1L of saline have on bciarbonate
decrease by 3mmol/L
What effect does 1L of saline have on osmoreceptors
0.2mosm/kg change
Therefore <1% and no change
What effect does 1L 0.9% saline have on oncotic pressure? How is this corrected?
Osmoreceptors not activated – as change is 0.2mosm/kg (<1% or <2.8mosm/kg), dilution of oncotic pressure drop from 30mmHg to 28.5mmHg glomerulotub. Bal
What effect does 1L of hartmans have on Na and Cl
Trivial sodium elevation 0.5-1mmol/L, chloride elevation up to 3mmol/L, decreased bicarbonate and base excess up to 3mmol/L. Osmoreceptors not activated – as change is 0.2mosm/kg (<1% or <2.8mosm/kg), dilution of oncotic pressure drop from 30mmHg to 28.5mmHg glomerulotub. Bal.
For Hartamns ½ rise in Na and Cl.
What si the pH of hartmains
5-7
What is the electrolyte content of NaCl
154 Na
154 ClW
What is the osmolality of saline?
286 measured (freezing point) (308 calculated)
What is the electrolyte content of Hartmans
131mmol Na
5mmol K
2mmol Ca
112mmol Cl
28mmol lactate – metabolised not osmotically active
What is the electrolyte content of Plasmoluyte
140 Na
5 K
1.5mmol Mg
23mmol gluconate
27mmol acetate
98mmol Cl
What is the pH of plasmolyte
7.4
What is the Osmolality of Hartmans
276 (effective osmolality is 248)
What is the osmolality of Plasmalyte?
294mosm calc. 244 reality
What it he duration of action of saline
20-40 minutes in health euvolaemic longer in shock up to 8hrs (RAAS)
What is the duration of action of 1L of hartmans or plasmolyte?
50% of infused volume out of IV space in 30mins, finishes in another 30min
What is the bioavailability and absorption of saline
100% bioavailability, well absorbed
What is the Vd of saline?
0.2L/kg, in ECF 25% intravascular – 250mls – redistribution delay means during infusion ~400-450mls
75% interstitial – 750mls
1L fo saline results in what response in circulatory reflexes?
Below circulatory reflex activation 5%, volume expansion maximal prior to redistribution(during infusion) . See action at other organ system for electrolyte and osmolality effects
What is the redistribution of Hartmans after 1L is given? Baroreceptors affected? Osmolality?
900ml extraC, 100ml intraC, 25:75 ratio leaves 225ml IV. Below Baroreceptor.
No lactic acidosis (no H+ ion) – incorporated in ciritc acid cycle consuming H+ion (decreased total body acidity) making CO2
1L = 9 calories. Osmolality change 1mmol/L change <1%.
What is the fate of lactate in hartamns
900ml extraC, 100ml intraC, 25:75 ratio leaves 225ml IV. Below Baroreceptor.
No lactic acidosis (no H+ ion) – incorporated in ciritc acid cycle consuming H+ion (decreased total body acidity) making CO2
1L = 9 calories. Osmolality change 1mmol/L change <1%.
What effect does plasmolyte have on IV fluid post 1L total given? What effect does it have on osmolaliuty?
Same as Hartmans but 227mls IV. Osmo ~3%
Acetate enter citric acid cycle CO2 and water (consume H+ ion)
1L 15calories. K+ inside cells, Mg mostly extracell. Gluconate excreted in urine unchanged.
What is the fate of acetate in plasmolyte
Same as Hartmans but 227mls IV. Osmo ~3%
Acetate enter citric acid cycle CO2 and water (consume H+ ion)
1L 15calories. K+ inside cells, Mg mostly extracell. Gluconate excreted in urine unchanged.
What is the fate of gluconate in plasmolyte?
Same as Hartmans but 227mls IV. Osmo ~3%
Acetate enter citric acid cycle CO2 and water (consume H+ ion)
1L 15calories. K+ inside cells, Mg mostly extracell. Gluconate excreted in urine unchanged.
Describe the pharmaceutics of 5% dextrose?
Crystalloid fluid – isotonic monosaccharie solution
50g dextrose, IV. From hydrolysis of corn starch, Sterile, no buffers or bacteriostatic agents
pKa 12.9 i.e. non ionised, water solubility
pH 3.5 – 6.5 (regardless of conc of glucose)
pKa of dextrose 5%
Crystalloid fluid – isotonic monosaccharie solution
50g dextrose, IV. From hydrolysis of corn starch, Sterile, no buffers or bacteriostatic agents
pKa 12.9 i.e. non ionised, water solubility
pH 3.5 – 6.5 (regardless of conc of glucose)
pH of 5% dextrose
Crystalloid fluid – isotonic monosaccharie solution
50g dextrose, IV. From hydrolysis of corn starch, Sterile, no buffers or bacteriostatic agents
pKa 12.9 i.e. non ionised, water solubility
pH 3.5 – 6.5 (regardless of conc of glucose)
Where does dextrose come from for the manufactuer of fluids/
Crystalloid fluid – isotonic monosaccharie solution
50g dextrose, IV. From hydrolysis of corn starch, Sterile, no buffers or bacteriostatic agents
pKa 12.9 i.e. non ionised, water solubility
pH 3.5 – 6.5 (regardless of conc of glucose)
Describe the redistribution of 5% dextrose
Expands extracellular fluid volume and ICF – 8% of infused volume after 15-20 minutes remains intravascular. 2.5% change in osmolality sensed by OVLT osmosesnor leading to decreased vasopressin release and diuresis.
What is the change in osmolality after 1L fo dextrose is infused?
Expands extracellular fluid volume and ICF – 8% of infused volume after 15-20 minutes remains intravascular. 2.5% change in osmolality sensed by OVLT osmosesnor leading to decreased vasopressin release and diuresis.
Side effects of 5% dextrose
Hyperglycaemia + Hyponatraemia
Higher concentration dextrose RBC lysis (hyperosmolar fluid out of RBC) thrombosis and phlebitis
Osmolality fo 5% dextrose
250 (calculated 278mmol/L 278mosm/L) –
(556 for 10%, 2780 for 50%)
Half life of volume expansion from 5% dextrose
15-20 minutes
Vd of 5% dextrose? Redistribution volumes
Vd 0.6L/kg – distributed widely after 20 minutes
- 66% intracellular 660mls
- 26% intersitital 260mls
- 8% intravascular 80mls
Metabolic fate of 5% dextrose?
Each glucose metabolised by all tissues with aerobic metabolism to 6H20 and 6CO2 but especially the liver – thus from 1L makes extra 30ml of fluid
Eliminated by kidney and lungs
Effect on electrolytes and osmolality of 5% dextrose 1L being given?
Below circulatory threshold (80ml^ = 1.5%)
2.5% change in osmolality (6.5mmol) OVLT stimulated and decreased vasopressin (diuresis).
Na drop 4mmol/L angiotensin 2 + aldosterone ction
Decrease bicarbonate and base excess 3mmol/L
198 calories
What is the OVLT
Organum vaculosum laminae terminalis
Circumventricular organs
Where does albumin come from?
Concentrated human plasma albumin/ Colloid - From multiple whole blood donor/ plasma apheresis collection.
How is albumin prepared from blood?
Ethanol fractionation or chromatographic separation methods. Pasteurised by heat at 60 degrees for 10 hours. Octanoate preservative weakly antimicrobial and antifingual, stops denaturing in pasteurisation
What is the purpose of octanoate in albumin
Ethanol fractionation or chromatographic separation methods. Pasteurised by heat at 60 degrees for 10 hours. Octanoate preservative weakly antimicrobial and antifingual, stops denaturing in pasteurisation
What is the molecular weight of albumin
MW 67000 daltons. Shelf life 36 months. Hypotonic saline carrier fluid, weak acid pKa 6.75 good water solibility
What is the shelf life of albumin
MW 67000 daltons. Shelf life 36 months. Hypotonic saline carrier fluid, weak acid pKa 6.75 good water solibility
What is the pKa of albumin
MW 67000 daltons. Shelf life 36 months. Hypotonic saline carrier fluid, weak acid pKa 6.75 good water solibility
Is albumin an acid or base?
MW 67000 daltons. Shelf life 36 months. Hypotonic saline carrier fluid, weak acid pKa 6.75 good water solibility
What is baseline oncotic pressure? What proportion of this is due to albumin?
Oncotic mediated expansion of extracellular fluid volume– increasing circulating volume, albumin exerts 75% of the total 20-30mmHg oncotic pressure
100ml of 20% albumin draws how much fluid into the vasculature?
100ml of 20% albumin draws interstitial fluid and intracellular fluid over 15 minutes, and negative charge attracts sodium adding another 50% to intrinsic osmotic activity
Combined effect
- Interstitial fluid -32mls
- Intracellular fluids -88mls
- IV +220mls (inclusive of the 100mls given)
What non fluid and electrolyte factors does giving albumin lead to?
Neutralises vasodilating effects of nitric oxide
Buffer in intersitital space (only one)
Immunomodulatory – antioxidant by binding copper and iron which cause production of reactive oxygen species; addit binding bilirubin and homocysteine; and neutralising oxygen radicals/nitrites.
Transport – endogenous + exogenous binding – calcium, fatty acids, bile acids, zinc
Side effects and cons to using albumin
May worsen TBI mortality, ?efficacy (see notability)
Allergic and anaphylactic reactions possible
Hyperoncotic – risk of fluid overload
More expensive than crystalloid
What is the make up of 4% albumin
Na 140
Cl 128 (or in normal saline)
Albumin 40g/L – makes it isooncotic with blood (no extra water attracted interstitial)
Electrolyte effect similar to salineW
What is the make up of 20% albumin?
Na 48-100
Octanoate 32mmolLL
Albumin 200g/L (0.03mmol/L) 20g
Osmolality of albumin 20%
Hypotonic saline carrier (130mosm/kg electrolytes, total 210-262 mosm/Kg, 20%)
Lifespan of albumin
27 days
Volume benefits of giving albumin lasyt how long
6-12 hours
Vd of albumin?
Vd 0.07L/kg – confined to circulating volume. 4% per hour redistribution of albumin to interstitial fluid – septic can be 10% per hour. 50% lost from vascular compartment per day (interstitial). 100ml of 20% albumin draws an addition 120ml of interstitial fluid over 15 minutes (11ml per g), keeping the 100ml originally given intravascular.
Albumin redistribution
Vd 0.07L/kg – confined to circulating volume. 4% per hour redistribution of albumin to interstitial fluid – septic can be 10% per hour. 50% lost from vascular compartment per day (interstitial). 100ml of 20% albumin draws an addition 120ml of interstitial fluid over 15 minutes (11ml per g), keeping the 100ml originally given intravascular.
How much fluid does 1g of albumin generally attract
11ml per g
How is albumin digested
By fibroblasts and macrophages (reticuloendothelial system) - 50% muscle and skin, 15% liver, 10% kidneys to free amino acids; 10% lost in gut.
Minimal renal excretion, most degraded by macrophages and 10% eliminated through the gut
What effect does albumin administration have on osmolality
The attraction of free water intravascularly by 20% albumin would seem to risk decreasing osmolality, and triggering osmoreceptors however the Gibbs Doonan effect drags positively chanrged ions preventing significant changes.
4% albumin 500mls may trigger barocreceptor reflex, does not trigger osmoreceptors,
What is the distribution of 4% albumin
50% intravascu;alr compared to 25% of NaCl
Baroreflex activiated
4% albumin osmolality and oncotic pressure
Isoosmolar
Isooncotic
Define a colloid
a fluid with heterogeneity, multiphasic constituents and insoluble particles in solution.
A fluid containing particles unable to pass through physiological semipermeable membranes
Colloid characteristics
- Scatter light
- Susended in solvent without precipitating and separating
- Subject to Brownian movement
- All have the same charge keeping them separated by electrostatic propulsion
Pharmaceutics of an ideal colloid
◦ No special storage requirements
◦ No need for crossmatching, or interference with crossmatching
◦ Long shelf life
◦ Not susceptible to biological contamination (eg. by acting as a substrate for microbial growth, or by allowing donor-recipient viral transmission)
◦ Cheap and readily available
◦ Acceptable to all patients (i.e. no cultural objections)
Pharmacokinetics of an ideal colloid
◦ No special limitations on volume that can be infused
◦ Low viscosity
◦ Distributed to intravascular compartment only
◦ Cleared completely and without reliance on organ function
◦ No toxic metabolites or accumulation
Pharmacodynamics of an ideal colloid
◦ High oncotic effect
◦ No interference with organ function (including red cell function)
◦ Non-pyrogenic, non-allergenic & non-antigenic
◦ No interference with haemostasis, coagulation, or acid-base balance
Why theoretically are colloids good fluids for resuscitation?
- The mechanisms which drive this distribution include:
◦ Oncotic pressure of the colloidal particles
◦ Gibbs-Donnan effects of the charge of the colloidal particles (for example, the negatively charged albumin attracts additional osmotically active sodium into the intravascular space) - A minor volume expanding effect is also attributable to the volume of the dispersed molecules themselves, which is non-trivial for large molecules. For example, the volume of normal plasma consists of 7-8% colloid.
- Ergo, if the goal is to increase the circulating volume, fluid solutions containing substances with a large molecular weight should be more efficient, in terms of intravascular volume increase per volume of infused fluid
Classify colloids
- Synthetic colloids
◦ Polyvinylpyrrolidone - Semi-synthetic colloids
◦ Gelatins (eg. gelofusine, polygeline, )
◦ Dextrans (they are all called “dextran X”, where X is the molecular mass in kDa)
◦ Starches (eg. hydroxyethyl starch) - Plasma derivatives
◦ Purified plasma proteins (eg. albumin)
◦ Whole plasma products (eg. fresh frozen plasma)
What are gelatin fluid sourced from
Succynylated bovin gelatin
What is the carrier fluid for geltains
0.9% saline
What is the viral and bacterial infection risk of gelatins
Minimal
CJD not ruled outAntigenic r
Risk of gletains
Anaphylactogen
Decrease clot integrity
Cost of geltains
Cheap
Packaging of geltains
PVC flexible bags with logn shelf life in years
Packaging of starch fluds
PVC flexible bags with logn shelf life in years
Duration of effect of geltains
4-6 hours
Starch fluids derived from?
Maize or corn
Carrier fluid for starches
0.9% saline
Bacterial and viral infection risk of starches
Minimal to zero
Side effects of starches
Anaphylaxis
Renal failure
Pruritis
Duration of action of starches as a fluid
6 hours
Describe the autonomic effects of losing 1000mls of blood
- Arterial hypotension causes baroreflex activation + low pressure volume receptors of the right atrium and great veins + if severe (with reduced cardiac output/fall in pH) may also induce chemoreceptor activation peripherally accentuating the response
- Both reflexes result in autonomic phenomena:
◦ Decreased vagal stimulus; thus increased heart rate
◦ Sympathetic activation both directly and indirectly through systemic catecholamine release from adrenal glands, which has multiple effects:
‣ Increased peripheral vascular resistance - increased blood pressure
‣ Redistribution of blood flow away from the cutaneous, skin and splanchnic circulation - reduced renal and gut blood flow
‣ Precapillary constriction and reduced blood flow —> reduced hydrostatic pressure in downstream capillaries as net reabsorption leading to autotransfusion
‣ Venoconstriction mobilising venous reservoir - increased venous return
‣ Stimulation of vasopressin release via the projections from the nucleus of the solitary tract to the hypothalamus
‣ Stimulation of renin release by sympathetic stimulation of the juxtaglomerular cells, and due to lower renal perfusion - Net effect
◦ Reduced SBP and DBP
◦ Reduced pulse pressure
◦ Tachycardia - Increased inotropy
- Increased PVR with vasoconstriction
◦ Cardiac output will be intitially reduced but with compensation will improve towards normal
Maximal response within 30 seconds
Describe the neurohormonal effects of losing 1000mls of blood
- Renin secretion causes:
◦ Vasoconstriction (by angiotensin)
◦ Increased sodium retention (by aldosterone) leading to increased reabsorption of water
◦ Increased thirst - Vasopressin release causes:
◦ Vasoconstriction (by V1 receptors), augments noradrenaline mediated arteriolar vasoconstriction
◦ Increased water retention (by V2 receptors) - Venous hypotension decreases atrial natriuretic peptide secretion, which causes:
◦ Decreased renal blood flow
◦ Decreased urinary water and sodium excretion - Catecholamines - see above
- The net effect is decreased urine output and increased retention of sodium and water
What impact does >20% loss of blood have
Compensatory mechanisms overwhelmed resulting in reduced BP and tissue perfusion with anaerobic metabolism and lactic acidosis. Decreased catecholamine sensitivity
Medium to longer term response to blood loss
- Erythropoerisis is stimulated by EPO release from the kidney stimulated by decreased oxygen delivery leading to increased RBC production - happens within the first 24 hours but takes 4-8 weeks to fully restore circualting RBC voluem
- Albumin synthesis is stimulated in the liver and restores circulating protein levels to normal within a few days
- Plasma volume returns to normal within 12-72 hours
Describe the classes of hypovolaemic shock
During the infusion of 1L of NaCl as a bolus what initiailly occurs?
- Volume effect is greater during the infusion (prior to redistribution)
- During this time, the blood volume may be expanded by 50-70% of the infused volume
- This increases stroke volume by increasing preload causing an increase in cardiac output (frank Starling relationship) and blood pressure due to initially normal SVR, and therefore stimulates cardiovascular reflexes
What reflex action is taken during the bolus of 1L of 0.9% saline
◦ Initially, a short-lived increase in heart rate (Bainbridge reflex, atrial stretch)
◦ Followed by a decrease in heart rate (baroreceptors - aortic arch/carotid sinus) - stimulated by increased pressure/stretch –> decreased outflow to vasomotor centres –> reduced SNS outflow
◦ Decrease in SVRI (baroreceptors)
◦ Decreased secretion of renin by renal juxtaglomerualr cells as increased Na delivery to macula densa, with subsequent decreases in angiotensin and aldosterone - reduced vasoconstriction and reduced afterload, dropping BP and aldosterone reducing sodium reabsorption
◦ Tubuloglomerular feedback activation: increased salt delivery to the nephron results in decreased glomerular blood flow, which decreases salt delivery (i.e. this is a negative feedback mechanism)
◦ Natriuretic peptide release increases due to atrial stretch
◦ Brief period of pressure diuresis possible, and a brief drop in circulating ADH while plasma volume expansion >10% before returning to normal with redistribution - affected by RAAS also
What is tubuloglomerular feedback and how does it play into administration of saline fluid
◦ Tubuloglomerular feedback activation: increased salt delivery to the nephron results in decreased glomerular blood flow, which decreases salt delivery (i.e. this is a negative feedback mechanism)
How long does redistribution of a 1L fluid bolus of saline take?
- Redistribution begins immediately, and is complete within 25-30 minutes
Distribution
* VOD=0.2L/kg, basically confined to the extracellular fluid
* (thus: 25% remains intravascular, 75% becomes interstitial)
Describe the changes in electrolytes and osmolality after a 1L bolus of saline
Changes in electrolytes and osmolality
* Change in osmolality: minimal (<1%) ; unnoticed by osmoreceptors (saline is isotonic)
* Change in plasma oncotic pressure: Dilution of plasma proteins increases the fraction of filtered water at the glomerulus, increasing the urine output (i.e. excretion of both water and sodium)
* Change in biochemistry:
◦ trivial sodium elevation (~0.5-.0 mmol/L)
◦ nontrivial chloride elevation (up to 3 mmol/L)
◦ decrease in bicarbonate and base excess (also up to 3 mmol/L)
◦ Metabolic acidosis (this fluid has SID = 0)
Describe how glomerular tubular balance plays into the response to a fluid bolus
Increased free water excretion due to
◦ Decreased peritubular capillary oncotic pressure causing
◦ Reduced water reabsorption from proximal tubule
◦ Therefore the degree to which plasma is concentrated by increased filtration or dilution of plasma proteins before reaching the kidney determines reabsorptino
What is the osmolality of a 3% saline bag
- 900mosm/kg –> 3x that of plasma
- Na remains in ECF, water will distribute according to osmolality, Cl remains in ECF
What effect does 1L of 3% saline have on body fluid balance
70kg person with TBW of 42L. ICF is 23L and ECF 19L with osmolality 290mosm/kg
Before infusion
* Total body solute content = 42L x 290 = 12 180 mosm
* ECF solute content - 19 x 290 = 5510
* ICF solute content = 23 x 290 = 6670 mosm
After infusion
* 43L of total body water
* ECF solute content = 5510 + 900 = 13 080
* ICF solute content = 6670 (unchanged)
Therefore osmolality = 13080/42 = 304 mosm/kg
ECF volume 21.1 L and ICF volume 21.9L
* Decreased ICF volume
* Interstitial volume expansion insufficient to cause oedema, interfere with gas transfer or nutrient or waste transfer
- ECF increased by 2.1L with 1/4 or so intravascular 500mls.
◦ Blood volume increased by 10% –> 7-10% is the trigger for volume receptors –> ANP
‣ ANP promotes sodium excretion at the kidney and inhibits renin secretion
‣ Decreased renin stimulation (high Na content delivery to DCT)
* Aldosterone inhibition - reduced Na reabsorption
* Decreased angiotensin - reduced Na reabsorption, increased GFR
◦ This will also lower the sensitivity of the volume receptors and will inhibit ADH secretion
◦ Volume receptors more powerful than osmoreceptor response - Plasma osmolality increased by 4.8% –> triggers osmoreceptors ++ and ADH secretions increases to retain water and driving thirst
◦ This will slow down the rate of excretion of excess water
What effect would 1L 3% saline infusion have on ECF
- ECF increased by 2.1L with 1/4 or so intravascular 500mls.
◦ Blood volume increased by 10% –> 7-10% is the trigger for volume receptors –> ANP
‣ ANP promotes sodium excretion at the kidney and inhibits renin secretion
‣ Decreased renin stimulation (high Na content delivery to DCT)
* Aldosterone inhibition - reduced Na reabsorption
* Decreased angiotensin - reduced Na reabsorption, increased GFR
◦ This will also lower the sensitivity of the volume receptors and will inhibit ADH secretion
◦ Volume receptors more powerful than osmoreceptor response - Plasma osmolality increased by 4.8% –> triggers osmoreceptors ++ and ADH secretions increases to retain water and driving thirst
◦ This will slow down the rate of excretion of excess water
What effect would a 1L 3% saline bolus have on osmolality?
- ECF increased by 2.1L with 1/4 or so intravascular 500mls.
◦ Blood volume increased by 10% –> 7-10% is the trigger for volume receptors –> ANP
‣ ANP promotes sodium excretion at the kidney and inhibits renin secretion
‣ Decreased renin stimulation (high Na content delivery to DCT)
* Aldosterone inhibition - reduced Na reabsorption
* Decreased angiotensin - reduced Na reabsorption, increased GFR
◦ This will also lower the sensitivity of the volume receptors and will inhibit ADH secretion
◦ Volume receptors more powerful than osmoreceptor response - Plasma osmolality increased by 4.8% –> triggers osmoreceptors ++ and ADH secretions increases to retain water and driving thirst
◦ This will slow down the rate of excretion of excess water
Describe the ADME of a oral water absorption
Absorption is near-complete ~98.5% bioavailability, rapid, and mainly occurs in the proximal small bowel
* As water enters it becomes isotonic by mixing with saliva, stomach juices and intestinal fluids
* Most of the diffusion is transcellular
◦ It is driven by osmotic mechanisms (active absorption of other electrolytes, especially sodium)
Distribution is equal into all body fluid compartments, and proportional to their relative sizes:
* 66% into the intracellular fluid
* 340ml or 33% to extracellular fluid
◦ 25.5% into the interstitial fluid
◦ 8.5% into the circulating blood volume –> 80ml
Elimination is by renal excretion, where the filtered fraction is reabsorbed by a highly regulated mechanism. Hlaf life of a litre of water is about an hour
What is the distribution of oral water
Absorption is near-complete ~98.5% bioavailability, rapid, and mainly occurs in the proximal small bowel
* As water enters it becomes isotonic by mixing with saliva, stomach juices and intestinal fluids
* Most of the diffusion is transcellular
◦ It is driven by osmotic mechanisms (active absorption of other electrolytes, especially sodium)
Distribution is equal into all body fluid compartments, and proportional to their relative sizes:
* 66% into the intracellular fluid
* 340ml or 33% to extracellular fluid
◦ 25.5% into the interstitial fluid
◦ 8.5% into the circulating blood volume –> 80ml
Elimination is by renal excretion, where the filtered fraction is reabsorbed by a highly regulated mechanism. Hlaf life of a litre of water is about an hour
What effect would 1L of oral water ingestion have on osmaolity
Osmolality decreases
* For one litre of pure water, this would be a 2.5% decrease in osmolality (40L of fluid diluted by 1L)
◦ Osmolality drop from 280 to 273
* This is sensed by the osmosensitive circumventricular organs (OVLT); even 1% would be enough
◦ Organum vasculosum of lamina terminalis
* Afferent –> fibres from osmoreceptors decrease vasopressin release in posterior pituitary –> reducing V2 receptor stimulation and reduced apical expression of aquaporin in the collecting duct of nephrons reducing water reabsorption and promoting diuresis
What si the absorption and bioavailability of oral water? How fast does this occur?
Absorption is near-complete ~98.5% bioavailability, rapid, and mainly occurs in the proximal small bowel
* As water enters it becomes isotonic by mixing with saliva, stomach juices and intestinal fluids
* Most of the diffusion is transcellular
◦ It is driven by osmotic mechanisms (active absorption of other electrolytes, especially sodium)
Distribution is equal into all body fluid compartments, and proportional to their relative sizes:
* 66% into the intracellular fluid
* 340ml or 33% to extracellular fluid
◦ 25.5% into the interstitial fluid
◦ 8.5% into the circulating blood volume –> 80ml
Elimination is by renal excretion, where the filtered fraction is reabsorbed by a highly regulated mechanism. Hlaf life of a litre of water is about an hour
What is the half life of 1L of water orally ingested
Absorption is near-complete ~98.5% bioavailability, rapid, and mainly occurs in the proximal small bowel
* As water enters it becomes isotonic by mixing with saliva, stomach juices and intestinal fluids
* Most of the diffusion is transcellular
◦ It is driven by osmotic mechanisms (active absorption of other electrolytes, especially sodium)
Distribution is equal into all body fluid compartments, and proportional to their relative sizes:
* 66% into the intracellular fluid
* 340ml or 33% to extracellular fluid
◦ 25.5% into the interstitial fluid
◦ 8.5% into the circulating blood volume –> 80ml
Elimination is by renal excretion, where the filtered fraction is reabsorbed by a highly regulated mechanism. Hlaf life of a litre of water is about an hour
What effect does 1L of oral fluid ingestion have on sodium
Plasma sodium concentration decreases
* This increases the stimulus for angiotensin and aldosterone release
* The net effect of these is to increase the reabsorption of sodium in the nephron
What effect does 1L of oral water ingestion have on blood volume
Blood volume increases (very slightly)
* For one litre of pure water, this would be a 80ml increase in volume, or about 1.6%
* This change is below the sensitivity threshold of the cardiovascular regulatory reflexes, and should not lead to any change in blood pressure for a normal healthy person
Losing 1L of body fluid to dehydration results in what change in fluid compartments? In osmoallity? Volume? Baroreceptor response?
Losing 1L is the loss of 1.4% of total body weight for a 70kg patient
* The loss fo water from any one compartment rapidly is corrected by inflow of water from another compartment.
◦ 80mls lost from intravascular space
◦ 250ml lost from interstitial fluid
◦ 670ml from intracellular fluid
* Osmolality change 2.5%, and 1.6% change in volume
◦ Sufficient to trigger the osmoreceptor but not he baroreceptors –> ADH release
* Electrolyte changes
◦ Na rise from 140 –> 143
* No baroreceptor response as 2% change insufficient
* Glomerulotubular balance - Intravascular protein concentration increases reabsorption of fluid from the proximal tubule retaining water
At extremes of dehydration what response is seen?
- Dehydration results in haemoconcentration, and haemoconcentration predictably leads to increased blood viscosity, though the relationship is unpredictably non-linear - whole blood viscocity increases markedly more than linearly would be predicted from haemoconcentration and plasma viscocity increases
- Heart has to work harder due to decreased circulatory volume in exercise + having to perfuse the areas it would shut down (skin/muscle) in haemoarrhage i.e. uncompensate hypovolaemia
Describe the physiology of intracellular fluid at baseline? % of body mass? L in a 70kg man? % of total body water?
- Intracellular Fluid = 33% of total body mass ( 23.1 litres) ; this volume is regulated by the movement of free water.
◦ 55% of total body water
◦ 70% of intracellular contents is water, and viscocity is very near water but diffusion through this compartment takes 4x longer
Extracellular compartment at baseline is what % of body mass? % of body water>. L in a 70kg man? Regulated by?
- Extracellular Fluid = 27% (18.9 litres); this volume is regulated by the movement of sodium. and 45% of total body water
Extracellular fluid is made up of what subcompartments of fluid?
◦ Plasma volume (2.8L) (1/4 of ECF/ 7.5% of total fluid)
‣ Red cells 2.5% of body mass, 4.5% of total fluid (nearly 2L) BUT inside cells
‣ Blood volume is 12% of total fluid or 7% of body mass
◦ Interstitial and lymph fluid
‣ 12% of body mass, 20% of total fluid 8.4L
◦ Dense connective tissue and bone
‣ 15% of total body fluid, 9% of total mass however slow to mobilise and dose not participate in infusion physiology. The rest is functional ECF
◦ Adipose tissue
What % fo total fluid is plasma volume?
◦ Plasma volume (2.8L) (1/4 of ECF/ 7.5% of total fluid)
‣ Red cells 2.5% of body mass, 4.5% of total fluid (nearly 2L) BUT inside cells
‣ Blood volume is 12% of total fluid or 7% of body mass
◦ Interstitial and lymph fluid
‣ 12% of body mass, 20% of total fluid 8.4L
◦ Dense connective tissue and bone
‣ 15% of total body fluid, 9% of total mass however slow to mobilise and dose not participate in infusion physiology. The rest is functional ECF
◦ Adipose tissue
What proportion of total body fluid does intersittial fluid take u
◦ Plasma volume (2.8L) (1/4 of ECF/ 7.5% of total fluid)
‣ Red cells 2.5% of body mass, 4.5% of total fluid (nearly 2L) BUT inside cells
‣ Blood volume is 12% of total fluid or 7% of body mass
◦ Interstitial and lymph fluid
‣ 12% of body mass, 20% of total fluid 8.4L
◦ Dense connective tissue and bone
‣ 15% of total body fluid, 9% of total mass however slow to mobilise and dose not participate in infusion physiology. The rest is functional ECF
◦ Adipose tissue
What is transcellular fluid and what % of body fluid does it contribute
- Transcellular fluid: ~1.5% of body mass or 2.5% of total body fluid (1050ml); fluid formed by the secretory activity of cells,
What 3 factors trigger humeral responses to fluid administration
- to the increase in renal perfusion
◦ Renin, angiotensin and aldosterone secretion is depressed
◦ As the result, the reabsorption of sodium and water in the distal nephron is decreased - to the change in atrial stretch
◦ Natriuretic peptide release increases, as atrial stretch stimulates their release, which in turn stimulates natriuresis and diuresis - to the change in osmolality
◦ The change in osmolality is sensed by the hypothalamus
◦ Vasopressin secretion from the posterior pituitary is then altered to produce the desired change in the urine concentrating function of the distal nephron
What non humeral reflexes are present that are affected by infusion of fluids
- Atrial stretch receptors sense the increase in venous pressure, and briefly increase the heart rate (Bainbridge reflex) - when the patient is hypovolaemic baroreceptor reflex overrides this, seen more with euvolaemia
- Baroreceptors sense the increase in arterial pressure generated by the increase in stroke volume, and decrease the heart rate and the systemic vascular resistance, thereby renormalising the blood pressure
What is contained within 500ml of 20% mannitol
500ml of 20% mannitol –> 100g of mannitol. 1100mmol/L. Mannitol distributed evenly into extracellualr fluid but not mechanism of entry into cells.
What effect does mannitol have on osmotic pressure and fluid distributiuon when 500ml is infused?
◦ Intracellular dehydration, including brain parenchyma
◦ Rheological effects of mannitol infusion - improved RBC deformability due to shrinkage –. decreased blood viscocity improving microvascular perfusion
◦ Extracellular volume expansion - redistribution completely equally between interstitial and intravascular (same conc) –> 1100mmol in 14L ECF leads to big rise in osmolality 25mmol/L causing redistribution of fluid –>
‣ IV increase by 360mls –> 7% blood volume increase –> minimal baroreceptor response
‣ interstitial 1L, and
‣ drop in intracellular by 930mls –> 10-12% drop in intracranial pressure in mammals, 30% with hypocapnoea within 5-15 minutes and over 2-3 hours returns to baseline (hyeprtonic saline lasts 130 minutes)
What electrolyte effects are induced by 500ml fo 20% mannitol being given?
◦ Hyperosmolar hyponatremia
‣ Triggers osmoreceptors –> increased ADH but less effective due to mannitol osmotic effect in tubules (effect diuresis). More water is lost than Na
‣ Increase in free water intravascularly drops Na from 140 to 127mmolL –> as mannitol is excreted though this improves
◦ Hyperkalemia - combination fo solute drag with fluid moving out of cells but also intracellular dehydration increasing K concentraiton favouring movement out
What are the electrolyte and osmolar contents of 1 unit of pRBC
Due to ranging volumes, haematocrit, and duration of storage effects the effect is uncertain. Let us assume 250mls is given of which its haematocrit is 60%. Therefore 150mls of cells, 100mls of fluid. 100ml of water has an osmolality of 340mosm/L so giving 100ml you get 34mmol of electrolytes
* Na 15mmol remaining ECF
* K 2mmol - note this is just the free extracellualr K, the cells containg 150mmol/L (i.e. 15mmol)
* Cl 15mmol ECF
* HCO3 1mmol ECF
* Lactate 1 mmol metabolised by the liver
What happens to the fluid of 1 unit of pRBC
Redistribution
* Over 15 minutes
* ECF now has a slight bump in osmolality causing some minor redistribution from intracaellular fluid
◦ 26ml of water remains intravascular + 150ml of cells
◦ Interstitum has 79mls extra
◦ Intracellular -6mls
* Haematocrit change - if haematocrit started at 0.3 then this was 1500ml of 5000 –> increased by 150mls so 6% increase (when measured it is more likely 2% increase)
* Hb rises by 10g/L
What is the osmolality, baroreceptors ad electrolyte outcome of 1 unit of PRBC
Response
* Osmolality reamins constant as essentially isoosomolar
* Baroreceptors - intravascular volume increases by 176mls from 5000 to 5176 a 3.5% change
* Electrolytes
◦ Largely stable
◦ Citrate chelates 1mmol of Ca per pRBC and as 31mmol in ECF
