Muster Week 1 Flashcards
body fluid compartments
- intracellular
- intravascular
- interstitial
TBW
60% water M
50% water F
55,500 mM (millimoles)
“stuff”
Na, K, Cl, urea, HCO3-, WOA, albumin, glucose, Mg, Ph
osmolality
total free solute (mM)/Kg of solvent
osmolarity
total free solute (mM)/L of solvent
milliosmoles
units of osmolarity or millimoles of total free solute
primary solutes in plasma (intravascular)
Na+ (140mM)* K+ (5mM)* glucose (5mM/90mg) Ca++ (4mM) PO4- (6mM)* anions (20mM)* Cl- (105mM) HCO3- (25mM) urea (6mM)
in mM/L
primary solutes in interstitum
Na+ (140mM)*
K+ (5mM)*
PO4- (6mM)*
anions 0*
in mM/L
primary solutes intracellular
Na+ (~3mM)** K+ (140mM)** PO4- (10mM)** Cl- (10mM) anions (45mM)** protein- IMPERMEABLE
THIS ONE IS DIFFERENT
in mM/L
charge of albumin
A-
(-)(-)(-)(-)(-)!!!
RESPONSIBLE FOR ANION GAP
anion gap = albumin
[Na+ -(Cl- + HCO3-)] = 8-12
*should get a gap/difference in charges (+/-) by concentration because haven’t accounted for albumin (-) = anion gap
anion gap
think albumin (-) anion gap = albumin = 8-12
- if off, have some other ion put into the blood stream (other +/- stuff or acids/bases) because albumin balances with Ca, FA, H, drugs, etc.
ex: sickness, diabetic ketoacidosis, etc.
osmolality/L of plasma
~300mM/L
interstitial fluid is plasma without ______
ALBUMIN.
so no negative charges….creates concentration/electrochemical gradient
capillary wall characteristics
FENESTRATED
semi-permeable membrane
constantly under pressure (blood pressure)
impermeable to albumin
in general, under NORMAL circumstances, the capillary pressure (Pc) is…
opposed EQUAL AND OPPOSITE by the oncotic capillary pressure (Pic)
kf [(Pc + Pii) - (Pi + Pic)] in mmHg = filtration equation/NET STATE OF FLOW
kf[(25 + 0) - (0 + 25)] = 0
stuff moves but the capillaries don’t leak!
Net state of flow equation
kf (force favoring filtration) - (forces favoring reabsorption) = net state of flow
kf [(Pc + Pii) - (Pi + Pic)] in mmHg
forces favoring filtration
pressure within capillary (Pc)
oncotic pressure within interstitial space (Pii)
forces favoring reabsorption
oncotic pressure within capillary (Pic)
pressure within interstitial space (Pi)
protein osmotic pressure names (Pic)
= oncotic pressure
colloid pressure
osmotic pressure
oncotic pressure
- created by the ~1mM plasma albumin within a permeable capillary that is impermeable to A-
- draws fluid into capillary space
- measured in mmHg but is just another way to measure [Alb-]
- force of draw is ratio of oncotic pressure:hydrostatic pressure; albumin:blood pressure
force of draw into capillary space
oncotic pressure:hydrostatic pressure;
albumin:blood pressure
osmolality of intracellular
~300mM/L
same
Differences between intracellular and plasma…
MORE K+
LESS Na+
How is this change (between intracell and intersti/plasma) maintained?
How?! —> ATPase
Something has to keep the gradient otherwise cells burst and die (because cell membrane controlled, not fenestrated)
Why is digitalis (digoxin) so dangerous?
Because it inhibits Na+/K+ ATPase…disrupts membrane concentration gradient…CELLS BURST AND DIE –> MAJOR DAMAGE –> FATAL
isosmotic
- any solution that has ~300mOsms
isotonic
- any solution that will NOT change the volume of a cell
- need 300mOsom of impermeable solutes
isoncotic
- any solution with 1mM of plasma albumin or ~4.5g/100mL
OR - any solution with protein osmotic pressure of ~25mmHg
Fluids are _____.
drugs
Losing blood problem… hypotensive and tachycardic
intravascular problem
SOB problem… hypotensive and bradycardic, pitting edema, elevated creatinine
interstitial problem
Types of fluid
Normal saline (0.9%)
1/2 NS (0.45%)
D5
NS
osmolality: 308mM/L
Na+: 154 mM/L
Cl-: 154mM/L
1/2 NS
osmolality: 150mM/L
Na+: 75mM/L
Cl-: 75mM/L
D5
osmolality: 300mM/L
Na+: 0
Cl-: 0
glucose: 280mM/L
TBW = Vd
changes when patients are critically ill (like in sepsis)
intracellular fraction TBW
2/3
extracellular fraction TBW
1/3
interstitial (extracellular) fraction TBW
3/4
plasma (extracellular) fraction TBW
1/4
average patient weight
70kg
So…TBW, intracell, etc. breakdown per L (using weight)
TBW: 42L intracellular water: 28L extracellular: 14L interstitial (extracellular): 11L plasma (extracellular): 3L
Amount TBW in plasma and importance of it
plasma: 3L (7.5% of TBW)
* that’s not much, which is why if have arterial bleed, can die within 10 minutes!!!
If you drink water, where does it distribute?
It will distribute proportionately according to the volume of the compartments, to ALL, nothing stopping it.
1L: 3/42 to plasma, 11/42 to interstitial, 28/42 to intracellular
= 333mL to extracellular, 666mL to intracellular
What allows water to distribute to all body fluid compartments?
- fenestrations of capillaries
- aquaporins of cell membranes
If you infuse 1L NS, where does it distribute?
It will distribute to interstitial and plasma (extracellularly).
1L: 3/14 to plasma, 11/14 to interstitial = 214mL to plasma, 786mL to interstitium
Situations calling for NS
- DKA
- sepsis: haven’t lost fluid, but inflamed/dilated vessels so DECREASED BP (give fluids to fill up that extra cellular space and increase BP)
- secretory diarrhea: losing Na, Cl, and water (replace)
Give 1L 1/2 NS, where will it distribute?
1/2 amount want to give, distribute JUST LIKE NS JUST HALF THE AMOUNT
1/2 amount want to give, distrusted JUST LIKE WATER
Situations calling for 1/2 NS
- sweat losses (athletes losing 1/2 NS)
- elderly (same)
- hospitalization (febrile)
Give 1L D5W (5% dextrose = 5g/100mL water), where will it distribute?
Distributes JUST LIKE WATER
- glucose gets completely removed and water follows
IF CANT DRINK WATER, GIVE 5DW
Situations calling for D5
DI (nephron entice or central)
Severe hypoglycemia
What does it mean to order a serum [Na+]?
Does NOT necessarily reflect volume status.
Volume depletion definition
EXTRACELLULAR volume loss from any cause (most often loss of NaCl and water).
Dehydration definition:
Presence of HYPERNATREMIA (increased serum [Na+]) due to pure water loss.
Serum [Na+] does not equal
Volume
Give NS… Effect on serum [Na]
- no change in serum [Na+]
- only goes to EXTRACELLULAR so increase VOLUME of same osmolality
Give water… Effect on serum [Na+]
- decreased serum [Na+] (decreasing osmolality by adding more solvent)
- small increase in volume (extra and intra cellularly)
Give pure salt…lots of it… Effect of [Na+]
- increase [Na+]
- increased osmolality EXTRACELLULARLY –> water floods out of cells into EXTRACELLULAR –> BAD
= why hypernatremia is bad…what if this is happening in brain (then water rushed back in and cells burst and die–> gonzo bad)
Functions of kidney
HOMEOSTASIS Filtration Maintain BP Na+ homeostasis (volume) Water homeostasis K+ homeostasis Bone mineral, vitamin D, PO4-, Ca++ Acid/base homeostasis RBC production and regulation of EPO gluconeogenesis (also an endocrine organ)
Kidney in most basic sense:
Fluid in –> filtered –> fluid excreted in urine OR fluid returned to blood
If kidney cannot filter…
Cannot excrete…cannot maintain homeostasis
Ex: if cannot filter K+ –> cannot excrete K+ –> hyperkalemic –> DIE
How many glomeruli in kidney
1 million glomeruli per kidney
Fluid IN to kidney:
- Blood
- 20% first pass CO (1000mL/min) of blood flow…!
- 60% of this is plasma (40% of blood is hematocrit/RBCs) = RPF, renal plasma flow
Why isn’t renal vein blue?
High P O2, kidney is highly oxygenated organ –> it senses small changes in P O2 –> can crank up EPO production –> more RBC –> add more O2 by more RBCs
How many capillaries per glomeruli
20
How many mesangial cells per glomeruli
2-3
Physical structure of glomerulus restricts what can be filtered by:
- size
- charge
Ex: albumin doesn’t get through here (unless damage GBM)
Components of glomerulus filtration barrier
- capillary endothelium: FENESTRATED
anything but cells and protein can pass here - basement membrane: ANIONIC
- podocytes: cells exterior to GMB form NEGATIVELY CHARGED SLITS
*damage to any one of these three will result in filtration of things don’t want filtered
How does DM damage filtration barrier?
Damages capillaries and mesangial cells –> albumin in urine
How does vasculitis damage filtration barrier?
Damages capillaries –> leak RBCs into urine
How does Anti-GBM NPGD damage filtration barrier?
Anti-basement membrane disease causes fat, think, ribbon like deposits on top or into BM –> interrupts BM –> “stuff” falls through
How does Minimal Change diesase or Membraneous Change disease damage filtration barrier?
Podocytes damaged –> HUGE amounts of albumin in urine
What is typical size of plasma components (in daltons; mass proportional to size)?
Na: 23 K: 39 Cr: 113 urea: 60 albumin: 66,000Da
What sizes are freely filtered?
What size would be completely excluded in normal state?
> 70,000 Da
Charge of GMB
anionic (-)(-)(-)
so NEGATIVELY CHARGED BIG STUFF HAS HARD TIME GETTING THROUGH
= easy for Na+, K+ (small and cationic)
Definition of GFR:
the movement of FLUID and SOLUTE across from the capillary lumen INTO Bowman’s space across ALL (2 million) glomeruli in both kidneys
Calculation of GFR
kf (constant) [(Pgc + Pibs) - (Pbs + Pigc)]
Remember: gc = glomerular capillary
bs = bowman’s space
Pi = oncotic pressure = albumin
What does low/reduced GFR mean?
Means kidney’s ability to filter blood is not how it should be, it is sub-par = can’t get stuff from capillaries to bowman’s space (nephron/urine) effectively
Kf constant is
the glomerular filtration coeffiecient or degree of “openness” of capillary pores
- about 10% open
GFR = net _______ pressure
GFR = net ULTRAFILTRATION pressure
= that is what the kidney does! Filter!
Pgc
60mmHg
higher than other capillaries in body
Pbs
15mmHg
have tons of fluid trying to get into small proximal tubule from bowman’s space
Pi gc
29mmHg
little higher than other spaces
Pi bs
0
no albumin filters through GBM
Net ULTRAfiltration pressure of glomerulus?
16mmHg
= HUGE pressure gradient across each glomeruli!
Normal GFR
180L/day or 125mL/min
putting 180L/day into urinary tubular space every day, pee out 2L/day, reabsorb 178L/day WOW
If any factors contributing to net filtration P are damaged…
will change the net GFR
Angiotensin II has great effect on which glomerular arteriole?
EFFERENT
Where do prostaglandins work and what do they do (to glomerulus/arterioles)
PGs on AFFERENT arteriole DILATE
Normal RPF
600mL/min
Can change/control (P/Pi) (gc/bs)???
Can control/change the Pgc (pressure inside glomerular capillary)
REMEMBER PGC FAVORS FILTRATION
Cannot change Pi gc (can’t change albumin in 5 minutes), Pbs (can’t change size of bs), Pi bs (is 0)
REMEMBER: (Pgc + Pibs) favoring filtration - (Pbs + Pigc) favoring reabsoprtion = net filtration pressure
Kink in afferent arteriole…effect on Pgc and GFR
Pgc decreases
(in front of kink is high pressure, just after is low pressure)
GFR decreases
Dilated afferent arteriole…effect on Pgc and GFR
Pgc increases
(more flow into glomerulus)
GFR increases
(increased P and no change in reabsorption = increase GFR)
Constricted efferent arteriole…effect on Pgc and GFR
Pgc increases
(in front of kink is high pressure, just after is low pressure)
GFR stays same (hopefully)
(if compensatory mechanisms kick in, will stay the same)
What would constrict the efferent arteriole?
angiotensin II
usually compensatory to low pressure
Dilated efferent arteriole…effect on Pgc and GFR
Pgc decreases
(pressure across glomerulus decreases)
GFR decreases
Constricted SNS response on both afferent and efferent artieroles…effect on Pgc and GFR
Pgc NO CHANGE
(NO renal plasma flow)
= NO RPF = NO GFR
(in septic shock, SNS kicks in, kidney is shut down like this, shunts blood to brain)
Remember…Pgc favors ______.
FILTRATION
Filtration fraction
20%
percent RPF (Na, K, H20, Cr, urea) is being filtered into bs every minute
Filtered load
[X serum] * GFR
how much “stuff” in actual amounts is filtered
Filtered load of sodium
[X serum] * GFR
140mM/L x 180L/day = 25,000mM Na+ filtered PER DAY
–> but not all is peed out, so REMEMBER REABSORPTION
Filtered load of glucose
[X serum] * GRF
5mM/L x 180L/day = 900mM glucose filtered PER DAY
—> but none of it is in urine, so REMEMBER REABSORPTION
Excretion rate
urine flow rate * [solute in urine]
filter certain amount –> excrete certain amount
Excretion rate of Na+
200mM/day = 4.5g salt/day
if pee 2.5L/day
Excretion rate should be…
whatever is required to excrete to keep you in HOMETOSTASIS/BALANCE
In some cases, the filtered load equals the excretion rate (no reabsorption)…
Solute is completely filtered…not reabsorbed, secreted, destroyed or produced…
Ex: Creatinine, inulin, iohexol, iothalamate
GFR = (of unique solute where filtration rate = excretion rate)
GFR = excretion rate of unique solute / plasma concentration of unique solute
GFR = URF [Xu] / [Xp]
If GFR is 180L/day…the kidney is CLEARING 180L/day of plasma
So…of all creatinine CLEARED per day, excreting all creatinine from that 180L
Therefore clearance = _____
GFR
under ideal circumstances
If you know the plasma concentration of a “special” solute…you can measure the urinary concentration and know urine volume to calculate _______
GFR
what you filter comes out in urine
Creatinine clearance 24 hour urine measure requires
steady state
*order urine creatinine (to determine if was collected appropriately)
CrCl should be (in theory) equal to _____?
GFR
Female CrCl normal
about 20mg/kg/day
Male Cr Cl normal
about 25mg/kg/day
Estimation of Cr Cl
Cockcroft-Gault
Cockcroft-Gault equation
(140 - age)(weight in kg)(0.82 if female) / serum [Cr]mg/dL * 72
Estimation of GFR
MDRD: modification of diet in renal disease study
MDRD equation
GFR (in mL/mim) = (186.3)(serum Cr)(age)(0.742 if female)(1.21 if black)
Limitations of estimation of Cr Cl and GFR of Cr…
- Neither of these are valid in normal or near normal renal function.
- Creatinine is SECRETED depending on renal function, is ramped up in early phases of GFR decline
- if renal function falls by 1/2…would see a doubling of creatinine (but not true in early phases of renal loss due to secretion)
- Creatinine can have variable production based upon age, illness, etc.
- When finally see Cr doubled, it has exceeded its secretion rate, BAD HAS BEEN HAPPENING FOR A WHILE
