physiology of the renal tract Flashcards
what is osmolarity?
Concentration of osmotically active particles present in a solution
what are the units of osmolarity?
mosmol/l for body fluids as these are weak salt solutions.
what are the two factors that need to be known for osmolarity to be calculated?
the molar concentration of the solution, and
2) the number of osmotically active particles present
what measures osmolarity?
osmometer
what is the difference between osmolality and osmolarity?
Osmolality has units of osmol/kg water
Osmolarity has units of osmol/l
For weak salt solutions (incl. body fluids) these 2 terms are interchangeable
what is the osmolarity of body fluids?
~300 mosmol/l
i.e. the same osmolarity as 150mM NaCl and 100mM MgCl2.
what is tonicity?
Tonicity is the effect a solution has on cell volume
A solution can be either hypo-, hyper- or iso-tonic
what happens when you put a cell in a hypotonic solution?
more water outside, cell lysis
less than 300mosmols/l
what happens when you put a RBC in an isotonic solution?
normal RNC appearance
what happens when a cell is placed in a hypertonic solution?
greater than 300mosmols/l, decreased in cell volume, cells shrink
what else should be considered related to osmolarity and tonicity?
also takes into consideration the ability of a solute to cross the cell membrane.
what is the osmolarity of urea and sucrose?
300mM, hence the osmolarity will be the same because they do not dissociate into other particles
sucrose is —-tonic solution?
isotonic
urea is ——-tonic solution to cells?
hypo, because the red blood cell membrane is very permeable to urea because they have transporters that move urea from the outside to the inside, leaving behind water molecules and setting up a water gradient, causing an increase in water in the cell, meaning it is a hypotonic solution
what is the total body water in males?
~60% of body weight
what is the total body weight in females?
~50% of body weight
what are the two major compartments of total body water?
ICF and ECF which is 67% and 33% respectively
ECF includes?
Plasma (~20% of ECF)
Interstitial fluid (~80% of ECF)
Lymph (negligible) + Transcellular fluid (negligible)
how do we measure the volume of these particular fluid compartments?
‘Tracers’
Obtain the ‘distribution volume’ of a tracer
what are useful tracers?
TBW: 3H2O
ECF: Inulin
Plasma: labelled albumin
what is the equation of TBW?
ECF + ICF
to measure the distribution of volume of a tracer?
Add a known quantity of tracer X (QX; mol or mg) to the body
Measure the equilibration volume of X in the body ([X])
Distribution volumes (litres) = Qx(mol/{x{(mol/litre)
water balance or homeostasis?
inputs - outputs
what are inputs?
fluid intake, food intake, metabolism
what are the outputs?
insensible loss: no physiological or regulatory control/ unpreventable:
skin, lungs
sensible loss: regulatory mechanisms that can change how much is lost
sweat, faces, urine
what is the greatest loss of water in the body?
urine, depending of body hydration status, extremely hydrated = more urine produced
water imbalance is manifested as changes in?
body fluid osmolarity, imbalance is treated by changes in distribution of what is inside and outside of the cells and normal osmotic equilibrium is restored
effects of environmental temperature on water loss in adults?
lungs lose less volume of water, you sweat more and you produce less urine
effects of prolonged heavy exercise on water loss in adults?
lungs produce more water, you sweat much more, and you produce less urine,
why do you still produce urine when you are extremely dehydrated?
because some of the products that are excreted in urea can only be excreted in solution, hence no matter what urine must be produced
how is water balance maintained in the body?
Water balance is maintained by increased water ingestion. Decreased excretion of water by the kidneys alone is insufficient to maintain water balance
what are the concentrations of individual ions in the ICF?
Na+ -10
K+ -140
Cl- 7
HCO3- 10
what are the concentrations of individual ions in the ECF?
Na+ 140
K+ 4.5
Cl- 115
HCO3- 28
what causes changes in the concentrations of individual ions?
different tissues and animals will have different concentrations of ions
what enables cells to maintain internal environments that differ in composition compared to their surroundings?
The cell membrane and membrane transport mechanisms enable cells to maintain internal environments that differ in composition compared to their surroundings
what are the main ions in the ECF?
Na+, Cl-, HCO3-
what are the main ions in the ICF?
: K+, Mg2+, -vely charged proteins
cell membranes are?
selectively permeable
despite the selective permeability of the cell membranes what is true about the osmotic concentrations?
ECF and ICF are identical (~300 mosmol/l)
Because changes in solute concentrations lead to immediate changes in water distribution, the regulation of fluid balance and electrolyte balance are tightly intertwined.
what is fluid shift?
Movement of water between the ICF and ECF in response to an osmotic gradient.
what happens to the ECF and ICF volume if the osmotic concentration of the ECF increases?
ECF becomes hypotonic and ICF volume increases, because of the water gradient, hence ECF decreases
what happens to the ECF and ICF volume if the osmotic concentration of the ECF decreases?
ECF becomes hypertonic and ICF volume decreases because of the water gradient, hence ECF volume increases
gain or loss of water?
= change in fluid osmolarity
Similar changes in ICF & ECF volumes (both increase or decrease)
gain or loss of NaCl?
change in fluid osmolarity
a) Na+ “excluded” from ICF (recall ion distributions
(b) Osmotic water movements
what are the two factors that combine to produce opposite effects in ICF and ECF?
These two factors combine to produce opposite changes in ICF and ECF volumes:
ECF NaCl gain: ECF ↑ ICF ↓
ECF NaCl loss: ECF ↓ ICF ↑
gain or loss of isotonic fluid?
(e.g. 0.9% NaCl solution) = no change in fluid osmolarity
Change in ECF volume only
kidneys do what to the composition and volume of ECF?
Kidney alters composition & volume of ECF
why is regulation of ECF volume vital?
for long term regulation of blood pressure
electrolyte balance occurs when?
rates of gain = rates of loss
what are the two important reasons for electrolyte balance?
1) Total electrolyte concentrations can directly affect water balance (via changes in osmolarity)
2) The concentrations of individual electrolytes can affect cell function
which two ions are particularly important in electrolyte balance?
sodium and potassium
why is sodium and potassium particularly important in electrolyte balance?
They are major contributors to the osmotic concentrations of the ECF and ICF, respectively
b) They directly affect the functioning of all cells
sodium balance, why is it vital to regulate sodium?
> 90% of the osmotic concentration of the ECF results from the presence of sodium salts
The total amount of sodium in the ECF represents a balance between two factors (input and output).
Na+ is mainly present in the ECF therefore it is a major determinant of ECF volume (rule-of-thumb: “water follows salt”)
potassium balance is vital because?
Minor fluctuations in plasma [K+] can have detrimental consequences
what is the role of potassium?
establishing membrane potential
small leakages or increased cellular uptake may severely affect the concentration of potassium in plasma leading to?
muscle weakness → paralysis
(ii) cardiac irregularities → cardiac arrest
hence
[K+]plasma must be closely monitored and regulated
salt balance intake?
fluids and food
salt balance output?
sweat and faces, urine causes the most excretion of salt
what is salt imbalance manifested as?
ECF volume
regulation of ECF volume is important for?
long term regulation of blood pressure
what are the filtrations barriers?
Glomerular Capillary Endothelium (barrier to RBC)
(2) Basement Membrane (basal lamina) (plasma protein barrier) (3) Slit processes of podocytes (plasma protein barrier) (Glomerular epithelium)
what is the difference between the glomerular capillary and the pores in other capillaries in other tissues?
they are much bigger, making the walls of the glomerular capillary endothelium quite leaky
the basement membrane
acellular layer
what makes the inner layer of the bowman’s capsule?
the podocytes, foot like cells
what moves through the lumen of the capillary to the lumen of the bowman’s capsule?
things big enough to cross
what happens to negatively charged proteins across the basement membrane?
the basement membrane is negatively charged, hence the proteins are repelled. The basement membrane acts to retain the proteins. because the RBCs are too big, they should not get through the molecular sieve. if you find blood in urine, then there is something wrong with this mechanism
fluid filtered from the glomerulus into the Bowman’s capsule must pass through?
the three layers that make up the glomerular membrane
what type of process is glomerular filtration?
passive, instead this process is driven by the balance of forces acting on the membrane
what are th 4 process that drive filtration?
glomerular capillary blood pressure, capillary oncotic pressure, bowman’s capsule hydrostatic fluid pressure, bowman’s capsule oncotic pressure, anything that can bypass this pressure will enter the bowman’s capsule
what are the 2 fluid pressures?
pressure of blood, glomerular capillary blood pressure - 55mmHg, largest of the four pressure, key determinant, sets up the net filtration
Bowman’s capsule hydrostatic (fluid) pressure - this pressure opposes the glomerular capillary blood pressure - 15mmHg
the glomerular capillary is special because?
the pressure stays the same from start to the end, the diameter of the afferent is bigger than the efferent, building up of the back daming effect, maintaining the pressure of the blood constant
what are the 2 oncotic pressures?
colloid/osmotic - pressure of plasma proteins
Capillary oncotic pressure and Bowman’s capsule oncotic pressure , you should not have plasma proteins in the Bowman’s capsule oncotic pressure, across this membrane, exerting an osmotic effect, dragging anything small enough to cross the membrane, opposes blood pressure - 30mmHg
what is the pressure of the Bowman’s capsule oncotic pressure?
it is 0mmHg, because there are no plasma proteins present in the bowman’s capsule
to find the net filtration pressure:
the difference between the sum of the fluid pressures and the oncotic pressures - giving us a net filtration pressure of 10mmHg, this is the pressure that pushes fluid and anything that can bypass the membrane to form the initial glomerular fluid
what are the starling forces?
the balance of hydrostatic pressure and osmotic forces
what is the composition of tubular fluid
same compositions as the start of the tubular fluid as roughly as plasma apart from the large plasma proteins
what is GFR?
rate at which protein-free plasma is filtered from the glomeruli into the Bowman’s capsule per unit time.
- collective across both kidneys and across all nephrons, this is dependent on how holy or how large the holes are
how do you decrease GFR?
kidneys are filtering less, so less urine produced
what is the major determinant of the GFR?
glomerular (blood) pressure is the major determinant of GFR
GFR =
Kf x net filtration pressure where Kf = filtration coefficient = how “holey” the glomerular membrane is
what is the extrinsic regulation of GFR?
sympathetic control via baroreceptor reflex
what is the autoregulation of GFR instrinic?
Myogenic mechanism (b) Tubuloglomerular feedback mechanism
what mechanisms keep the GFR constant-ish?
extrinsic and intrinsic mechanisms
if you have contraction of the muscle in the afferent arteriole?
there is less blood flowing though the blood capillary, decreased net filtration pressure, decreased GFR
if you have vasodilation in the afferent arteriole?
more blood flowing, increase net filtration pressure, increased GFR
fall in blood volume (e.g. hemorrhage) (extrinsic control)
decreased blood pressure, detected by aortic and carotid sinus baroreceptors, increased sympathetic activity, generalized arteriolar vasoconstriction and constriction of afferent arterioles, decreased BPgc and decreased GFR and decreased urine volume, reducing fluid loss form the body helping to compensate for the initial loss of volume in the body
intrinsic control of blood pressure?
increase in blood pressure during exercise, so GFR is increased, prevention of losing lots of fluids and salts is constant GFR, allows individual to produce enough urine and this occurs through auto regulation of GFR
what is auroregulation?
Autoregulation prevents short term changes in systemic arterial pressure affecting GFR
what protects changes in MABP?
RBF & GFR protected from changes in MABP over wide range of MABP
what are the two ways that auto regulation occurs?
myogenic and tubuloglomerular feedback
what is myogenic auto regulation?
If vascular smooth muscle is stretched (i.e. arterial pressure is increased), it contracts thus constricting the arteriole
what is the tubuloglomerular feedback auto regulation?
Involves the juxtaglomerular apparatus (mechanism remains unclear),
If GFR rises, more NaCl flows through the tubule leading to constriction of afferent arterioles
what are the macula dense cells?
sense NaCl content tubular fluid, in response to increase in salt, the macula dense release chemicals that causes the contraction of the afferent arteriole, decreasing blood flow down the glomerular capillary, decreasing net filtration pressure, in a negative feedback fashion
kidney stones
buildup of fluid due to a kidney stone - increasing the bowman’s capsule fluid pressure causing a decrease in GFR, due to decrease in net filtration pressure
diarrhea?
plasma proteins are still present within the capillary, and will exert a greater pressure, dehydrated, so increase in capillary oncotic pressure leading to a decreased in GFR
severely burned patients?
loss of plasma proteins, causing a loss of capillary oncotic pressure leading to an increase in GFR
decrease in filtration coefficient?
change in surface area available for filtration - reducing GFR, because is affects the rate at which urine Is produced and excreted
what is renal plasma clearance?
A measure of how effectively the kidneys can ‘clean’ the blood of a substance
Equals the volume of plasma completely cleared of a particular substance per minute
Each substance that is handled by the kidney will have it’s own specific plasma clearance value
what are the units of clearance?
ml/min - clearance of substance X
inulin
not produced by the body, is found in garlic and onions etc. it is not metabolized by the kidney, not toxic and it is easily measured in urine and blood and it is freely filtered at the glomerulus and is neither absorbed not secreted
inulin clearance?
is GFR because the substance is not reabsorbed at any point, 125ml/min, there is 125ml of inulin-free plasma returned to the plasma
rate of filtration?
inulin plasma x GFR = conc. urine x Vurine
what can be used instead of inulin/
creatinine, giving us a close approximation, this is because inulin has to administered and has to be measured multiple times
glucose
normally filtered, passes through the sieve, normally all the glucose filtered is reabsorbed by the proximal convoluted tubule, normally not secreted - clearance is therefore 0
urea
metabolic waste products excreted in urine, partly reabsorbed and not secreted, clearance < GFR, only a portion of the plasma is cleared
hydrogen ions
secreted but not reabsorbed, therefore clearance > GFR, all of the filtered plasma is cleared of a substance, and the peritubular plasma from which the substance is secreted, is also cleared
tubular reabsorption or secretion?
if clearance is GFR then substance is secreted into tubule
if all the PAD in the plasma that escapes filtration>
it is secreted from the peritubular capillaries
what is PAH?
Para-amino hippuric acid (PAH) = exogenous organic anion
Used clinically to measure renal plasma flow (= 650 ml/min)
why use pAH?
PAH is 1) freely filtered at glomerulus,
2) secreted into the tubule (not reabsorbed) & 3) completely cleared from the plasma
used to clinically measure renal plasma flow
creatinine
(Creatinine is a muscle metabolite produced at a near constant rate. It is freely filtered and not reabsorbed but is slightly secreted, gives a close approximation of GFR and is easier to measure than inulin clearance)
what is an ideal marker to find a GFR marker?
Non-toxic
(2) Inert (i.e. not metabolised) (3) Easy to measure
(a) A GFR marker should be filtered freely; NOT secreted or reabsorbed
what is the an idea RPF marker?
should be filtered and completely secreted.
Non-toxic
(2) Inert (i.e. not metabolised)
(3) Easy to measure
what is the filtration fraction?
Filtration fraction is the fraction of plasma flowing through the glomeruli that is filtered into the tubules
i.e. ~20% of the plasma that enters the glomeruli is filtered.
The remaining 80% moves on to efferent arterioles and then the peritubular capillaries.
how do you calculate filtration fracture?
GFR/RPF = 0.19 = 20% in a healthy person
what is GFR in a healthy person?
125 ml/min (calculated from inulin clearance)
= 180 litres/day !! (= 60x plasma volume!!)
what is RPF in a healthy person?
650ml/min calculated from PAH clearance
what is RBF in a healthy person?
RPF x 1/1-HCT = ~1200ml/min
how much of CO does the kidney receive?
~24% of CO when CO =5litres/min at rest
RPF
collectively through both kidneys and individual nephrons, how much plasma is flowing through them
