Renal Physiology Flashcards
Define Osmolarity
measure of osmotically active particles within a solution
so 150mM of NaCl = 300 mosmol/l
100nM of MgCl2 = 300 mosmol/l
Explain the effect hypertonic/hypotonic solutions have on cell volume
How can a solution of 300mMol Urea burst a cell?
The cellular membrane is permeable to urea and there is no urea within the cell. The isotonic solution of urea will have a hypotonic effect
what percentage of our TBW is water?
What proprtion is intra/extracellular?
What proportion of exracellular flui is plasma/ Interstitial fluid?
•Total body water (TBW):
Male = ~60% of body weight
Female = ~50% of body weight
•Total body water exists as 2 major compartments:
Intracellular fluid (ICF) (= 67% of TBW)
Extracellular fluid (ECF) (= 33% of TBW)
•Extracellular fluid includes:
Plasma (~20% of ECF)
Interstitial fluid (~80% of ECF)
How can we measure the volume of the body fluid compartments?
With a tracer
List different types of tracers and which body compartment they are used for
TBW: 3H2O
ECF: Inulin
Plasma: labelled albumin
TBW = ECF + ICF
what is the equation that calculates the volume of a body compartment using a tracer?
what volume of fluid is lossed through sensible/ insensible causes per day?
what is the ionic composition of ICF/ECF?
The primary anion of the ECF is…..
Chloride
Define Fluid Shift
•Movement of water between the ICF and ECF in response to an osmotic gradient.
What would happen to the ECF/ICF volume if there was a Gain or loss of water?
Similar changes in ICF & ECF volumes (both increase or decrease)
What would happen to compartment volumes with a gain or loss of NaCl
(a) Na+ “excluded” from ICF (recall ion distributions)
(b) Osmotic water movements
These two factors combine to produce opposite changes in ICF and ECF volumes:
ECF NaCl gain: ECF ↑ ICF ↓
ECF NaCl loss: ECF ↓ ICF ↑
what would happen to compartment volumes when you drink isotonic fluid?
no change in fluid osmolarity
Change in ECF volume only
•> 90% of the osmotic concentration of the ECF results from the presence……
of sodium salts
What percentage of nephrons are juxtamedullary?
20%
What does the rate of excretion equal?
rate of excretion = rate of filtration + rate of secretion - rate of reabsorption
what are the equations for the rate of filtration, the rate of excretion and the rate of reabsorption?
Use Cl- as an example
Cl- filtered = [Cl-]plasma × GFR
= 110 mmol/l × 0.12 litre/min
= 13.2 mmol/min
Cl- excreted = [Cl-]urine × Vu
= 200 mmol/l × 0.001 litre/min
= 0.2 mmol/min
Rate of filtration > rate of excretion
Therefore, net reabsorption of Cl- has occured
Cl- reabsorbed = 13.2 – 0.2 = 13 mmol/min
describe the forces involved in glomerular filtration
what is the equation for GFR?
what is anormal GFR?
What is the major determinent of GFR?
GFR = Kf × net filtration pressure
(where Kf = filtration coefficient = how ‘holey’ the glomerular membrane is)
‘normal’ GFR = 125 ml/min
Glomerular capillary fluid (blood) pressure (BPGC) is the major determinant of GFR
how is renal blood flow and gfr regulated?
- Extrinsic regulation of GFR
(a) Sympathetic control via baroreceptor reflex - Autoregulation of GFR (Intrinsic)
(a) Myogenic mechanism
(b) Tubuloglomerular feedback mechanism
describe the negative feedback loop that occurs after a fall in blood pressure and how the gfr is altered to compensate for this?
describe the 2 types of autoregulation in the kidneys
what other determinants affect GFR?
what is plasma clearance?
•Equals the volume of plasma completely cleared of a particular substance per minute
is their tubular reabsorption of secretion in this example…..
Urine flow rate (Vu) = 1 ml/min
[Na+]u = 70 mmol/l
[Na+]p = 140 mmol/l
Inulin clearance = 125 ml/min
If clearance < GFR (inulin clearance) then substance is REABSORBED
what is para-amino hippuric acid (PAH) used to calculate and why?
Renal Plasma Flow
all PAH is either filtered or secreted and none is reabsorbed
RPF = 650ml/min
what are the issues of using inulin to measure GFR and what is an easier way to measure GFR?
The blood has to be constantly perfused with inulin
Creatinine is easier to measure but it is slightly less accurate because some creatinine is secreted
how is the filtration fraction calculated
GFR/ RPF
Define Facilitated diffusion
Primary active transport
and
Secondary Active transport
•Primary active transport
Energy is directly required to operate the carrier and move the substrate against its concentration gradient
•Secondary active transport
The carrier molecule is transported coupled to the concentration gradient of an ion (usually Na+)
•Facilitated diffusion
Passive carrier-mediated transport of a substance down its concentration gradient
Define Primary active transport, Secondary active transport and facilitated diffusion
define transport maximum
transport maximum (alternatively Tm or Tmax) refers to the point at which increases in concentration do not result in an increase in movement of a substance across a membrane.
what is the transport max for glucose?
2mmol/min
why does a very high measure of plasma PAH not give an accurate measure of renal plasma flow?
Because when concentrations of PAH exceed the transport maximum not all PAH is cleared from the plasma. There is too much PAH to be fully secreted.
define renal threshold
the renal threshold is the concentration of a substance dissolved in the blood above which the kidneys begin to remove it into the urine.
ie. the renal threshold for glucose is 10-12mol/l. Plasma concentrations higher than this result in glucose being excreted by the kidneys
How is Na+ reabsorbed across the epithelium?
How is glucose reabsorbed in the proximal tubule?
Explain why the osmolarity of tubular fluid does not change along the proximal tubule
water follows sodium out of the tubule via the paracellular root
tubular fluid is iso-osmotic (300mosmol/l)
what drives Cl- reabsorption through the paracellular pathway in the proximal tubule?
Na+ reabsorption
what is absorbed in the descending and ascending loops of Henle?
Descending loop is water-permeable with no active salt reabsorption
Ascending Loop is water-impermeable with active salt reabsorption
where is the NA+/K+/Cl- triple co-transporter?
thick ascending loop of Henle
what is countercurrent multiplication?
Vasa recta acts as a …….
Together, the Loop of Henlé and vasa recta form a ………..
COUNTERCURRENT EXCHANGER
•Capillary blood equilibrates with interstitial fluid across the “leaky” endothelium
•
• Blood osmolality rises as it dips down into the medulla (i.e. water loss, solute gained)
•
• Blood osmolality falls as it rises back up into the cortex (i.e. water gained, solute lost)
COUNTERCURRENT SYSTEM
what subtance is pumped out of the collecting ducts and contributes to approximately half or medullary osmolality?
Urea
Describe the handling of Na+, K+ and H+ by distal tubule
Na+-K+-2Cl- co-Transporter reabsorbs NaCl in the early distal tubule
Na+ is reabsorbed in the late distal tubule
K+ is also reabsorbed in the distal tubule unless there is an incrases in aldo sterone in which case K+ is secreted
H+ is also secreted in the distal tubule
Explain the formation of hypertonic and hypotonic urine
hypotonic urine is created when there is low amounts of ADH. The collecting ducts are not very permeable to water and therefore more water is excreted.
Hypertonic urine is created when there are high volumes of ADH. ADH increases the permeability of the collecting ducts and more water is reabsorbed making the urine more concentrated.
Explain the mechanism of the action of ADH
Increases permeability of
luminal membrane to H2O
by inserting new
water channels (aquaporins)
summarise tubular permeability properties
(A) Proximal Tubule and Descending Loop of Henlé
· Na+ reabsorbed by transcellular mechanisms (**PT only)
· Water moves between inter-cellular junctions
· These produce net fluid reabsorption
· Na+ and water coupling
(B) Ascending Loop of Henlé and Distal Tubule
· Low water permeability of epithelium (ADH-dependent)
· Na+ & Cl- reabsorption
· These produce dilution of urine
· Na+ & Cl- coupling
(C) Collecting Duct
· Modulation of water / urea permeability
· This contributes to determination of final urine osmolarity
·
(D) Distal Tubule / Collecting Duct
· Site of hormone action (ADH, Aldosterone, Atrial Natriuretic Peptide)
Draw a graph to illustrate the changes in osmolarity of the tubular fluid as it flows along the nephron.
What two sensors trigger secretion of ADH?
hypothalamic osmoreceptors
volume receptors in left atrium
by what two mechanisms does ADH raise BP
vasoconstriction and by increasing water permeability of collecting ducts
to what response is aldosterone secreted?
- In response to rising [K+] or falling [Na+] in the blood. K+ directly stimulates the adrenal cortex. Na+ indirerectly stimulates aldosterone secretion by means of the juxtaglomerular apparatus.
- activation of the renin-angiotensin system
What is responsible for the fluid retention associated with congestive heart failure?
Drop in BP causes an increase in R-A-A system.
This leads to Na+ and water retention which excerbates the heart failure
what is the henderson hasselbach equation?
pH= pK + log(A-/HA)
What is the mechanism of [HCO3-] reabsorption in the proximal tubule?
How is new bicarbonate formed?
What is titratable acid?
the amount of H+ secreted as H2PO4-
what is the maximum amount of titratable acid that can be excreted within a day?
40mmol/day
what are the three things that H+ secretion by the tubule does?
drives reabsorption of HCO3-
Forms acid phosphate (causes around 20 mmol/day of H+ to be excreted)
Forms ammonium ion (causes excretion of around 40mmol/day of H+)
what’s the difference between compensation and correction?
- If normal acid-base balance is disrupted, the first priority is to restore pH to 7.4 as soon as possible
- This is compensation for an A-B disturbance
- Compensation is the restoration of pH irrespective of what happens to [HCO3-]p and PCO2
- Correction of an A-B disturbance is restoration of pH and [HCO3-]p and PCO2 to normal
what is the renal compensation for respiratory acidosis?
H+ secretion is stimulated
All filtered HCO3- is reabsorbed (i.e. no HCO3- excretion)
H+ continues to be secreted and generates titratable acid (TA) and NH4+
Acid is excreted and “new” HCO3- is added to the blood
what is the renal compensation for respiratory alkalosis?
The H+ secretion is insufficient to reabsorb the filtered HCO3-, even though the load is lower than normal
\ HCO3- is excreted and urine is alkaline
No titratable acid (TA) and NH4+ is formed, so no “new” HCO3- is generated
what are causes of metabolic acidosis?
Excess H+ from any source other than CO2
E.g.
Ingestion of acids or acid-producing foodstuffs
Excessive metabolic production of H+
(e.g. lactic acid during exercise or ketoacidosis)
Excessive loss of base from the body
(e.g. diarrhoea – loss of HCO3-)
what is the respiratory compensation for metabolic acidosis?
CO2 is blown off through increased respiration
this causes more H+ and HCO3- to form Carbonic acid which in turn forms CO2 and H2O to replace the blown off CO2
A reduction in H+ equals a lowering of pH
what is the correction of metabolic acidosis?
Filtered HCO3- is very low and very readily reabsorbed
H+ secretion continues and produces TA & NH4+ to generate more “new” HCO3-
The acid load is excreted (urine is acidic) and [HCO3-]p is restored
Ventilation can then be normalised
N.B. Acid load cannot be excreted immediately therefore respiratory compensation is essential
what is the compensation for metabolic alkalosis?
slow ventilation
retain CO2
CO2 cobines with water to form Carbonic acid
Carbonic acid forms bicarbonate and H+
raises H+ which lowers pH
how is metabolic alkalosis corrected?
Filtered HCO3- load is so large compared to normal that not all of the filtered HCO3- is reabsorbed
No TA or NH4+ is generated
HCO3- is excreted (urine is alkaline)
[HCO3-]p falls back towards normal
