What is the range of urine osmolarity that the kidneys can excrete?
50 mosm / L (very dilute) to 1400 mosm / L (very concentrated)
What is the purpose of excreting a dilute urine?
Get rid of excess water (body fluid osmolarity is reduced)
What is the purpose of excreting a concentrated urine?
Conserve water (body fluid osmolarity is increased)
There is a decrease in what hormone when ECF concentration is low (excess body water in relation to solutes)?
ADH production and secretion (by post pit) is decreased
This causes decreased permeability of the DT and CT to water (water is not reabsorbed)
Water is then excreted
Where are the osmoreceptors that control ADH secretion located?
Hypothalamus
When ADH secretion is decrease, what happens to cause decreased water reabsorption?
Decreased number of aquaporins in the DT and CT, this causes water to NOT be reabsorbed, but secreted
Explain how a dilute urine is created (differences in tubular reabsorption in the different tubules)
Tubular fluid remains isosmotic in PCT (solute and water reabsorbed equally)
Tubular fluid becomes concentrated (water is reabsorbed) in the desc LoH (in the medulla)
Tubular fluid becomes dilute in the asc LoH as solutes (Na, K, Cl) are reabsorbed, this portion is impermeable to water, so dilution occurs
More dilution occurs in the DT and CT (solutes reabsorbed, water is NOT reabsorbed)
In the distal and collecting tubules, what affects water reabsorption?
ADH
T or F, the ascending LoH is very permeable to water due to the effect of ADH
F, this area is NOT affected by ADH levels
Even in the presence of high ADH levels, the ascending LoH is impermeable to water
What is the stimulus for excreting a concentrating urine?
Increased plasma ECF
Obligatory urine volume
The minimum amount of urine that must be excreted to get rid of waste products from metabolism
For a 70 kg pt, 600 mosm of waste must be excreted
Max urine concentration is 1200 mosm/ L
600/ 1200- 0.5 L / day
This is where min UO of 20-30 ml / hr is derived from
What 2 factors allow us to produce a concentrated urine?
#1- Hyperosmolar medullary interstitial fluid (provides an osmotic gradient to allow water reabsorption)
#2- High levels of ADH (increase in # of aquaporins to allow increased reabsorption)
What are the vasarecta?
Blood vessels to the LoH
Part of the peritubular capillaries
What solutes are key contributors to a hyperosmolar medullary interstitial gradient?
Na Cl
Urea
What is the only part of the LoH that's permeable to water?
Descending limb
In the thick ascending LoH, what solutes get reabsorbed (back into blood) and what get excreted?
Reabsorbed- Na, Cl, K, Ca, bicarb, Mg
Excreted- H
What factors contribute to the build up of solute in the renal medulla to create a hyperosmolar medullary interstitial gradient?
Active transport of Na out of LoH and into medullary interstitial
Co-transport of K, Cl, and other ions with Na
Facilitated diffusion of urea into medullary interstitial
Limited diffusion of water from tubules into medullary interstitium
Countercurrent mechamism
process that allows creation of hyperosmolar medullary interstitial gradient
What is the driving force behind counter current mechanism?
Osmolarity
Explain the main activities occurring in counter current mechanism
Active pump in thick ascending LoH moves Na and Cl into medullary ISF (increased osm in ISF)
To balance this out, water moves out of desc LoH into medullary ISF
Solutes keep getting reabsorbed and tubular fluid gets more concentrated, and this process gets repeated
Concentration gradient established by active transport gets multiplied
Urine gets very concentrated as water gets reabsorbed to dilute medullary ISF
ADH causes water to be reabsorbed, does it get reabsorbed in the medullary or cortical ISF? Why?
Water gets reabsorbed into the cortical ISF, if it got reabsorbed into the medullary ISF it would dilute it and counteract the hyperosmolar gradient (that serves to allow urine concentration)
When a substance is reabsorbed, where is it going?
Back into the blood
What is the only part of the LoH that allows water reabsorption?
Descending
What percent of the hyperosmolar medullary interstitial gradient is urea?
40-50%
500-600 mosm / L
Is urea passively or actively reabsorbed from the tubules?
Passively
What is the significance of urea ?
Urea cycles through the tubules multiple times before excretion
Urea contributes to the hyperosmolar medullary interstitial gradient (water gets reabsorbed from the collecting ducts and urea is concentrated, this allows facilitated diffusion to move urea from tubules into medullary ISF)
Where does urea reabsorption occur?
medullary collecting duct
What happens after urea is reabsorbed into the medullary collecting ducts?
Contributes to hyperosmolar medullary interstitial gradient
Urea then diffuses into thin LoH and passes again thru the distal tubules
Process repeats a few times, until urea is finally excreted
What 2 features of the renal medially blood flow contribute to preservation of hyperosmolarity?
1) Low blood flow, < 5% of total renal BF, this minimizes solute loss from medullary interstitium
2) Vasarecta serve as countercurrent exchanges, this minimizes washout of solutes
T or F, the purpose of countercurrent exchange with VR is not to create hyperosm state in medullary interstitium but rather to prevent it from being dissipated?
T
How does the VR help to maintain medullary hyper osmotic state?
Desc LoH:
Solute leaves medullary ISF and goes into VR
Water goes from blood (VR) into medullary ISF
Asc LoH:
Solutes leave VR and go into medullary ISF
Water leaves medullary ISF and enters medulla
Both things make the blood less concentrated and the tubular fluid more concentrated
What stimulates ADH secretion?
Plasma osm, BP and BV (both mediated by baroreceptors, N/V, hypoxia, medications (morphine)
What's an easy way to estimate plasma osm?
Na x 2.1
What happens to ADH secretion if plasma osm is increased?
Increase in ADH secretion and insertion of aquaporins (to increase water reabsorption in DT and CD)
Quantitatively, which has more of an effect on blood volume- blood volume or plasma osm?
Plasma osm- a 1% increase stimulates ADH release vs. a 10% decrease in blood volume
Is most K ICF or ECF?
ICF
Normal K concentration in the plasma?
4 meq/L
What factors will cause K to move from ECF to ICF?
Insulin (occurs after a meal)
Aldosterone
Catecholamines (beta 2 mechanism)
Metabolic alkalosis
What factors will cause K to move from ICF to ECF?
Metabolic acidosis, exercise, cell lysis, increased ECF osmolarity (causes cellular dehydration, water moves out of the cell, so does K)
Why is a diabetic pt at particular risk for hyperkalemia?
Impaired insulin release (insulin causes K to move into the cell), K levels are increased after a meal
What % of K gets reabsorbed in the PCT?
65%
Where does the majority of K secretion (into tubular fluid) occur?
principle cells of the DT and CCT
What are the principle cells?
Special tubular epithelial cells
Make up 90% of the tubular epithelial cells in the DT and CCT
How do the principle cells of the DT and CCT secrete K?
1) uptake of K into principle cells (Na/K/ATPase pump)
2) passive diffusion of K from principle cell to tubular fluid (principle cells have unique channels that allow K diffusion into tubular fluid)
What is the major stimulant for K secretion by the DT and CCT?
Plasma K level
T or F, an increase in plasma K will stimulate aldosterone secretion, that will in term cause K secretion?
T
Renal K excretion is determined by the sum of….?
Rate of K filtration (GFR x plasma K concentration)
minus rate of tubular reabsorption
Plus rate of tubular secretion
What does PTH do?
Increases plasma Ca levels by bone resorption and vitamin D activation
Also causes increased Ca reabsorption by the tubules and decreased Phos absorption
What does calcitonin do? Where is it released from?
Decreases plasma Ca levels
Thyroid
Normal ionized Ca level
2.4 meq/L
What form of Ca can be filtered by the kidneys?
The ionized as the rest is complexed to anions or protein bound
What % of filtered Ca gets reabsorbed? Where does most of the reabsorption occur?
99%
PCT
In what 3 locations in the tubules does Ca reabsorption occur? What controls the reabsorption at each site?
PCT- 65%- volume status
LoH- 25-30%- PTH
DT and CT- 4-9%- PTH
How does plasma phos level affect Ca levels?
Increased plasma Phos causes an increase in PTH
Ca reabsorption is increased
Ca excretion is decreased
What effect will metabolic acidosis have on Ca reabsorption?
