PSIO 241 CH 14 pt. 2

sympathetic control

is involved in long-term regulation of arterial blood pressure. In cases of dehydration, would override autoregulation and decrease GFR to conserve salts and water

sympathetic activity

results in a decrease of GFR

macula densa 

in distal tubules sense salt delivery; high salt delivery rate means GFR•increased above normal 

\- In response _ cells produce constriction of afferent arteriole to adjust GFR

adenosine

most likely vasoconstrictor is **_**

macula densa cells

salt sensing cells

67%

_ of filtered Na+ and the filtered water is reabsorbed in proximal tubule

isometric reabsorption

The tight coupling between Na and water reabsorption

100%

_ of nutrients reabsorbed in proximal tubule

80%

_ of filtered HCO3- is reabsorbed in proximal tubule

secondary active transport

glucose transport is considered _

normal plasma glucose (N)

all filtered glucose is reabsorbed; __**red**__ and __**orange**__ lines superimposed; __**green**__ line is zero

renal threshold for glucose

blood glucose levels so high that **transporters are saturated; n**ot all filtered glucose can be reabsorbed __**red**__ and __**orange**__ lines moving apart; glucose that is not reabsorbed **appears in urine**; __**green**__ line is increasing

urea

• a waste product from protein degradation

• 50% of the filtered urea is reabsorbed this way

• The level of urea in the blood - blood urea nitrogen (BUN) - is measured clinically as a crude assessment of kidney function; ↑BUN means impaired function

plasma threshold

glucose; approx 200 mg/dL

transport maximum

400 mg/min

secreting organic ions

• one for organic anions and one for organic cations

• most important function of these systems is to secrete foreign organic substances

• Secretion of these substances may be viewed as a **supplement to glomerular filtration** to help eliminate these compounds from the body.

loop of henle

1. Descending limb permeable to water, not salt. **Water drawn out of descending limb by vertical osmotic gradient**
2. Ascending limb permeable to salt not water. **Salt pumped (active transport)** out of ascending limb and contributes to osmotic gradient
3. Much of this **salt remains in the interstitial space to maintain the vertical osmotic gradient.**
4. The collecting ducts pass through the vertical gradient  and in the presence of ADH add urea to the vertical osmotic gradient to strengthen it to aid in water reabsorption (important for concentrating urine under **ADH control**). 

osmotic pressure in loop of henle

1. Filtrate enters the loop of Henle __**isotonic**__ (300 mOsm) 
2. At the tip of loop filtrate is __**hypertonic**__ (1200 mOsm) 
3. Filtrate leaves loop of Henle __**hypotonic**__ (100 mOsm)

descending limb

* water reabsorption; water moves into vasa recta
* 15% water

ascending limb

salt reabsorption (NKCC transporter) some of the salt moves into vasa recta, some stays in interstitial space to contribute the vertical gradient

loop diuretics

• **Loop diuretics (Lasix/ Furosemide)** -loop diuretics inhibit NK transporters

• **More electrolytes left in filtrate, so water remains in filtrate**

• **Weakens the vertical osmotic gradient**, so less water reabsorbed in collecting ducts

• Large diuretic action; but also causes electrolyte loss

early distal tubule

* permeable to salt not water
* 5% of filtered Na+ reabsorption via the Na-Cl transporter
* utilizes Na/Cl co-transporter on apical surface
* cells also involved in controlled calcium reabsorption via the hormone parathyroid hormone (PTH)

late distal tubule

* The **principal cells site** of Na+ reabsorption (3%) controlled by **aldosterone.**
* In the presence of aldosterone, these cells increases sodium reabsorption.
* Aldosterone release stimulated by **low blood pressure** via __Renin-Angiotensin Aldosterone__ system
* 2-3% Na+ reabsorption
* utilizes Epithelial Na channels (ENaC) on apical surface

aldosterone and sodium

Aldosterone enhances sodium reabsorption by the principal cells by:


1. Synthesis and insertion of **new epithelial Na channels (ENaC),** which is the channel by which Na from the urine enters the cell
2. Synthesis and insertion of new Na/K ATPase, which moves Na into the blood
3. Changes in metabolic pathways to promote ATP production

Renin-Angiotensin-Aldosterone System (RAAS)

* granular cells sensitive to BP, in response to decrease in BP, cells release **renin**
* renin triggers a cascade of events that causes the production of hormones that influence BP by altering sodium reabsorption

proximal tubule (uncontrolled)

% of Na reabsorbed: 67%

* plays role in reabsorbing glucose, amino acids, H2O, Cl, and urea

ascending limb of the loop of Henle (uncontrolled)

% of Na reabsorbed: 25%

* plays critical role in kidneys ability to produce urine ofnvaeying concentrations

early distal tubule

% of Na reabsorbed: 5%

* NaCl transportes, no regulation

principal cells of late distal tubules (controlled)

% of Na reabsorbed: 3%

* variable and subject to hormonal control (aldosterone); plays role inn regulating **ECF volume**

potassium

• Potassium in ICF, 98%, huge store of K+ since ICF is twice volume of ECF; body has more K+ than Na+.

• Plasma K+ concentration in **ECF** tightly regulated to maintain normal membrane excitability in muscles and nerves

• Hyperkalemia (elevated ECF \[K\]) stimulates the release of **insulin, epinephrine** and directly stimulates adrenal cortex to release **aldosterone**; bypasses renin system.

handiling K+ load of a meal

• The ingestion of a K+ load is  quickly absorbed in the GI  tract and increases plasma  \[K+\].

• The absorbed K+ is  rapidly taken up into the  large ICF  K+ pool buffering plasma K+

•Hormones **insulin, epinephrine**  promote the transfer of K+ from extracellular to intracellular fluid.

• The ingested K+ load is then  slowly excreted by the  kidney over the next several  hours via **aldosterone stimulation.**

aldosterone and potassium secretion

Aldosterone enhances potassium secretion by the principal cells by:

\

1. Synthesis and insertion of new Na/K ATPase to bring K+ into the cell
2. Synthesis and insertion of new K+ channels in apical surface to secrete K+ into the urine
3. Changes in metabolic pathways to promote ATP production

hyponatremia nad hypotension

RAAS is activated, and the combination of elevated Angiotensin II and aldosterone promotes the reabsorption of sodium to return BP to normal

hyperkalmeia

the elevated ECF potassium **directly stimulates the adrenal gland to release aldosterone.** In this process there is not an increase in Angiotensin II, only aldosterone, so the focus of aldosterone is to promote K+ secretion to return K+ levels to normal.

water reabsorption-collecting ducts

• Reabsorbed in all tubule regions (except ascending limb of Loop of Henle)

• Normally 1% excreted but variable depending on needs

• Range 0.5-10 liters/day, normal rate 1.5 l/day

• **Controlled water absorption via ADH at collecting ducts.**

ADH secretion

• The **osmoreceptor neurons** in the hypothalamus are **extremely sensitive** and can maintain ECF osmolarity within a very narrow range **(1%).** 

• **ADH stimulates the collecting ducts to reabsorb water, producing a low volume, concentrated urine=water conservation.**

• **Low levels of ADH results in large volumes of dilute urine=water loss.**

aquaporins

* **Aquaporin1** –  most important  water channel  in early nephron; **NOT sensitive to ADH**
* **Aquaporin2** – most  important **ADH  sensitive** water  channel

plasma clearance

the volume of plasma cleared of a substance each minute by the kidney. 

renal clearance

• 10 ml of blood enters the kidney containing particle X

• After the kidney processes particle X a certain amount is found in the urine

• This means that the kidney has “cleared” some of particle X out of the blood

• Clearance calculations measure the clearance of particle X to be **2 ml/min**

• This means that of the 10 ml of blood containing particle X that entered the kidney:

– 2 ml no longer has particle X (it's been cleared out of this much blood)

– 8 ml still contains particle X

filtered and partially absorbed

Substance filtered and then reabsorbed:

• Plasma Clearance  **is less than GFR.**

• Water, salts, sugars, amino acids, phosphate, etc.

plasma clearance-filtered only

**Substance filtered only**; **clearance= GFR**

• **Inulin**, a fructose polymer, its clearance is a measure of **GFR**

filtered and completely reabsorbed

• Plasma Clearance  **is less than GFR.**

ex: glucose

filtered and partially secreted

Substance filtered and secreted:

• Plasma Clearance **is greater than GFR**

• Excretion rate exceeds filtration rate

• Some substances are partially secreted (K+, H+)

filtered and completely secreted

• Plasma Clearance **is greater than GFR**

filtered and slightly secreted

• Creatinine is a  metabolite of creatine

• Filtered and slightly secreted

• **Can be used to estimate GFR, slightly overestimates GFR**