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Renal physio
renal physio
95
Physiology
Undergraduate 4
04/18/2009

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Term
Molarity
Definition
Measure of amount of substance dissolved in a solution
-measured in moles/liter
-(amt/liter)/ (molecular wgt)
Term
Equivalence
Definition

-Similar to osmolarity but accounts for dissociative properties

-eg: 150mM of NaCl has 150mM of Na+ and 150mM of Cl-

Term
Osmolarity
Definition
[solute]*#of dissociative particles
Term
Calculating mOsm/L
Definition
(mmol solute*# of dissociative parts)/Liters of solvent
Term
What percent of total body weight is water? ICF? ECF? PLamsa? Interstitial fluid?
Definition

TBW=60%

ICF=40%

ECF=20%

IF= 15%

Plasma= 5%

Term
Osmolality
Definition

=#of particles/ Kg H20

*NOT dependent on temp b/c weight of water doesn't change with temp

Term

T or F

If a membrane is permeable only to wate and two compartments seperated by this membrane initially contain different solute concentrations, when the compartments reach equilibrium the volumes of the compartments will be equal.

Definition

False. They will end at the same concentration of solute and water, but different volumes.

Term
Hypertonic
Definition

Solution that is more concentrated outside of the cell and causes the cell to shrink

Term
What happens during iso-osmotic rehydration?
Definition

Increased volume in ECF, but not changes in osmolarity therefore no change occurs in ICF.

Term
What happens during hyperosmotic rehydration?
Definition

1. Initially large increase in ECF volume and   osmolarity

2. Leads to water flow from the ICF to ECF

3. Leads to an increase in osmolarity of ICF

 

Term
What happens during hypo-osmotic overhydration?
Definition

1. ECF volume increases --> decrease in ECF osmolarity

2. Water flow TO the ICF --> increase ICF volume

 

Term
How do you determine change in osmolarity after fluid loss?
Definition

1. Find initial total osmolarity TBW(kg)*osmolarity

2. Subtract total excreted osmolarity=kg*osmolarity

3. Divide by change in body water (L)

Term
What is the major cation in the ECF? ICF?
Definition

ECF= Na+

ICF= K+

Term
About how many nephrons are there in 1 kidney?
Definition
1.2million/ kidney
Term
What is the renal medulla?
Definition
Inner portion of the kidney, composed of 8-18 pyramids
Term
Where does the base of a renal pyramid start?
Definition
At the cortico-medullary junction
Term
What is the papilla?
Definition

*The apex of a renal pyramid

*Leads to the minor calyx, then the major calyx, then the pelvis

Term
What does the pelvis connect to?
Definition

*Major calyx and ureter/ urinary bladder

*Is technically an expanded portion of the ureter

Term
Desribe the flow of filtrate in a nephron
Definition

Glomerular capillaries (thru visceral epithelia) -> bowman's space -> Promixal convoluted then straight tubules -> descending loop of Henle ->thin ascending LH -> thick ascending LH -> (macula densa) ->distal convulted tubule -> cortical collecting duct -> medullary collecting duct -> renal pelvis -> OUT

Term
What are photocytes?
Definition

*Epithelial cells around the Bowman's capsule

*AKA visceral layer

Term
Vasa recta
Definition

*Blood vessels that run entire length of loop of Henle

*Only found in juxtamedullary nephrons

*Allow concentration of urine

 

Term
Cortical/Superficial nephrons
Definition

-Renal corpsule is located in the cortex

-Has a short loop of Henle

-Lower filtration rates b/c nephrons are smaller

-No vasa recta

Term
Juxta Medullary nephrons
Definition

*Have vasa recta

*Long loops of Henle

*Located toward medulla and loops extend into medulla

Term
What comprises the renal corpsule?
Definition

Glomerulus

Bowman's space (both parietal and visceral layers)

Term
How is protein filtered by the renal corpsule?
Definition

*Glomerular capillaries contain fenestre

*Capillaries surrounded by basement membrane

*Photocytes of Bowman's capsule surround glomerular capillaries/BM and have slits that allow the filtration of water

Term
How big are the slits in btwn the foot processes of photocytes? IS there any charge associated? What are the implications on molecule movement?
Definition

*Slits= 40 Angstrom and have a negative charge

*Up to 20 A, free filtration

*20-42 A, filtration is variable

 

Term
Juxtaglomerular Apparatus
Definition

1. Macula densa: specialized cells that sense changes in [NaCl]

2. Granular (juxtaglomerular) cells: Produce Renin

3. Extraglomerular mesangial cells: SM like cells interspersed in extraglom space

Term
What are the functions of the kidney??
Definition

1.Salt/ H2O regulation

2. Vit D regulation via Ca absorption/excretion

3. RBC production via erythropoietin in peritubular capillary endothelial cells

4. BP regulation

5. Excretion of xenobiotics (substances not normally found in the body, usually drugs, etc)

6. Excretion of metabolic waste

Term

True or false

The proximal convuluted tubule lacks a brush border and mitochondria

Definition

False: the proximal convoluted tubule has a brush border to aid in reabsorption. It also has mitochondria

Term
How are renal disease and anemia related?
Definition
In chronic renal disease, there is decreased erythropoietin produced -> fewer RBCs -> anemia
Term

True or flase:

The ascending (thin and thick) loop on Henle has lots of mitochondria

Definition

False: they have few mitochondria

Term
What is inulin used for?
Definition

*Inulin clearance is used as a basis of comparision for clearance of other substances because is not secreted, reabsorbed, metabolized, or synthesized and is freely filtered

*Can be used to calculate GFR

 

Term
Peritubular Capillaries
Definition

*Blood vessels that travel alongside nephrons

*Allows reabsorption and secretion bwtn blood and lumen of nephron

Term
What happens renally when there is decreased O2?
Definition
More erythropoietin is produced -> more RBCs 
Term
Glomerular Filtration Rate
Definition

*Rate of movement of fluids and solutes from glomerular capillaries into Bowman's space

GFR=Kf* (Hydrostatic glomerular capillary Pressure- hydrostatic Bowman's space pressure) - (osmotic pressure of glomerular capillary)

Term
What forces drive fluid toward the glomerulas? Toward the Bowman's Space?
Definition

Glomerulas: Bowman's space hydrostatic pressure

 and oncotic pressure of glomerulus

 

Bowman's: GC hydrostatic, Bowman's oncotic

Term
Which pressure increases along the glomerular capillary network (toward efferent)? Why?
Definition
The glomerular capillary oncotic pressure increases because [protein] increases due to filtration of water into Bowman's space
Term
What is the filtration fraction?
Definition

FF= GFR/RPF

RPF= (1-Hematocrit)* RBF

Term
Where are there sharp decreases in pressure across the arterioles?
Definition

There are sharp decreases across the afferent and efferent arterioles

Term
What happens when the afferent arteriole is constricted?
Definition
Hydrostatic pressure in the glomerular capillaries decreases -> decreased GFR
Term
What happens when the efferent arteriole is constricted?
Definition
The hydrostatic pressure in the glomerular capillary increases -> GFR increases
Term
What does renal autoregulation refer to?
Definition

*Afferent arteriole resistance is changed to compensate for changes in BP

 

*Between a renal arterial pressure 80-160, GFR and renal blood flow remain constant

Term
Tubuloglomerular feedback
Definition

*Afferent arteriolar resistance is regulated by changes in flow rate in the tubule

*Change in arteriolar pressure -> change in glomerular pressure and plasma flow -> change in GFR -> change in Osm and NaCl whiched is sensed by macula densa, which sends signal to afferent arteriole --> changes in preglomerular resistance

Term
Autoregulation: Myogenic Mechanism
Definition

*Regulates the tone of the afferent arteriole

*Tendency to contract when stretched

*Increased arteriolar pressure -> increased afferent arteriolar stretch -> increased contraction -> RBF and GFR are normalized

Term
In regards to the kidney, what does the law of mass balance indicate?
Definition

*If a substance is not metabolized or synthesized,

*Arterial input= Venous output + urine output

Term
Clearance
Definition

*Volume of plasma cleared of a specific substance  per unit time

*clearance= (urine[x]*urine flow rate)/Plasma[x]

Term
What happens when there is a sudden decrease in GFR?
Definition

*Initial decrease in excretion of creatinine, but it slowly increases back to normal

*No initial change in production of creatinine

* Increase in plasama [creatinine]

 

Term
About how much water, Na, Cl, HCO3-, Glucose are reabsorbed?
Definition

Between 99.2 and 99.9

Term
Where is the primary site for glucose/ AA reabsorption?
Definition
Proximal Tubule
Term
What is the typical osmolarity of urine?
Definition
500-800mOsm/kg of H2O
Term
Name some compounds that are not in urine.
Definition

Amino acids, protein, blood, ketones, leukocytes, and bilirubin

Term
What happens when the filtered load surpasses the capacity of a transporter?
Definition
The excess is excreted.
Term
Give an example of cotransport and countertransport
Definition

Na/Glucose transporter = cotransport

Na/H = countertransport

Term
Give examples of secondary active transport
Definition

*Na+/AA

*Na+/H+

*Na+/Ca

*Cl/HCO3

Term
Na+ reabsorption in the proximal tubule
Definition

*Na/H countertransporter

*Carbonic anhydrase on apical membrane converts bicarbonate into water and CO2

*In cell, water and CO2 are converted back to HCO3- by CA

 

Term
Na reabsorption in the thick ascending LH
Definition

*Na-K-Cl symporter drives into cell

*Leads to K secretion

*Na, Ca, K, and Mg cations can be reabsorped via paracellular transport

 

**Thick ascending LH is impermeable to water therefore it is called the diluting segment of the nephron

Term
Describe Na reabsorption in the early distal tubule.
Definition

*Cotransport of Na/Cl

*Impermeable to water

Term
Reabsorption in the late DCT and collecting ducts
Definition

-Na via ENaC channels

-K/H antiporter (K in, H out) in apical

-Carbonic Anhydrase in epithelial cell converts H2CO3 -> HCO3- and H+, HCO3- diffuses to IF, H into lumen

 

-H2O only reabsorbed if ADH present

Term
Where is the ENaC channel found? What does it do? What inhibits it?
Definition

-Late distal tubule/ collecting duct

-Diffusion of Na into the cell

-Inhibited by ameloride (Potassium sparing diuretic)

Term
What is TF/P? What does it measure?
Definition

TF= concentration of substance or osmolarity in the proximal tubule fluid

 

P= blood plasma concentration

 

*Relative concentrations

*If proximal tubule reabsorbs 1/2 of water, and no inulin, the Tf/P value would double (because it is now twice as concentrated)

Term
Which aquaporin is regulated by ADH?
Definition
Only AQP2
Term
Is the IF or the tubular lumen slightly hypertonic?
Definition

The IF is slightly/ "effectively" hypertonic because solutes are transported with a high affinity

Term
What parts of the nephron do not allow water reabsorption?
Definition

Never: Thin and thick ascending loop of henl, distal convoluted tubule, and cortical tubule 

 

Only when ADH present: Cortical collecting duct and Inner-medullary collecting duct

Term
What is mannitol used for? How/ where does it work?
Definition

Works in the proximal tubule by making the lumen/ fluid hypertonic -> less H2O reabsorption/ water remains in tubule -> excretion

Term
What is diamox used for? Where/How does it work?
Definition

Diamox is a diuretic used in the proximal tubule.

It inihbits the carbanic anhydrase -> eventual inhibition of flux -> more sodium in tubule -> increased excretion

Term
What are thiazides? Where/how do they work?
Definition

Thiazides are duiretics that work in the distal convoluted tubule by inhibiting Cl- transport (which is coupled in cotransporter to Na+)

*work at TSC1

Term
What are furosemide/ bumetanide? Where/how do they work?
Definition

Furosemide and bumetanide work in the thick ascending limb. They compete for with the Cl- on the 2Cl/Na/K cotransporter (BSC1)

 

These are considered K wasting (b/c potassium is excreted) and are not used on patients with heart conditions.

Term
Where/ how do ameloride and triamterene work?
Definition

-Works on the ENaC channel in the collecting duct.

-Inhibits Na reabsorption by binding to ENaC

-K sparing because it has little affect on K reabsorption

Term

What is an example of something that is not filtered?Filtered, secreted and excreted? filtered and reabsorbed? Filtered and completely excreted (no reabsorption)?

Definition

1. Erythrocytes, proteins

2. Penicillin

3. Glucose

4. Creatinine

Term
What is/are the major determinants of plasma osmolality?
Definition

Na+

Cl-, HCO3-

Term
Describe the tubular fluid osmolality along the nephron.
Definition

*No change in proximal tubule because H2O/Na reabsorbed iso-osmotically

*Sharp increase in TF/P in the descending loop of Henle then sharp decrease in the ascending

*Past here it depends on conditions of diuresis or antidiuresis

 Antiduiresis: Osmolality increases a lot as water is

  reabsorbed and solute is not

 Diuresis: Osmolality decreases as some solute is

   reabsorbed and water is not

 

Term
What is antidiuresis? Diuresis?
Definition

Anti: State of water conservation because of water restriction

 

Diuresis: Excess water -> excretion

Term
Is a lot or little water excreted when AVP is low?
Definition
Lots
Term
What stimulates ADH release from posterior pit?
Definition

Plasma osmolality and volume contraction

Term
What is the relationship between ADH levels, urine osmolality and total solute excreted?
Definition

Increased ADH -> less water excreted -> increased urine osmolality

 

*Total solute excreted is constant, osmolality changes because of changing water amounts

Term
How much change in blood volume or pressure is necessary to regulate ADH secretion?
Definition
5-10%
Term
How does change in vol/pressure --> changes in ADH secretion?
Definition

Baroreceptors on coratid sinus, aortic arch, left atrium, and pulmonary vessels detect Vol/P change

-->

Stimulation of afferent vagus and glossopharnygeal nerves

-->

Input relayed to supraoptic and paraventricular nuclei

-->

Secretion of ADH

Term
Mechanism for ADH action in collecting ducts
Definition

AVP binds V2 receptor ->

cAMP -> PKA ->
AQP2 insertion in apical membrane of epithelial cells

 

Term
Mechanism of water diuresis
Definition

1. Fluid leaving proximal tubule is iso-osmotic

2. Water is passively reabsorbed in the thin descending loop, no solute reabsorption

3. NaCl absorption in thin/thick ascending but no water

4. Distal tubule and collecting ducts impermeable to water w/o ADH therefore

5. Medullary CD actively absorbs NaCl

Term
What is Diabetes Insipidus?
Definition

Central: caused by trauma or pituitary surgery; decreased ADH production -> polyuria

 

Nephrogenic: Caused by mutations in V2 receptor or AQP2 gene; results in ADH resistance -> Polyuria

Term

True or false:

When sodium intake is increased it leads to an increase in body weight because of a delay between intake and increased excretion

Definition
True: There is a positive sodium balance for a few days
Term
Describe the basic feedback mechanisms for control of blood volume/ ECF
Definition

ΔIn blood Vol -> Δ in CO -> Δ in arterial pressure -> Δ in urinary output -> Δ in ECF vol -> Δ in blood vol

Term
ECF sensors
Definition

1. Vascular

    a. low pressure: cardiac atria & pulmonary vasc

    b. High pressure: carotid sinus, aortic arch,

       juxtaglomerular apparatus

2. CNS

3. Hepatic

Term
Intrarenal mechanisms for control of Na excretion
Definition

*Autoregulation of renal plasma flow

*Tubuloglomerular feedback (increase GFR -> increased solute in macula densa -> decrease in resistance)

* Glomerulotubular balance

Term
Glomerulotubular balance
Definition

Increase GFR -> increased filtered load -> increased NA and H2O reabsorption by proximal tubules

 

*Glom sends signal to tubules to Δ

**constant fraction of Na/H2O is reabsorbed from proximal tubule despite Δs in GFR

 

Term
Direct effects of pressure/vol on Na excretion
Definition

↑ arterial pressure -> ↑ renal perfusion pressure -> ↑ medullary blood flow -> ↓ medullary tonicity -> ↑ renal interstitial hydrostatic pressure -> ↓H2O absorption from TDLH of juxtamedullary nephrons -> ↓ [Na] delivered to TALH -> ↓ Na retention -> ↑ Na excretion

Term
Describe the Renin-Angiotensin system
Definition

1. Angiotensinogen is produced in the liver and is cleaved by renin (produced in the kidney)-->

2. Angiotensin I

3. Angiotensin I is converted to Angiotensin II

4. Angiotensin II acts in two places

    a. Leads to vasoconstriction

    b. Leads to production of aldosterone

        --> increased salt/ water retention

       --> increased BP

 

 

Term
What things decrease the secretion of renin?
Definition

1. Increased angiotensin

2. Increased ECF

3. Increasd Systemic arterial pressure

4. Increased TPR/ vasoconstriction

5. Increased aldosterone

6. Increased Na retention

7. Increased GFR/ decreased proximal reabs. of Na

8. Change in sodium at macula densa

Term
What is the mechanism of Angiotensin II-mediated increase in proximal tubule reabsorption?
Definition
Term
Action of angiotensin II
Definition

Renal

-Increase Na reabsorp in proximal tubules thru direct effect ( ) and through increased filtration fraction (via increased plasma oncotic P to favor reabsorption)

-Increase sensivity of tubuloglomerular feedback

-Decreased renin secretion

-Decrease medullary blood flow

 

Extrarenal

-Arteriolar vasoconstriction

-Increase aldosterone

-Increase ADH secretion

-Increase thirst

Term
What are the two most important factors leading to aldosterone secretion?
Definition

1. Increase in [angiotensin II]

2. Increase in plasma [K]

3.

Term
Cellular mechanism of aldosterone action
Definition

Aldosterone binds receptor in cytosol -->

goes to nucleas --> change in gene expression

--> increase in expression/activity of ENaC and in Na/K ATPase

*Increased Na reabsorption

**Ramps up system

Term
Time course of aldosterone action
Definition

Latent pahse: 1/2 hr before response

Early phase: Increase in proteins that increase the activity of ENaC

Late phase: Increase in ENaC/ NaATPase  gene expression

Term
Atrial Natiuretic Peptide
Definition

1. Secreted in response to increase in blood pressure and ECF volume

2. Decreases blood pressure by decreasing TPR and enhancing NaCl and H2O secretion

3. Inhibits NaCl reabsorption by medullary portion of collecting duct

4. Inhibits ADH stimulated water reabsorption in collecting ducts

5. Inhibits ADH secretion from posterior pituitary

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