Integrative Physiology: Renal

In cortical nephrons, blood passes into what structure after leaving the efferent arteriole? A. Afferent arteriole B. Glomerulus C. Renal artery D. Renal vein E. Peritubular capillaries F. Vasa recta

E. Peritubular capillaries

True or false when you are actively voiding urine both the muscarinic and nicotinic receptors are activated?

False, muscarinic receptors are activated, but the nicotinic receptors are not

Combination of myogenic response and tubuloglomerular feedback is what keeps what constant?

GFR

Sympathetic activity at the afferent arteriole causes?

It causes GFR to go down from constriction of afferent arteriole

Thick portion of Ascending Limb Na/K/2Cl- transporter (NKCC2), potassium is involved in this transport into the thick ascending limb and where does most of it travel?

Most of it travels back into the filtrate to create a positive charge in the urine

Pathology -With Nephrotic Syndrome is there much change in the disease with children?

No its minimal

Tubular reabsorption in the proximal tubule: Where are hydrogen ions pumped?

Outside the proximal tubule

most important factor affecting GFR...?

Renal plasma flow

Tubular reabsorption in the proximal tubule: Filtrate Reabsorption on the luminal side?

Sodium (Na+) is coupled with the cotransport of glucose, amino acids, and phosphate lactate or citrate into the proximal tubule

A 23-year-old woman comes to the physician because of acute onset of cloudy urine and back pain. Laboratory studies show increases in both renal plasma flow and GFR. Which of the following is the most likely underlying cause of the increases in these two values? a)Constriction of afferent arteriole b)Constriction of efferent arteriole c)Dilation of afferent arteriole d)Dilatation of efferent arteriole e)Stenosis of the renal arteries f)Stenosis of the renal veins

a) Dilation of afferent arteriole

A patient is taking blood pressure medication that inhibits sympathetic activity. Which of the following urinary functions might also be affected by this drug? A.Relaxation of the external urethral sphincter B. Relaxation of the detrusor muscle C. Contraction of the detrusor muscle D. Contraction of the external urethral sphincter E. Activity involving muscarinic receptors F. Activity involving nicotinic receptors

B. Relaxation of the detrusor muscle

Order of the Vascular system in the urinary system?

1. afferent arteriole (brings blood to the glomerulus), 2. glomerulus capillary, 3. efferent arteriole (carries blood out of the glomerulus), 4. peritubular capillaries, 5. vasa recta

GFR is held constant over time (autoregulation), but can change depending on...?

Body needs

Urine production in a single day?

1.0-1.5 L/day; range 0.5-15 L/day.

Mechanism of tubuloglomerular feedback (TGF)? (5 steps)

1.An increase in arterial pressure leads to increases in glomerular capillary pressure, RBF (renal blood flow), and GFR. 2.Increased GFR leads to an increased delivery of Na+, Cl− to the macula densa cells of the JGA. 3.These cells contains many different salt transporters and as they reabsorb NaCl they release paracrine agents, particularly adenosine and ATP, which breaks down to adenosine. 4.Adenosine, binding to A1 adenosine receptors on the smooth-muscle cells, triggers contraction of nearby vascular smooth-muscle cells in the afferent arteriole. 5.Increased afferent arteriolar resistance decreases GFR, counteracting the initial increase in GFR, returning GFR to normal.

What are the four steps of micturition?

1.Bladder filling is due to relaxation caused by sympathetic activity. 2.Urine accumulation in bladder stimulates stretch receptors 3.Stimulated stretch receptors trigger a parasympathetic reflex in which acetylcholine binds to muscarinic (M) receptors that causes the smooth muscle in bladder wall to contract; internal sphincter opens and bladder contracts 4.However, urine is only expelled if we voluntarily relax the external sphincter via activity of somatic motor system. This sphincter contracts when acetylcholine binds to nicotinic (N) receptors.

Glomerular Permeability and Pressure: Why is there a high rate of ultrafiltration? What is important to note about the size of the efferent and afferent arteriole that contributes to the high rate of ultrafiltration?

1.Fenestrations-pores in capillary wall 2.Glomerular blood pressure higher than that found in other beds 3.Blood pressure does not fall across the glomerulus 4.Important to note that size of afferent and efferent arteriole can be regulated, which in turn regulates glomerular pressure which in turn impacts GFR

Loop of Henle Summary (first three steps)?

1.Filtrate enters the loop of Henle isotonic (300 mOsm) 2.Descending limb permeable to water, not salt and it continues in this fashion down this limb. Water drawn out of descending limb by vertical osmotic gradient (15 % reabsorbed into vasa recta) 3.At the tip of loop filtrate is hypertonic (1200 mOsm)

What is an example of the various filtration forces that determine the net filtration pressure or NFP? (NFP=10 mm Hg)

1.Glomerular Blood Pressure= 55 mm Hg 2.Plasma Colloid Osmotic Pressure= 30 mm Hg; exists because of plasma proteins 3.Bowman's Capsule Hydrostatic Pressure= 15 mm Hg; fluid accumulates in capsule and forces fluid back into glomerulus **Net filtration pressure (NFP) differences in the forces; NFP= 55-30-15= 10 mm Hg

What are the five general structures of the kidney?

1.Kidneys supplied by single renal artery & vein 2.Body roughly divided into cortex and medulla 3.Human kidneys are partially segmented with the medulla consisting of pyramids 4.The urine is collected by minor and major calices; drains into pelvis and to ureter 5.Abundant sympathetic innervation of vasculature and tubules

Glomerular Filtration: Three physical forces involved in filtration; first two are same forces we discussed in terms of bulk flow across any capillary bed?

1.glomerular capillary blood pressure 2.plasma-colloid osmotic pressure 3.Bowman's capsule hydrostatic pressure is an additional force to consider

How much plasma enters that glomerulus is filtered?

20-25% of the plasma that enters the glomerulus is filtered.

Loop of Henle Summary (last three steps)?

4. Ascending limb permeable to salt not water. Salt diffuses out of thin ascending limb and actively transported out of thick ascending limb (upper portion of the ascending limb) 5.Some of the salt is reabsorbed into the plasma of the vasa recta. Some of this salt remains in the interstitial space to contribute to the vertical osmotic gradient (25%). 6.Filtrate leaves loop of Henle hypotonic (100 mOsm)

Glucose Reabsorption Kinetics: Transport maximum?

400 mg/min

A decrease in which factor will produce the largest increase in net filtration pressure across the glomerulus? a)Efferent arteriole resistance b)Glomerular renal blood flow c)Glomerular renal plasma flow d)Afferent arteriole resistance

a)Afferent arteriole resistance

The graph shows three relationships as a function of plasma glucose. Curves X and Z are superimposed because: a)Reabsorption and excretion of glucose are equal b)Filtered load of glucose is equal to the amount reabsorbed c)Renal threshold for glucose has been exceeded d)Glucose cotransport has been inhibited e)Glucose clearance is equal to GFR

a)Filtered load of glucose is equal to the amount reabsorbed (once the threshold for reabsorption is passed the rest is excreted in the blood causing the Z line to plateau

GFR Fluctuations Important concepts: Changes in GFR affect sodium excretion and total body sodium content affect...?

affects ECF volume and MAP

Glucose Reabsorption in PT: Glucose co-transported with sodium at what membrane?

apical membrane

A new drug is being developed to treat a form of diabetes. The goal of this medication is to lower blood glucose levels by increasing glucose excretion in the urine. Which of the following is the likely action of this drug? a)Stimulates the Na/K pump in the late distal tubules b)Blocks the SGLT transporter in the proximal tubules c)Stimulates the GLUT transporter in the proximal tubules d)Increase the plasma renal threshold for glucose transport e)Decrease the filtered load of glucose

b)Blocks the SGLT (sodium glucose linked transporters) transporter in the proximal tubules

Due to acute changes in GFR, salt delivery to the distal tubule is increased. Which of the following is consistent with this circumstance? a)The acute condition resulted in a decreased GFR b)The compensatory action by the kidney will be afferent arteriole constriction and decreased glomerular pressure c)The compensatory action by the kidney will be afferent arteriole constriction and increased glomerular pressure d)The acute condition is likely renal artery stenosis

b)The compensatory action by the kidney will be afferent arteriole constriction and decreased glomerular pressure

At plasma concentrations of glucose higher than its Tm (transport maximum): a)excretion rate of glucose equals the filtration rate b)glucose is found in the blood and urine c)reabsorption rate of glucose equals the filtration rate d)renal vein and renal artery blood glucose levels are equal

b)glucose is found in the blood and urine (glucose is not normally found in the urine, but transport maximum for reabsorption has been reached so some of it is released into the blood)

Why is the loop of henle called the counter current system?

because the fluid goes down one side and up the other side in the loop of henle

Both autoregulation control and sympathetic control glomerular blood flow by..

by regulating the radius of the afferent arteriole.

What is the Ureter

carries urine into bladder from kidney

Both types of nephrons drain into?

common collecting ducts.

GFR Fluctuations Important concepts: Changes in urine output (what is it controlled at and what does it affect?

controlled at tubule by the hormone ADH; this affects ECF osmolarity and ICF volume

The remaining 1.5 liters left of the plasma is?

excreted as urine.

In glomerulus hydrostatic pressure > osmotic pressure this process is known as?

filtration

Nephron

functional unit of kidney consists of filtering glomerulus and tubule system surrounded by capillaries

Juxtamedullary nephrons?

have long Loops of Henle, surrounded by vasa recta and contribute electrolytes to the vertical osmotic gradient which we will see later, is important for water conservation.

Superficial (cortical) nephrons?

have short Loops of Henle, surrounded by peritubular capillaries

Urine is temporarily stored in...? and emptied by?

in the bladder and emptied by micturition.

Glomerular Filtration is the first step in?

in the process of making urine

Control of GFR: sympathetic control?

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

Tubular secretion: Urine excretion is?

is the elimination of substances from the body in the urine.

Loop of henle and collecting ducts are important for...?

loop of Henle and collecting ducts are important in water conservation (it allows your body to be able to conserve water downstream in this system because of creating a hypotonic environment in the urine)

What happens to GFR when Bowman's capsule hydrostatic force goes up to 20 mm Hg? What is a specific example where this number increases?

lower net filtration pressure ultimately leading to a lower GFR -example: kidney causes urine to backup which leads to bowmans capsule hydrostatic force to increase

During micturition what neurotransmitter does the sympathetic nervous system release on the smooth muscle within the bladder?

norepinephrine

Normal human physiology is on

on the water-conserving side of urine production

Glomerular Exchange Pathway results in?

protein-free filtrate containing water, electrolytes, nutrients and wastes

In peritubular capillaries osmotic pressure > hydrostatic pressure this process is known as?

reabsorption

Blood is filtered creating a fluid known as?

renal filtrate

Area of the kidney that is most important for water conservation?

renal medulla (long loop of henle goes through this section) and ADH (hormone helps conserve water; levels of ADH increase when your dehydrated)

The external sphincter is?

skeletal muscle and its voluntary -allowed to you to hold onto urine until you allow it to void from the bladder

Bladder wall-detrusor muscle is?

smooth muscle

The internal sphincter?

smooth muscle, involuntary

Tubuloglomerular feedback (TGF) to further autoregulate GFR: As GFR changes, what happens to the amount of sodium delivered to cells in the distal tubule

so does the amount of sodium that is delivered to cells in the distal tubule; these cells monitor sodium levels as a reflection of GFR

tubular reabsorption in the proximal tubule: Sodium (Na+) that is pumped into the cell involved with cotransport is pumped out of the cell by...? What side does this occur on?

sodium-potassium pump to maintain sodium levels (important because it allows the molecules to absorbed into the proximal tubule by cotransport) -basolateral side or side that the blood is on

Tubular secretion provides additional route for?

substances to enter the renal tubules from the blood.

What do the peritubular capillaries allow for?

tiny blood vessels that travel alongside nephrons allowing reabsorption and secretion between blood and the inner lumen of the nephron

Urine move from

ureters to the urinary bladder my peristalsis.

The filtrate passes through what?

various regions of the tubule.

GFR does not really affect how much urine we produce, but affects?

what's in the urine (electrolytes and wastes)

Dilating afferent and/or constricting efferent arteriole will cause?

will lead to elevated GFR due to elevated glomerular pressure.

Glucose Reabsorption Kinetics: Plasma threshold?

• for glucose; approx 200 mg/dL. (once this number is surpassed the glucose in the plasma that gets filtered will be excreted in the urine)

Glomerulur filtration involves specialized capillary exchange but?

• general rules of bulk flow across capillary bed apply.

Urea Reabsorption-PT: What is urea?

• is a waste product from protein degradation. (helps get rid of nitrogenous waste)

On average, of the 180 liters of plasma filtered per day, how many liters are reabsorbed?

•178.5 liters are reabsorbed.

Proximal Tubule Overview: Reabsorption big picture: What are the first three things that are absorbed here?

•67% of filtered Na+ reabsorbed. •67% of the filtered water reabsorbed. The tight coupling between Na and water reabsorption is called isosmotic reabsorption. This bulk reabsorption of Na and water is critically important for maintaining ECF volume. •Approximately 67% of other electrolytes (Cl-, etc.)

Glucose Reabsorption Kinetics: Normal plasma glucose?

•70-140 mg/dL

Last five kidney functions?

•Eliminating wastes of bodily metabolism, especially urea. •Excreting foreign compounds. •Producing erythropoietin. •Producing renin. •Converting vitamin D into its active form

•Glomerulur filtration: Greater rate of exchange compared to other capillaries because?

•Higher permeability •Higher capillary hydrostatic pressure •BP constant across glomerulus

First five kidney functions?

•Maintain H2O balance in the body. •Maintain proper osmolarity of body fluids •Regulate the quantity and concentration of most ECF ions. •Maintain proper plasma volume. •Help maintain proper acid-base balance.

Organic Ion Secretion-PT (proximal tubule): How is organic ion secretion done in the proximal tubule?

•Proximal tubule contains 2 distinct carriers for secreting organic ions, one for organic anions and one for organic cations in the urine (drug metabolites). Most important function of these systems is to secrete foreign organic substances.

What does the filtrate look like Bowman's space? (4)

•Reflects composition of plasma (if the concentration of something in the blood is 10 units than the concentration of it in bowmans space is the same) •Contains same solutes and concentrations as plasma except for proteins •Includes water, nutrients, electrolytes and wastes •300 mOsm •Most of the solutes and water are reabsorbed in the proximal tubules

Organic Ion Secretion-PT (proximal tubule): Secretion of these organic substances is supplement to what?

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

Autoregulation- Myogenic Control

•Smooth muscle of afferent arteriole responds to changes in pressure •When stretched (increased pressure) vessel constricts to decrease flow and maintain GFR •Opposite occurs when pressure falls, muscle relaxes to increase flow

Autoregulation- Myogenic Control (is this enough to maintain GFR)?

•This itself is not enough to maintain GFR, so the kidney also uses tubuloglomerular feedback (TGF) to further autoregulate GFR

Micturition involves?

•bladder contraction and opening of both the internal and external urethral sphincters.

Micturition reflex causes?

•involuntary emptying of the bladder after the filling phase.

What is GFR stand for?

•is the glomerular filtration rate (ml/min) -measure of how well your glomerulus is filtering fluid

glomerulur filtration: Net filtration pressure?

•is the net difference in the three physical forces involved in filtration that favors filtration.

Tubular reabsorption is? What are examples of what gets absorbed during tubular reabsorption

•is the selective transfer of specific substances in the filtrate back into the blood of the peritubular capillaries. -Reabsorption rates vary for different substances. -glucose, sodium, amino acids, water, and anything else that your body does not want to get rid of

Tubular secretion is?

•is the selective transfer of substances from the peritubular capillary blood into the tubular lumen. -Process is opposite of reabsorption

Filtering Membrane: Glomerular basement membrane?

•made up of a matrix of extracellular negatively charged proteins and other compounds

Control of GFR: Autoregulation?

•prevents spontaneous GFR changes; kidney regulates itself via intrinsic controls that keeps GFR constant. (can control this by controlling diameter of afferent and efferent arteriole)

Filtrate is modified by?

•reabsorption and secretion and what's left behind in the tubules is excreted as urine

Where does filtration occur?

•specialized capillary beds in the kidney called the glomerulus.

Filtering Membrane: Capillary endothelial wall with fenestrations?

•that have a magnitude greater than proteins; in addition, the wall is covered with negatively charged compounds

Urea Reabsorption-P: How is the crude assessment of kidney function measured?

•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 (from increase in levels of urea in the blood)

The bladder can accommodate

•up to 250 to 400 ml of urine before stretch receptors initiate the micturition reflex that causes the individual to urinate

Pathology - Nephrotic Syndrome

-there is marked disruption of the filtering membrane; results in loss of negative charges from filtration barrier (diabetics can have this condition) -Plasma proteins now pass through the membrane and are eliminated in urine (can lose 4-5 over a 24 hour period) -Associated with a non-inflammatory injury to glomerular membrane system •"O" nephrOtic and prOtein loss

What are the tubular components of the urinary system (whats the order)?

1. Bowman's Capsule 2. Proximal Tubules 3. Loop of Henle 4. Distal Tubules 5. Collecting ducts

Filtering Membrane: The membrane of the glomerulus consists of 3 main structures, what are they?

1. Capillary endothelial wall with fenestrations, 2. Glomerular basement membrane, 3. Epithelial cell layer of podocytes *all of these are designed to prevent protein from leaving the blood

How many nephrons are in the kidney?

About 1 million nephrons per kidney (±200,000)

Micturition can be voluntarily prevented by??

deliberately tightening the external sphincter and pelvic diaphragm.

Proximal Tubule Overview: Reabsorption big picture: What are the first last three things that are absorbed here?

-100% of nutrients reabsorbed (like glucose; if it is not reabsorbed here it is excreted as urine which this issue is commonly found in diabetics) 80% of filtered -HCO3- is reabsorbed here (100% is reabsorbed in the kidney overall), the other 20% in other nephron segments. -50% of the urea (waste product) is reabsorbed here

Urea Reabsorption-P: How does urea get reabsorbed? What is important to know about this process?

-As water is reabsorbed the urea concentration within the tubular fluid increases. -A concentration gradient is created for urea to passively be reabsorbed. **50% of the filtered urea is reabsorbed this way.

Nephrotic Syndrome: Signs, what are the most common clinical signs?

-Marked proteinuria > 3.5 gm/day -Edema (loss of plasma osmotic pressure) -Hypoalbuminemia (albumin lost in urine) -Hyperlipidemia (high levels of fat in blood)

Organic Ion Secretion-PT (proximal tubule): How are the organic ions secreted in the proximal tubule converted in order to be secreted at this part of the renal tubule into the urine?

-The liver can convert many foreign substances to an anionic metabolite, which its rate of secretion and elimination from the body by the organic anion secretory pathway in the kidneys.

vasodilation vs vasoconstriction in the afferrent arteriole?

-decreases blood flow into the glomerulus -increases blood flow into the glomerulus

On average, 100-125 ml of glomerular filtrate is formed each minute, what is this known as? how much does this amount to each day?

-glomerular filtration rate or GFR. -This amounts to 180 liters each day.

Glomerular Filtration?

-is the formation of protein-free plasma as blood flows through the glomerulus.

Loop diuretics (Lasix/ Furosemide): what does this drug block in the kidney tubule to help get rid of pulmonary edema? However what is lost from the action of this drug?

-loop diuretics inhibit NK transporters in the thick ascending loop of henle -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 (most important electrolyte lost here is potassium so people on these drugs may need to take potassium supplements)

What is the vertical osmotic gradient?

-measure of the interstial fluid osmolarity in the kidney -in the cortex its 300 mOsm, but as you go into the medulla it becomes more concentrated and it reaches 1200 mOsm -it is created by the nephrons

Filtering Membrane: Epithelial cell layer of podocytes?

-next to Bowman's space; the podocytes have foot processes bridged by filtration slit diaphragms

In the Glucose Reabsorption Kinetics graph what does "N" represent?

-normal plasma glucose; all filtered glucose is reabsorbed; red (represents reabsorption) and orange (filtered load) lines superimposed; green (excretion) line is zero

The kidney has potent auto-regulatory ability. Renal blood flow remains...? GFR is auto-regulated over a similar range.

-relatively constant from about 80 to almost 200 mmHg -Yes

In the Glucose Reabsorption Kinetics graph what does "T" represent?

-renal threshold for glucose; blood glucose levels so high that transporters are saturated. Not all filtered glucose can be reabsorbed (red and orange lines moving apart showing that not all the glucose being filtered is being reabsorbed and instead its excreted) glucose that is not reabsorbed appears in urine (green line is increasing)

Glucose Reabsorption in PT: What is the major mechanism for glucose entry into the cell? What then happens to glucose in the PT? What is the second process called?

-sodium glucose linked transporter (SGLT) through facilitated diffusion -Glucose is then concentrated inside the PT and moves outward through the basolateral membrane via GLUT2 transporter down its , which does not rely on Na+. Na+ moves out of basolateral side via Na-K pump. Energy from pump drives the entire process, so glucose transport considered secondary active transport (transport of glucose is secondary to the active transport of glucose

Dilating the afferent arteriole causes what to the glomerulus?

The glomerular blood pressure will increase

Thick portion of Ascending Limb: What is the Na/K/2Cl- transporter (NKCC2) role at this part of the renal tubule and what happens here?

This is an electroneutral transport resulting in the reabsorption of about 25% of the filtered sodium, chloride, and potassium. Then sodium crosses the limb to the other side to be transported out by a sodium potassium pump into the blood. Potassium either flows into the blood with calcium (already present in the thick ascending limb) or Back flow of K+ into filtrate, produces a positive net voltage in the urine and results in paracellular reabsorption of calcium and magnesium.

In the thick ascending loop of Henle, the tubular fluid undergoes which of the following changes? a)Decreased volume and decreased osmolarity b)Decreased volume and increased osmolarity c)No change of volume with decreased osmolarity d)No change of volume with increased osmolarity e)Increased volume and decreased osmolarity f)Increased volume and increased osmolarity

c)No change of volume with decreased osmolarity

An investigator collects urine from a subject who has been on a very low sodium diet and finds that the person is excreting urine with low osmolalities as well as low sodium concentrations. The investigator tests the graduate student's knowledge of renal physiology by asking, "In which part of the nephron does the renal tubular fluid first become hyposmotic to plasma?" a)Proximal tubule b)Thin descending limb of the loop of Henle c)Thick ascending limb of the loop of Henle d)Distal tubule Collecting tubule

c)Thick ascending limb of the loop of Henle