Renal Physiology Module 13.2 Questions Spring 2010

Front 1

Case: 15 year old cat, depressed, anorexic, weight loss. PU/PD, vomiting.

Exam: dehydrated, Pale MM, small kidneys, PCV 22%, Creatinine increased, BUN increased, specific gravity is 1.012.

Most likely diagnosis?

Back 1

Chronic renal failure.

Elevated blood levels indicates reduced GFR, urine is not concentrated, anemia is due to decrease in erythropoietin production by kidneys--all indicate renal failure.

Front 2

What is the relationship between GFR (Glomerular Filtration Rate) and levels of plasma creatinine?

Back 2

As GFR increases, plasma levels of creatinine decrease due to increased filtration.

Front 3

The glomerulus produces a filtered fluid that is very similar to what?

Back 3

Plasma.

Front 4

The _____ is the rate of glomerular filtration and this value is used clinically to assess renal function.

Back 4

Glomerular Filtration Rate (GFR)

Front 5

What units is GFR expressed as?

Back 5

mL/min/kg.

Front 6

What is the normal range of GFR in the dog?

Back 6

2.15-4.95 ml/min/kg with an average at about 3.55 ml/min/kg.

Front 7

What are the three layers of the filtration barrier?

Back 7

Capillary Endothelium

Basement Membrane

Visceral Epithelium.

Front 8

The capillaries of the glomerulus are covered by epithelial cells, called ____ which form the visceral layer of Bowman's capsule. The visceral cells are reflected at the vascular pole to form the parietal layer of Bowman's capsule. The space between the visceral and parietal layer is called ______, which at the urinary pole of the glomerulus becomes the lumen of the proximal tubule.

Back 8

Podocytes, Bowman's Space.

Front 9

The _____ is an acellular structure composed of various glycoproteins.

Back 9

Glomerular basement membrane.

Front 10

What three things determine the glomerular filtration rate?

Back 10

Mean net filtration pressure.

Permeability of the filtration barrier.

Area available for filtration.

Front 11

The forces favoring filtration across the glomerular capillary wall are:

Back 11

Hydrostatic pressure of the blood

Oncotic pressure of the fluid in the Bowman's space (= 0 )

Front 12

The forces opposing filration across the glomerular capillary wall are:

Back 12

Capillary oncotic pressure.

The hydrostatic pressure in the Bowman's space.

Front 13

As filtration proceeds along the length of the capillary, the plasma oncotic pressure increases significantly. What is the net result of this?

Back 13

Filtration pressure will decrease along the capillary bed.

Front 14

GFR = _____ x _______

Back 14

GFR = Pf x Kf

Kf is the product of the intrinsic permeability of the glomerular capillary and the glomerular surface area available for filtration.

Front 15

What are three ways to physiologically alter Pgc and thus, GFR?

Pgc (Pressure of glomerular capillary)

Back 15

Changes in afferent arteriole resistance (Decrease R and increase Pgc and GFR)

Changes in efferent arteriolar resistance (Decrease R and Decreased Pgc and GFR)

Changes in renal arteriolar pressure (Increase BP will increase Pgc and enhance GFR)

Front 16

Glomerular filtration barrier restricts filtration of molecules based on size and charge. What will happen to the following sizes of molecules?

Neutral molecule with a radius of less than 2.0 nm (20 A)

Molecules with a radius greater than 4.2 nm (42 A)

Molecules between 2.0-4.2 nm (20-42 A)

Back 16

Neutral <20 A: Freely filtered

Molecules >42 A: NOT filtered

Molecules 20 < X < 42 A: Filtered to various degrees.

Front 17

How does net electrical charge effect whether or not a molecule is filtered?

Back 17

Negative charged glycoprotein residues are incorporated into the glomerular basement membranes and coat the endothelial and epithelial cells.

The negative charges of the basement membrane then repel negatively charged plasma proteins, decreasing their filtration.

Front 18

What happens if a glomerular disease causes the negative charge on the filtration barrier to be lost?

Back 18

The filtration of proteins is increased and they appear in the urine (proteinuria)

Front 19

Name some factors that affect GFR.

Back 19

Changes in renal blood flow.

Changes in glomerular capillary hydrostatic pressure (systemic blood pressure changes or afferent/efferent arteriolar constriction)

Changes in hydrostatic pressure in Bowman's capsule (ureteral obstruction, edema of kidney inside tight renal capsules)

Changes in concentration of plasma proteins (dehydration, hypoproteinemia, etc)

Changes in Kf (changes in glomerular capillary permeability, changes in effective filtration surface area)

Front 20

As flow rate increases, oncotic pressure in the capillary increases less rapidly, and _____ (more/less) filtrate is formed before the capillary oncotic pressure rises sufficiently to stop filtration.

Back 20

More!

Front 21

If plasma flow rate decreases, oncotic presure in the capillary increases more rapidly, and ____ (more/less) filtrate is formed before the capillary oncotic pressure rises sufficiently to stop filtration.

Back 21

Less!

Front 22

Filtration pressure (Pf) = Pgc - (_________ )

Back 22

Pf = Pgc - (PIgc + Pb)

PIgc = colloid osmotic pressure

Pb= Bowman's capsule pressure?

Pgc= Pressure glomerular capillary

Front 23

___ is decreased by contraction of the mesangial cells, which reduces the area available for filtration.

Back 23

Kf.

Front 24

What are some things mesangial cells do?

Back 24

Provide structural support for glomerular capillaries.

Secrete extracellular matrix.

Exhibit phagocytic activity.

Secrete prostaglandins.

Front 25

Name the three most common agents/drugs that affect mesangial cells. (One increases contraction, the other two manage relaxation)

Back 25

Contraction: Angiotensin II

Relaxation: Dopamin, PGE2

Other Contractors: Endothelins, ADH, NE, Platelet-activating factor, Platelet-derived growth factor, Thromboxane A2, PGF2, Leukotrienes C and D, Histamine.

Other Relaxors: ANP, cAMP.

Front 26

True or False:

Despite changes in systemic blood pressure and RBF, the kidney usually maintains GFR at a constant level.

Back 26

True!

Front 27

What are some ways the kidney can maintain a constant GFR despite other systemic changes?

Back 27

Altering systemic blood pressure.

Altering intravascular blood volume.

(These two are done by the renin-angiotensin-aldosterone system)

Intrinsic control mechanisms mediated by systems controlling resistance to flow in afferent and efferent arterioles.

Front 28

Angiotensinogen + Renin --> Angiotensin I + _____________ --> Angiotensin II ---> ____ and ____.

Back 28

ACE (Angiotensin Converting Enzyme)

Vasoconstriction and Aldosterone Release.

Front 29

Vasoconstriction leads to _____.

Aldosterone release leads to ____.

Back 29

Vaso --> Increased blood pressure ---> Increased renal perfusion

Aldosterone ---> Increased Na and H2O retention ---> Increased extracellular volume ----> Increased blood pressure ---> Increased renal perfusion.

Front 30

____ Renal perfusion leads to an increase in renin production to stimulate the Angiotension cascade.

Back 30

Decreased renal perfusion.

Front 31

What is the phenomenon where RBF and GFR are maintained at a constant rate?

Back 31

Autoregulation.

Front 32

What does RBF stand for?

Back 32

Renal blood flow.

Front 33

Autoregulatino of RBF and GFR are largely due to changes in _______.

Back 33

Resistance of the afferent arteriole.

Increase resistance leads to leveling of GFR and RBF. It takes a LARGE decrease in Vascular resistance before GFR and RBF are majorly affected.

Front 34

What are the two reflexes in the kidney itself that affect autoregulation of flow?

Back 34

Myogenic reflex (Responds to arterial pressure changes--related to intrinsic tendence of vascular smooth muscle to contract when stretched)

Tubuloglomerular Feedback (Responds to changes in tubular flow rate)

Front 35

Describe the tubuloglomerular feedback mechanism.

Back 35

Increased GFR --> Increased NaCL delivery to Loop of Henle ---> Sensed by macula densa and converted into a signal --> increases resistance of the afferent arteriole ---> decreases GFR

Front 36

True or False:

Autoregulation is present at arterial pressures less than 99 mmHg and above 180 mmHg.

Back 36

False!

Autoregulation is present only when arterial pressure is between 90-160 mmHG

Front 37

True or False:

Despite autoregulation, GFR and RBF can be changed under appropriate conditions by several hormones.

Back 37

True!

Front 38

Name three hormones that cause vasoconstriction, increase vascular resistance and thus decrease RBF and GFR.

Back 38

Epinephrine.

Norepinephrine.

Angiotension II

Front 39

Name two hormones that cause vasodilation, decrease vascular resistance and thus increase RBF (but have NO change on GFR).

Back 39

PGE2.

PGI2.

(The above two have NO change on GFR)

(Others: NO and Bradykinin-These INCREASE GFR)

Front 40

___ Enhances water reabsorption by the kidney and increases blood volume, thus increasing blood pressure.

Back 40

ADH/Vasopressin

Front 41

____ and ____ increase blood volume, increase GFR and inhibit the actions of ADH/Vasopressin.

Back 41

Glucocorticoids and Progesterone.

Front 42

___ stimulation activates the renin-angiotensin system (causing vasoconstriction of the afferent and efferent arterioles and decreasing RBF).

Back 42

Beta-adrenergic stimulation.

Front 43

Which is more sensitive to Angiotensin II? The efferent or the afferent arteriole?

Back 43

The efferent arteriole.

Low concentrations of An II can cause predominate efferent arteriole constriction. High levels constrict both efferents and afferents, thus lowering RBF and GFR.

Front 44

_____ stimluation causes renal vasoconstriction. (Afferents and efferent arterioles are innervated by sympathetic neurons that release NE, decreasing RBF and GFR).

Back 44

Alpha-adrenergic stimulation.

Front 45

True or False:

Vasoconstrictors cause relaxation of mesangial cells within the glomerulus, increasing the area available for filtration.

Back 45

False!

They cause contraction of mesangial cells, thus DECREASING area available for filtration.

Front 46

Why are prostaglandins important in dampening the effects of vasoconstrictors like An II and sympathetic stimulation?

Back 46

Limits the decrease in RBF and GFR preventing severe and potentially harmful renal vasoconstriction.

Front 47

The amount of substance in urine reflects the coordinated action of the nephron's various segments, and represents these 3 general processes:

Back 47

Glomerular filtration.

Reabsorption of the substance from the tubular fluid back into the blood

Secretion of the substance from the blood into the tubular fluid.

Front 48

Amount Excreted = ____ - _____ + ____.

Back 48

Amount Excreted = Amount filtered - Amount reabsorbed + Amount secreted.

Front 49

What is clearance?

Back 49

The rate at which plasma is cleared of a substance.

Front 50

How is clearance determined?

Back 50

Rate of elimination in the urine divided by the plasma concentration of that substance.

Cx = [Ux]V / [Px]

Cx= Volume of plasma cleared of substance X per unit time.

Ux = Urine concentration of substance X

V = Volume of urine collected divided by the time period of collection

Px= Plasma concentration of substance x.

Front 51

When would the clearance rate of Substance X equal the GFR?

Back 51

When the substance is only filtered out and does not undergo secretion of reabsorption.

Front 52

What characteristics make a substance suitable for measuring GFR?

Back 52

Freely filtered.

Not reabsorbed or secreted by tubules.

Not metabolized.

Not stored in kidneys.

Not toxic.

No effect on filtration rate.

Preferably easy to measure in plasma and urine.

Front 53

What substance is the GOLD STANDARD for determining GFR?

Back 53

Inulin!

Front 54

CLINICALLY, what is the mostly widely used substance used to measure GFR?

Back 54

Endogenous creatinine.

Front 55

How much of excreted creatinine is secreted into the tubule?

Back 55

10%

Front 56

Glucose is a substance that is filtered and undergoes tubular reabsorption. The amount of glucose filtered is called the ____.

Back 56

Filtered load.

Front 57

The amount of glucose reabsorbed has a maximum transport rate called _____.

Back 57

The tubular transport maximum (Tm)

Front 58

The plasma glucose concentration at which glucose first appears in the urine is called ____ .

Back 58

The plasma threshold.

Front 59

Another substance that is filtered and undergoes tubular secretion is ____.

Back 59

PAH.(para-aminohippurate)

Front 60

True or False:

PAH is produced by the body, and thus does not need to be infused before measuring values.

Back 60

False!

PAH is NOT produced by the body, so must be infused!

(It is however, excreted into the urine by glomerular filtration and tubular secretion of the proximal tubules)

Front 61

What is the human Tm (Transport maximum) of PAH? (para-aminohippurate)

Back 61

80 mg/min.

Front 62

PAH clearance can be used to estimate GFR and ____ .

Back 62

RBF (Renal Blood Flow) or RPF (Renal plasma flow)

Front 63

How do you convert RPF (Renal plasma flow) to RBF? (Renal blood flow)

Back 63

RBF = RPF/ 1- HCT

HCT = Hematocrit/PCV

Front 64

___ is the basis for determining GFR and RBF.

Back 64

Renal clearance.

Front 65

The rate at which a substance is excreted into the urine is proportional to ____.

Back 65

The Plasma concentration of the substance. (IE more excretion = lower plasma concentration)

Front 66

What makes inulin so nice for measuring GFR?

Back 66

The amount excreted in the urine per minute equals the amount of inulin filtered at the glomerulus each minute.

(This is because it is not reabsorbed by the kidneys)

Front 67

What is the normal filtration fraction of plasma in the glomerulus? (The filtration fraction is how much is filtered by the glomerulus alone)

Back 67

0.15- 0.20 (15-20% of plasma that enters glomerulus is actually filtered.)