Intro to Renal

Question 1

What are the functions of the kidney?

Answer 1

1) Excretion
2) Regulation (volume and composition of body fluids)
3) Endocrine (renin, erythropoietin, precursor to Vitamin D)

Question 2

Segments of the nephron

Answer 2

Glomerulus

Proximal tubule

Thin descending loop of Henle

Thin ascending loop of Henle

Thick ascending loop of Henle

Macula densa (part of thick ascending loop of Henle and part of JGA)

Early distal tubule

Cortical collecting tubule

Medullary collecting duct (many nephrons can share same collecting duct!)

Question 3

Two types of nephrons

Answer 3

Cortical nephrons (80-85%; glomerulus in outer cortex and short loop of Henle that just dips barely into medulla, basketweave vessels)

Juxtamedullary nephrons (15-20%; glomerulus at cortico-medullary junction, larger glomeruli, higher GFR, long loop of Henle that goes deep into inner medulla/papilla, vasa recta vessels)

Question 4

Renal vasculature

Answer 4

Renal artery

Segmental artery

Interlobar artery

Arcuate arteries (at cortico-medullary junction)

Interlobular artery

Afferent arteriole

Glomerular capillaries

Efferent arteriole

Peritubular capillaries

(Vasa recta)

Interlobular vein

Arcuate vein

Interlobar vein

Renal vein

Question 6

Renal clearance

Answer 6

Volume of plasma completely cleared of a substance by the kidneys per unit time

(substance with highest renal clearances are completely removed on single pass of blood thru kidneys)

C = ([U]_x x V)/[P]_x

Question 6

Inulin

Answer 6

Filtered but not reabsorbed or secreted

Whatever inulin is filtered gets excreted

Clearance = GFR

Note: inulin is not endogenous! Must be infused IV

Question 7

Mechanisms of renal autoregulation

Answer 7

1) Myogenic hypothesis: increased renal arterial pressure stretches walls of afferent arterioles which have stretch-activated Ca2+ channels that open and cause contraction/vasoconstriction, leading to increased arteriolar resistance and keeps RBF constant
2) Tubuloglomerular feedback: when renal arterial pressure increases, RBF and GFR bring more solute and water to macula densa (part of JGA), which secretes vasoactive substance and constricts afferent arterioles, bringing RBF and GFR back down to normal
3) Adrenergic innervation (alpha1)

Question 8

Regulators of afferent and efferent arterioles

Answer 8

Myogenic mechanism: afferent

Alpha1 adrenergic: afferent

Tubuloglomerular feedback: afferent mostly

Angiotensin II: efferent mostly

Question 9

PAH and renal plasma flow (RPF)

Answer 9

Whatever PAH enters the kidney (via renal artery) is excreted (renal vein concentration of PAH is zero). No other organ extracts PAH so we can measure PAH concentration in any peripheral vein. So is used to calculate renal plasma flow (RPF)

RPF = ([U]_PAH x V)/([RA]_PAH - [RV]_PAH)

Effective RPF = ([U]_PAH x V)/([P]_PAH) = C_PAH

Question 10

Dfference between inulin and PAH

Answer 10

The amount of PAH that enters the kidney is removed by filtration or secretion.

The amount of inulin that enters the kidney is not necessarily removed, but all the inulin that is filtered is excreted (it is not secreted like PAH is). Since inulin is freely filtered, its CONCENTRATION is the same in the plasma and in the filtrate (but that same concentration of inulin still in the blood that doesn’t get filtered goes into peritubular capillaries and does not get excreted)

Question 11

Ultrafiltration

Answer 11

Filtration that excludes big proteins but allows small molecules to pass

Ultrafiltrate = water and small solutes but no proteins/blood cells

Question 12

Layers of glomerular capillary (filtration barrier)

Answer 12

Endothelium: (innermost) has pores (fenestrae) that let solutes and plasma proteins through

Basement membrane: contains laminin and collagen Type IV but is very thick; 3 layers: lamina rara interna then lamina densa then lamina rara externa; does not allow plasma proteins/albumin through!

Epithelium: (outermost) has podocytes attached to basement membrane by foot processes; podocytes have foot processes that give off pedicels that interdigitate and form filtration slits in between

Mesangial cells: glomerular cells that are modified smooth muscle cells–are not podocytes and not endothelial cells; phagocytic, provide structural support, contract to regulate GFR

Question 13

Charged molecules getting filtered

Answer 13

The filtration barrier has negatively charged glycoproteins on it so positively charged solutes are attracted and filtered (even if they’re kinda big) but negative charged solutes are not filtered

Plasma proteins are negatively charged and large so are not filtered

However, for small solutes Na+, K+, Cl-, HCO3-, charge doesn’t matter and they’re freely filtered

Question 14

Starling equation for GFR

Answer 14

GFR = K_f [(P_GC - P_BS) -pi_GC]

GFR depends on net ultrafiltration pressure, which depends on sum of starling pressures (hydrostatic and oncotic)

Oncotic pressure of Bowman’s space (pi_BS) is zero because no filtration of protein so no protein in there

Question 15

Why is the glomerulus such a good filter?

Answer 15

1) High K_f (filtration coefficient) because high surface area and high intrinsic water permeability
2) High hydrostatic pressure for filtration
3) Filtration rate along glomerular capillary so high that protein concentration rises along its length so filtration ceases before efferent end; however, no pressure drop along short capillary

Question 16

Constriction of afferent arteriole

Answer 16

GFR decreases (less blood flow into capillary)

P_GC decreases

RPF decreases

Causes: sympathetic nervous system, HIGH angiotensin II

Question 17

Constriction of efferent arteriole

Answer 17

GFR increases (blood restricted from leaving capillary)

P_GC increases

RPF decreases

Causes: LOW angiotensin II

Question 18

Markers to measure for GFR

Answer 18

Inulin is perfect

Creatinine overestimates GFR: is secreted to a small extent (so GFR calculated by creatinine suggests higher GFR than real), but is endogenous so easier to measure in practice

BUN underestimates GFR: blood urea nitrogen is reabsorbed passively

Use average of creatinine and BUN to estimate GFR

Note: decrease in GFR means increase in markers because they’re not adequately filtered, and will reach a higher steady state level for when input = output. If GFR decreases to 10% of normal, creatinine (etc) will increase 10-fold!

Question 19

Prerenal azotemia

Answer 19

Hypovolemia (dehydration) results in decreased renal perfusion and decreased GFR, and also increased proximal reabsorption of all solutes

BUN increases more than serum creatinine because BUN is reabsorbed and creatinine is not, so ratio of BUN/creatinine increases to more than 20

Note: in renal failure, there is no increase in ratio of BUN/creatinine

Question 20

Filtration fraction

Answer 20

Fraction of plasma flowing through the kidney that is filtered

Filtration fraction = GFR/RPF

Typical filtration fraction is 0.2 or 20%

Remember, the 80% that is not filtered leaves glomerular capillaries via efferent arterioles and becomes peritubular capillary blood flow!

Question 21

How do you tell if a substance is secreted or reabsorbed?

Answer 21

Secreted (penicillin): filtered load is less than excretion; C > GFR

Reabsorbed (glucose): filtered load is greater than excretion; C < GFR

Neither reabsorbed nor secreted, and freely filtered (inulin): C = GFR

Question 22

Basic anatomy of kidney

Answer 22

Cortex: outside

Medulla: inside, contains 6-12 renal pyramids

Renal lobe: renal pyramid plus cortical dissue at base

Renal papilla: apical part of renal pyramid

Renal column: area between renal pyramids

Capsule: tough fibrous covering

Hilum: medial area where nerves, blood, lymph vessels, and ureter enter/exit the kidney

Renal pelvis: expanded upper end of ureter

Major calices: 2 or 3 where renal pelvis divides

Minor calices: off of major calices

Renal sinus: area surrounding minor calix

Question 23

Two capillary beds (portal circulation)

Answer 23

1) Glomerular capillaries (part of nephron)
2) Peritubular capillaries (not part of nephron)

Question 24

How much do the kidneys actually get rid of?

Answer 24

Only 1% of filtered volume excreted and 99% is reabsorbed

However, some substances that were never filtered (just went into peritubular capillaries) get secreted into tubular fluid to be excreted

Question 25

Oncotic pressure gradient (colloid osmotic pressure)

Answer 25

Albumin and other large molecules in blood cause osmolality of blood to be slightly higher than the filtrate in Bowman’s space. This causes fluid to move INTO the capillary (counteracts hydrostatic pressure out of capillary)

Question 26

Which arterioles are used for autoregulation at high and low pressure?

Answer 26

Higher pressures: afferent constricts

Lower pressures: efferent constricts

Curves intersect, and pressure in capillary is regulated by ratio of these resistances

Question 27

Tubuloglomerular feedback

Answer 27

Macula densa cells in thick ascending loop of Henle (part of JGA) sense high Cl- which indicates high renal blood pressure/expanded volume state –> afferent arteriole constricts –> reduce GFR –> Cl- delivery to macula densa decreases

Question 28

Equations for filtration and excretion

Answer 28

Filtration = P_x x GFR

Excretion = U_x x V

Units: mmoles/min = mmoles/mL x mL/min

Question 29

Urea (BUN)

Answer 29

Blood urea nitrogen

Can be used to measure GFR, but not great because not produced at constant rate (more BUN if eat more protein), is passively reabsorbed

Is involved in countercurrent multiplier.

Concentrating the urine causes urea reabsorption (b/c it diffuses passively?) and plasma urea concentration will increase

Question 30

When GFR changes, how does reabsorption in the PCT change?

Answer 30

DON’T THINK THIS IS RIGHT, NEED ANOTHER EXPLANATION

Maybe have to take into account the reason for GFR change…if severely decreased volume then you’ll reabsorb higher percent and that will increase your plasma CONCENTRATION of solutes in the end!

Decreased GFR means decreased AMOUNT of solute is reabsorbed because less is flowing through.

Decreased GFR means that a higher PERCENTAGE of solute that does get through gets reabsorbed because it is flowing slower. (is this really true in the PCT? maybe this is other places in the kidney?)

Glomerulotubular balance makes sense because the AMOUNT reabsorbed when GFR increases is greater but the PERCENTAGE reabsorbed is the same

Question 31

MDRD (Modification of Diet for Renal Disease formula)

Answer 31

Equation to estimate GFR from just plasma concentration of creatinine (P_Cr)

GFR = 175 x PCr - 1.154(Age) - 0.203

For women multiply by 0.742

For African American multiply by 1.210

DON’T NEED TO MEMORIZE THIS FORMULA

Question 32

Glucose reabsorption

Answer 32

Glucose freely filtered

Until 200 mg/dL, whatever is filtered is reabsorbed. After 200 have glucose excreted that is not reabsorbed

T_m is transport maximum, when glucose reabsorption saturated (375 mg/dL)

Filtration - excretion = max reabsorption rate (the vertical difference between the two lines)

Question 33

[TF/P]_x ratio

Answer 33

Compares concentration of substance in tubular fluid to its concentration in systemic plasma

[TF/P] = 1 in Bowman’s space means freely filtered because the concentrations are equal because no solute was blocked from going through

Also, [TF/P] = 1 at end of PCT for Na+ because it is reabsorbed isosmotically

Question 34

[TF/P]_x/[TF/P]_inulin double ratio

Answer 34

Used to correct [TF/P]_x for water reabsorption.

Can’t tell from just [TF/P]x what percentage of Na+ was reabsorbed, because it was reabsorbed isosmotically. Using double ratio, you can tell that 70% Na+ was reabsorbed in the PCT.

[TF/P]_inulin tells you what percentage of water was reabsorbed

Question 35

Calculate kidney water reabsorption rate

Answer 35

GFR - V

(GFR - urine flow rate)