Intro to Renal Flashcards
What are the functions of the kidney?
1) Excretion
2) Regulation (volume and composition of body fluids)
3) Endocrine (renin, erythropoietin, precursor to Vitamin D)
Segments of the nephron
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!)
Two types of nephrons
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)
Renal vasculature
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
Renal clearance
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
Inulin
Filtered but not reabsorbed or secreted
Whatever inulin is filtered gets excreted
Clearance = GFR
Note: inulin is not endogenous! Must be infused IV
Mechanisms of renal autoregulation
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)
Regulators of afferent and efferent arterioles
Myogenic mechanism: afferent
Alpha1 adrenergic: afferent
Tubuloglomerular feedback: afferent mostly
Angiotensin II: efferent mostly
PAH and renal plasma flow (RPF)
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) = CPAH
Dfference between inulin and PAH
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)
Ultrafiltration
Filtration that excludes big proteins but allows small molecules to pass
Ultrafiltrate = water and small solutes but no proteins/blood cells
Layers of glomerular capillary (filtration barrier)
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
Charged molecules getting filtered
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
Starling equation for GFR
GFR = Kf [(PGC - PBS) -piGC]
GFR depends on net ultrafiltration pressure, which depends on sum of starling pressures (hydrostatic and oncotic)
Oncotic pressure of Bowman’s space (piBS) is zero because no filtration of protein so no protein in there
Why is the glomerulus such a good filter?
1) High Kf (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
Constriction of afferent arteriole
GFR decreases (less blood flow into capillary)
PGC decreases
RPF decreases
Causes: sympathetic nervous system, HIGH angiotensin II
Constriction of efferent arteriole
GFR increases (blood restricted from leaving capillary)
PGC increases
RPF decreases
Causes: LOW angiotensin II
Markers to measure for GFR
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!
Prerenal azotemia
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
Filtration fraction
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!
How do you tell if a substance is secreted or reabsorbed?
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
Basic anatomy of kidney
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
Two capillary beds (portal circulation)
1) Glomerular capillaries (part of nephron)
2) Peritubular capillaries (not part of nephron)
How much do the kidneys actually get rid of?
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
Oncotic pressure gradient (colloid osmotic pressure)
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)
Which arterioles are used for autoregulation at high and low pressure?
Higher pressures: afferent constricts
Lower pressures: efferent constricts
Curves intersect, and pressure in capillary is regulated by ratio of these resistances
Tubuloglomerular feedback
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
Equations for filtration and excretion
Filtration = Px x GFR
Excretion = Ux x V
Units: mmoles/min = mmoles/mL x mL/min
Urea (BUN)
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
When GFR changes, how does reabsorption in the PCT change?
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
MDRD (Modification of Diet for Renal Disease formula)
Equation to estimate GFR from just plasma concentration of creatinine (PCr)
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
Glucose reabsorption
Glucose freely filtered
Until 200 mg/dL, whatever is filtered is reabsorbed. After 200 have glucose excreted that is not reabsorbed
Tm is transport maximum, when glucose reabsorption saturated (375 mg/dL)
Filtration - excretion = max reabsorption rate (the vertical difference between the two lines)
[TF/P]x ratio
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
[TF/P]x/[TF/P]inulin double ratio
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
Calculate kidney water reabsorption rate
GFR - V
(GFR - urine flow rate)
