Renal Flashcards
1
Q
Where in the renal vasculature are the major sites of resistance?
A
the afferent and efferent arterioles
2
Q
What is the effect of a pre-renal problem on GFR? A post-renal problem?
A
- both will lower GFR, but by different mechanisms
- a pre-renal problem lowers the hydrostatic pressure of plasma
- a post-renal problem increases the hydrostatic pressure of bowman’s space
3
Q
What is the ultrafiltration coefficient? What is it’s utility?
A
- the ultrafiltration coefficient, K(uf), reflects the surface area and permeability of the glomerular membrane
- in conjunction with the filtration forces, it defines GFR
- GFR = K(uf) x P(uf)
4
Q
Describe the layers of the glomerular filtration membrane.
A
- fenestrated endothelium
- atop a basement membrane
- under which podocyte foot processes, called pedicels, form the epithelial layer
5
Q
What component of the glomerular filtration membrane forms the charge barrier? What sorts of ions pass through most easily?
A
negatively charged glycoproteins in the basement membrane allow small cations to pass through more readily than anions of the same size
6
Q
What transport drives nearly all absorption and secretion in the renal tubules? Describe it’s action.
A
Na/K-ATPases pump three sodium ions out of the basal surface of the epithelial cells and two potassium ions in across that surface
7
Q
What electrical gradient exists across the tubular epithelium?
A
-50mV, with the tubular lumen more negative (makes sense because the gradient is set up by the Na/K-ATPase which pumps three cations out of the cell and two into it)
8
Q
Where is most calcium reabsorbed in the kidney? Through what mechanism?
A
most is reabsorbed in the proximal tubule via the paracellular pathway
9
Q
What substance is used to estimate GFR? Why is it a good marker of GFR?
A
- creatinine is used because it is freely filtered, not reabsorbed, and minimally secreted
- furthermore, unlike inulin, it requires no infusion or emptying of the bladder beforehand
10
Q
What is a normal value for GFR?
A
roughly 100-125 mL/min
11
Q
What equation is used to calculate GFR from creatinine?
A
GFR = (urine creatinine)(rate of flow of urine)/(plasma creatinine)
12
Q
How is fractional excretion of a solute calculated?
A
FE = (solute excreted)/(solute filtered) = (urine solute)(urine flow rate)/(GFR x plasma solute) = (plasma creatinine x urine solute)/(urine creatinine x plasma solute)
13
Q
What is the normal value for fraction excretion of sodium?
A
1-3 percent
14
Q
What substance is used to calculate renal plasma flow? What characteristics make this a good marker?
A
para-amniohippuric acid (PAH) is used because between filtration and secretion, there is nearly 100% excretion of all PAH that enters the kidney
15
Q
What equation is used to calculate renal plasma flow? How about renal blood flow? What are normal values for these two measures?
A
- RPF =(urine PAH)(urine flow rate)/(plasma PAH) = 660 mL/min
- RBF = RPF/(1-Hct) = 1.2 L/min
16
Q
What is the normal BUN/Cr ratio? What does it represent?
A
- it is an important indicator of both glomerular and tubular function (creatinine is mainly filtered while urea is filtered and reabsorbed)
- the normal value is roughly 15
17
Q
How does the BUN/Cr ratio and FE(sodium) change in someone with prerenal, intrarenal, or post-renal failure? In which cases is the kidney’s ability to concentrate urine affected?
A
- BUN/Cr > 15, and FE is normal in someone with pre-renal failure
- BUN/Cr < 15, and FE > 3% in someone with intra-renal failure
- BUN/Cr is not a particularly good indicator for post-renal failure, but the FE > 3%
18
Q
What is filtration fraction? How is it calculated? What is a normal value?
A
FF = GFR/RPF = 0.2
19
Q
How do control of ECF osmolarity and ECF volume differ?
A
- for volume, the system changes urinary excretion of sodium
- for osmolarity, the system changes the urinary excretion of water
20
Q
What causes the release of ADH? What are it’s overall effects? Through what mechanisms does it elicit these changes?
A
- a rise in ECF osmolarity is detected by osmoreceptors in the hypothalamus (supraoptic and paraventricular nuclei)
- these sensors trigger the thirst mechanism and release of ADH from the pituitary
- secondarily, ADH can be released in response to low volume to a lesser degree
- ADH has a high affinity for V2 receptors on the basolateral surface of principal cells in the epithelium of the collecting tubules
- binding to V2 activates Gs and rising cAMP levels trigger expression of aquaporin2 molecules in the apical surface
- these aquaporin2 molecules promote reabsorption of water from the hypotonic fluid passing the the collecting tubule
- ADH has a lower affinity for V1 receptors found in the periphery on endothelial cells
- when it binds V1 receptors, it works through a Gq signal transduction mechanism to induce vasoconstriction
21
Q
Describe the countercurrent mechanism of the LoH.
A
- the descending limb is permeable to water and the medulla becomes more hypertonic as you descend, drawing fluid out of the tubular lumen
- the result is an extremely hypertonic solution at the bottom of the LoH
- the ascending limb is permeable only to salt, so as the fluid rises, solutes are drawn out
- the resulting fluid is hypotonic as it enters the distal tubule
22
Q
What is the purpose of the vasa recta countercurrent exchange? Describe the characteristics of the vasa recta that allow it to carry out this purpose.
A
- it is essential for conserving the composition of the medullary interstitium, which provides the foundation for the Loop of Henle’s countercurrent mechanism
- the hairpin structure and slow rate of blood flow allow minimal disruption of the medulla’s gradient while still allowing the vessel to supply nutrients to cells
23
Q
How does the rate of blood flow in the vasa recta or the length of the loop of hence affect the ability of the kidney’s to concentrate urine?
A
- slow blood flow in the vasa recta prevents it from disturbing the medullary salt gradient and diminishing the countercurrent effect of the LoH
- the length of the LoH lowers or extends the vertical osmotic gradient to which the fluid is subjected, changing the degree to which it is concentrated
24
Q
What triggers the release of ANP and BNP? What are it’s effects? What mechanisms elicit these effects?
A
- ANP and BNP are released from the atrial and ventricular walls in response to increased blood volume and distension of those walls
- in the adrenal cortex, ANP reduces aldosterone production
- in the hypothalamus, it reduces ADH secretion
- in the tubules it promotes closure of ENaC sodium channels, inhibiting Na reabsorption, thus promoting elimination of water
- it reduces sympathetic input to the kidneys, causing vasodilation of the afferent arteriole while also inducing vasoconstriction of the efferent arteriole
- the net effect of this is increased GFR, which increases sodium delivery to the macula densa and impairs renin release
25
What is CNP?
brain natriuretic peptide
26
What is urodilatin?
renal natriuretic peptide
27
Describe the six changes elicited by the renin-angiotensin system.
- ATII binds receptors on vascular smooth muscle in the periphery, inducing vasoconstriction to increase BP
- ATII causes constriction of efferent arterioles, increasing FF in low-volume states to preserve GFR and renal function
- ATII induces an increase in aldosterone which increases sodium channel and Na/K pump activity and expression, potassium excretion, and proton excretion in the collecting tubules, favoring water reabsorption
- ATII induces ADH secretion, which increases water reabsorption from the collecting tubules
- ATII increases Na/H pump activity in the PCT, increasing water, bicarb, and sodium reabsorption
- ATII stimulates the thirst center, driving water intake
28
What triggers the release of renin? What senses each change?
- low BP, sensed by the juxtaglomerular apparatus, which detects reduced tension on the afferent arteriole
- low Na delivery, sensed by the macula densa
- increased sympathetic tone (B1)
29
What role does renin play in the renin-angiotensin system?
- renin catalyzes the conversion of angiotensinogen produced in the liver to angiotensin I
- angiotensin I is then converted to angiotensin II by ACE
30
ACE is an enzyme with what two catalytic functions?
- conversion of angiotensin I to angiotensin II
| - breakdown of bradykinin
31
What adrenergic receptor is expressed by juxtaglomerular cells?
B1-adrenergic receptors
32
What is the net effect and mechanism of aldosterone. From where is it secreted?
- secreted by the adrenal gland
- responds to low blood volume states by increasing Na/K pump activity and expression in principal cells of the collecting duct, enhancing K excretion, and raising H+ ATPase activity in a-principal cells of the collecting duct
- net effect is sodium and water reabsorption
33
How does efferent sympathetic nerve activity affect the functions of the kidney?
- alpha receptors mediate afferent and efferent arteriole constriction (lower GFR, lower RBF, but higher FF)
- alpha receptors mediate an increase in tubular reabsorption
- beta receptors on granular cells in the juxtamedullary apparatus induce an increase in renin release
34
Where in the nephron is urea reabsorbed and secreted?
- 50% reabsorbed in the proximal tubule via paracellular route
- 60% secreted in the LoH via UT2
- 50% reabsorbed in the collecting tubule via UT1 and UT4
35
Which class of diuretic is most effective? Why is this the case and how does it work?
- loop diuretics (e.g. furosemide) work in the LoH by blocking the NKCC transporter
- they are very potent because there is very little nephron after the LoH to compensate for its effects
36
Where in the tubule are protons and bicarbonate secreted? Absorbed?
- in the proximal tubule, protons are secreted while bicarbonate is reabsorbed
- in the collecting tubules, a-intercalated cells secrete protons and reabsorb bicarbonate
- in the collecting tubules, B-intercalated cells secrete bicarbonate and reabsorb protons
37
What role does carbonic anhydrase play in the tubules?
it catalyzes CO2 + H2O H2CO3, important for urine acidification
38
What three molecules are used to buffer acid in the renal tubules?
- bicarbonate
- phosphate
- ammonium
39
How is ammonium produced in the renal tubules?
- an ammonia group is removed from glutamate, forming a-ketoglutarate and NH3
- NH3 diffuses into the tubule lumen and binds to protons, forming ammonium, which associates with chloride ions
40
What is the equation for the urine anion gap?
UAG = [Na] + [K] - [Cl]
41
What is the equation for plasma anion gap?
PAG = [Na] - ([Cl] + [HCO3])
42
How is urine anion gap interpreted?
- a negative UAG indicates normal ammonium production
| - a positive UAG or value of zero indicates low ammonium production
43
How is the equation for plasma anion gap interpreted?
- normal ranges between 8-16 mEq/L
| - it increases in metabolic acidosis when the HCO3 concentration in blood lowers
44
What induces the release of EPO by the kidneys?
reduced oxygen tension in the kidneys
45
What effect does PTH have in the kidneys? What triggers it's release?
- secreted in response to diminishing plasma calcium, increasing plasma phosphate, or diminishing calcitriol
- increases calcium reabsorption in the DCT, reduces phosphate reabsorption in the PCT, and increases calcitriol production
46
What is calcitriol?
the active form of VitD, which increases reabsorption of calcium from the intestine, bone, and renal tubules
47
What is calciferol?
the inactive form of VitD
48
What is the most common cause of acute renal failure?
shock
49
Why is rapidly progressive glomerulonephritis a unique renal pathology?
because it is essentially the only glomerular disease that can cause acute renal failure (others are prerenal or tubular)
50
How many nuclei should you expect in a normal, healthy glomerulus?
50-100
51
What are the features of nephrotic syndrome?
- a massive proteinuria (>3.5 gm/day)
- hypoalbuminemia
- generalized edema
- hyperlipidemia and lipiduria
52
Nephrotic syndromes typically indicate a defect in what part of the nephron?
a malfunction of the glomerular filtration barrier (rather than destruction of the filter by an inflammatory process)
53
Most nephrotic syndromes are characterized by a selective proteinuria of which protein?
albumin
54
What is the most common cause of chronic renal failure in the US?
diabetic glomerulosclerosi
55
Describe Diabetic glomerulosclerosis.
- the most common cause of chronic renal failure in the US
- begins with GBM thinkening, but with poor control it may progress to classic Kimmelsteil-Wilson nodular sclerosis
- light microscopy reveals acellular, spherical nodules of matrix situated in the periphery of the glomerulus that are PAS-positive
56
What features are characteristic of a nephritic syndrome?
usually seen with acute inflammatory conditions
- mild to moderate hypertension
- proteinuria (< 3.5 gm/day)
- hematuria (and red cell casts)
- azotemia
- oliguria
57
Describe the pathogenesis of nephritic syndromes.
- usually seen with an acute inflammatory condition
| - severe damage to the glomerular basement membrane allows leakage of large proteins and RBCs into the urinary space
58
Most often, what are RBC, WBC, and epithelial cell casts indicative of?
- RBCs: glomerulonephritis
- WBCs: acute pyelonephritis
- epithelial: acute tubular necrosis
59
How does chronic glomerulonephritis present?
- it is the end-stage of most glomerular diseases but in rare cases may also arise without any antecedent history
- slowly progresses with the development of chronic renal failure, uremia, and hypertension
- glomeruli reflect the changes associated with the underlying disease but eventually become acellular, eosinophilic PAS-positive masses
60
What are the main clinical applications for diuretics?
- heart failure
- hypertension
- acute and chronic renal failure
- nephrotic syndrome and cirrhosis
61
Drugs ending in the suffix "-zolamide" have what function?
they are carbonic anhydrase inhibitors (diuretics)
62
Why are most diuretics potassium wasting?
most block sodium reabsorption, and when more sodium reaches the collecting duct, more potassium is secreted in an effort to reabsorb more sodium than usual
63
What is the clinical use of an SGLT2 inhibitor?
- potentially a diuretic but not used as such
- third-line therapy for type 2 diabetes because they block glucose reabsorption in the proximal tubule and can reduce A1C by 0.5-1%
64
Drugs ending in the suffix "-agliflozin" function in what way?
they are SGLT2 inhibitors
65
Through what mechanism does the macula densa sense sodium delivery and induce renin release form granular cells?
- an NKCC detects Na and Cl concentrations
- when levels fall, activation of COX-2 induces PG formation and there is also an elevated production of adenosine
- adenosine binds a receptor on the granular cell as does prostaglandin
- both serve to regulate cAMP levels, which control renin release
66
Which diuretic is used clinically for hypertension?
thiazides
67
Which group of diuretics is still effective, even when GFR is low?
loop diuretics because they can also have a vascular effect mediated by prostaglandins and their effect on the renin system
68
Drugs ending in "-vaptan" have what mechanism of action?
they are ADH antagonists
69
How are the ADH antagonists conivaptan and tolvaptan clinically used?
- management of Syndrome of Inappropriate ADH Secretion when water restriction isn't sufficient
- congestive heart failure when ADH is elevated due to low blood volume
70
What is the primary osmotic diuretic?
mannitol
71
How does mannitol function as a diuretic? How is it used clinically?
- it is filtered by not reabsorbed, increasing the osmolarity of the ultra filtrate and promoting water diuresis
- greatest effect is in PCT and descending limb where the tubules are freely permeable to water
- used primarily for rapid reduction of intracranial pressure
72
What are the adverse effects of mannitol and other osmotic diuretics?
- may cause osmotic diarrhea since they are poorly absorbed
| - can cause severe dehydration, hypernatremia, headache, nausea, and vomiting
73
What is the first choice diuretic for patients with CHF? Why?
- loop diuretics (furosemide or athacrynic acid if allergic to sulfonamides)
- this is because other diuretics lose efficacy when combined with a vasodilator which reduces renal blood flow
74
What is the preferred thiazide-like diuretic?
chlorthalidone because of it's long-half life and proven reduction of CV disease
75
What is the clinical benefit of potassium-sparing diuretics?
they are weak and only used in combinations with other diuretics to avoid hypokalemia
76
What is normal pH, PCO2, and [HCO3-]?
- pH = 7.4
- PCO2 = 40 mmHg
- [HCO3-] = 24 mEq/L
77
Which acids and bases are eliminated via the lungs? Which via the kidneys?
- lungs: volatile acids as CO2
| - kidneys: non-volatile acids and bases
78
Describe acid-base regulation within the PCT.
- CO2 diffuses into epithelial cells and is converted to bicarb by the action of carbonic anhydrase
- bicarb is broken down into a proton and HCO3-
- the proton is secreted via a Na/H exchanger in the apical membrane
- bicarb is reabsorbed via a Na/HCO3 cotransporter on the basolateral surface
79
Describe acid-base regulation in the DCT.
- CO2 diffuses into epithelial cells and is converted to bicarb by the action of carbonic anhydrase
- bicarb is broken down into a proton and HCO3-
- the proton is secreted by either an H-ATPase or via a H/K exchanger in the apical membrane
- the bicarb molecule is reabsorbed via a bicarb/Cl exchanger in the basolateral membrane
- this process occurs in the DCT epithelium and alpha-intercalated cells of the collecting duct but is flipped in the beta-intercalated cells to facilitate wasting of bases and reabsorption of acids
80
What compounds are used as buffers in the urine?
- H2PO4-
| - HCO3-
81
Describe ammonium production in the renal tubules.
- in the tubular epithelium, cells convert glutamine to glutamate and then alpha-ketoglutarate with the production of an ammonia molecule
- ammonia is then able to diffuse into the lumen where it combines with a proton
- or it can combine with a proton in the epithelial cell and be pumped into the lumen via a ammonium/sodium exchanger
82
What are possible causes of a respiratory acidosis?
- airway obstruction
- acute lung injury
- chronic lung disease (COPD)
- obesity hypoventilation syndrome
- opioids or sedatives
- wearing of respiratory muscles (neuromuscular disease like MG, muscular dystrophy, or Guillain-Barre)
83
What are possible causes of an anion gap metabolic acidosis?
MUDPILES (some additional anion or loss of a cation)
- methanol (formic acid)
- uremia
- diabetic ketoacidosis
- propylene glycol
- iron tablets or INH
- lactic acidosis
- ethylene glycol
- salicylates (late)
84
What are possible causes of non-anion gap metabolic acidosis?
HARDASS
- hyperalimentation
- addison disease
- renal tubular acidosis
- diarrhea
- acetazolamide
- spironolactone
- saline infusion
85
What are possible causes of respiratory alkalosis?
- hysteria and hyperventilation
- hypoxemia
- salicylates (early)
- tumor
- pulmonary embolism
86
What are possible causes of metabolic alkalosis?
- loop or thiazide diuretics
- hyperaldosteronism
- Cushing's syndrome
- antacid ingestion
- vomiting
87
Describe the changes along a Davenport diagram that occur during a compensated respiratory acidosis.
- initially, there is a shift to the left along the non-bicarbonate buffer line
- then with renal compensation, there is an increase in HCO3- made available and there is a shift up the PCO2 curve
88
Describe the changes along a Davenport diagram that occur during a respiratory and renal compensated metabolic acidosis.
- initially, there is a shift down the PCO2 curve
- then with respiratory compensation, there is a shift to the right along the non-bicarbonate buffer line
- finally with renal compensation, there is a shift back up the PCO2 curve as more HCO3- is retained
89
What is winter's formula?
- a formula used to predict respiratory compensation for a simple metabolic acidosis
- If PCO2 = 1.5[HCO3-] + 8 +/- 2, then there is appropriate compensation, if PCO2 is less than predicted, there is a concomitant respiratory alkalosis, and if PCO2 is more than predicted, there is a concomitant respiratory acidosis
