Renal Flashcards
Why is the left kidney taken during donor transplantation?
Because it has a longer renal vein
Path of renal blood flow, beginning with the renal artery?
Renal artery -> segmental artery -> interlobar artery -> arcuate artery -> interlobular artery -> afferent arteriole -> glomerulus -> efferent arteriole -> vasa recta/peritubular capillaries -> enous outflow
Explain the fluid compartments of the body.
- Total body water (TBW - 60% of body mass) + non water mass (NWM - 40% of body mass) = Body mass
- Total body water = Intracellular fluid (ICF - 2/3 TBW) + Extracellular fluid (ECF - 1/3 TBW)
What is the 60-40-20 rule?
% of body weight for average person:
60% total body water
40% ICF
20% ECF
What are the components of ECF?
Interstitial fluid (75% ECF) Plasma (25% ECF)
How can plasma volume be measured?
Radiolabeling albumin
How can ECF volume be measured?
With inulin or mannitol
What is normal osmolality?
285-295 mOsm/kg H2O
What are the components of the glomerular filtration barrier?
- Fenestrated capillary endothelium
- BM with type IV collagen chains and heparan sulfate
- Epithelial layer consisting of podocyte foot processes
How does the glomerular filtration barrier select for filtration?
Charge and size
What creates the charge barrier?
All three layers of the barrier contain negatively charged glycoproteins, preventing negatively charged molecule entry (eg, albumin)
What creates the seize barrier?
Fenestrated capillary endothelium prevents entry of >100 nm molecules/blood cells
Podocyte foot processes interpose with BM -> slit diaphragm (prevents entry of molecules >50-60 nm)
Renal clearance of a substance = ?
[(Urine concentration of X)(Urine flow rate)]/Plasma concentration of X
What is renal clearance?
The volume of plasma from which the substance is completely cleared per unit time (mL/min)
What is happening if clearance does not equal GFR?
If clearance is greater than GFR, net tubular secretion
If clearance is less than GFR, net tubular reabsorption
What can be used to calculate GFR? Why?
Inulin clearance; it is freely filtered and neither reabsorbed nor secreted
GFR = ?
UV/P (of inulin)
Normal GFR = ?
~100 mL/min
What is an approximate measure of GFR? Why is it a slight overestimate?
Creatinine clearance; slightly overestimates GFR because creatinine is moderately secreted by renal tubules
What is used to estimate effective renal plasma flow (eRPF)?
Para-aminohippuric acid (PAH) clearance; between filtration and secretion via the proximal tubule, there is nearly 100% excretion of all PAH that enters the kidney (slight underestimate of the true RPF)
eRPF = ?
UV/P (of PAH)
Renal blood flow (RBF) = ?
RPF/(1 - Hct)
FF = ?
GFR/RPF
Normal FF?
20%
Filtered load = ?
GFR x plasma concentration
mg/min
What preferentially dilates the afferent arteriole and what medication blocks this?
Prostaglandins preferentially dilate the afferent arteriole; NSAIDs block this
What preferentially constricts the efferent arteriolar and what medication blocks this?
Angiotensin II preferentially constricts the efferent arteriole; ACEIs block this
Effect of afferent arteriole constriction vs. efferent arteriole constrict on GFR, RPF, and FF?
Afferent arteriole constriction - decreased GFR, decreased RPF, no change in FF
Efferent arteriole constriction - increased GFR, decreased RPF, increased FF
Effect of increased plasma protein concentration vs. decreased plasma protein concentration on GFR, RPF, and FF?
Increased plasma protein concentration - decreased GFR, no change in RPF, decreased FF
Decreased plasma protein concentration - increased GFR, no change in RPF, increased FF
Effect of constriction of ureter on GFR, RPF, and FF?
Decreases GFR, no change in RPF, decrease in FF
Effect of dehydration on GFR, RPF, and FF?
Decreases GFR, greatly decreases RPF, increases FF
Filtered load = ?
GFR x P
P = plasma concentration of X
Excretion rate = ?
V x U
V = urine flow rate U = urine concentration of X
Reabsorption rate = ?
Filtered - excreted
Secretion rate = ?
Excreted - filtered
Fe(Na) = ?
Na excreted/Na filtered = [P(creatinine) x U(sodium)]/[U(creatinine) x P(sodium)]
What happens to glucose normally in the kidneys?
Glucose at a normal plasma level (range 60-120 mg/dL) is completely reabsorbed in the PCT by Na+/glucose
When does glucosuria begin in adults?
~200 mg/dL (plasma glucose)
When are all glucose transports in the kidney fully saturated?
~375 mg/min
Why can glucosuria and aminoaciduria occur in normal pregnancy?
Decreased ability of the PCT to reabsorb glucose and amino acids
What are the key regions of the nephron?
- Early PCT
- Thin descending loop of Henle
- Thick ascending loop of Henle
- Early DCT
- Collecting tubule
What are the apical transporters of the early PCT? The basolateral?
Apical (urine):
- Na/glucose co-transporter (into cell)
- Na/H exchanger (Na into cell, H into urine)
- Cl/base exchanger (Cl into cell, base into urine)
- CO2 diffuses into the cell
Basolateral (blood):
- Na/K ATPase (Na into blood, K into cell)
- HCO3- transporter into blood
In the cell: CO2+H2O -> H2CO3 (by CA) -> H+ + HCO3-
What is the role of the early PCT?
Reabsorbs all glucose and amino acids
Resorbs most HCO3, Na, Cl, PO4, K, H2O, and uric acid
Generates and secretes NH3 (enables kidney to secrete more H+)
How much Na+ is absorbed in each part of the nephron?
Early PCT - 65-80%
Thick ascending loop - 10-20%
Early DCT - 5-10%
Collecting tubule - 3-5%
Which portion of the nephron contains a brush border?
Early PCT
What hormones act on the early PCT?
- PTH - inhibits Na/PO4 cotransport -> PO4 excretion
2. AT II - stimulates Na/H exchange -> increased Na, H2O, and HCO3 reabsorption (permits contraction alkalosis)
Which diuretics act on the early PCT?
Acetazolamide (CA inhibitor)
What is the role of the thin descending loop of Henle?
Passively reabsorbs H2O via medullary hypertonicity
Impermeable to Na
Makes urine hypertonic (concentrates the urine)
What are the apical transporters of the thick ascending loop of Henle? The basolateral?
Apical:
- Na/K/2Cl transporter (all into cell)
- K+ channel (diffuses out into lumen)
- Mg, Ca paracellular transport (into cell -> blood)
Basolateral:
- Na/K ATPase (Na into blood, K into cell)
- K+ and Cl- channels (diffuse into blood down gradient)
What is the purpose of the thick ascending loop of Henle?
Reabsorbs Na, K, Cl
Indirectly induces paracellular reabsorption of Mg and Ca through a positive lumen potential generate by K+ backleak
Impermeable to water (makes urine less concentrated as it ascends)
Which portions of the nephron are impermeable and to what substances?
Thin descending loop - impermeable to Na+
Thick ascending loop - impermeable to H2O
Which diuretics work on the thick ascending loop?
Loop diuretics (block Na/K/2Cl transporter)
What are the apical transporters of the early DCT? The basolateral?
Apical:
- Na/Cl cotransporter (into cell)
- Calcium channel (diffuses into cell)
Basolateral:
- Na/K ATPase (Na into blood, K into cell)
- Receptor for PTH
- Na/Ca exchanger (Na into cell, Ca into blood)
- Chloride channel diffusion (into blood)
What is the role of the early DCT?
Reabsorbs Na, Cl
Makes urine fully dilute (hypotonic)
What hormones act on the early DCT?
PTH - increase Ca/Na exchange -> increase Ca reabsorption
What diuretic acts on the early DCT?
Thiazide diuretics (blocks Na/Cl cotransporter on apical membrane)
What ar ethe three types of cells in the collecting tubule?
- Principal cell
- Alpha-intercalated cell
- Beta-intercalated cell
What are the apical transporters of the principal cells of the collecting tubule? The basolateral?
Apical:
- H2O channels (into cell)
- K+ channels (diffuse into urine)
- Na+ channels (diffuse into cell)
- Cl- channels (paracellular - diffuse into cell -> blood)
In cell - Aldosterone receptors
Basolateral
- V2 receptors
- Na/K ATPase
What is the role of the collecting tubule?
Reabsorbs Na+ in exchange for secreting K+ and H+
What are the apical transporters of the alpha-intercalated cells of the collecting tubule? The basolateral?
Apical:
- H+ ATPase (H+ into urine)
- K/H ATPase (K into cell, H into urine)
In cell - Aldosterone receptors
Basolateral:
1. HCO3/Cl exchanger (HCO3 into blood, Cl into cell)
What are the apical transporters of the beta-intercalated cells of the collecting tubule? The basolateral?
Apical:
1. Cl/HCO3 exchanger (Cl into cell, HCO3 into urine)
Basolateral:
1. H+ ATPase (H+ into blood)
What are the effects of aldosterone on principal cells?
Increase apical K+ conductance, increase Na/K pump, increase ENaC activity -> lumen negativity -> K+ secretion
What are the effects of aldosterone on alpha-intercalated cells?
Lumen negativity -> increased H+ ATPase activity -> increased H+ secretion -> incraesed HCO3-/CL- exchanger activity
What are the effects of ADH in principal cells?
Insertion of aquaporin H2O channels on apical side
What diuretics act on the principal cells?
Amiloride, triamterene (block ENaC)
What are the components of the JGA?
- Mesangial cells
- JG cells (modified smooth muscle of afferent arteriole)
- Macular densa (NaCl sensor, part of DCT)
What is the role of the JGA?
Macula dense cells sense decreased NaCl delivery to DCT -> increase renin release -> efferent arteriole vasoconstriction -> increased GFR
JG cells secrete renin in response to decreased renal blood pressure and increased symapthetic tone (B1)
Where is EPO released from in the kidney?
Interstitial cells in the peritubular capillary bed
Where in the kidney is 25-OH vitamin D3 converted to 1,25-(OH)2 vitamin D3 (calcitriol, active form)?
PCT cells (via 1-alpha-hydroxylase enzyme, activated by PTH)
What is the role of dopamine in the kidney?
Secreted by PCT cells, promotes natriuresis; at low doses, it dilates interlobular arteries, afferent and efferent arterioles -> increased RBF, little or no change in GFR; at high doses, acts as a vasoconstrictor
ANP is secreted in response to ___. How does it affect the kidney?
Increased atrial pressure; causes increased GFR and increased Na filtration with no compensatory Na reabsorption in distal nephron -> Na and volume loss
Ang II is synthesized in response to ___. How does it affect the kidney?
Decreased BP; causes efferent arteriole constriction -> increased GFR and increased FF, but with compensatory Na reabsorption in proximal and distal nephron -> preserved renal function in low-volume state with simultaneous Na reabsorption (both proximal and distal) to maintain circulating volume
Aldosterone is secreted in response to ___. How does it affect the kidney?
Decreased blood volume (via AT II) and increased plasma K+
Causes increased Na reabsorption, and increased H and K secretion
ADH is secreted in response to ___. How does it affect the kidney?
Increased plasma osmolarity and decreased blood volume
Causes increased water reabsorption
Henderson-Hasselbalch equation = ?
pH = 6.1 + log([HCO3-]/(0.03xPCO2))
DDx - metabolic acidosis with increased anion gap
Methanol (formic acid) Uremia Diabetic/alcohol ketoacidosis Paraldehyde, propylene glycol Isoniazid, iron tablets Lactic acidosis Ethanol/ethylene glycol (metabolized to oxalic acid) Rhabdomylolysis, renal failure Salicylates (late) "MUDPILERS"
DDx - metabolic acidosis, non-anion gap
Hyperalimentation Acetazolamide, Addison disease Renal tubular acidosis Diarrhea Uretero-pelvic junction Post-hypocapnia Spironolactone, saline infusion "HARDUPS"
DDx - respiratory acidosis
Ultimately, anything that causes hypoventilation:
CNS depression (drugs, CVA) COPD and restrictive lung disease (causes chronic) Hemo/pneumothroax Airway obstruction Myopathy (weakened respiratory muscles) Pneumonia Pulmonary edema "CCHAMPP"
DDx - metabolic alkalosis
Contraction Licorice Syndrome of apparent mineralocorticoid excess Conn's, Cushing's, Bartter's, Gitelman's, Liddle's Vomiting, NG suction Excess alkali (antacid use) Refeeding alkalosis Post-hypercapnia Diuretics
Which causes of metabolic alkalosis are NOT associated with high urine chloride levels?
Vomiting, NG suction
Post-hypercapnia
DDx - respiratory alkalosis
Ultimately, anything that causes hyperventilation
CNS disease Hypoxia/hypoxemia Anxiety Mechanical ventilators Progesterone, PE Salicylates (early), sepsis Tumor
DDx - RBC casts
Glomerulonephritis, hypertensive emergency
DDx - WBC casts
Tubulointerstitial inflammation, acute pyelonephritis, transplant rejection
DDx - fatty casts (“oval fat bodies”)
Nephrotic syndrome
DDx - granular (“muddy brown”) casts
Acute tubular necrosis
DDx - waxy casts
Chronic renal failure/end-stage renal disease
DDx - hyaline casts
Non-specific finding, often normal, can e seen in concentrated urine
The presence of casts indicates what?
That the hematuria or pyuria is of glomerular or renal tubular origin
Which causes of hematuria present with NO casts?
Bladder cancer, kidney stones
Which causes of pyuria present with NO casts?
Acute cystitis