Renal Physiology and Anatomy Flashcards
Mannitol
Marker for ECF (cannot cross cell membranes); ECF is 20% of body weight (1/3 of TBW); Sulfate and Inulin may also be used as markers for ECF
Used clinically to decrease acutely raised ICP and to treat oliguric renal failure.
Mannitol’s osmotic properties also allow it to be used as a facilitating agent for the transport of drugs across the BBB (mannitol shrinks endothelial cells of BBB, allowing passage of drugs across tight junctions).
Evans blue
Marker for plasma volume (1/12 of TBW); binds to serum albumin.
Renal clearance
The volume of plasma cleared of a substance per unit time.
Clearance = [Urine concentration * Urine vol/t] / Plasma concentration
Para-aminohippuric acid (PAH)
PAH is filtered and secreted by renal tubules
Clearance of PAH measures effective renal plasma flow (RPF) and underestimates true RPF by 10% (does not measure RFP to regions of kidney that do not filter and secrete PAH)
RPF is measures by the clearance of PAH at plasma concentrations lower than the Tm of PAH secretion
Renal blood flow = RPF / ( 1 - Hct )
Inulin
Inulin is filtered but not reabsorbed or secreted by the renal tubules.
Clearance of inulin measures GFR
Concentration of inulin in the tubular fluid vs. the plasma is used as a marker for water reabsorption along the nephron; TF/Pinulin increases as water is reabsorbed
TF/Px / TF/Pinulin ratio gives the fraction of filtered load remaining at any point along the nephron
Filtration fraction
Filtration fraction = GFR / RPF
Normally 20%.
Increases in FF (constriction of efferent arteriole) result in increased protein concentration in peritubular capillary blood, which increases reabsorption in the proximal tubule (glomerulotubular balance)
Decreases in FF (increased serum protein, ureteral stone) decrease reabsorption in the proximal tubule.
Splay
Represents excretion of substance in urine (threshold) before saturation of reabsorption (Tm) is fully achieved.
On the glucose titration curve, splay represents the region betwen threshold and Tm (plasma concentrations between 250 and 350 mg/dL)
Explained by heterogeneity of nephrons and relatively low affinity of Na-glucose carrier in proximal tubule
Causes of increased distal K+ secretion
- High K+ diet (increased intracelluar driving force)
- Hyperaldosteronism (increased Na+ entry into cells, increased luminal membrane K+ channels)
- Alkalosis - H/K exchange
- Thiazide and loop diuretics (dilute luminal K concentration)
- Luminal anions (e.g. HCO3-)
Causes of decreased distal K+ secretion
- Low-K+ diet
- Hypoaldosteronism
- Acidosis
- K-sparing diuretic (spironolactone, triamterene, amiloride)
Causes of hyperkalemia
- Insulin deficiency
- B-adrenergic antagonists
- Acidosis
- Hyperosmolarity
- Digitalis (inhibits Na/K pump)
- Exercise
- Cell lysis
Free water clearance (CH20)
Estimates the ability to concentrate or dilute the urine. The free water clearance is positive in the absence of ADH and it is negative in the presence of ADH.
CH20 = Urine flow rate (V) - Osmolar clearance (Cosm)
Effect of PTH on kidneys
Acts on basolatearl receptor to increase adenylate cyclase and cAMP
Decrease phosphate reabsorption in the proximal tubule, increases Ca reabsorption in the distal tubule, and stimulates 1-alpha hydroxylase in the proximal tubule
Effect of ADH on the kidneys
Act on the basolateral V2 receptor to increase adenylate cyclase and cAMP (V1 receptors act on blood vessels via IP3)
Increase water permeability in the late distal tubule and collecting duct principal cells
Effect of aldosterone on the kidneys
- Increase Na reabsorption via ENaC in distal tubule principal cells
- Increase K secretion in distal tubule principal cells
- Increase H secretion in distal tubule alpha-intercalated cells
Effect of ANP on the kidneys
Act via guanylate cyclase to increase GFR and decrease Na reabsorption
Effect of angiotension II on the kidneys
Increase Na-H exchange and HCO3 reabsorption in the proximal tubules (leading to contraction alkalosis)
Salicylate intoxication
Presents with metabolic acidosis and respiratory alkalosis
Type 1 Renal Tubular Acidosis
Failed H+ secretion and K+ reabsorption by the alpha-intercalated cells in the distal tubule (distal, urine pH > 5.5)
Normal anion gap metabolic acidosis and hypokalemia
Increased risk of calcium phosphate stones (due to increased urine pH and increased bone turnover)
Causes: amphotericin B toxicity, analgesic nephropathy, multiple myeloma, congenital abnormalities
Type 2 Renal Tubular Acidosis
Failed HCO3- reabsorption in the proximal tubules (proximal, urine pH < 5.5). Urine is acidified by alpha-intercalated cells in collecting tubule
Normal anion gap metabolic acidosis and hypokalemia. Increased risk for hypophosphatemic rickets
Causes: Fanconi syndrome, chemicals toxic to proximal tubule (e.g. lead, aminoglycosides), carbonic anhydrase inhibitors
Type 4 Renal Tubular Acidosis
Hypoaldosteronism, aldosterone resistance, or K+-sparing diuretics. Hyperkalemia impairs ammoniagenesis in the proximal tubule (pH < 5.5)
Mild normal anion gap metabolic acidosis, ECF contraction, and hyperkalemia
Potter sequence
“POTTER”:
- Pulmonary hypoplasia
- Oligohydramnios (trigger)
- Twisted face (low-set ears and retrognathia)
- Twisted skin
- Extremity defects
- Renal failure (in utero)
Release of Renin
JG cells (modified smooth muscle of afferent arteriole) secreted renine in response to decreased renal blood pressure (JG cells), decreased NaCl delivery to distal tubule (macula densa cells) and increased sympathetic tone (B1 receptors)
Winter formula (calculates predicted respiratory compensation for a simple metabolic acidosis)
PCO2 = 1.5 [HCO3- ] + 8 +/- 2
ECG findings of hypokalemia
- U waves (repolarization of papillary muscles)
- Flattened T waves
ECG findings of hyperkalemia
- Wide QRS
- Small P waves
- Peaked T waves
ECG findings of hypocalcemia
- QT prolongation
Causes of increased anion gap metabolic acidosis
“MUDPILES”:
- Methanol (formic acid)
- Uremia
- Diabetic ketoacidosis
- Propylene glycol
- Iron tablets or INH
- Lactic acidosis
- Ethylene glycol (oxalic acid)
- Salicylates (also cause early respiratory alkalosis)
