Bob Delaney Flashcards
Describe the movement of ions/molecules across the membrane of the PCT
70% water, sodium and potassium
100% glucose + amino acids
80% of bicarbonate
50% urea + Chloride
Variable calcium, phosphate, magnesium
On the basolateral side of tubular epithelial cells, Na+/K+ ATPase pumps maintain high levels of intracellular K+ and low levels of intracellular Na+ which creates an electrochemical gradient.
sodium-glucose/amino acids symporters allow for glucose/AA’s to enter with sodium. Glucose enters blood stream via facilitated diffusion transporters. Sodium is pumped out via ATPase pump.
Chloride enters apical end, swapped for a base. This chloride travels out into blood stream driven by the leakage of K+ back out through the basolateral end down the gradient created by ATPase pump.
Carbonic anhydrase produce H2CO3 which produces H+ and HCO3. Bicarb diffuses into blood via facilitated diffusion, H+ enters lumen via and Na+/H+ antiporter.
Increased osmotic pressure into the blood causes movement of water paracellularly from lumen into blood.
List 3 causes of intra-renal AKI
- Acute tubular necrosis
-> Death/necrosis of the tubular epithelial cells resulting in sloughing of cells into urine forming muddy casts on urinalysis - Acute Interstitial Nephritis
-> Immune reaction to an agent such as drugs, infections or due to auto-immune condition can result in immune attack of the tubules and interstitial tissue causing renal impairment. - Acute Glomerulonephritis
->immune-led damage to the glomerulus leading to glomerular dysfunction
Explain possible causes of hyperkalemia in AKI
“In AKI, hyperkalemia can occur for several reasons:
(1) Reduced GFR decreases the kidney’s ability to filter potassium, leading to its retention in the blood.
(2) The impaired ability of the distal nephron to secrete potassium into the urine results in further potassium accumulation.
(3) Tissue breakdown, such as in rhabdomyolysis, can cause a significant release of intracellular potassium into the bloodstream.
(4) Metabolic acidosis, often due to impaired bicarbonate reabsorption and hydrogen ion excretion, causes hydrogen ions to move into cells in exchange for potassium, leading to an increase in serum potassium levels.
Explain the relevance of FeNa for diagnosis of AKI
This test measures how much sodium is being excreted in the urine relative to the amount filtered by the kidneys.
FeNa <1% typically indicates pre-renal AKI, where the kidney is under-perfused but the tubular function is still intact. The low FeNa suggests that the kidneys are conserving sodium (and water) in response to reduced blood flow, indicating the tubules are functioning properly to retain sodium.
FeNa >2% suggests intrinsic (intra-renal) AKI, such as acute tubular necrosis (ATN). Here, the kidney tubules are damaged and unable to reabsorb sodium effectively, leading to excessive sodium loss in the urine.
FeNa between 1-2% is less specific and may indicate mixed causes of AKI or evolving renal injury.
Explain the expected BUN: Creatinine ratio findings in pre-renal AKI. How might this compare to intrinsic and post renal AKI?
In pre-renal AKI, the BUN
ratio is typically elevated above 20:1. This is due to decreased renal perfusion, which reduces the glomerular filtration of both urea and creatinine, leading to their accumulation in the blood.
However, in response to underperfusion, the kidneys reabsorb more water and sodium to preserve volume. This increased water reabsorption also enhances the reabsorption of urea in the collecting duct, while creatinine is not reabsorbed.
As a result, BUN levels rise disproportionately compared to creatinine, increasing the BUN
ratio above the normal range of 10-20:1.
Intrinsic AKI: Both are elevated but the ratio may be normal because the kidneys have lost filtration and reabsorption capability and so neither rises to a greater extend than the other.
Post-renal: The ratio may be elevated due to increased pressure within the tubules due to obstruction causing BUN to be forced out into the intersitium.
Compare expected urine osmolality findings between pre-renal and intrinsic renal AKI
Pre-renal: Urine osmolality would be high because there is increased water resabsorption by the nephron.
Intrinsic renal: Low urine osmolality because there is loss of resabsorption abilities in the nephron and so water is lost in the urine.
What are the clinical signs of acute tubular necrosis and why?
Signs of fluid depletion or overload and hypotension or hypertension may be present, depending on the extent of the disease and the underlying cause. Pre-renal AKI, commonly caused by hypoperfusion due to hypovolemia, may present initially with signs of fluid depletion and hypotension. However, as ATN develops, fluid overload and edema become more likely due to reduced GFR and the kidneys’ impaired ability to excrete sodium and water, leading to fluid retention in the blood
Hyperkalemia and acidosis: The tubules have lost secretory capabilities and so potassium remains elevated in blood. Additionally, the inability to reabsorb HCO3 and secrete H+ results in acidosis. The elevated H+ ions can cause intracellular K+ to move out of cell in exchange for H+ further precipitating hyperkalemia.
Oliguria or anuria: Reduced GFR can occur due to tubular lumen blockage following cast formation from necrotic epithelial cells which have shed off into the lumen thereby occluding it.
Low urine osmolality: the tubules have lost ability to concentrate urine.
FeNa >2%: Tubules have lost ability to reabsorb sodium which is then lost in the urine.
BUN: Creatinine ratio: normal to low: Reduced GFR coupled with reduced ability of tubules to reabsorb urea means that both components rise in the blood but may not rise disproportionately to each other.
List 5 indications for RRT
A E I O U
Acidosis
Electrolyte imbalance
Intoxication/Poisoning
Overload (fluid)
Uremic complications (e.g. Pericarditis, encephalopathy, pulmonary edema)
Explain why hyperkalemia occurs in ATN
(1) Tubular epithelial cells cannot effectively reabsorb sodium in exchange for potassium secretion- this leads to potassium retention in the blood.
(2) Metabolic acidosis which arises due to low HCO3- can cause H+ ions to shift intracellularly which causes K+ ions to shift extracellularly into blood.
(3) Rhabdomyolysis, which is itself a potential cause of ATN, can cause release of intracellular K+ into the blood following skeletal muscle breakdown
(4) Necrotic debris that slough into tubular lumen can back up fluid and increase pressures within bowman’s capsule. This reduces GFR meaning less K+ is filtered and is instead retained in blood.
urinalysis in ATN would show what?
High urinary sodium (cant reabsorb)
Low urine osmolality (cant reabsorb water i.e. cant concentrate urine i.e. urine very dilute) < 500 mOsm/kg
muddy brown casts (if severe)
FeNa > 2%
Explain how severe vomiting causes contraction alkalosis
(1) Prolonged vomiting leads to a loss of H⁺ and Cl⁻ from the stomach. This means less H⁺ enters the duodenum, reducing the need for pancreatic bicarbonate (HCO₃⁻) to neutralize the acid. As a result, more bicarbonate is retained in the bloodstream, contributing to metabolic alkalosis.
(2) Dehydration from vomiting decreases kidney perfusion, activating the RAAS.
Angiotensin II promotes increased sodium (Na⁺) and bicarbonate reabsorption in the proximal tubule, raising blood bicarbonate levels.
Aldosterone increases potassium (K⁺) excretion, leading to hypokalemia. Hypokalemia causes K⁺ to shift from cells into the ECF, in exchange for H⁺ moving into cells, further decreasing H⁺ in the blood and worsening the alkalosis.
(3) ECF contraction from volume loss concentrates bicarbonate in the blood, worsening the alkalosis due to the reduced dilution of HCO₃
Discuss the differences in ion and water permeability between the descending and ascending limbs of the loop of Henle, and how these differences contribute to the overall process of urine formation and concentration.
- The descending limb is permeable to water but impermeable to ions (solutes)
- The ascending limb is impermeable to water but permeable to ions (solutes).
- These differences in permeabilities creates the counter-current multiplier system to aid in urine concentration.
- The ascending limb produces a hypertonic medullary interstitial space which causes the movement of water through osmotic gradient out of the descending limb for reabsorption. Na+/K+/2Cl transporter is that responsible for ion reabsorption in ascending limb (thick part).
- This creates a hypertonic filtrate as it descends towards the hump of the loop of henle.
- As it ascends through the ascending limb it becomes more hypotonic as ions are pumped out into the intersitial space.
Describe the role of the proximal diluting segment of the distal convoluted tubule in the maintenance of sodium and water balance.
- This segment reabsorbs sodium (Na⁺) actively via sodium-chloride (Na⁺/Cl⁻) co-transporters on the apical membrane of the tubular cells. This occurs without concurrent water reabsorption, due to the water impermeability of the early DCT. This characteristic leads to the “diluting” effect, where the filtrate becomes more hypotonic as sodium is reabsorbed without water.
- Contribution to Sodium Balance: By fine-tuning the amount of sodium that continues downstream, the proximal diluting segment indirectly influences the final sodium content in the urine, which is crucial for maintaining sodium homeostasis in the body.
What is the role of juxtaglomerular apparatus?
- The juxtaglomerular apparatus (JGA) is composed of juxtaglomerular cells located adjacent to the afferent and efferent arterioles and macula densa cells in the distal convoluted tubule (DCT).
- The macula densa cells monitor sodium-chloride levels, which serve as a surrogate indicator for the glomerular filtration rate (GFR). When sodium-chloride levels are low, indicating a low GFR, the macula densa cells signal the juxtaglomerular cells to release renin. Renin initiates the renin-angiotensin-aldosterone system (RAAS), in which angiotensin II stimulates efferent arteriole vasoconstriction, raising glomerular hydrostatic pressure and thereby increasing GFR.
- Additionally, RAAS promotes sodium and water retention to support blood volume and blood pressure. When sodium levels in the DCT return to normal, the macula densa cells stop stimulating renin release, thus regulating the system via negative feedback.
Explain the effect of RAAS on potassium excretion.
- RAAS results in increased angiotensin II levels which increase the secretion and release of aldosterone from the adrenal cortex.
- Aldosterone works to increase sodium reabsorption in the principal cells of the late distal tubule and collecting ducts which subsequently causes obligatory potassium secretion and excretion.
