DSA 10

1. What are the major characteristics and early signs of acute renal injury?

2. What is azotemia? What is oliguria?

3. What does an elevated ratio of BUN to serum creatinine indicate?

characterized by a rapid deterioration of renal function (typically within days to a week),

resulting in the accumulation of nitrogenous wastes in the blood that would normally be excreted in the urine. The patient presents with a rapidly rising BUN (ie, azotemia) and serum creatinine.

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azotemia: a rapidly rising BUN

Oliguria: diminished urine volume

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Elevated Ratios of BUN to Serum Creatinin = Prerenal azotoma

What are common causes of pre-renal, intra-renal, and post-renal acute kidney injury?

Prerenal:

• volume depletion can result in the development of azotemia

  • excessive volume losses (renal, GI, or cutaneous in origin),

  • low fluid intake,

  • low effective circulating volume.

• Drugs:

  • Some patients who are dependent on prostaglandin-mediated vasodilation to maintain renal perfusion can develop renal failure from ingesting nonsteroidal anti-inflammatory drugs (NSAIDs). Similarly, patients with renal hypoperfusion (eg, renovascular disease) who are dependent on angiotensin II–mediated vasoconstriction of the efferent renal arterioles to maintain renal perfusion pressure may develop acute kidney injury on ingesting ACE inhibitors.

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Intra-renal:

• toxic effects of aminoglycoside antibiotics and rhabdomyolysis

  • Rhabdomyolysis: myoglobin, released into the bloodstream after a crush injury to muscle, precipitates in the renal tubules

• Sepsis:

  • prerenal: renal hypoperfusion owing to the hypotensive, low systemic vascular resistance of the septic state

  • intrarenal: cytokine dysregulation

    • elevated blood levels of tumor necrosis factor,

    • interleukin-1,

    • interleukin-6, → intrarenal inflammation, sclerosis, and obstruction

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Post-Renal:

• urinary tract obstruction

What is “cardiorenal syndrome”? Explain the mechanism of azotemia in patients with cardiorenal syndrome

decompensated heart failure with poor cardiac output and diminished renal perfusion

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Mechanism:

↓ Cardiac output → ↓ Renal perfusion → ↑ Sympathetic activity + ↑ RAAS → ↑ Na⁺ & H₂O retention → ↑ Venous congestion → ↑ Renal interstitial pressure → ↓ GFR → ↓ Tubular flow → ↑ Urea reabsorption (b/c more time) → ↑ BUN (disproportionate to Cr) → ↑ BUN/Cr ratio → Azotemia

Explain the mechanism of kidney injury after ingestion of nonsteroidal anti-inflammatory drugs or ACE inhibitors.

NSAID-Induced Kidney Injury:

• NSAID → ↓ PG → afferent arteriole constriction → ↓ renal blood flow → ↓ GFR → Prerenal Azotemia

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ACE Inhibitor-Induced Kidney Injury:

• ACE inhibitor → ↓ Ang II → efferent arteriole dilation → ↓ glomerular pressure → ↓ GFR.

What are the existing theories for the development of acute tubular necrosis?

tubular theory, cellular debris occludes the tubular lumen, forming a cast that increases intratubular pressure sufficiently to offset perfusion pressure and decrease or abolish net filtration pressure

vascular theory proposes that decreased renal perfusion pressure from the combination of afferent arteriolar vasoconstriction and efferent arteriolar vasodilation reduces glomerular perfusion pressure and, therefore, glomerular filtration.

When exposed to the same toxic insult, why do some patients develop acute tissue injury and
others do not?

Research has implicated cytokines and endogenous peptides, such as endothelins, and the regulation of their production as possible explanations for why, subjected to the same toxic insult, some patients develop acute kidney injury and others do not, and why some with acute kidney injury recover and others do not.

What are the initial and later symptoms of acute renal injury?

initial symptoms:

• fatigue and malaise, probably early consequences of the loss of the ability to excrete water, salt, and wastes via the kidneys.

Later Symptoms:

• dyspnea, orthopnea, rales, a prominent third heart sound (S₃), and peripheral edema. Altered mental status reflects the toxic effect of uremia on the brain, with elevated blood levels of nitrogenous wastes and fixed acids.

What are typical abnormal findings that indicate the development of acute renal necrosis in patients with pre-renal azotemia?

Perhaps the earliest manifestation of prerenal azotemia is an elevated ratio of BUN to serum creatinine. Normally 10–15:1, this ratio may rise to 20–30:1 in prerenal azotemia, with a normal or near-normal serum creatinine. If the patient proceeds to acute tubular necrosis, this ratio may return to normal but with a progressively elevated serum creatinine.

1. What are the most common causes of CKD?

2. What is Uremia?

In developed nations, the most common cause of CKD is diabetes mellitus (see Chapter 18), followed by hypertension; GN is a distant third cause (Table 16–7). Polycystic kidney disease, obstruction, and infection are significant but less common causes of CKD. In addition, episodes of acute kidney injury are associated with an increased risk for later development of CKD and end-stage renal disease.

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Uremia:

• accumulation of waste products (urea, creatinine, and other toxins) in the blood

What is the major pathophysiological difference between acute kidney injury and CKD?

acute injury to the kidney leads to death and sloughing of tubular epithelial cells, often followed by their regeneration with the re-establishment of normal architecture, chronic injury results in the irreversible loss of nephrons.

Starting from compensatory hyperfiltration, describe the development of uremia in patients
with CKD

↓ Nephron number → ↑ Hyperfiltration → ↑ Glomerular pressure → Glomerular injury → Nephron loss → ↓ GFR → ↓ Excretion of H⁺, K⁺, phosphate and ↑ Uremic toxins → Multisystem effects → Uremia

Why is a common recommendation for patients with CKD to avoid excess salt intake?

Patients with CKD typically have some degree of excess Na⁺ and water, reflecting loss of the renal route of salt and water excretion. A moderate degree of Na⁺ and water retention may occur without objective signs of extracellular fluid excess. However, continued excessive Na⁺ ingestion (as found in a typical Western diet) leads to further fluid retention and contributes to heart failure, hypertension, peripheral edema, and weight gain

What is the recommended daily fluid intake for patients with CKD? Why?

common recommendation for the patient with chronic kidney disease is to limit sodium to 2 g/d or less and to restrict fluid intake so that it equals urine output plus 500 mL (to compensate for insensible losses).

17. What is normal GFR? What is the mechanism of hyperkalemia in patients with CKD?

Early in CKD, as the GFR falls, aldosterone-mediated K⁺ transport in the distal tubule increases in a compensatory fashion to maintain normal potassium levels → K+ sparring diuretics → Hyperkalemia

What is the mechanism of metabolic acidosis in patients with CKD?

The diminished capacity to excrete acid and generate base in CKD results in metabolic acidosis

What are the key factors in the pathogenesis of bone diseases in patients with CKD?

The key factors in the pathogenesis of these disorders include (1) diminished absorption of Ca²⁺ from the gut; (2) overproduction of PTH; (3) disordered vitamin D metabolism; (4) retention of phosphorus; and (5) chronic metabolic acidosis. All these factors contribute to enhanced bone resorption.

Hyperphosphatemia contributes to the development of hypocalcemia and thus serves as an additional trigger for secondary hyperparathyroidism, elevating blood PTH levels. The elevated blood PTH further depletes bone Ca²⁺ and contributes to osteomalacia of CKD

What are cardiovascular risk factors in patients with CKD? Explain the development of hypertension in inpatients with CKD

Hypertension = due to fluid and Na⁺ overload.

decreased renal perfusion → RAAS

Pericarditis can develop from irritation and inflammation of the pericardium by uremic toxins.

Cardiovascular Risk factor:

• hypertension, hyperlipidemia, glucose intolerance, chronic elevated cardiac output, and valvular and myocardial calcification uremic milieu.

What are common skin changes in patients with CKD?

• pallor because of anemia, skin color changes related to accumulated pigmented metabolites,

• gray discoloration resulting from transfusion-mediated hemochromatosis, ecchymoses and hematomas as a result of clotting abnormalities, and pruritus and excoriations as a result of Ca²⁺ deposits from secondary hyperparathyroidism.

Why do diabetic patients with CKD need lower doses of insulin?

In CKD, the kidney’s role in insulin degradation decreases, increasing the half-life of insulin. This often has a stabilizing effect on diabetic patients whose blood glucose was previously difficult to control and can lead to a decreased need for insulin and other hypoglycemic medications.