Renal Physiology and Acute Kidney Injury

1. Normal function first

The functional unit of the kidney is the nephron; each kidney has about one million. Each nephron has a filtering part (the glomerulus inside Bowman's capsule) and a tubular part (proximal tubule, loop of Henle, distal tubule, collecting duct). The kidneys receive about 20–25% of cardiac output as renal blood flow. At the glomerulus, water and small solutes are pushed by hydrostatic pressure into Bowman's capsule — glomerular filtration — and the volume filtered per minute is the glomerular filtration rate (GFR), normally about 90–120 mL/min. Cells and large proteins are held back, so filtrate is essentially protein-free plasma. The tubules then modify it: reabsorption returns useful substances (water, sodium, glucose, bicarbonate) to the blood, while secretion adds waste (hydrogen, potassium, some drugs) to the urine. The kidneys also autoregulate, adjusting afferent arterioles to keep renal blood flow and GFR steady across a wide blood-pressure range.

2. What changes in disease

Acute kidney injury (AKI) is an abrupt (hours to days) decline in kidney function, recognized by a rise in serum creatinine and/or a drop in urine output. Causes are grouped by site:

• Prerenal AKI — the most common — is reduced blood flow from hypovolemia (bleeding, dehydration), low cardiac output (heart failure), or systemic vasodilation (sepsis). The kidney tissue is initially intact; filtration falls because perfusion falls.
• Intrinsic (intrarenal) AKI is direct kidney damage, most often to the tubules. Ischemic injury occurs when prolonged under-perfusion deprives tubular cells of oxygen; nephrotoxic injury occurs when substances concentrated in or secreted by the tubules — certain medications, contrast dye, myoglobin, hemoglobin — damage tubular cells directly. Injured cells may slough into the tubule lumen and obstruct it, and inflammation further reduces filtration.
• Postrenal AKI is obstruction of urine outflow from the renal pelvis to the urethra (for example, an enlarged prostate, a stone, or a tumor); back-pressure reduces filtration.

3. Why the changes matter

When GFR falls, the kidneys can no longer clear nitrogenous wastes such as urea and creatinine, producing azotemia (elevated BUN and creatinine). If the decline is severe or prolonged, retained solutes produce uremia — nausea, fatigue, confusion, and itching. Urine output often falls: oliguria is under about 400 mL/day (or <0.5 mL/kg/hour); anuria is essentially no output (under about 100 mL/day), often signaling complete obstruction or severe intrinsic injury. Retained fluid causes edema and pulmonary congestion; failure to excrete potassium and hydrogen ions raises the risk of hyperkalemia and metabolic acidosis; and disrupted sodium and water handling can cause hyponatremia or fluid overload. These changes explain why AKI is monitored through urine output, serum creatinine and BUN, and electrolytes.

How it works

1. Blood enters the glomerulus under pressure, and about 20% of the plasma is filtered into Bowman's capsule (the GFR).
2. The tubules reabsorb roughly 99% of that filtrate while secreting hydrogen, potassium, and organic wastes into it.
3. When perfusion, tubular integrity, or outflow is compromised, GFR falls and waste clearance drops; serum creatinine rises within a day or two, and urine output falls.
4. Retained water, potassium, and acid produce fluid overload, hyperkalemia, and metabolic acidosis — the immediate dangers of AKI — while retained wastes progress toward azotemia and, if severe, uremia.

Common confusions

Memory aids

Use the three "where" questions of AKI — In → In → Out: is the problem before the kidney (Prerenal — flow in), inside it (Intrinsic — the machinery), or after it (Postrenal — flow out)?

Quick review

Topic Recap

• The nephron filters blood (glomerular filtration → GFR) and modifies the filtrate through reabsorption and secretion, supported by renal blood flow and autoregulation.
• AKI is an abrupt decline in GFR classified by site: prerenal (low flow), intrinsic (ischemic or nephrotoxic injury), and postrenal (obstruction).
• Falling GFR produces azotemia; severe retention produces uremia; urine output falls to oliguria or anuria.
• Lost excretion of potassium, hydrogen ions, and water creates the hallmark dangers — hyperkalemia, metabolic acidosis, and fluid overload.

Knowledge Check

1. Which AKI category results from reduced blood flow to the kidneys rather than direct kidney damage?
2. A person's serum creatinine rises sharply over two days after major blood loss. What laboratory term describes this accumulation of nitrogenous wastes?
3. How do ischemic and nephrotoxic tubular injury differ in mechanism?
4. A person is producing essentially no urine after surgery. What term applies, and which AKI category should be considered?
5. Why does AKI predispose a person to hyperkalemia and metabolic acidosis?

Answers and Rationales

1. Answer: Prerenal AKI. Why: It is caused by reduced renal perfusion; the kidney tissue is initially intact, so restoring flow early can reverse it.
2. Answer: Azotemia. Why: Azotemia is the laboratory finding of elevated nitrogenous wastes (BUN and creatinine), reflecting falling GFR.
3. Answer: Ischemic injury is inadequate oxygen delivery to tubular cells; nephrotoxic injury is direct chemical damage by substances concentrated in the tubules; they often occur together. Why: This clarifies why both low-flow states and certain drugs/toxins can cause intrinsic AKI.
4. Answer: Anuria; postrenal obstruction should be considered (along with severe intrinsic injury). Why: Near-complete cessation of urine output raises concern for complete urinary obstruction, especially postoperatively.
5. Answer: The kidneys normally excrete potassium and hydrogen ions; when GFR falls, these are retained, causing hyperkalemia and metabolic acidosis. Why: These are among the most immediately dangerous consequences of AKI.