Pathophysiology
The cells that secrete renin that line the afferent arteriole
What are the juxtaglomerular cells
Serum creatinine levels do not start to rise until GFR is reduced by about ... ?
A) 40%
B) 50%
C) 60%
D) 70%
B) 50%
Concept - creatinine-blind range
What are some confounding factors that can cause falsely elevated creatinine?
Can you tell us the normal reference values for a BMP? Remember to include all 7 measurements and draw it out on the board!
Na+ = 136 - 146 mEq/L
K+ = 3.5 - 5.0 mEq/L
Cl- = 95 - 105 mEq/L
HCO3- = 22 - 28 mEq/L
BUN = 7 - 18 mg/dL
CR = 0.6 - 1.2 mg/dL
Glucose = 70 - 100 mg/mL (fasting); <140 mg/mL (random, non-fasting)
Which of the following physiological effects is primarily mediated by angiotensin II to help maintain glomerular filtration rate (GFR) in the setting of hypovolemia?
A) Vasodilation of the afferent arteriole
B) Vasoconstriction of the efferent arteriole
C) Inhibition of aldosterone release
D) Stimulation of renin degradation
E) Decreased sodium reabsorption in the proximal tubule
Answer: B) Vasoconstriction of the efferent arteriole
Explanation: Angiotensin II preferentially constricts the efferent arteriole to maintain GFR despite decreased renal perfusion. This compensatory mechanism helps sustain filtration pressure in pre-renal states.
What does a CMP have that BMP does not have?
BMP: Glucose, sodium, potassium, bicarb, chloride, BUN, creatinine.
What are these additional labs useful for evaluating?
Calcium, total serum protein, albumin, ALT, AST, ALP, bilirubin
Discuss briefly second question about what these labs evaluate
Which of the following best describes the role of urea in the kidney?
A) Urea is only filtered and secreted, contributing to nitrogen waste removal.
B) Urea is reabsorbed and plays a key role in maintaining medullary osmolarity for water reabsorption.
C) Urea is actively secreted in the proximal tubule to facilitate sodium balance.
D) Urea is solely excreted in the urine and does not contribute to renal function.
E) Urea undergoes tubular secretion and is responsible for creatinine clearance.
Answer: B) Urea is reabsorbed and plays a key role in maintaining medullary osmolarity for water reabsorption.
Explanation:
Urea is produced in the liver from ammonia, making it a less toxic form of nitrogen waste. In the kidney, urea is filtered at the glomerulus and can be reabsorbed in the renal tubules. It plays a critical role in maintaining medullary osmolarity through countercurrent exchange, which helps concentrate urine and promote water reabsorption from the collecting duct. This process is essential for conserving water, particularly in states of dehydration.
Blood urea nitrogen (BUN) is a waste product produced by liver in the urea cycle after protein degradation, and is filtered/excreted by kidneys. Which of the following are causes of elevated BUN? (multiple right answers, must get them all).
A. protein catabolism
B. protein anabolism
C. high protein diet
D. increased GFR
E. decreased GFR
A, C, E
A 78-year-old male presents to the clinic for a routine health evaluation. He has a history of systemic hypertension and dyslipidemia but is otherwise healthy. Laboratory tests indicate a normal serum creatinine level. Which of the following best explains the expected changes in his glomerular filtration rate (GFR) with aging?
A) GFR remains stable at approximately 140 mL/min/1.73 m² throughout his lifetime.
B) GFR begins to decline after 40 years of age, by approximately 8 mL/min/1.73 m² per decade.
C) GFR begins to decline after 20 years of age and by age 90 is reduced by 20% from youth levels.
D) GFR declines linearly beyond age 30, with a reduction of approximately 46% by age 90 due to age-related factors and comorbidities.
Correct Answer: D) GFR declines linearly beyond age 30, with a reduction of approximately 46% by age 90 due to age-related factors and comorbidities.
Explanation: GFR steadily declines with age, as supported by studies showing a linear reduction beyond age 30. By age 90, GFR can be reduced by an average of 46% from youth levels. Factors such as systemic hypertension, smoking, and dyslipidemia can further accelerate this decline. The other options are inconsistent with the data: GFR does not remain stable throughout life (Option A), nor is the decline restricted to after 40 years of age only (Option B). Similarly, a 20% reduction by age 90 (Option C) underestimates the typical decline seen in apparently healthy individuals.
Age-related declines in GFR start around 40 years old, all of the following are associated with an acceleration in loss of renal function EXCEPT:
A: Obesity
B: Excessive water intake
C: Male
D: Lead exposure
B: Excessive water intake
Can indirectly harm the kidneys, but does not accelerate age-related loss of renal function
A 58-year-old woman with a history of hypertension and osteoporosis is started on hydrochlorothiazide. How does this medication affect calcium handling in the kidney?
(A) Increases calcium excretion by inhibiting the Na⁺/K⁺/2Cl⁻ transporter
(B) Increases calcium reabsorption in the distal tubule
(C) Decreases calcium reabsorption in the proximal tubule
(D) Increases calcium excretion by blocking aldosterone receptors
(E) Has no effect on calcium reabsorption
Correct Answer: (B) Increases calcium reabsorption in the distal tubule
Explanation:
Thiazide diuretics (e.g., hydrochlorothiazide, chlorthalidone) inhibit the Na⁺/Cl⁻ symporter in the distal tubule, leading to increased sodium excretion. This results in enhanced calcium reabsorption via passive mechanisms, making them useful in preventing kidney stones and treating osteoporosis.
A 55-year-old man with a history of chronic kidney disease presents with dizziness and fatigue. His blood pressure is 88/55 mmHg. Laboratory studies reveal a serum osmolality of 280 mOsm/kg, sodium of 140 mEq/L, and creatinine of 2.1 mg/dL (baseline 1.9 mg/dL). Which of the following compensatory mechanisms is most likely contributing to his current physiologic states?
A) Increased atrial natriuretic peptide release
B) Increased renin secretion from the juxtaglomerular cells
C) Decreased sympathetic nervous system activity
D) Decreased aldosterone synthesis
E) Decreased vasopressin release
Answer: B) Increased renin secretion from the juxtaglomerular cells
Explanation: The patient's hypotension and chronic kidney disease suggest pre-renal hypoperfusion, which stimulates the renin-angiotensin-aldosterone system (RAAS). The juxtaglomerular cells of the kidney release renin in response to low renal perfusion (low BP sensed by renal baroreceptors), increased sympathetic stimulation (via β-1 receptors), and low sodium delivery (detected via macula densa cells in the DCT).
BUN and Creatinine can be used together to calculate the BUN/Creatinine ratio, which is helpful in evaluating the underlying cause of AKI. Match each ratio (A,B,C) with the correct interpretation (1,2,3).
A. 10:1 - 20:1
B. Greater than or equal to 20:1
C. Less than or equal to 15:1
1. prerenal cause
2. intrarenal cause
3. postrenal cause or normal
A - 3; postrenal or normal
B - 1; prerenal; urea reabsorption is increased, which is typical in patients w/ dehydration or hypoperfusion
C - 2; intrarenal; renal damage is causing decreased urea reabsorption
Which of the following patients would most benefit from isotonic fluid resuscitation (e.g., Ringer’s lactate or 0.9% NaCl)?
A) A 28-year-old woman with hyponatremia due to SIADH
B) A 45-year-old man with vomiting and diarrhea for three days, leading to dehydration
C) A 62-year-old woman with heart failure experiencing pulmonary edema
D) A 50-year-old man with end-stage renal disease and hyperkalemia
E) A 30-year-old woman with cerebral edema after traumatic brain injury
Correct answer: B
INCORRECT A) SIADH already leads to excess water retention
INCORRECT C) Patient is already fluid overloaded
INCORRECT D) Would not give because it could worsen hyperkalemia in a patient with end-stage renal disease
INCORRECT E) Isotonic fluid would not reduce cerebral edema
Which of the following best describes the kidney’s response to metabolic acidosis?
(A) Decreased ammonium (NH₄⁺) excretion
(B) Increased bicarbonate (HCO₃⁻) reabsorption
(C) Decreased hydrogen ion (H⁺) secretion
(D) Decreased phosphate excretion
(E) Increased bicarbonate excretion
Which of the following best describes the kidney’s response to metabolic acidosis?
(A) Decreased ammonium (NH₄⁺) excretion
(B) Increased bicarbonate (HCO₃⁻) reabsorption
(C) Decreased hydrogen ion (H⁺) secretion
(D) Decreased phosphate excretion
(E) Increased bicarbonate excretion
Correct Answer: (B) Increased bicarbonate (HCO₃⁻) reabsorption
Explanation:
In metabolic acidosis, the kidneys increase H⁺ excretion via NH₄⁺ (ammonium) production while reabsorbing more bicarbonate to restore acid-base balance.
List what each letter of the VINDICATE mnemonic stands for
Vascular
Infectious
Neoplastic
Degenerative
Congenital
Autoimmune
Endocrine
A 65-year-old man with a history of hypertension and coronary artery disease is admitted for dehydration after several days of vomiting and diarrhea. His blood pressure is 88/56 mmHg, and labs show an elevated serum creatinine. Which of the following compensatory mechanisms is most likely initially occurring in his kidneys to maintain glomerular filtration rate (GFR) in response to reduced renal blood flow?
A) Dilation of both the afferent and efferent arterioles
B) Constriction of both the afferent and efferent arterioles
C) Constriction of the afferent arteriole and dilation of the efferent arteriole
D) Dilation of the afferent arteriole and constriction of the efferent arteriole
E) Increased sodium excretion to enhance tubular flow
Correct: D) Dilation of the afferent arteriole and constriction of the efferent arteriole
A 45-year-old woman presents to the clinic with complaints of fatigue and dark urine for the past three days. She reports feeling unwell over the past week, with reduced oral intake due to nausea and loss of appetite. On physical examination, she appears dehydrated, with dry mucous membranes and a heart rate of 105 bpm. Gross urine assessment reveals dark amber, clear urine. Dipstick analysis shows a pH of 5.5, specific gravity of 1.034, and 1+ protein. Other parameters, including glucose, ketones, leukocyte esterase, nitrite, and heme, are negative. What is the most likely explanation for her proteinuria?
A) Glomerular damage
B) Tubular damage
C) Pre-renal proteinuria due to dehydration
D) Nephrotic syndrome
C) Pre-renal proteinuria due to dehydration
Explanation: The patient's symptoms of fatigue, reduced oral intake, and physical signs of dehydration, along with an elevated specific gravity, are consistent with pre-renal causes of proteinuria. Dehydration leads to reduced renal perfusion, causing transient proteinuria due to increased filtration of albumin. The absence of other abnormalities (e.g., hematuria, glucose, or ketones) helps rule out glomerular damage, nephrotic syndrome, or other causes.
Which of the following are symptoms of pre-renal kidney disease? (Select all that apply)
A: Dizziness
B: Hematuria
C: Edema and ascites
D: Tachycardia
E: Dysuria
F: Flank pain
Correct: A, C, D
A) Can be caused by severe volume depletion
C) If due to heart failure, cirrhosis, or nephrotic syndrome
D) Compensatory response
INCORRECT
B) hematuria is caused by structural damage, not typically part of pre-renal kidney disease
E) pre-renal kidney disease does not include infection or inflammation
F) more indicative of an obstruction
A 65-year-old man with chronic hypertension is found to have elevated levels of angiotensin II. Which of the following physiological effects is mediated by angiotensin II binding to the AT1 receptor?
A) Vasodilation of the afferent arteriole
B) Decreased sodium reabsorption in the proximal tubule
C) Increased aldosterone synthesis in the zona glomerulosa
D) Inhibition of antidiuretic hormone (ADH) release
E) Decreased cardiac contractility
Answer: C) Increased aldosterone synthesis in the zona glomerulosa
Explanation:
Angiotensin II is a potent vasoconstrictor that binds to the AT1 receptor and exerts several effects to increase blood pressure and maintain renal perfusion. These include:
Vasoconstriction of systemic arteries, increasing blood pressure and cardiac contractility.
Preferential constriction of the efferent arteriole to maintain GFR during low renal blood flow.
Increased sodium reabsorption in the proximal tubule.
Stimulation of aldosterone synthesis in the adrenal cortex (zona glomerulosa).
Promotion of ADH release from the posterior pituitary.
A 62-year-old man comes to the physician for a follow-up examination. One month ago, therapy with lisinopril was initiated for treatment of hypertension. His blood pressure is 136/86 mm Hg. Urinalysis shows a creatinine clearance of 92 mL/min, and his estimated GFR is within normal limits. The patient's serum creatinine concentration is most likely closest to which of the following values?
A. 1.4 mg/dL
B. 2.3 mg/dL
C. 2.0 mg/dL
D. 1.1 mg/dL
E. 1.7 mg/dL
Creatinine is freely filtered and minimally secreted/reabsorbed, therefore, creatinine clearance can be used to estimate GFR.
Even though this patient's CrCl is slightly below normal (92 mL/min), his estimated GFR is within normal limits, therefore, his serum creatinine is in the normal range (0.6 - 1.2 mg/dL). Of the values provided, 1.1 mg/dL is the only value within normal range.
A 72-year-old woman with a history of chronic kidney disease presents to the emergency department with weakness and dizziness. She reports experiencing persistent vomiting and diarrhea over the past three days. Her blood pressure is 90/60 mmHg, and her heart rate is 110/min. Laboratory studies reveal:
Serum sodium: 138 mEq/L (135-145 mEq/L)
Serum osmolality: 285 mOsm/kg (275-295 mOsm/kg)
BUN: 30 mg/dL
Creatinine: 1.4 mg/dL
Which of the following is the most likely classification of this patient’s dehydration?
A) Hypertonic
B) Hypotonic
C) Isotonic
D) Euvolemic
E) Overhydration
Answer: C) Isotonic
Explanation:
This patient presents with signs of dehydration, including hypotension and tachycardia, likely due to excessive vomiting and diarrhea. In isotonic dehydration, both sodium and water are lost proportionally, maintaining normal serum osmolality. Causes include vomiting, diarrhea, burns, sweating, hyperglycemia, hypoaldosteronism, and kidney disease.
Hypertonic dehydration (Choice A) water loss exceeds sodium, increasing serum sodium and osmolality. Water loss occurs through the lungs, kidneys, and skin. Causes include fever, diabetes insipidus, and increased respiration
Hypotonic dehydration (Choice B) caused by diuretics, which cause sodium loss greater than water loss.
Euvolemic state (Choice D) is incorrect, as the patient is clearly volume-depleted.
Overhydration (Choice E) is incorrect, as there is no evidence of fluid overload.
Matching activity!
Match the following urinalysis components with what they measure/determine!
Paper handout
A - 9, B - 5, C - 3, D - 10, E - 7, F - 1, G - 6, H - 4, I - 11, J - 8, K - 2
A 65-year-old man with congestive heart failure (CHF) is prescribed furosemide for volume overload. Which of the following best describes the mechanism of action of loop diuretics?
(A) Inhibition of the sodium-chloride symporter in the distal convoluted tubule
(B) Inhibition of the Na⁺/K⁺/2Cl⁻ cotransporter in the thick ascending limb of the loop of Henle
(C) Blockade of aldosterone receptors in the collecting duct
(D) Inhibition of carbonic anhydrase in the proximal tubule
(E) Antagonism of vasopressin (ADH) at V2 receptors in the collecting duct
Correct Answer: (B) Inhibition of the Na⁺/K⁺/2Cl⁻ cotransporter in the thick ascending limb of the loop of Henle
Explanation:
Loop diuretics (e.g., furosemide, bumetanide, torsemide, ethacrynic acid) inhibit the Na⁺/K⁺/2Cl⁻ cotransporter in the thick ascending limb, preventing sodium reabsorption and increasing diuresis. They are potent diuretics used in CHF, nephrotic syndrome, and acute pulmonary edema.
A 65-year-old man is brought to the emergency department after being found confused and lethargic. His vital signs on arrival are:
On physical exam, his mucous membranes are dry and he displays poor skin turgor. An IV fluid bolus is administered. After the infusion, his vital signs are:
The patient also becomes more lucid, and his skin turgor improves. Which of the following best explains the decrease in heart rate following IV fluid administration?
A) Increased vagal tone due to baroreceptor activation
B) Direct suppression of cardiac pacemaker activity by increased circulating volume
C) Redistribution of blood flow improving oxygenation and reducing metabolic demand
D) Reflex inhibition of sympathetic tone due to changes in vascular resistance
E) Decreased need for compensatory tachycardia due to improved stroke volume
CORRECT: A) Increased vagal tone due to baroreceptor
INCORRECT: B) Increased circulating volume does not directly suppress SA node
INCORRECT: C) Does not play immediate role in HR reduction
INCORRECT: D) Sympathetic inhibition is not primary trigger in HR reduction
INCORRECT: E) Baroreceptor activation is primary trigger, not improved cardiac output alone
Draw the RAAS and list the outcomes of the pathway. Make sure to start with the DCT adjacent to the glomerulus. (No need to draw the entire nephron. Only include the substrates involved in the pathway).
See Diagram.