Week 3

Question 1

A 34-year old woman feels compelled to drink water all the time. Her serum sodium is low, as is her serum osmolality. The physician is unsure whether this patient has psychogenic water intoxication versus diabetes insipidus. Which of the following would reliably differentiate between the 2 disorders?

1. Urinary electrolytes compared with serum electrolytes
2. Urinary osmolality compared with serum osmolality
3. Serum ADH levels
4. Restriction from drinking water

Answer 1

Learning objective – SM207 Water balance + SM214 hyponatremia

Explanation: D is correct. Psychogenic water intoxication has the appearance of diabetes insipidus. Owing to the marked hypotonic fluid ingestion, the body attempts to excrete free water, thus ADH secretion is inhibited (C is incorrect). Both serum and urine sodium and osmolality are very low (A and B are incorrect). However, in psychogenic water intoxication, when water is restricted, the body will produce and respond to ADH eventually, leading to normalization of the serum osmolality and concentration of urine. In DI, even with water restriction, the patient will produce very dilute urine and will not be able to concentrate the urine.

Question 2

A 44-year old man comes to the office for a routine check-up. On physical examination, the patient’s blood pressure is 160/100 mm Hg. He is started on enalapril, an ACE inhibitor. During the first 7 days of therapy, his GFR drops from 90 ml/min to 75 ml/min. Which of the following structures was affected by enalapril and responsible for this patient’s renal response?

1. Afferent arterioles
2. Distal tubules
3. Efferent arterioles
4. Proximal tubules
5. Vasa recta

Answer 2

Learning objective: SM206 – Sodium balance, RAAS

Explanation: All ACE inhibitors decrease circulating levels of angiotensin II, a substance that causes the following: systemic vasoconstriction, preferential constriction of the glomerular efferent arteriole, enhancement of adrenal aldosterone secretion. As a result, reduced angiotensin II production would be expected to acutely decrease efferent arteriolar resistance and systemic vascular resistance. Selective efferent arteriolar dilation combined with reduced renal perfusion pressure causes a reduction in GFR. (C is correct).

Question 3

60-year old male presents to the clinic to review labs. He has a history of hypertension, diabetes and lung cancer for which he is currently undergoing treatment. Other than his chemotherapy, medications include metformin and lisinopril. His blood pressure sitting is 124/82 and standing is 122/80. Labs reveal: HgbA1c 6.4%, CBC unremarkable, CMP normal except for a sodium level of 123 mg/dL. Serum osmolarity is 250 mOsm/L. On physical exam, there is no evidence of JVD, lower extremity edema or other abnormalities. He denies vomiting and diarrhea. Which of the following is the best treatment for his hyponatremia at this time?

1. Furosemide
2. 3% normal saline
3. 0.9% normal saline
4. Fluid restriction
5. 5% dextrose in water

Answer 3

Learning objective – SM 214 Hyponatremia

Explanation: This patient has a low sodium level with a low serum osmolarity. Next step is to assess fluid volume status. He does not have jugular venous distention (JVD), lower extremity edema or any other signs of fluid overload to suggest hypervolemia. This patient denies any vomiting, diarrhea, blood loss and when vital signs were checked, he did not become orthostatic, which indicates that he is not volume depleted or hypovolemic.

Thus, this patient has hypotonic, euvolemic hyponatremia, which can result from ectopic production of anti-diuretic hormone (ADH) from his lung cancer -> SIADH. In patients with SIADH, best choice is to restrict daily water intake (Choice D is correct).

Choice A is incorrect, patient is not fluid overloaded. Choice B could be considered if patient had mental status changes, to quickly correct his hyponatremia. Choice C is incorrect, would be used if patient was volume depleted. Choice E is incorrect, patient is not hypoglycemic and this would further exacerbate his hyponatremia.

Question 4

A 58-year old man has undergone a lengthy colon cancer surgery. On the first post-op day, he is noted to have significant hyponatremia with a sodium level of 128 mEq/L. You suspect that the hyponatremia is due to the intravenous infusion of hypotonic solution. Which of the following laboratory findings support your diagnosis?

1. Urine sodium > 20 mmol/L
2. Urine osmolality > 200 mOsm/L
3. Serum osmolarity < 280 mOsm/kg
4. Serum potassium > 5.0 mEq/L

Answer 4

Learning objective – SM214a Hyponatremia

Explanation: In a patient with hyponatremia due to the infusion of excessive hypotonic solution, the serum osmolarity should be low (C is correct). The kidneys in responding normally should attempt to retain sodium and excrete water, therefore urine sodium concentration should be low and urine osmolarity should be low (A and B are incorrect). When the infusion of hypotonic saline is used, serum potassium level will also be low (D is incorrect). Note: if patient had mineralocorticoid deficiency, sodium level would be low and potassium high.

Question 5

A 56 year old patient has a history of diabetes and hypertension. He has had proteinuria for 5 months now. He reports that he “always feels tired” and has peripheral edema. His albumin to creatinine ratio is 33 mg/g and his GFR is 40 cc/min/1.73 m2.

What is the best next step in management for the patient?

A) Referral to transplant

B) Discuss dialysis options

C) Assess GFR and albuminuria annually and maintain serum bicarbonate levels at 22 mmol/l

D) Recommend a high protein diet

Answer 5

• SM 211: Chronic Kidney Disease Clinical Learning objective covered:*
• 3. Explain the approach to management of CKD based on the stage of disease (MKS3a, MKS3b)*

The correct answer is C. The patient has stage 3 chronic kidney disease. GFR and albuminuria should be monitored to track any disease progression. In addition, his diabetes and hypertension should be managed. Some studies have shown that maintaining serum bicarbonate levels with alkali therapy reduces progression of CKD.

A is not correct. The patient should be referred to transplant if his GFR <20.

B is not correct. Dialysis should be discussed with patients in stage 4 CKD (GFR between 15 to 29).

D is not correct. A balanced protein intake is recommended that avoids uremia from too much protein and malnutrition from not enough protein intake. Some studies suggest that a high protein diet > 1.3 g/kg/day may worsen CKD progression and so should be avoided.

Question 6

A 12-year old boy is brought to the physician’s office due to rust-colored urine and facial swelling. Vital signs and physical examination show a blood pressure of 140/90 mmHg and periorbital edema. Blood chemistry show an elevated BUN and creatinine. Urinalysis shows hematuria, RBC casts and 1+ protein. Which of the following is the most likely diagnosis?

1. Benign hematuria
2. Glomerulonephritis
3. Nephrotic syndrome
4. Nephrolithiasis

Answer 6

Learning objective: SM 211a: Pathophysiology and Clinical Aspects of Nephrotic Syndrome

Explanation: This question involves recognizing nephritis vs nephrotic syndrome symptoms. Nephrotic syndrome encompasses massive proteinuria (more than 3 g/day), hypoalbuminemia, hyperlipidemia, lipiduria and generalized edema. The hyperlipidemia is caused by the liver’s increase in all synthetic functions in an effort to make more albumin. There are no RBCs and RBC casts in patients with nephrotic syndrome. Urine sediment is bland and this signifies the absence of inflammation in the glomeruli.

RBC casts in the urine and modest protein (usually less than 1 gm/day) is characteristic of nephritis. Examination can reveal facial and periorbital edema, as well as moderate hypertension. Elevation of creatinine and BUN might also be present. (B is correct) (C is incorrect).

In benign familial hematuria, there is usually no edema, proteinuria or azotemia (A is incorrect).

Typical presentation of nephrolithiasis is in middle aged patient with characteristic severe flank pain and hematuria. Usually there is no hypertension and edema and no RBC casts in the urine (D is incorrect).

Question 7

A 35-year old woman comes to the office due to frequent urination. She describes drinking excessive amounts of water due to unquenchable thirst. She does not take any medications. Her blood glucose level is 84 mg/dL. A standard water deprivation test is performed. The results of urine osmolality during 4 hours of dehydration are presented below. The patient was administered vasopressin subcutaneously after 3 hours of water deprivation.

Time (hours)

1

2

3

4

Urine osmolality (mOsm/L)

90

100

100

790

Which of the following is the most likely diagnosis?

1. Central diabetes insipidus
2. Nephrogenic diabetes insipidus
3. Diabetes mellitus type 2
4. Post-obstructive polyuria

Answer 7

Learning objective: SM207a – Water balance

Explanation: Diabetes insipidus is caused by either ADH deficiency (central DI) or unresponsiveness of the kidney to ADH (nephrogenic DI). The end result is free water loss in the urine with production of very dilute urine (low mOsm/L) and dehydration that causes excessive thirst. A water deprivation test with desmopressin administration can differentiate between central and nephrogenic DI. When desmopressin is administered, patients with central DI show a rapid increase in urine osmolality (A is correct), whereas those with nephrogenic DI do not (B is incorrect).

Patient had normal blood glucose levels (C is incorrect). Relief of urinary obstruction (eg Foley catheter) may result in post-obstructive diuresis, but urine osmolality remains within normal limits, ADH is present and functioning (D is incorrect).

Question 8

A 59-year old man complains of periorbital edema and ankle swelling which has been gradually increasing over the last few months. Blood pressure is 120/80 mm Hg. Urinalysis shows a 4+ proteinuria with no cells or casts. Serum albumin is moderately decreased, but BUN and creatinine are normal. Which of the following is the most likely diagnosis?

A. Acute proliferative glomerulonephritis

B. Diabetic nephropathy

C. IgA nephropathy

D. Membranous glomerulopathy

Answer 8

Learning objective: Construct a differential for nephrotic syndrome.

Explanation: This patient has nephrotic syndrome as indicated by the edema, 4+ proteinuria and hypoalbuminemia. The most common cause in adults is membranous nephropathy (D is correct). Acute proliferative glomerulonephritis produces nephritic syndrome picture (A is incorrect). Diabetic nephropathy does produce proteinuria, but hypertension is often present alongside indication of chronic renal failure (elevated creatinine), neither of which is seen in this case (B is incorrect).

IgA nephropathy = Berger disease, is a cause of nephrotic syndrome but with hematuria often associated with an upper respiratory infection (C is incorrect).

Question 9

A 56 year old patient has a history of diabetes and hypertension. He has had proteinuria for 5 months now. He reports that he “always feels tired” and has peripheral edema. His albumin to creatinine ratio is 33 mg/g and his GFR is 40 cc/min/1.73 m2. What stage of kidney disease should this patient be classified under?

1. He does not have chronic kidney disease
2. Stage 1
3. Stage 2
4. Stage 3
5. Stage 4
6. Stage 5

Answer 9

• SM 211: Chronic Kidney Disease Clinical*
• Learning objective covered:*
  1. Define chronic kidney disease (CKD) and its stages (MKS1a)

The correct answer is D) Stage 3. This stage is chronic kidney disease since the GFR is below 60, he has had abnormal kidney function (proteinuria) for greater than 3 months with implications for health, and markers of kidney damage (albuminuria). In stage 3 of kidney disease, the GFR is between 30 and 59.

A is incorrect because the patient has chronic kidney disease by definition. If the patient had GFR<60 but the duration of kidney damage was less than 3 months, then the patient may not have chronic kidney disease, but may have an AKI.

B is incorrect. In stage 1 kidney disease the patient has normal renal function (GFR>90) but an abnormal finding (kidney cysts, proteinuria, or hematuria).

C is incorrect. In stage 2 the patient has a GFR between 60 and 89.

E is incorrect. In stage 4 the patient has a GFR between 13 to 29.

F is incorrect. In stage 5, or end stage renal disease, the patient has a GFR<15 and may or may not be on dialysis.

Question 10

A 13 year old boy presents to the clinic with a fever and bloody diarrhea. He ate hamburgers at a barbecue a few days earlier, and also reports bleeding from his gums and decreased urine output. On physical exam, petechial hemorrhages are seen on the skin. His laboratory report showed hemoglobin of 10.7 g/dL, platelet count 65,300/mm3, WBC count of 6490/mm3, and elevated D-dimer levels. What is the most likely cause of this patient’s renal dysfunction?

A) autoantibodies to Factor H

B) cobalamin deficiency

C) Shiga-like toxin binding the Gb3 receptor

D) bacterial neuraminidase production

E) decreased ADAMTS13 enzyme

Answer 10

• SM 210: Thrombotic microangiopathies*
• Learning objectives covered:*
• 1. Describe the clinical features of thrombotic microangiopathy. (MKS 1b)*
• 2. List the current classification of thromobotic microangiopathies. (MKS 1b)*
• 3. Explain the pathophysiology of various forms of thrombotic microangiopathies. (MKS1b)*

The correct answer is C. The patient’s symptoms of fever, bloody diarrhea, skin and mucosal bleeding, and decreased output are typical of hemolytic uremic syndrome (HUS). The most common cause of hemolytic uremic syndrome is exposure to E coli O157:H7, usually from eating undercooked beef. The bacteria produce Shiga-like toxin (also known as verotoxin) that enters the circulation and binds the Gb3 receptor on glomerular endothelial cells, leading to platelet thrombi formation and renal dysfunction. HUS thus leads to thrombocytopenia (low platelet count), an elevated D-dimer, and anemia (microangiopathic hemolytic anemia due to shearing of RBCs on the microthrombi). HUS is usually seen in children.

A is not correct. Autoantibodies to Factor H are usually seen in atypical HUS (around 10% of cases), which is caused by abnormal complement regulation, usually seen with mutations in the gene for Factor H or autoantibodies to Factor H.

B is not correct. Cobalamin (Vitamin B12) deficiency is a rare cause of HUS.

D is not correct. Streptococcus pneumonia can lead to neuraminidase production by bacteria. This exposes an antige on endothelial cells leading to endothelial damage and microthrombi formation. This is also a rare cause of HUS (less than 5% of cases)

E is not correct. Decreased ADAMTS13 enzyme is the cause of thrombotic thrombocytopenic purpura (TTP). ADAMTS13 cleaves multimers of von Willebrand Factor, so its deficiency leads to more platelet aggregation and thrombus formation. Microangiopathic hemolytic anemia, skin and mucosal bleeding, fever, and renal insufficiency is also seen in TTP. However, CNS abnormalities are more common in TTP, and the clinical presentation of the patient is more likely due to HUS than TTP in this case.

Question 11

Scientists studying the kidney’s response to hypoperfusion apply a clip to the right renal artery of a rat, which significantly reduces blood flow to the kidney. After 6 months, they perform a right nephrectomy and examine the glomeruli microscopically. Which of the following cell types are most likely to undergo hyperplasia and hypertrophy?

1. Cuboidal epithelial cells of proximal tubules
2. Endothelial cells of efferent arteriole
3. Intra-glomerular mesangial cells
4. Modified smooth muscle cells of the afferent arteriole

Answer 11

Learning objective: SM206a – Sodium balance

Explanation: Clipping of the renal artery prevents enough blood from reaching the kidney and normal glomerular filtration rates drop significantly. This is sensed by the juxtaglomerular apparatus, which consists of macula densa and juxtaglomerular cells. Macula densa cells are located in the distal tubule and monitor salt content and tubular flow rate. This information is transmitted to JG cells, modified smooth muscle cells with renin-containing zymogen granules that are located in the wall of the afferent arteriole.

Significant renal hypoperfusion leads to a compensatory increase in renin synthesis and secretion by JG cells. Severe, long-term renal artery stenosis causes the JG cells of the affected kidneys to undergo hypertrophy and hyperplasia (D is correct).

Choices A, B, C – are not components of the JG apparatus. They would not be expected to undergo hyperplasia and hypertrophy secondary to long term activation of the renin-angiotensin-aldosterone axis.