PT disorders (panda's sheet)

Question 1

Cystinuria

Answer 1

Defective AA Reabsorption
1. Autosomal recessive; 1/20,000
2. Mutation in brush border transporter of CYSTINE, ORNITHINE, LYSINE, ARGININE
Cystine stones, cystine crystals (hexagonal)

Question 2

Hypophosphatemia

(Defective Phosphate Reabsorption)

Answer 2

Defective Phosphate Reabsorption
1. Inherited cause:
X-Linked Hypophosphatemia (PHEX mutation) —Rickets in kids; osteomalacia in adults
Autosomal Dominant Rickets (FGF-23 mutation)
Autosomal Recessive Hypohposhatemic Rickets (FGF-23 OR Na/Pi IIc transporter)
2. Acquired causes:
Oncogenic Hypophosphatemic Osteomalacia (Increased FGF-23 production)
***PHEX mutation decrease FGF-23 degradation
***Increased FGF-23 down regulates phosphate transporter activity (not a mutation in transporter) — FGF ↓Calcitriol = ↑PTH –> ↓P = Hypophosphatemia ***Also inhibits activation of Vit D

Question 3

Hartnup Disease

Answer 3

Defective neutral amino acid transporter

Question 4

Hypo/hyperuricemia

Answer 4

Defective uric acid handling
1. Decreased reabsorption = hypouricemia 2. Defective secretion = hyperuricemia

Question 5

Vitamin D-Dependent Rickets Type 1

Answer 5

Mutation in 1alpha-hydroxylase
**Leads to hypophosphatemia and rickets

Question 6

Etiology of Fanconi’s Syndrome

Answer 6

Generalized PT Dysfunction

1. Acquired > Inherited
2. Possible Mechanisms:
   - -Defecting binding of Na to transport proteins –Defecting inserting of carriers
   - -Leaky membrane tight junctions
   - -Inhibit Na/K ATPase
   - -Impaired mitochondria energy generation

Question 7

What are the metabolic abnormalities in Fanconi’s syndrome?

Answer 7

1. Aminoaciduria
2. Glucosuria (with normal serum glucose)
3. Hypophosphatemia (multifactorial: decreased Na/P carrier, decreased Vit D)
4. Increased bicarb excretion = metabolic acidosis
5. Hypokalemia (more delivery to distal tubule)
6. Uricosuria

Question 8

What are the clinical manifestations of Fanconi’s syndrome?

Answer 8

1. Polyuria/polydipsia from osmotic diuresis
2. Volume depletion from osmotic diuresis
3. Cardiac issues (k+)
4. Proteinuria
5. Rickets
6. Renal stones
7. Growth retardation

Question 9

What drugs can induce Fanconi’s syndrome?

Answer 9

1. Tenofovir (anti-HIV)
2. Lead
3. Toluene (Toxin)
4. Aristolochic Acid (weight loss)

Question 10

What is the most common electrolyte disorder?

Answer 10

Hyponatremia

Question 11

What casues Hypovolemic Hyponatremia?

Answer 11

Caused by decrease in TBNa that exceeds decrease in TBW

↓↓ TBna > ↓ TBW

Question 12

What is the presentation of hypovolemic hyponatremia?

Answer 12

Decreased BP, poor skin turgor, absence of dependent edema (pull skin and no recoil), prerenal azotemia (disproportionate increase in BUN relative to serum creatinine)
Renal Losses: diuretics, aldosterone deficit

GI Losses: diarrhea, vomitting, bleeding

Skin losses: burns, sweating

Question 13

How do you distinguish between Renal vs. Extra-Renal Sodium Loss in hypovolemic hyponatremia?

Answer 13

• Renal Sodium Loss: Urine Na > 20
• Extrarenal Sodium Loss: Urine Na < 20
Explanation: if hyponatremic, there are three mechanisms that are increasing Na reabsorption. Your kidney should be reabsorbing as much Na as possible, not excreting it. Therefore, in hyponatremic state your Na will say if renal damage is the cause or somewhere else.

Question 14

What causes Euvolemic Hyponatremia?

Answer 14

Caused by increase in TBW; no ∆TBNa ↑↑ TBW

Question 15

What is the presentation for euvolemic hyponatremia?

Answer 15

Decreased serum osmolality, inappropriate urinary concentration, high urinary Na, anti-psychotic drugs, glucocorticoid deficiency
Tx: Loop diuretics

Question 16

What casues Hypervolemic Hyponatremia?

Answer 16

Caused by increase in TBW that exceeds decrease in TBNa ↑

TBna < ↑↑ TBW

Question 17

What is the presentation of hypervolemic hyponatremia?

Answer 17

EDEMA, heart failure, liver failure, kidney failure
Most commonly seen with: CHF, Liver cirrhosis, and nephrotic syndrome

Question 18

DDX: Acute vs. Chronic Hyponatremia?

Answer 18

DDX: Acute vs. Chronic Hyponatremia 1. Acute hyponatremia has constitutional symptoms Nausea, malaise, headache, seizures, coma
2. Chronic hyponatremia has few symptoms
Too much water produces cerebra edema –> brain responds by losing intra/extra-cellular solutes to make room for H2O
Brain adapts to Chronic Hyponatremia. Avoid cerebral demylination syndrome by altering treatment (.5 mEq/L/hr)

Question 19

What causes Hypovolemic Hypernatremia?

Answer 19

↓↓ TBW > ↓ TBNa

Question 20

What is the presentation of hypovolemic hypernatremia?

Answer 20

Presentation: lethargy, weakness, irritable, seizure, coma Give isotonic saline! Volume loss (Na) more important.

Question 21

What causes Euvolemic Hypernatremia?

Answer 21

↓↓ TBW

Question 22

How would you treat euvolemic hypernatremia?

Answer 22

Treat underlying cause: replace water

Question 23

What causes Hypervolemic Hypernatremia?

Answer 23

↑↑ TBna > ↑ TBW

Question 24

How do you treat hypervolemic hypernatremia?

Answer 24

Get sodium out of body, furosemide, dialysis

Question 25

How do patients become hypernatremic?

Answer 25

Patients don’t become hypernatremic unless they don’t have access to water (intubated patient; de

Question 26

How would you differentiate between renal and extra renal sodium loss in hypernatremia?

Answer 26

Renal vs. Extra-Renal Loss
• Renal Sodium Loss: urine not concentrated
• Extrarenal Sodium Loss: urine appropriately concentrated

Question 27

What are the two types of Diabetes Insipidus?

Answer 27

Cental and Nephrogenic

Question 28

What is the etiology of Central Diabetes Insipidus?

Answer 28

NO ADH (trauma, tumor, congenital)

Question 29

How would you treat cetral diabetes insipidus?

Answer 29

DDAVP (exogenous vasopressin)

Question 30

What is the etiology of Nephrogenic Diabetes Insipidus?

Answer 30

ADH resistance V2 receptor mutation, cAMP defect

Question 31

What is the presentation of nephrogenic diabetes insipidus?

Answer 31

Presentation: CKD, hypokalemia, lithium, demeclocycline, sickle cell disease, pregnancy (vasopressinase); treat with thiazides

Question 32

How do you treat treat nephrogenic diabetes insipidus?

Answer 32

treat with thiazides

Question 33

How would you DDx between central DI vs. nephrogenic DI ?

Answer 33

give DDAVP and look for change (no change will occur in nephrogenic)



Question 34

What is Primary Polydipsia/Polyuria?

Answer 34

Increase in urine volume > 3L/day (V = Cosm + Cwater)

Question 35

What is the clinical relevance of polyuria?

Answer 35

One of the few causes of increased Cwater

Question 36

DDX between DI and Primary Polydipsia?

Answer 36

To DDx primary polydipsia – deprive from water source and watch the urine osmolarity increase