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)
(Defective Phosphate Reabsorption)
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
Defective neutral amino acid transporter
Defective uric acid handling
1. Decreased reabsorption = hypouricemia 2. Defective secretion = hyperuricemia
Vitamin D-Dependent Rickets Type 1
Mutation in 1alpha-hydroxylase
**Leads to hypophosphatemia and rickets
Etiology of Fanconi's Syndrome
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
What are the metabolic abnormalities in Fanconi's syndrome?
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)
What are the clinical manifestations of Fanconi's syndrome?
1. Polyuria/polydipsia from osmotic diuresis
2. Volume depletion from osmotic diuresis
3. Cardiac issues (k+)
6. Renal stones
7. Growth retardation
What drugs can induce Fanconi's syndrome?
1. Tenofovir (anti-HIV)
3. Toluene (Toxin)
4. Aristolochic Acid (weight loss)
What is the most common electrolyte disorder?
What casues Hypovolemic Hyponatremia?
Caused by decrease in TBNa that exceeds decrease in TBW
↓↓ TBna > ↓ TBW
What is the presentation of hypovolemic hyponatremia?
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
How do you distinguish between Renal vs. Extra-Renal Sodium Loss in hypovolemic hyponatremia?
• 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.
What causes Euvolemic Hyponatremia?
Caused by increase in TBW; no ∆TBNa ↑↑ TBW
What is the presentation for euvolemic hyponatremia?
Decreased serum osmolality, inappropriate urinary concentration, high urinary Na, anti-psychotic drugs, glucocorticoid deficiency
Tx: Loop diuretics
What casues Hypervolemic Hyponatremia?
Caused by increase in TBW that exceeds decrease in TBNa ↑
TBna < ↑↑ TBW
What is the presentation of hypervolemic hyponatremia?
EDEMA, heart failure, liver failure, kidney failure
Most commonly seen with: CHF, Liver cirrhosis, and nephrotic syndrome
DDX: Acute vs. Chronic Hyponatremia?
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)
What causes Hypovolemic Hypernatremia?
↓↓ TBW > ↓ TBNa
What is the presentation of hypovolemic hypernatremia?
Presentation: lethargy, weakness, irritable, seizure, coma Give isotonic saline! Volume loss (Na) more important.
What causes Euvolemic Hypernatremia?
How would you treat euvolemic hypernatremia?
Treat underlying cause: replace water
What causes Hypervolemic Hypernatremia?
↑↑ TBna > ↑ TBW
How do you treat hypervolemic hypernatremia?
Get sodium out of body, furosemide, dialysis
How do patients become hypernatremic?
Patients don’t become hypernatremic unless they don’t have access to water (intubated patient; de
How would you differentiate between renal and extra renal sodium loss in hypernatremia?
Renal vs. Extra-Renal Loss
• Renal Sodium Loss: urine not concentrated
• Extrarenal Sodium Loss: urine appropriately concentrated
What are the two types of Diabetes Insipidus?
Cental and Nephrogenic
What is the etiology of Central Diabetes Insipidus?
NO ADH (trauma, tumor, congenital)
How would you treat cetral diabetes insipidus?
DDAVP (exogenous vasopressin)
What is the etiology of Nephrogenic Diabetes Insipidus?
ADH resistance V2 receptor mutation, cAMP defect
What is the presentation of nephrogenic diabetes insipidus?
Presentation: CKD, hypokalemia, lithium, demeclocycline, sickle cell disease, pregnancy (vasopressinase); treat with thiazides
How do you treat treat nephrogenic diabetes insipidus?
treat with thiazides
How would you DDx between central DI vs. nephrogenic DI ?
give DDAVP and look for change (no change will occur in nephrogenic)
What is Primary Polydipsia/Polyuria?
Increase in urine volume > 3L/day (V = Cosm + Cwater)
What is the clinical relevance of polyuria?
One of the few causes of increased Cwater
DDX between DI and Primary Polydipsia?
To DDx primary polydipsia -- deprive from water source and watch the urine osmolarity increase