Secondary forms of hypertension

Lisa Cohen recently summarized rare "genetic" forms of hypertension including Liddle's syndrome and PHA type II (Gordon's syndrome).

I want to summarize other causes of "secondary" hypertension which are not inherited (at least not typically in a Mendelian transmission) and which are potentially "fixable".

These phenotypes are distinct from primary hypertension which affects the vast majority of our patients. Secondary forms of hypertension affect typically less then <5% of patients with hypertension.

In order to identify a reversible cause for hypertension following data needs to be obtained:

• HPI
• Family history
• Physical exam
• Initial labs including Chem7, Lipid panel, Urine analysis, EKG
• Indications for further labs include abnormal initial tests (high Ca++ levels, low K+ levels), abrupt onset of hypertension, young age (<30),>50), hypertension resistant or refractory to 3+ medications, worsening hypertension in a previously well controlled patient, BP >180/110 at onset.
  

The most common forms of secondary hypertension are:

1. Renovascular hypertension
2. Coarctation of aorta
3. Cushing’s syndrome
4. Primary Aldosteronism
5. Thyroid/parathyroid disease
6. Pheochromocytoma

Typically others causes such as CKD or sleep apnea are not considered "secondary" forms of hypertension. Physical and laboratory findings can help and guide in ruling out secondary forms of hypertension: If you find this -> think this !!!

1. Truncal obesity and striae -> Cushing's syndrome
2. Labile hypertension -> Pheochromocytoma
3. Abdominal bruits -> renovascular hypertension
4. Decreased BP and Pulse in lower extremities -> Coarctation of aorta
5. Abdominal flank masses -> Polycystic kidney disease
6. Elevated Crea and/or abnormal UA -> parenchymal kidney disease
7. Hypercalcemia -> Hyperparathyrodism
8. Hypokalemia -> Hyperaldosteronism (also Cushing's syndrome and Pheochromocytoma can present with this).

Last but not least, a few more facts on the three most common secondary forms of hypertension:

1. Renovascular hypertension- Renal artery artherosclerosis (males>50, Fibromuscular dysplasia (females<40),Other (rarer) causes include vasculitis, scleroderma, Takayasu arteritis, etc. - Labs show typically hypokalemia and hyper-reninemic hyperaldosteronism - Screening tests recommended are Doppler US, MRA, CT angio, captopril renogram - Gold standard is arteriography which could show “string of beads” vs. single stenosis
2. Hyperaldosteronism: Aldo causes increased Na+ uptake in distal tubule -> increase in intravascular volume
   -Suspect in patients with unexplained low K+
   -Main causes are adrenal adenomas (~ 70%) and b/l adrenal hyperplasia (~ 25%)
   -Screening by checking stimulated PRA or PRC which will be undectable or low
   -Confirm screening tests with salt/fluid loading -> "elevated" Aldo level will NOT be suppressed
3. Pheochromocytoma:
   -Rare tumors arising from chromaffin tissue of the adrenal gland
   -90% occur in the adrenal medulla
   -10% are b/l, 10% are malignant and 10% are familial!
   -Associated with MEN II
   -Remember that 33-50% of patients have sustained hypertension !
   -Suspect it if refractory to treatment
   -Screen for serum or urine metanephrines
   -CT adrenals or/and MIBG scan (meta-iodo-benzyl-guanidine) to detect tumors

The urine's the thing...

Vomiting or nasogastric tube (NG) decompression can lead to metabolic alkalosis, often associated with hypokalemia. When asked what the source of the K loss is, most people assume it is lost in the gastric fluid. However, gastric fluid only contains about 9 mEq/L of potassium, hardly enough to lead to profound hypokalemia. While it is true that cellular shift due to alkalosis could explain some of the hypokalemia, the primary source of potassium loss is via the urine.

Metabolic alkalosis induced by GI loss leads to volume depletion. In this setting, secondary hyperaldosteronism ensues, leading to sodium retention and potassium wasting, hence the hypokalemia. Further, such GI losses are also associated with chloride depletion. Maintenance of electroneutrality usually obligates chloride reabsorption along with sodium retention. But in chloride depleted states, this is not possible. Instead the lumen-negative gradient (due to sodium reabsorption without chloride following) obligates cation excretion, usually potassium or hydrogen ions. Additionally, the hyperaldosteronism increases H+ excretion via effects on the H-ATPase. Together these explain the paradoxical aciduria associated with GI loss-induced metabolic alkalosis as hydrogen is excreted despite alkalemia. The chloride depleted state, as well as the sodium retention induced by volume depletion, also lead to maintenance of the alkalosis by limiting bicarbonate excretion by a variety of mechanisms. It is for this reason that such alkaloses are termed saline responsive, indicated by a low urine chloride - administration of saline leads to correction of hypovolemia and therefore removes the stimulus to aldosterone, while at the same time chloride replenishment allows for the excretion of bicarbonate while minimizing H+ excretion, leading to an appropriately alkaline urine and rapid correction of the electrolyte abnormalities.

But is metabolic alkalosis the only acid-base disturbance that results from NG decompression? Some anecdotal experience suggests not. As noted above gastric fluid contains little potassium and almost no bicarbonate. So at first glance the answer seems to be no. However, there is a not-so-infrequent clinical scenario where NG decompression can result in metabolic acidosis. More distal fluids, such as bile, pancreatic secretions, and small bowel fluids all have high concentrations of bicarbonate (45, 92, and 50 mEq/L respectively). When NG suction is employed to decompress a small bowel obstruction, more distal fluids can be suctioned, leading to bicarbonate loss. In general though, the suctioned fluid will also contain gastric acid and there will be limited net change in acid-base status. However, if gastric acid production is limited by a proton pump inhibitor, metabolic acidosis can ensue. This was the case with a patient we were consulted on with a metabolic acidosis and bicarbonate of 13 in the setting of NG decompression for a partial small bowel obstruction. The patient was also on a PPI. He was not having diarrhea. To test our theory, we checked the pH of his NG fluid (pH testing was more readily available than electrolytes). The pH was 6.9, far above what would be expected from a PPI alone. We suggested holding his PPI. His acidosis resolved quickly, though in the context of discontinuation of NG decompression and bicarbonate administration, so we can't say for sure that holding the PPI during NG decompression solved the problem. Nonetheless, sharing our case with other colleagues revealed similar anecdotal experiences, suggesting that the phenomenon of metabolic acidosis resulting from upper GI loss of bicarbonate in the setting of partial or complete small bowel obstruction, NG decompression, and concomitant PPI administration should at least be kept in the back of the mind.