Hypertension

Question 1

Normal Blood Pressure

Answer 1

• Systolic < 120mmHg & diastolic <80mmHg

Question 2

Elevated blood pressure

Answer 2

• Systolic 120-129mmHg & diastolic 80-89 mmHg

Question 3

Hypertension

Answer 3

• BP ≥ 140/90 mmHg, unless DM (≥ 130/80mmHg) or age ≥ 80 (≥ 150/90mmHg)
  
  • If there is disparity in category between systolic and diastolic, the higher value determines is patient has hypertension
• Definition of hypertension is based on the relationship between blood pressure and risk of cardiovascular event

Question 4

Isolated hypertension

Answer 4

• Isolated systolic hypertension - BP ≥ 140/ <90mmHg
• Isolated diastolic hypertension - BP <140/ ≥ 90mmHg

Question 5

Hypertensive urgency and emergency

Answer 5

• Hypertensive urgency
  
  • Systolic BP >210 or diastolic BP >120 with miminal or no target-organ damage
• Hypertensive emergency
  
  • Severe hypertension (diastolic >120) + acute target-organ damage
  • Accelerated hypertension - significant recent increase in BP over previous hypertensive levels associated with evidence of vascular damage on fundoscopy, but no papilledema
  • Malignant hypertension - sufficient elevation in BP to cause papiledema and other manifestation of vascular damage (retinal hemmorrhages, bludging didcs, mental status change, increase creatinine)

Question 6

Primary/essential hypertension

Answer 6

• A form of hypertension that has no identifiable cause. It is the most common type of hypertension (<90%)
• Pathogensis - maintenance of arterial BP is necessary for organ perfusion
  
  • BP = CO X systemic vascular resistance (SVR)
  • BP changes to maintain organ perfusion over a variety of conditions - factors that determine BP = sympathetic nervous system, RAAS, and plasma volume (controlled by the kidneys)
  • Pathogensis for primary hypertension is unknown, but it is likely due to the combined effects of genetic and environmental factors that affect cardiovascular and renal structure and function.

Question 7

Risk factors for primary hypertension

Answer 7

• Advancing age
• Obesity
• Family history
• Race - more common, more severe, and greater target organ damage in blacks
• Reduced nephron number - reduced nephron mass is associated with hypertension. May be related to genetic factors, developmental disturbances, premature birth, and postnatal environment
• High sodium diet (>3g/day) increase risk for hypertension
• Excessive alcoholc consumption
• Physical inactivity

Question 8

Secondary hypertension

Answer 8

• Raised blood pressure secondary to another medical condition
• Renal
  
  • Renovascular hypertension
  • Renal parenchymal disease, glomerulonephritis, pyelonephritis, polycystic kidney
• Endocrine
  
  • Primary hyperaldoesteronism
  • Pheochromocytoma
  • Cushings syndrome
  • Hyperthyroidism
  • Hyperparathyroidism
  • Hypercalcemia of any cause
• Vascular
  
  • Coaractation of the aorta
  • Renal artery stenosis
• Drug-induced
  
  • Estrogens/OCP
  • MAOIs
  • Cocaine
  • Steriods
  • Lithium
  • Amphetmaines
  • NSAIDs
  • Decongestants
  • Alcohol

Question 9

Complications of Hypertension

Answer 9

• Hypertension is assocaited with increased risk of adverses cardiovascular and renal outcomes
  
  • Left ventricular hypertrophy
  • Heart failure - both systolic (HrEF) and diastolic (HpEF)
  • Ischemic stroke
  • Intercerebral hemorrhage
  • Ischemic heart disease (MI)
  • Chronic kidney disease and end-stage renal disease
• As BP increases, the risk of complications increase - for every 20mmHG increase systolic and 10mmHg increase in diastolic, the risk of death from heart disease or stroke doubles
  
  • Over age 50 - systolic pressure is better predictor of mortality
  • Under age 50 - diastolic pressure is better predictor of mortality

Question 10

Labortary Testing Hypertension

Answer 10

• All patients with newly diagnosed hypertension should have the following tests done
  
  • Electrolytes, creatinine (to calculate GFR), fasting glucose of Hba1c, Urinarlysis, CBC, TSHm lipid profile, ECG
• For specific patient subgroups
  
  • DM or chronic kidney disease - urinary protein excretion
  • Suspected renovacular hypertension - renal ultrasound, captopril renal scan (if GFR >60ml/min)
  • Suspected enocrine cause - plasma renine and aldosterone

Question 11

Treatment hypertension -Lifestyle

Answer 11

• Lifestyle modification
  
  • Diet
    
    • DASH (dietary approaches to stop hypertension) - high fruits, veggies, wholes grains, low-fat, dairy, polutry, fish and nuts. Low in surgars and red meats.
    • Limit sodium intake
    • Increase dietary postassium may help
  • Moderate intensity dynamic exercise: 30-69mins, 4-7X/week
  • Smoking cessation
  • Reduction in alcohol intake
  • Weight loss
  • CBT for stress management

Question 12

Treatment hypertension - Pharmacological

Answer 12

• First line - thiazide/thiazide-like diuretic, ACE-inhibitor, Angiotension II receptor blockers (ARBs), long-acting calcium channel blocker, B-blocker (if age <60)
  
  • If BP is >15mmHh above goal, will likely need to add a second agent (more effective to combine therepies than to double dose of one agent)
  • Best to combine either an ACE-inhibitor or an ARB with a thiazide diuretic and/or long-acting calcium channel blocker

Question 13

Indications for hypertensive medications

Answer 13

• dBP ≥ 90mmHg with target organ damage or independent cardiovascular risk factors
• dBP ≥ 100mmHg or sBP ≥160mmHg without targer organ damage or cardiovascular risk factors
• sBP ≥ 140 with target organ damage

Question 14

Overall safety of antihypertensive medications in pregnancy

Answer 14

• All antihypertensive medications cross the placenta
• There is evidence suggestions that women with chronic hypertension (both treated and not treated) are at higher risk of congential malformations in offspring (particularly cardiac malformations).
• It is recommended to give antihypertensive medication to prevent maternal cardiovascular morbidity and mortality

Question 15

Medications with acceptable safety profile in pregnancy

Answer 15

• Methyldopa
  
  • Widely used in pregnant women and has shown long-term safety for the fetus
  • Only mid antihypertensive agent with slow onset of action - many will not achieve BP goals
• Labetalol (β-blocker) - has both α and β-adrenergic blocking agent, and may maintain uteroplacental blood flow to greater extent than traditional β-blockers
  
  • Faster oneset of action than methyldopa
  • Shown to be generally safe in pregnancy, but may increase increase risk of maternal hepatotoxicity
• Hydralazine - IV hydralazine is commonly used in preclampsia for acute treatment of severe hypertension

Question 16

Diuretics MOA

Answer 16

• Act by reducing sodium reabsorption at different sites in the nephron, increasing urinary sodium and water excretion

Question 17

Major classes of diuretics

Answer 17

1. Loop diuretics - act in thick ascending limb of loop of Henle
2. Thiazide-type diuretics - act in dital tublue and connecting segment
3. Potassium-sparing diuretics - works on aldosterone -sensitive principal cells in cortical collecting tubule
4. Acetazlomide and mannitol - act at least partially at proximal tubule

Question 18

What determines the potency of diuretics?

Answer 18

• Where the diuretic works in the nephon is the main factor determining the potency of the diuretic
• Since most sodium is reabsorbed at the proximal tubule (60-65%) and loop of Henle (20%) one would think that proximally acting diuretics would incude large losses of sodium and water. However, this does not happen because almost all the excess fluid can be reabsored more distally at loop Henle and some at distal tubule.

Question 19

Explain the mechanism of Loop Diuretics

Answer 19

• Act in medullary and cortical aspects of thick ascending limb and macula densa in early distal tubule.
• At these locations, sodium entery is mediated by Na2CIK carrier in the lumen that is activated when all 4 sites are filled. Loop diuretics work by competing for the chloride site on the carrier, reducing net reabsorption.
• Important to note that Ca²⁺ reabsorption occurs passively at the loop of Henle, driven by electrochemical gradient by NaCI transport. Inhibiting NaCI reabsorption results in reduction in calcium reabsorption, thus increase calcium excretion.

Question 20

Explain the mechanism of Thiazide diuretics

Answer 20

• Acts mainly by inhibiting sodium transport at the distal tubule, and may slightly inhibit sodim transport at the cortical collecting tubule. Reabsorbs less then loop of Henle so there is limited effectiveness for treatment of edema
• Thiazide inhibits Na⁺ reabsorption by completing for CI^- site in Na-CI transporter
• Thiazide causes an increase in calcium reabsorption

Question 21

Potassium sparing diuretics

Answer 21

• Act in principal cells in the cortical collecting tubule. Here, sodium entry occurs via aldosterone-sensitive sodium channels. The reabsorption of Na⁺ without an anion (-) creates a lumen-negative electrical gradient that favors potassium & H⁺ excretion. Thus, inhibition of Na⁺ at these sites can potentally lead to hyperkalemia and metabolic acidosis due to secondary reduction in potassium and H⁺ excretion.
• Work either by completing with aldosterone, or directly blocking the ENaC channel

Question 22

Why do NSAIDs worsen heart failure?

Answer 22

• In heart failure the kidney is dependent on prostagladins for vasodilation in order to maintain renal perfusion and salt and water balance
• NSAIDs inhibit COX-1 (produces thromboxane) and COX-2 (produces prostagladins).
• By inhibiting prostagladin synthesis, we see an increase in salt and water retension and a decrease in renal blood flow and glomerular filitration rate.
• In patients with pre-exisiting heart failure, this may lead to cardiac compensation