Hypertension Q

an increased PCW (pulmonary capillary wedge) which is about the same as left ventricular end diastolic pressure. increase hydrostatic pressure in lungs and due to Starling’s forces cause interstitial edema which decreases lung compliance thus contributing to the dyspnea. This is definitely an abnormal response.

The explanation for an increased PCW in setting of a decrease in stroke volume is seen in heart failure with normal ejections fraction (HFNEF) also known as heart failure with preserved ejection fraction (HFPEF) It was previously know as diastolic failure. Note his ejection fraction (EF) (LVEDV – LVESV)/LVEDV at 56% is normal ie >50%


 
2.The other explanation for dyspnea/fatigue is inadequate cardiac output to skeletal muscles in the setting of increased demand.
Cardiac output does not go up due to the above explanation of decreased lusitropy resulting in decreased ability to increase SV. It has also been shown that even if they are not on a beta blocker their heart rate does not rise as much as expected ie chronotropic failure.
Since this patient was on a beta blocker it affected the peak HR at the end of exercise. In addition they also have shown the expected increase in EF does not happen. Fatigue is what many patients complain about when exercising.

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See below as to why PCW increased and SV decreased (known as failure of Frank Starling mechanism).
 
In this patient, the curve at baseline is shifted up and to the left explaining baseline increased LV end diastolic pressure (20 mm Hg).
With exercise there is a further shift of curve up and to the left meaning an actual decrease in EDV at the same time as an increase in LV end diastolic pressure.
Potential mechanisms to explain this decreased lusitropy are
 
a. the increase in systolic blood pressure during exercise directly decreases lusitropy of the left ventricle
b. the patient develops functional ischemia which could be explained by increased demand secondary to increased heart rate, increased systolic pressure but at same time inadequate O2 supply due to decreased coronary blood flow related to less time in diastole.

Another important concept is decreased coronary perfusion pressure. Since the coronaries fill during diastole the CPP = aortic diastolic blood pressure – (any pressure drop if there is a stenosis) - LV end diastolic pressure. Note that in this patient the PCW increased to 40 mm Hg thus decreasing CPP.
The ischemia can also decrease lusitropy. It is not likely in this patient since he had normal coronaries but it does not preclude microvascular disease.

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Normally the pressure falls in the LV due to isovolumetric relaxation and the drop in pressure is so rapid it falls below left atrial pressure. As a result in early diastole there is normally a gradient between the left atrium and left ventricle (suction affect).
Due to the stiff ventricle in this patient, flow is not as rapid in early diastole and reliance is significantly increased on the atrial kick at the end of diastole to fill; flow is actually greater due to atrial kick compared to passive filling.

With atrial fibrillation the atrial kick is lost and this causes decreased filling of ventricle (or if it fills it is due to increased pressure in the left atrium). With a rapid ventricular response in atrial fibrillation there are beats where there is very little time available to fill due to a decreased RR interval resulting in a decreased SV. Even though there are beats with an increased RR interval that have increased time to fill the ventricle has such a decrease in lusitropy it can’t significantly increase EDV in order to increase SV. This decrease in SV increases preload and in the setting of a ventricle with decreased lusitropy this results in very high end diastolic pressures.

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he main reason the patient has peripheral edema is as a result of the patient having heart failure (HFNEF). He has components of both “left heart failure” with the dyspnea and evidence of high left sided filling pressures on catheterization (note LV filling pressures of 20 mm Hg which are high (normal <8 mm Hg). b. He also has signs of right heart failure with increased right atrial pressures and the edema. The patient has this sodium retention as a result of a low cardiac output and the kidney senses a decreased volume and due to activation of RAA in part reabsorbs increased amounts of sodium causing the positive sodium balance and peripheral edema. Note baseline LV filling pressures of 20 which are high (normal <8 mm Hg)
Amlodipine can also cause edema but is not the major reason in this patient. Amlodipine is a dihydropyridine calcium channel blocker. At the arterioles it lowers resistance. Change in pressure = flow x resistance. The drug does not change flow but will decrease peripheral resistance; thus, there is less of a pressure drop in the arterioles leading to an increased pressure at the arterial end of the capillary. Based on Starling forces ie increased capillary pressure results in more filtration of fluid. It does reach a new steady state due to the increased fluid in the interstitium causes an increased interstitial pressure bringing gradient between capillary – interstitial pressure back to steady state conditions. This is known as vasodilator edema.

If you give a patient amlodipine there is a decrease in arteriolar resistance. This decreased resistance causes less of a pressure drop in the arterioles since the pressure change in arterioles = flow x resistance.  This then causes an increase in P cap art depicted below.   Note that this increase in pressure on the arterial end of the capillaries will according to Starling forces favor fluid leaving the capillary thus leading to edema

The reason the edema does not continue to progress is that this increase in fluid in the interstitium will cause an increase in P interstitium.  As a result both the P cap art and  P interstitium will increase but at steady state the gradient at the arteriolar and venular end of the capillary will be the same as before giving amlodipine.  Note that if you remove the amlodipine there will be a drop in P cap art and P cap ven but due to the increase in P interstitium this will favor movement of fluid back into the capillaries
 

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The echocardiographic data show reduced EDV parameters and LV hypertrophy ; with a normal ejection fraction , systole is intact and this confirms the LV filling problem during diastole noted above

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Pulse pressure (systolic – diastolic)
Compliance of the aorta = change in volume (stroke volume)/change in pressure (pulse pressure)
VO2 = CO x (arterial-venous O2 content difference
cardiac output (increased stroke volume X increased heart rate)
Mean arterial pressure is diastolic pressure + 1/3 pulse pressure
CPP = aortic diastolic blood pressure – (any pressure drop if there is a stenosis) - LV end diastolic pressure.
FF = GFR/RPF
Filtered load= plasma ion x GFR

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Increaed pulse pressure at baseline due to decreased aortic compliance due to arteriosclerosis due to increase in arterial stiffening and decrease in arterial compliance.
-SV went down at exercise
-huge increase in MAP because SVR did not decrease as much as expected

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-needs incease in O2 delivery with exercise, which happens
with increased CO and lowering of mixed venous content. Increased CO happens with increased HR due to sympathetics and increase in SV
-increased SV due to increased lusitropy to make up for decreased time in diastole, vasodilatation in muscle vascular beds for decrease in afterload, increased VR/contractility,
-Pulse pressure increases due to increased SV
-some increase in MAP because of increased CO and decreased SVR

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Whenever someone is poorly controlled on 3 agents (one of which includes a diuretic) it is considered ‘resistant’ hypertension. Possibilities for this problem include:
 
a. Hypertensive renal disease based on history and urinalysis only having 1+ protein or large renal artery stenoses (especially if evidence of smoking and vascular disease)
b. Primary aldosteronism which can be tested for by aldosterone/renin ratio where if primary aldosteronism increased aldosterone and decreased renin. The reduced potassium ( K = 3.6 meq/L) is most likely due to furosemide but primary aldosteronism remains in the differential.
c. Most likely in this patient the uncontrolled hypertension is due to a combination of sodium overload and inadequate doses of medications. Amlodipine may be increased to 10 mg, doxazosin at 2 mg is relatively low dose and is rarely utilized. Furosemide is a loop diuretic but has a short half life (hence, after it wears off a positive sodium balance can redevelop). Metoprolol is not a very effective antihypertensive agent when the key problem is an increase in SVR or an increase in PV.
 
In this patient, other pharmacologic options would be to give a blocker of the renin-angiotensin-aldosterone system (RAAS).
These include renin inhibitors, angiotensin converting enzymes or angiotensin receptor blockers. The rational is that these drugs will reduce blood pressure by decreasing resistance and in the long term cause regression of LVH. With volume overload present, diuresis can be increased but need to be careful not to overdiurese since due to a stiff LV it is very easy to overdiurese resulting in decreased filling pressures and stroke volume.
 
In the past some felt a beta blocker would be beneficial to improve CO in patients with HFPEF. The rational was that if you gave a beta blocker to decrease heart rate during exercise ie more time to fill the EDV and SV would increase and even if heart rate did not go up as much there would still be an increase in CO. Since the ventricle is so stiff, SV does not change significantly but with the beta blocker decreasing peak HR during exercise the CO will likely actually decrease compared to not being on a beta blocker. One beneficial effect of beta blockers is to decrease LVH. Unfortunately no agent improves lusitropy.

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The bruit implies vascular disease and possible renal artery stenosis especially in setting of known claudication. However, there are many other potential etiologies include iliac and mesenteric arterial stenoses.

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When we see a patient with an increased creatinine and decreased creatinine clearance and GFR the differential diagnosis is
 
a. Prerenal: Low flow to the kidney due to decreased cardiac output (heart failure) or low flow due to obstructive arterial disease (renal artery stenosis) a likely possibility in this case due to known vascular disease and severe increase in blood pressure.
b. Glomerular or interstitial disease tubular disease. He could have some hypertensive glomerulosclerosis and the urinalysis of 1+ protein is consistent.
c. Least likely : Post renal processes including benign prostatic hypertrophy or carcinoma. Obstruction is ruled out based on normal renal ultrasounds.

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a) How does the kidney normally respond to decreased flow in attempting to help maintain GFR. In your answer comment on why the filtration fraction increases (GFR/RPF). Normally FF is about 20% GFR (120cc)/RPF(600cc)
 
When there is low flow to the kidney it attempts to compensate for low renal plasma flow by increasing filtration fraction.
FF = GFR/RPF Filtration fraction is increased by an increase in efferent arterial resistance causing increased glomerular pressure and based on Starling forces increased filtration of fluid. The predominant reason for the increased glomerular pressure is due to renal artery stenosis causing a low flow thus activating the RAAS. Angiotensin II will constrict the efferent artery thus increasing glomerular pressure and filtration fraction.
 
b) Why did the enalaprilat cause a decrease in renal function?
 
By giving enalaprilat the production of angiotensin II is reduced (it is an ACE inhibitor) thus causing dilation of the efferent artery thereby decreasing glomerular pressures and FF. In addition, as a result of the significant decreased blood pressure distal to the stenosis this would decrease glomerular pressure. It has been shown with RAS there is a required perfusion pressure and if you go below that pressure GFR decreases.

a) What is the mechanism for the increase in potassium after enalaprilat?
 
The plasma potassium increased due to decreased renal function decreasing the filtered load of potassium (plasma K X GFR) as well as decreasing angiotensin II leading to decreased aldosterone induced potassium secretion into the urine at the collecting duct..

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Increased SVR resistance likely due to RAS causing activation of RAA as a result of decreased flow but also implicated would be endothelin and catecholamines

In patients with anemia (hematocrit < 30%) an increased cardiac output would be required for normal oxygen consumption ; hematocrit over 30%, the body can compensate for anemia by increasing oxygen extraction (e.g., increase A-V difference due to decreased venous content).

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Evaluation:
 
a. Magnetic resonance angiography (MRA). the substance that ‘lights up the renal arteries’ (gadolinium) used in magnetic resonance imaging has been recognized as a very rare but dangerous toxin in patients with reduced GFR and should not be given.

b. Captopril scan. If the patient has evidence of decreased flow after captopril (ACE inhibitor) it implies that renal function was somewhat dependent on AII. In this patient we know based on enalaprilat , renal function was dependent on AII. One dose would still be all right for diagnostic purposes.

c. Ultrasonographic duplex scan showing scan and flow – this is effective and safe in patients with renal disease.

d. Direct angiogram – the ‘gold standard’ test – concerns always must include contrast toxicity to the kidneys and atheroembolic disease induced by the catheter traveling through the arterial system (knocks off plaque in the large arteries) – rare but nevertheless a concern.
 
In this patient with such severe hypertension, we would definitely consider direct angiogram with possible stent placement. Correcting renal blood flow is unlikely to ever normalize the BP but would make pharmacologic therapy better tolerated and hopefully preserve renal function. This patient is an excellent example of the 1 kidney, 1 clip Goldblatt model described in class. Recent papers question the use of invasive therapy for renal artery stenosis since it does not appear to affect outcomes.

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