Sustained Hypertension
Left ventricular systolic dysfunction -> decreased CO
Diastolic dysfunction -> less relaxation of ventricles -> increased stiffness -> decreased CO
Thus, both systolic and diastolic dysfunction lead to decreased CO with diastolic dysfunction
having increased issues as it relates to relaxation therefore, decreased relaxation, increased
stiffness
Main Consequences of Hypertension
1. Increased afterload – the resistance in which blood is expelled
2. Arterial damage – due to increased afterload and high blood pressure against arterial
walls
Kidneys in hypertension
Fail to eliminate fluid which leads to further fluid retention and more blood volume and higher
blood pressure
Damage of endothelial cells
Caused by high BP
Leads to
a. Atherosclerosis
b. Aneurysm (weakening of vessel walls)
c. Glomerular nephritis (damage)
Fluid retention in the kidney
Proximal tubule (65% of Na reabsorption)
Loop (25% of Na reabsorption)
Distal tubule (very little Na reabsorption)
Tubuloglomerular Feedback
Macula dense, which connects afferent arteriole and loop, senses increase Na in
nephron/glomerulus
Macula dense signals and causes vasoconstriction via afferent arteriole as it takes this high Na
to mean dehydration
Diuretics
1. Loop Diuretics: Furosemide
a. strong diuretic – but – stimulates kidney activation via RAAS (overcorrection)
b. only used in those with CKD (BP won’t drop too low b/c kidneys wont stim RAAS)
c. inhibit Na-K-2Cl symport
d. Cl not moved into interstitial space leading to decreased reabsorption of Mg and
Ca
e. K loss increases due to RAAS reflex
f. Uric acid retention contributes to gout
, 2. Thiazide: Indapamide
a. Distal tubule Na-Cl symport targeted
b. Better BP control for those with healthy kidneys
c. Ca can increase
d. Mg loss but not as much as Loop
e. Ineffective if GFR is below 30-40 mL/min
3. K+ Sparing
a. Distal tubule and collecting duct
b. Inhibit epithelial Na channels (ENaCs)
c. Exaggerates the polarization at epithelial membrane to discourage K+ excretion
d. Can be used in combination with diuretics to lessen the loss of K+
4. Carbonic Anhydrase Inhibitors
a. Blocks conversion of carbonic acid to water and carbon dioxide
b. Stops movement of carbonic acid into the cell which stops the symport of Na and
bicarbonate from being utilized which results in less Na reabsorption
c. NOT USED AS A DIURETIC
5. Osmotic Diuretics
a. Freely filtered and stay inside nephrons and create an osmotic effect to keep
water in urine
Problems found with both loop and thiazide diuretics
1. Electrolyte problems
a. Hypokalemia due to RAAS stimulation
b. Hyponatremia
c. Hypochloremia
d. Hypomagnesemia
e. Increased calcium (thiazide) and decreased calcium (loop)
2. Impact on plasma metabolites/compounds
a. Hyperuricemia
b. Decrease glucose tolerance
3. Hemodynamic effects
a. Hypotension
b. Reduced renal perfusion (decreased GFR)
c. Increases RAAS
Classes of Hormones that relate to BP
1. RAAS – activated by low pressure in glomerulus which triggers release of renin
2. Sympathetic NS Hormones
3. Vasopressin
4. Peptide Dilators
5. Nitric Oxide
, Three ways to trigger renin release
1. Low renal pressure (baroreceptors)
2. Low Na in loop (macula densa)
3. SNS activation (B1 receptor)
Angiotensin II
-Causes preferential vasoconstriction of the EFFERENT ARTERIOLES which leads to DECREASED
PRESSURE IN AFFERENT BLOOD VESSELS
-results in an INCREASED IN BP without increasing blood volume in the kidney
-increases GFR -> increased filtration and ability to manage fluids
-releases aldosterone
Aldosterone
-bodies main mineralocorticoid
-causes Na reabsorption and K+ excretion
-increases synthesis and activity of ENaCs
RAAS Inhibition Medications
1. ACE-I: Ramipril – first line agent for CKD
a. Inhibit ACE activity (Angiotensin I -> Angiotensin II disturbed)
b. Used for high blood pressure to cause vasodilation and decrease aldosterone
secretion
c. Used for heart failure and atherosclerosis to decrease the adverse effects of
aldosterone and angiotensin II on heart and blood vessels
d. Used for CKD to decrease glomerular pressure
e. Hypotension
f. Dry cough
g. Hyperkalemia via RAAS inhibition
h. Edema
2. ARBs: Valsartan – first line agent for CKD
a. Angiotensin II receptor blocker
b. Exact same actions as ACE-I: vasodilation and decrease aldosterone secretion
c. Hypotension
d. Hyperkalemia via RAAS inhibition
e. Edema
3. DRI
a. Direct renin inhibitors – bind to active site of renin
b. Blocks conversion of angiotensinogen to angiotensin I
4. MRA: Spironolactone
a. Mineralocorticoid receptor antagonist
b. Inhibits aldosterone receptor
c. Used in resistant hypertension that is due to aldosterone excess
d. Used in HF to block negative effects of aldosterone
e. Hyperkalemia and hormonal effects (stim of androgen and progesterone)
Left ventricular systolic dysfunction -> decreased CO
Diastolic dysfunction -> less relaxation of ventricles -> increased stiffness -> decreased CO
Thus, both systolic and diastolic dysfunction lead to decreased CO with diastolic dysfunction
having increased issues as it relates to relaxation therefore, decreased relaxation, increased
stiffness
Main Consequences of Hypertension
1. Increased afterload – the resistance in which blood is expelled
2. Arterial damage – due to increased afterload and high blood pressure against arterial
walls
Kidneys in hypertension
Fail to eliminate fluid which leads to further fluid retention and more blood volume and higher
blood pressure
Damage of endothelial cells
Caused by high BP
Leads to
a. Atherosclerosis
b. Aneurysm (weakening of vessel walls)
c. Glomerular nephritis (damage)
Fluid retention in the kidney
Proximal tubule (65% of Na reabsorption)
Loop (25% of Na reabsorption)
Distal tubule (very little Na reabsorption)
Tubuloglomerular Feedback
Macula dense, which connects afferent arteriole and loop, senses increase Na in
nephron/glomerulus
Macula dense signals and causes vasoconstriction via afferent arteriole as it takes this high Na
to mean dehydration
Diuretics
1. Loop Diuretics: Furosemide
a. strong diuretic – but – stimulates kidney activation via RAAS (overcorrection)
b. only used in those with CKD (BP won’t drop too low b/c kidneys wont stim RAAS)
c. inhibit Na-K-2Cl symport
d. Cl not moved into interstitial space leading to decreased reabsorption of Mg and
Ca
e. K loss increases due to RAAS reflex
f. Uric acid retention contributes to gout
, 2. Thiazide: Indapamide
a. Distal tubule Na-Cl symport targeted
b. Better BP control for those with healthy kidneys
c. Ca can increase
d. Mg loss but not as much as Loop
e. Ineffective if GFR is below 30-40 mL/min
3. K+ Sparing
a. Distal tubule and collecting duct
b. Inhibit epithelial Na channels (ENaCs)
c. Exaggerates the polarization at epithelial membrane to discourage K+ excretion
d. Can be used in combination with diuretics to lessen the loss of K+
4. Carbonic Anhydrase Inhibitors
a. Blocks conversion of carbonic acid to water and carbon dioxide
b. Stops movement of carbonic acid into the cell which stops the symport of Na and
bicarbonate from being utilized which results in less Na reabsorption
c. NOT USED AS A DIURETIC
5. Osmotic Diuretics
a. Freely filtered and stay inside nephrons and create an osmotic effect to keep
water in urine
Problems found with both loop and thiazide diuretics
1. Electrolyte problems
a. Hypokalemia due to RAAS stimulation
b. Hyponatremia
c. Hypochloremia
d. Hypomagnesemia
e. Increased calcium (thiazide) and decreased calcium (loop)
2. Impact on plasma metabolites/compounds
a. Hyperuricemia
b. Decrease glucose tolerance
3. Hemodynamic effects
a. Hypotension
b. Reduced renal perfusion (decreased GFR)
c. Increases RAAS
Classes of Hormones that relate to BP
1. RAAS – activated by low pressure in glomerulus which triggers release of renin
2. Sympathetic NS Hormones
3. Vasopressin
4. Peptide Dilators
5. Nitric Oxide
, Three ways to trigger renin release
1. Low renal pressure (baroreceptors)
2. Low Na in loop (macula densa)
3. SNS activation (B1 receptor)
Angiotensin II
-Causes preferential vasoconstriction of the EFFERENT ARTERIOLES which leads to DECREASED
PRESSURE IN AFFERENT BLOOD VESSELS
-results in an INCREASED IN BP without increasing blood volume in the kidney
-increases GFR -> increased filtration and ability to manage fluids
-releases aldosterone
Aldosterone
-bodies main mineralocorticoid
-causes Na reabsorption and K+ excretion
-increases synthesis and activity of ENaCs
RAAS Inhibition Medications
1. ACE-I: Ramipril – first line agent for CKD
a. Inhibit ACE activity (Angiotensin I -> Angiotensin II disturbed)
b. Used for high blood pressure to cause vasodilation and decrease aldosterone
secretion
c. Used for heart failure and atherosclerosis to decrease the adverse effects of
aldosterone and angiotensin II on heart and blood vessels
d. Used for CKD to decrease glomerular pressure
e. Hypotension
f. Dry cough
g. Hyperkalemia via RAAS inhibition
h. Edema
2. ARBs: Valsartan – first line agent for CKD
a. Angiotensin II receptor blocker
b. Exact same actions as ACE-I: vasodilation and decrease aldosterone secretion
c. Hypotension
d. Hyperkalemia via RAAS inhibition
e. Edema
3. DRI
a. Direct renin inhibitors – bind to active site of renin
b. Blocks conversion of angiotensinogen to angiotensin I
4. MRA: Spironolactone
a. Mineralocorticoid receptor antagonist
b. Inhibits aldosterone receptor
c. Used in resistant hypertension that is due to aldosterone excess
d. Used in HF to block negative effects of aldosterone
e. Hyperkalemia and hormonal effects (stim of androgen and progesterone)
