Flashcards in HTN & The Kidney Deck (58):
What 4 organ systems are involved in the regulation of BP?
1. Central and autonomic nervous system
2. CV system (heart and blood vessels)
4. Adrenal gland
What is prehypertension defined as? Stage I HTN? Stage II HTN?
Pre: systolic 120-139 and diastolic 80-89
Stage I: 140-159 and 90-99
Stage II: 160+ and 100+
What are the characteristics of essential HTN?
No identifiable etiology. Not a single disease. Age of onset between 40 and 50 yo. Genetic predisposition (70-80% have positive family hx).
What are the characteristics of secondary HTN?
Identifiable etiology. Many factors cause BP elevation by influencing CO or systemic vascular resistance. Bimodal age distribution: 50 yo.
What are 3 candidate genes that can lead to HTN?
1. M235T variant in angiotensinogen gene
2. ACE gene
3. Beta-2-Adrenergic receptor gene
What are 3 monogenic diseases that have been identified that lead to HTN?
1. Liddle's Disease: activating ENaC mutation
2. Glucocorticoid Remediable Aldosteronism: gene mutation leading to aldosterone synthetase that is responsive to ACTH
3. Apparent Mineralocorticoid Excess: inactivating mutations in the 11-beta-hydroxylase-dehydrogenase-2 gene
What are the 2 equations for calculating mean arterial pressure?
MAP=CO x SVR (systemic vascular resistance)
MAP=DBP + (1/3)(SBP-DBP)
What is the equation for calculating CO?
CO=SV x HR
(SV= stroke volume, HR= heart rate)
What 2 factors is stroke volume dependent upon?
Pre-load and cardiac contractility.
An increase in pre-load means an increase in one of which 2 things?
Increased venous tone or increased volume (and therefore increase in total body Na).
T or F. Increased CO in essential HTN persists throughout the course of the disease.
How do the kidneys play a role in BP regulation?
They regulate ECFV by altering Na and water via excretion or reabsorption. Sustained HTN is a result of defective ability of the kidney to excrete excess Na.
In the majority of patients, how is BP lowered?
Modulation of Na intake or excretion (via diuretics).
T or F. Kidney transplantation from a hypertensive patient to a normotensive patient will induce HTN in the recipient.
T: the vice versa is also true.
What are the 3 theories about the role of kidney physiology in the development of HTN?
1. Guyton AC: kidney as central cause
2. Brenner BM: reduced nephron mass
3. Laragh JH: RAAS
Elaborate on Guyton's theory.
The central role in the development of HTN is the inability of the kidneys to appropriately excrete Na (pressure natriuresis). Thus, impairment of pressure natriuresis is essential for elevated BP to persist.
Describe pressure natriuresis.
When perfusion pressure increases, renal Na output increases and ECF and blood volumes contract by an amount sufficient to return arterial BP to baseline.
T or F. Changes in Na excretion only occur with changes in GFR.
F: changs in Na excretion occur WITHOUT changes in GFR.
Where is the principle site of pressure natriuresis?
Outer medullary thick ascending limb. Changes in interstitial medullary pressure is a mediator of pressure natriuresis.
What is the one pro of Guyton's theory?
It allows for a normal blood volume despite an elevated pressure which is consistent with most volume measurements in hypertensive patients.
What are the cons of Guyton's theory?
It ignores the role of the autonomic nervous system in development of HTN. It fails to explain the increased BP in prehypertensive patients where the increase in CO is mainly driven by sympathetic activation.
What is long term autoregulation (transition of increased CO to increased systemic vascular resistance)?
An increase in CO leads to autoregulation and vasoconstriction of resistance vessels with an increase in systemic vascular resistance, and thus subsequent normalization of CO.
What is the role of ouabain in the transition from inc CO to inc SVR?
Ouabain binds to and inhibits the Na/K-ATPase.
What is the role of salt in HTN?
Increased salt leads to increased volume which leads to increased CO and thus HTN.
Describe salt-sensitive HTN.
An inc in BP is seen with a high salt diet and vice versa. Affects blacks more than whites. Salt sensitivity increases with age.
What are the possible mechanisms of developing salt-sensitive HTN?
Dec Na excretion by kidneys (main). Inc SNS activity. Inc activity of kidney Na/H exchanger. Inc intracellular Ca in vascular smooth muscle cells. Dec in NO.
What are the vasoconstrictors affecting systemic vascular resistance? The vasodilators?
Constrictors: ATII, norepinephrine, endothelin, ADMA.
Dilators: NO, prostacyclin, PGE2, PGD2, adenosine.
What are the humoral factors affecting systemic vascular resistance? The local factors?
Humoral: vasoconstrictors and -dilators mentioned above.
Local (aka autoregulation): mediated primarily by NO.
What is the overall goal of RAAS?
To increase BP in response to hypovolemia or hypotension.
How does Angiotensin II increase Na reabsorption?
Stimulates Na/K-ATPase. It also increases aldosterone secretion and increases systemic vascular resistance (vasoconstrictor).
What are the 3 types of cells in the JG apparatus?
1. Granular or JG cells
2. Macula Densa cells
3. Extraglomerular mesangial cells
What are the 3 types of receptors in JG cells and what happens to renin when activated?
1. Beta-1: inc renin
2. Adenosin2: dec renin
3. Prostaglandin: inc renin
Increased NaCl delivery to MD cells causes what? Decreased NaCl delivery?
Increased NaCl deliver causes an increase in adenosine. Decreased NaCl delivery causes an increase in NO and PGs.
T or F. Renin is elevated in everyone with HTN.
What is dry HTN?
HTN with high plasma renin activity.
What is wet HTN?
HTN with low plasma renin activity.
Describe Laragh's hypothesis of nephron heterogenesity.
Some nephrons are ischemic and produce high plasma renin activity, while others are not but will have impaired natriuresis from ATII. Total plasma renin activity is diluted and may be normal.
What is the model of unilateral renal artery stenosis (Goldblatt model I)?
HTN due to unilateral RAS is associated with both increased SVR and a right shift in natriuresis in the normal kidney. Normal kidney is able to excrete the excess Na and therefore volume does not play a role in the HTN. ACE inhibitors reduce BP in this case.
What is the model of bilateral renal artery stenosis (Goldblatt model II)?
Total kidney hypoperfusion. No off-setting natriuresis (bc no normal kidney). ACE inhibitors do not help.
What are the 4 types of secondary HTN?
1. Aldosterone excess
2. Glucocorticoid excess
3. Pseudohyperaldosteronism (11-beta-hsd inhibition, Liddle's syndrome)
4. Pseudohypoaldosteronism type 2=Gordon's syndrome
What are the characteristics of secondary HTN?
All are salt-sensitive HTN. All (except aldo excess) have low renin and low aldo. All (except Gordon's) have hypokalemia and metabolic alkalosis.
How is BP elevated with aldosterone excess?
Aldo activates Na/K-ATPase leading to increased Na reabsorption thus leading to increased BP.
Glucocorticoid excess is seen in what syndrome?
How is BP elevated with glucocorticoid excess?
Same mechanism as aldosterone.
What is the role of 11-beta-hydroxysteroid dehydrogenase?
Normally, it converts cortisol to cortisone which cannot bind to and stimulate the Na/K-ATPase. In glucocorticoid excess, the enzyme is overwhelmed and the excess cortisol binds.
Pseudohyperaldosteronism results from what?
Deficiency in 11-beta-hydroxysteroid DH. Note, chronic licorice ingestion (from candies or chewing tobacco) inhibits this enzyme.
What are the clinical features of pseudohyperaldosteronism?
HTN, hypokalemia, metabolic alkalosis, low renin, low aldosterone.
What is the inheritance pattern of Liddle's syndrome?
Liddle's syndrome is due to what?
Constituitive activation of Na channels in distal tubule due to mutation in beta or gamma subunits.
How do you treat Liddle's?
Triamterene or Amiloride
What is the mechanism of hypokalemia seen in Liddle's?
Increased Na entering tubular cells via ENaC in collecting duct will increase K secretion by creating a favorable gradient.
What is the mechanism of metabolic alkalosis in Liddle's?
Increased H secretion by H pump in response to activation of mineralocorticoid receptor. Hypokalemia causes intracellular shift of H into tubular cells and subsequent secretion to lumen.
Describe Gordon's syndrome (pseudohypoaldosteronism type II).
Constitutive activation of thiazide-sensitive Na-Cl channels in DCT due to mutations in WNK1 or WNK4. This reduces Na delivery to collecting duct.
What are the clinical features of Gordon's?
Salt-sensitive HTN, hyperkalemia, and metabolic acidosis.
Why is hyperkalemia seen in Gordon's?
Decreased Na delivery to the DCT results in a less positive charged tubular cell thus decreasing the drive for K secretion. Thus, less K is secreted, more is reabsorbed...hyperkalemia.
Blood pressure is a result of what 2 things?
CO and SVR
What is the most common cause of HTN?