Hypertension And The Kidney

Front 1

What is blood pressure?
How is it generated?
What does it ensure?

Back 1

Measurement of force applied to artery walls.

Generated by the cardiac contraction against vascular resistance --> driving force that moves blood through vascular system.

Ensures optimal delivery of metabolic substrates at the tissue level.

Front 2

Diastolic or systolic.

Heart contracts
Heart at rest

Back 2

Contract = systolic
Relax = diastolic

Front 3

What organ systems does blood pressure regulation involve?

Back 3

Central and autonomic nervous system
CV
Kidney
Adrenal gland

Front 4

For god's sake regurgitate the normal, pre-hypertension, etc. again.

Back 4

Front 5

Two types of hypertension: which one is most common? Causes of each.

Back 5

Primary: age = 40s and 50s, genetic

Secondary: age = young or old, changes in CO or SVR

Front 6

Overview of all the things that contribute to essential hypertension.

Back 6

Look it over.

Front 7

Do genetics play a role in HTN?

Back 7

Oh yes!

70-80% have a family history

Front 8

What are some candidate genes for HTN?

What leads to intermediate phenotypes?

Back 8

M235T variant in angiotensinogen gene, angiotensin-converting enzyme gene, B2-adrenergic receptor gene

Hypertensinogenic factors (environment and behavior)

Front 9

What monogenic diseases have been identified that lead to HTN?

Back 9

Liddle's disease = activating ENaC mutation

Glucocorticoid remediable aldosteronism: gene mutation that leads to aldosterone synthetase responsive ACTH

Mineralcorticoid excess: inactivating mutations in 11B-HSD-2 gene

Front 10

What is the equation for MAP?
What can increase in BP be?

Another equation for MAP?

Back 10

MAP = CO x SVR

Increase CO and/or SVR

MAP = (SBP-DBP)/3 + DBP

Front 11

What is the equation for CO?

How can you increase SV?

Back 11

CO = SV * HR

Increase pre-load or cardiac contractility --> increased SV

Front 12

What can increased pre-load be due to?

Does increased CO in essential HTN persist?
What is NOT a cardiac feature of essential HTN?

Back 12

Increased venous tone, increased volume--> must mean increase in total sodium (Na)

No!
Peripheral edema

Front 13

What is the role of kidney in BP regulation?

Back 13

Alter extracellular volume by altering NA and water excretion/reabsorption --> maintains healthy BP range

Front 14

What does the development of sustained HTN depend on?

What lowers BP in the majority of patients?

Back 14

Impairment in kidney ability to excrete excess sodium and therefore water.

Decrease Na intake, increase Na excretion (diuretics)

Front 15

True or false.
Hypertension follow the kidney.

Back 15

TRUE!

Kidney from hypertensive donor given to normotensive recipient will result in hypertensive patient.

Front 16

What is Guyton's theory of long-term BP control?

What does this imply?

Back 16

Essential HTN = ability of kidney to excrete sodium load

Homeostasis from pressure natriuresis = increase pressure, renal sodium output increases, EC fluid responds appropriately

Impairment in pressure-natriuresis = persistant elevated BP.

Front 17

Principal site of changes in Na excretion?
Does this affect GFR?
What is a mediator?

Back 17

No change in GFR
Principal site = TALH
Mediator = changes in interstitial medullary pressure

Front 18

How will the renal curve change in salt-sensitive hypertension?

Back 18

Decrease in slope?

Front 19

What are the pros of Guyton's theory?

Back 19

Allows for a normal blood volume despite an elevated pressure, in keeping with most volume measurements in hypertensive patients

Front 20

Cons of Guyton's theory?

Back 20

Ignores role of ANS in the development of HTN
Fails to explain BP↑ in prehypertension, where
↑ CO mainly driven by activation of SNS

Front 21

Draw the pathway of "long term autoregulation."

Back 21

What does an increase in CO lead to?

Front 22

What is the role of Ouabain in the transition from increased CO to increased SVR?

Back 22

Seems to decrease Na/K ATPase which would lead to increased Na+ in endothelium --> increased calcium --> decreased NO and increased endothelin --> vasoconstriction

Secreted by adrenal gland => also leads to increased sympathetic neurons => increased calcium => increased catecholamine release = > increased arterial tone => increased BP

Front 23

What is Brenner's hyppothesis of essential HTN?

Back 23

Reduction in nephron mass => makes kidneys unable to excrete normal sodium loads.

Front 24

What is the role of reduced nephron mass?

Back 24

Normal kidney = infusion of sodium --> small BP change

No kidney = infusion of sodium --> rapid BP rise

Progression of chronic kidney disease (decline in GFR) --> prevalence of HTN rises

Front 25

What is the role of salt in the development of HTN?

Back 25

Increased salt intake seems to correspond to higher BP.

Front 26

If there is no salt intake, even with aging, does HTN appear?

Back 26

No!

Front 27

What is the role of salt in HTN? Equation.
Not everyone is salt sensitive though. Which populations are more salt sensitive? Does salt sensitivity increase with age?

Back 27

Salt --> increased BV --> CO --> HTN

Front 28

What is the mechanism behind decreased kidney Na excretion that leads to HTN?

Back 28

Decrease kidney Na excretion --> increase activity of SNS --> activation of kidney Na/H+ exchanger --> increase in intracellular Ca in vascular smooth muscle cells --> decrease in NO

Front 29

What does MAP equal?

What are some factors that effect SVR? Vasoconstrictors and dilators?

What are some local factors (auto regulation)?

Back 29

MAP = CO x SVR

Vasoconstrictors = ATII, NE, endothelin, ADMA

Vasodilators = NO, prostacyclin, PGE2, PGD2, adenosine

Local = mediated by NO

Front 30

What is the pathway behind the renin-angiotensins-aldosterone system?

Back 30

Draw this out again.

Front 31

In the juxtraglomerular apparatus, what does the activation of each receptor do?

B1-Rc
Adenosine2-Rc
Prostaglandin Rc

Back 31

B1-Rc = increase renin secretion
Adenosine2-Rc = decease renin secretion
Prostaglandin Rc = increase renin

Front 32

In the macula dense, what is the effect of each?

Increase NaCl delivery
Decrease NaCl delivery

Back 32

Increase = increase adenosine production
Decrease = increase NO and prostaglandins

Front 33

What are extraglomerular mesangial cells?

Back 33

"Supporting cells"

Front 34

Is renin elevated in everyone with HTN?

Back 34

No!

20% high PRA (plasma renin acCvity): “Dry HTN” - 30% low PRA : “Wet HTN”
50% normal PRA

Front 35

What is Laragh's hypothesis of nephron heterogenesity?

Back 35

Some nephrons ischemic --> high PRA
Others not ischemic --> have imparied natriuresis from ATII

Total PRA is diluted and may be normal

Front 36

What is the role of RAAS in renal artery stenosis (secondary hypertension)? Use the Goldblatt model I.

What could be used to reduce BP?

Back 36

HTN associated with unilateral RAS is associated with increased SVR and right shift in pressure natriuresis in normal kidney --> excretes excess Na, volume does not play additional role in BP

ACE-inhibitors reduce BP

Front 37

What is the Goldblatt model II in the role of RAAS in BILATERAL renal artery stenosis?

Do ACE inhibitors work?

Back 37

Total kidney mass hypoperfusion
No off-setting pressure natriuresis (flash pulmonary edema)

Intolerance to ACE-inhibitors

Front 38

Is RAS more common in whites or black?

What does RAS get higher with?

Most common causes of RAS?

Back 38

32% whites with DBP > 125mmHg, only 4% black

increasing age, diabetics, PVD, DBP > 125mmHg

Atherosclerosis (85%)
Fibromuscular dysplasia

Front 39

What is the role of SNS in HTN?

Back 39

Cardiac output
Peripheral resistance
SNS

Front 40

What are some causes of secondary hypertension?

Back 40

Aldosterone excess
Glucocorticoid excess
Pseudohyperaldosteronism Type 1 (Liddle and 11B-hydroxysteroid dehydrogenase inhibition)
Pseudohyperalsoderonism type 2 (Gordon)

Front 41

What are all causes of secondary characterized by?

Back 41

Salt-sensitive hypertension

All (except aldosterone excess) => low renin and low aldosterone

All (except Gordon) => hypokalemia and metabolic alkalosis

Front 42

What are the mechanisms that lead to elevated BP with aldosterone excess?

Back 42

Front 43

what are the mechanisms that lead to volume expansion in glucocorticoid excess (Cushing's syndrome)?

Back 43

Front 44

What are the clinical features of pseudoHYPERaldosteronsm?
Two causes of 11B-hydroxysteroid dehyrdogenase deficiency or inhibition:

Back 44

HTN, hypokalemia, metabolic alkalosis, low renin, low aldosterone

Genetic = 11B-hydroxysteroid dehydrogenase deficiency
Acquired = chronic licorice ingestion inhibits 11B-HSD2

Front 45

What is the pathophysiology behind 11B-hydroxysteroid dehydogenase deficiency?

What is the treatment?

Back 45

Cortisol in presence of inhibition/deficiency --> epithelial sodium channel activation in CD --> increase Na reabsorption

Treatment = stop using substance if acquired, if genetic = use triamterene or amiloride

Front 46

How does Liddle's syndrome cause pseudohyperaldosteronism?

What is the therapy?

Back 46

Genetic defect = autosomal dominant mutation --> constitutive activation of Na+ channel in distal tubule due to mutation in B or gamma subunits

Triamterene or amiloride

Front 47

What is the mechanism behind hypokalemia?

Back 47

Increased Na reabsorption in CD --> increased K+ secretion by creating favorable gradient. --> intracellular shift of H+ into tubular cells --> secretion into lumen

Front 48

What is the mechanism of metabolic alkalosis?

Back 48

Increased H+ secretion by H-pump in response to activation of mineralcorticoid receptor

Hypokalemia --> intracellular shift of H+ into tubular cells --> secretion into lumen

Front 49

What is seen clinically with pseudoHYPOaldosteronism type II?
(Gordon syndrome)

Back 49

Salt-sensitive hypertension, hyperkalemia, and metabolic acidosis

Front 50

What is the mechanism behind Gordon syndrome?

How do you treat it?

Back 50

Constitutive activation of thiazide-sensitive Na-Cl channels in DCT --> increased Na+ reabsorption in DCT --> hypertension

Treat = thiazide diuretics

Front 51

BP = 185/102
HR = 78
Bicarb = 19
Creat = 1
k = 5.4


Increased function of which transporter or channel may explain hypertension?

Back 51

Sounds like metabolic alkalosis
Hyperkalemia

Gordon's syndrome (Pseudohypoaldosteronism type II)
Na-Cl co transporter in distal tubule.

Front 52

True or false:
The ability to maintain blood pressure in normal range with sodium loads is reduced in chronic kidney disease.

Back 52

True

Front 53

True or false:

If you eat a low sodium diet, you are less likely to develop hypertension even with aging.

Back 53

True

Front 54

When would RAS-blockers not be effective for blood pressure reduction?

Back 54

55 year old with low plasma renin level
Will work to LOWER BP in person with bilateral stenosis, but the patient will probably not be able to tolerate it.