PHR 946: Block 1 Exam

Which segments of the LOH provide final regulations of water excretion and acid-base balance?

Distal Tubule (DT) + Collecting Duct (CD)

How does fluid flow through a nephron?

Glomerulus --> Bowman's Capsule --> Proximal Convoluted Tubule --> Loop of Henle --> Distal Convoluted Tubule --> Collecting Duct

What is the difference between HR and SV?

HR: # of heart beats per minute SV: amount of blood pumped out by a ventricle with each beat

What foods are known to cause harm?

High-calorie foods: sugar, refined grains, sodium, red meat Fad diets: high-carb diets and low-carb diets; processed red meat

What is the most common cause of secondary HTN?

Primary aldosteronism Increased aldosterone conserves sodium, which also conserves water, leading to increased BP

Primary vs Secondary HTN

Primary: also called essential HTN, no known secondary cause Secondary: HTN that occurs secondary to another disease

Primary vs Secondary Prevention

Primary: prevent disease Secondary: reduce impact of disease that has already occurred

Which ion that is reabsorbed in the PCT determines the ECF volume and ultimately blood pressure?

Sodium

What are Collateral Routes and why are they important?

These are extra branches that ensure blood delivery gets to the heart even if major vessels are obstructed

What are peritubular capillaries?

Tiny blood vessels divided from efferent arterioles that travel alongside descending/ascending limbs of the nephron Allow for reabsorption of water and solutes from urine

What is the purpose of CV System?

Transport blood (oxygen and nutrients) to tissues in exchange for CO2 and other waste *heart and blood vessels are part of this system*

T or F: Angiotensinogen is released from the liver

True

T or F: In order to recover Na+, there HAS to be a loss of K+

True

T or F: Since the thin descending limb is permeable to water, water flows out of the tubule and in result urine is more concentrated

True

T or F: The more potent a drug is the less drug is required in order to make a therapeutic effect

True

T or F: Thiazides increase K+ excretion

True

T or F: Vasoconstriction can cause an increase in BP

True

T or F: Increases in Angiotensinogen result in increased Angiotensin II levels and BP

True; Ang II causes vasoconstriction which increases volume = increased BP

T or F: Angiotensin II increases urine output

True; Ang II causes vasoconstriction= increase volume/BP

T or F: Almost all the drugs used to treat HTN act in some way to alter kidney function

True; HTN happens because the kidneys fail to recognize and compensate for the elevated BP and volume expansion

T or F: Systole is the contraction of heart muscles

True; diastole is relaxation

T or F: Thiazides result in an increase in NaCl excretion

True; increase urinary volume and reduce ECF

T or F: Aliskiren decreases both Ang I and Ang II levels

True; it blocks renin which converts angiotensinogen to Ang I so neither Ang I or II are being made

T or F: Angiotensin-converting enzyme (ACE) is expressed by almost every endothelial cell in the body

True; renin is only produced by J. cells

What are Atrioventricular Valves?

Valves that lie between atria and ventricles and prevent back flow of blood into atria when ventricles contract Ex: Tricuspid, Bicuspid

What are the Semilunar Valves?

Valves that prevent back flow of blood into ventricles Aortic: between LV and aorta Pulmonary: between RV and pulmonary trunk

What does Angiotensin Converting Enzyme (ACE) do?

Converts Angiotensin I to Angiotensin II

What is Coronary Circulation?

Functional blood supply to the heart muscle itself

Aliskiren: Contraindications

Use with ACEi or ARB in patients with DM Increases risk for renal impairment, hyperkalemia, and hypotension Pregnancy

What is the average GFR?

120 mL/min

What is Stage 1 and 2 HTN?

1: 130-139 OR 80-89 2: 140 OR 90

What BMI is considered overweight?

25-29.9

Activity Recommendations

>150 minutes/week of moderate activity >75 minutes/week of vigorous activity

What is Bradykinin?

A vasodilator that promotes Na and water loss

What is the difference between atria and ventricles?

A: "receiving" chambers of the heart, thin walls because don't have to pump blood to the rest of the body V: "discharging" chambers of the heart, LV pumps blood into aorta (bigger/thicker than RV)

ABCCDDE of Primary Prevention

A: assess risk- aspirin B: blood pressure C: cholesterol C: cigarettes D: diet/weight D: diabetes E: exercise

What is the difference between afferent and efferent arteries?

A: blood flows into glomerulus through afferent E: carries blood away from kidney

Renin Inhibitors (1)

Aliskiren

What is the Cardiac Cycle?

All events associated with blood flow through the heart Systole and Diastole

What happens to the following when an ACEi is given: Ang II levels, bradykinin levels, vasodilation

Ang II: decrease Bradykinin: increase Vasodilation: increase

What stimulates ADH release?

Angiotensin II

How is Angiotensin II formed?

Angiotensinogen --> Angiotensin I *via Renin* Angiotensin I --> Angiotensin II *via Angiotensin-converting enzyme (ACE)*

What is the Point of Maximal Impulse (PMI)?

Apical pulse site of heart

What should be kept in mind with administration of Aliskiren?

Be consistent- don't change diets drastically because the absorption is decreased by high-fat meals *daily dosing*

Where is the juxtaglomerular apparatus located?

Between afferent/efferent arterioles and distal tubule

Thiazides: MOA

Block Na/Cl symporter in the distal tubule --> increased Na concentration = increased water excretion

Bowman's Capsule Function

Filtered blood/products enter here

What is normal vs elevated BP?

N: <120/80 E: 120-129/<80

What transporter is unique to the thick ascending loop?

Na+/K+/2Cl Transporter NaCl is actively reabsorbed here and pumped back into medullary interstitial --> dilute urine

Which transporter is unique to DT and CD?

Na/Cl Transporter

Increased levels of Sodium in the urine activate what?

Na/K ATPase Increases absorption of Na and increases excretion of K into the urine

T or F: TPR is the same as vasoconstriction

*Total Peripheral Resistance* True

ASCVD (5)

1. Acute Coronary Syndrome (ACS) or MI 2. Stable Ischemic Heart Disease (SIHD) or Unstable Angina (UA) 3. Coronary or other arterial revascularization 4. Stroke or TIA 5. Peripheral arterial disease

Aldosterone is released in response to what? (3)

1. Ang II 2. Hyponatremia 3. Hyperkalemia

2 Types of Heart Valves

1. Atrioventricular 2. Semilunar

Aliskiren: ADEs (4)

1. Diarrhea 2. Hyperkalemia 3. Hypotension 4. Fetal/neonatal morbidity

What are the 2 layers of the heart?

1. Epicardium (outer) 2. Endocardium (inner)

What does the Juxtaglomerular Apparatus of the Kidney regulate? (3)

1. Glomerular blood flow 2. Glomerular filtration rate 3. Renin release

What substances are reabsorbed in PCT?

1. Glucose 2. Amino Acids 3. K+, Ca++, phosphate, bicarbonate, uric acid 4. Cl-, water, urea

ACE Inhibitors (5)

1. Lisinopril 2. Quinapril 3. Enalapril 4. Ramipril 5. Captopril

3 Types of Primary HTN

1. Moderate/high renin 2. Low renin 3. Resistant

3 Causes of Secondary HTN

1. Renal/Vascular 2. Endocrine 3. Medications

What do RAS drugs block? (2)

1. Renin 2. Aldosterone

What are 3 targets in the RAS Pathway?

1. Renin: converts Angiotensinogen to Ang I 2. Angiotensin Converting Enzyme (ACE): cleaves Ang I to Ang II 3. Ang II Receptor: most closely associated with HTN

Angiotensin II Functions (4)

1. Stimulates ADH release 2. Promotes Na+ reabsorption in proximal tubule 3. Stimulates thirst center in hypothalamus 4. Increases aldosterone synthesis and secretion

What is the difference between coronary veins and coronary arteries?

CV: blood vessels that transport deoxygenated blood from the heart toward the right atrium CA: blood vessels that branch from the aorta and carry oxygen-rich blood to the heart muscle

Angiotensin II Function

Conserves Na and raises BP Stimulates release of Aldosterone from adrenal gland

How does blood flow through the heart and lungs?

Deoxygenated Blood: 1. Superior Vena Cava 2. Right Atrium 3. Tricuspid Valve 4. Right Ventricle 5. Pulmonary Valve 6. Pulmonary Artery TO LUNGS Oxygenated Blood: 7. Pulmonary Veins 8. Left Atrium 9. Bicuspid/ Mitral Valve 10. Left Ventricle 11. Aorta

What is Hypertension?

Elevation in systolic and/or diastolic BP

Why are heart valves important?

Ensure unidirectional blood flow through the heart and prevent back flow

What is renin?

Enzyme secreted by juxtaglomerular cells when BP decreases Relates to the formation of Ang II which releases aldosterone

T or F: ACE causes increased bradykinin levels

False; ACE degrades it, but an ACEi would therefore cause increased levels

T or F: Permeability of DT and CD to water is controlled by Angiotensin II

False; ADH (vasopressin) ADH increases permeability to water by increasing aquaporin channels

T or F: The Loop of Henle is the main site of active reabsorption and secretion of filtered substances

False; Proximal Convoluted Tubule (PCT)

T or F: Aliskiren causes a decrease in renin levels

False; although you're inhibiting the activity of renin, also inhibiting formation of Ang II Ang II acts back on this feedback to inhibit the production of renin and since we don't have this anymore our renin levels will be higher *this doesn't matter because only 50% of this renin is active, so we won't have an increase in BP because Aliskiren is inhibiting the actual activity of the enzyme even if the renin levels are increasing*

T or F: HTN is asymptomatic

False; cognitive, mood changes, dizziness, headache

T or F: An increase in BP causes ADH to be released

False; decrease *increase in osmolarity* *Ang II*

T or F: A and B blockers increase renal sympathetic tone in order to maintain renal blood flow and decrease renin release

False; decrease renal sympathetic tone

T or F: Medications like steroids, estrogen, and insulin cause an increase in BP due to an increase of Bradykinin levels which helps convert Angiotensin I to Angiotensin II

False; increase of angiotensinogen levels

T or F: An IV drug user is more likely to end up with an infected bicuspid valve than a tricuspid valve

False; inject into veins and the go through tricuspid valve first

T or F: Low renin is the most common type of primary HTN

False; mod-high renin

T or F: Due to the rise in number of individuals who are obese and have disease like DM, secondary HTN accounts for 90% of all hypertensives in US

False; primary

T or F: Cardiac Output (CO) is the amount of blood that is pumped by the aorta in 1 minute

False; pumped by each ventricle (L/min) Heart Rate (HR) + Stroke Volume (SV)

T or F: Thiazides increase uric acid excretion

False; reduce May have gout flare ups

T or F: Thiazides increase Ca++ excretion

False; reduce Less Na is in the cell and increases the concentration gradient for Na to flow into the cell via Na/Ca Exchanger --> this pumps more Ca into the interstitium

T or F: Afferent arterioles terminate in the glomerulus in the renal medulla

False; renal cortex

T or F: Retaining Na+ can result in a decrease in one's blood pressure

False; retaining Na means more water --> more volume --> higher BP

T or F: The thin descending limb and thick ascending limb are freely permeable to water and salt in the LOH

False; thin descending limb is permeable, thick ascending is impermeable to water

Aldosterone Function

Increases Na/water retention and K excretion

What role does Aldosterone play in the kidneys?

It is a mineralocorticoid that promotes the recovery of sodium in late distal tubule and collecting ducts *regulation of fluid volume*

How are variants of serine/threonine kinase associated with HTN?

Kinase phosphorylates Na/K/2Cl transport in thick ascending limb of LOH AND Na/Cl transporter in distal tubule Both transporters are activated and pull Na and water out of the urine and into the blood = increased BP

What does "lub-dub" noise mean?

Lub: AV valves close and beginning of systole (contraction) Dub: SL valves close when ventricular diastole (relaxation)

Where is ACE located?

Luminal surface of endothelial cells and expressed in almost all tissues

How do Macula Densa cells trigger vasoconstriction of the Afferent Arteriole?

Macula densa cells release an adenosine vasoconstrictor that acts on the afferent arteriole to reduce the glomerular filtration (because too much Na in distal tubule) *Constricting= slow down filtration, reduce how much blood is flowing into the glomerulus* *Renin is released from juxtaglomerular cells to vasoconstrict and decrease BF and filtration*

What is Hypertensive Crisis?

S: >180 D: >120 Acute, end organ injury: stroke, HF, MI, aneurysm

Where is ADH synthesized and released?

S: Hypothalamus R: Pituitary Gland

Function of Juxtaglomerular Apparatus

See how well kidneys work/produce urine and fix any problems Ex: remove more Na or water whatever is needed

Hypersensitivity to which antibiotic may cause an allergic reaction when taking Thiazides?

Sulfonamides

How does sympathetic stimulation lead to hypertension?

Sympathetic stimulation increases HR and decreases GI motility aka less urine excretion Less urine excretion = more volume= HTN *stimulation leads to excessive renin production* *increased renin= increased Ang II= increased aldosterone= Na retention and increases in blood volume= HTN*

What happens when there are high concentrations of NaCl in the distal tubule?

The juxtaglomerular cells sense the high concentration of sodium and send signals to other cells to fix it