ppom 2 block 1

What is blood flow?

Blood flow (Q) is the volume of blood passing a given point per unit time, typically measured in mL/sec or mL/min.
Formula:
Flow = Volume ÷ Time

What happens if fast sodium channels recover from inactivation more slowly?

The effective refractory period is prolonged, so premature re-excitation is more difficult.

What happens when delayed rectifier potassium current decreases?

Repolarization slows, Phase 2/3 lasts longer, and ventricular action potential duration increases.

Who is at highest risk for first-dose hypotension from an angiotensin-converting enzyme inhibitor?

Patients with high renin-angiotensin system activity, especially volume depletion or heart failure.

Which antihypertensive drug directly inhibits renin?

Aliskiren

Why are angiotensin-converting enzyme inhibitors and angiotensin receptor blockers used in proteinuric chronic kidney disease?

Efferent arteriole dilation → decreased glomerular pressure → decreased proteinuria.

Which calcium channel blockers most strongly slow atrioventricular nodal conduction?

Verapamil and diltiazem.

What is the most common adverse effect of dihydropyridine calcium channel blockers?

Peripheral edema.

Which calcium channel blockers are first-line therapy for variant angina because they relieve coronary vasospasm?

Calcium channel blockers as a class.

Which calcium channel blockers are most likely to cause bradycardia and atrioventricular block?

Verapamil and diltiazem

Which beta blocker has the shortest half-life and is useful when rapid titration is needed?

Esmolol

Which beta blockers also block alpha-1 receptors and therefore cause additional vasodilation?

Labetalol and carvedilol.

What is the principle of helium dilution?

Helium mixes within a closed gas system and becomes diluted in proportion to lung volume, allowing estimation of functional residual capacity.

What does nitrogen washout measure in the residual-volume section of this lecture?

It is an indirect method used to determine residual volume.

A patient is given 5% glucose in water. After glucose is metabolized, the solution behaves like:

Free water.

What are the 3 major triggers for renin release?

↓ afferent pressure, ↓ macula densa NaCl, ↑ beta-1 sympathetic stimulation.

Why do loop diuretics increase urinary Ca²⁺?

Block NKCC2 in thick ascending limb → ↓ K⁺ back-leak/lumen-positive potential → ↓ paracellular Ca²⁺ reabsorption → ↑ Ca²⁺ excretion.

Where do thiazides act, and what happens to Ca²⁺?

Early distal convoluted tubule; block Na⁺/Cl⁻ cotransporter → ↑ Ca²⁺ reabsorption → ↓ urinary Ca²⁺.

What transporter does angiotensin II stimulate in the PCT?

Na⁺/H⁺ exchanger (NHE3) → ↑ Na⁺ and HCO₃⁻ reabsorption

What does ADH do in the collecting duct?

V2 receptor → ↑ cAMP → ↑ AQP2 insertion → ↑ water reabsorption; also ↑ inner medullary urea permeability.

Why is the thick ascending limb called a diluting segment?

It reabsorbs NaCl but not water → tubular fluid becomes dilute.

Why does aldosterone increase K⁺ secretion?

↑ ENaC-mediated Na⁺ reabsorption → lumen becomes more negative → ↑ K⁺ secretion.

What does PTH do to phosphate in the kidney?

↓ phosphate reabsorption in PCT → ↑ phosphate excretion in urine.

What are PTH’s two major renal effects?

↓ PO₄³⁻ reabsorption in PCT + ↑ Ca²⁺ reabsorption in DCT.

Why can hyperaldosteronism cause metabolic alkalosis?

Aldosterone → ↑ H⁺ secretion by α-intercalated cells → ↑ HCO₃⁻ in blood.

What does low NaCl at the macula densa do?

↑ Renin → ↑ Ang II → ↑ aldosterone → ↑ Na⁺/water retention.

What does angiotensin II do in the PCT?

Stimulates Na⁺/H⁺ exchange → ↑ Na⁺, H₂O, and HCO₃⁻ reabsorption.

What is the basic valve/sound sequence through systole?

Mitral closes → S1 → aortic opens → aortic closes → S2.

ADH at V1 receptors causes what?

↑ intracellular Ca²⁺ → vascular smooth muscle contraction → vasoconstriction → ↑ blood pressure.

A patient is water deprived and has high ADH levels. Which pairing is most accurate?

• V1 on vascular smooth muscle → ↑ intracellular Ca²⁺ → vasoconstriction

• V2 on collecting-duct cells → ↑ adenylate cyclase → ↑ cyclic adenosine monophosphate → ↑ aquaporin-2 insertion → ↑ water reabsorption

A 44-year-old man with no known lung disease undergoes spirometry. After a maximal inspiration, he is instructed to exhale as much air as possible.

Which quantity is being measured?

Vital capacity

What does Fowler’s nitrogen washout method measure?

Anatomic dead space.

Loop diuretics we must know (Na+/K+/2Cl– symport (NKCC2)

Inhibitors)

Furosemide Torsemide, Bumetanide Ethacrynic acid

Epithelial Na+ channel (ENaC) inhibitors (K+-sparing) Drugs we need to know

Amiloride

“The formation of carbonic anhydrase is inhibited so bicarbonate can’t be reabsorbed” which drug?

Carbonic anhydrase inhibitors

“NKCC2 inhibited, gradient collapses affecting ROMK so magnesium and calcium are not reabsorbed” which drug

Loop diuretics

Thiazide diuretics (Na+-Cl– symport (NCC)

inhibitors) we need to know

Hydrochlorothiazide Chlorthalidone

What are the key histologic features of SA nodal cells?

Small modified cardiac myocytes with abundant autonomic innervation.

What causes S2?

Aortic + pulmonic valve closure → start of diastole.

Which phase has minimum/most negative dP/dt?

Isovolumetric relaxation → fastest fall in ventricular pressure.

Renin is mainly released when there’s

Low volume

Preferred initial therapy to hypertension

Angiotensin converting

enzyme inhibitors

− Angiotensin II AT

blockers

− Calcium channel blockers

(CCB), long-acting

− Thiazide-type / thiazide-like

diuretics

Captopril And Enalapril are both

Angiotensin converting enzyme inhibitors

The main classes of first-line agents for treating hypertension are

thiazide diuretics, ACE inhibitors or ARBs, and CCBs.

Thiazide diuretics Specifically target which symporter

Na⁺/Cl^– symporter at the distal convoluted tubule (DCT)

Side effects of thiazides

Hypokalemia (lower aldosterone),hyperuricemia which increases risk of gout (thiazide diuretics compete with urate for secretion by the organic anion transporter (OAT) at the proximal convoluted tubule), hyponatremia, and hypercalcemia

Thiazide diuretics contain a sulfa group so they should not be used in patients with

A sulfa allergy

Thiazide diuretics decrease

Lithium clearance

Angiotensin 2 has potent vasoconstriction properties via the __ receptors

AT1

___are a group of diureticdrugs that block the enzyme carbonic anhydrase (CA). CA catalyzes the conversion of carbon dioxide (CO₂) and water (H₂O) into bicarbonate (HCO₃^–) and protons (H⁺) and vice versa.

Carbonic anhydrase inhibitors

Blocking carbonic anhydrase reduces the reabsorption of sodium and

HCO₃^{– so they get excreted out of the body}

big adverse affects of carbonic anhydrase inhibitors

Renal stones (causes urine to become alkaline), tinnitus, paresthesias, metabolic acidosis (bicarbonate isn’t reabsorbed and potassium excreted)

Loop diuretics work on the

Loop of henle

More specifically, loop diuretics are ___, which is in the luminal membrane of the thick ascending limb of the loop of Henle which leads to water loss and calcium and magnesium excretion

inhibitors of the Na⁺/K⁺/2Cl^– cotransporter

Loop diuretics side effects

Ototoxicity

Which of the following conditions would least benefit from treatment with loop diuretics?

End stage kidney disease (the kidneys must work)

There are two main types of potassium-sparing diuretics. Both types operate in the distal nephron, specifically the principal cells of the

Collecting duct

What are the two main categories of potassium-sparing diuretics?

Aldosterone receptor antagonists and epithelial sodium channel (ENaC) blockers are the two main categories of potassium-sparing diuretics

The primary function of ___ is to increase blood volume and blood pressure.

Aldosterone

Aldosterone receptor-blockers inhibit all the effects of aldosterone in the collecting duct,

including sodium reabsorption and potassium secretion

What are the two mechanisms of action by which potassium-sparing diuretics work to block sodium reabsorption?

Potassium-sparing diuretics block intracellular aldosterone receptors and apical ENaCs.

What Are Some Possible Adverse Reactions to Potassium-Sparing Diuretics.

Hyperkalemia, type 4 renal tubular acidosis, anti androgen affects (Aldosterone receptor antagonists)

Thiazide diuretics list

Hydrochlorothiazide and chlorthalidone

All inhibit Na+-Cl– Cotransporter (NCC) Inhibitors

Contraindications for carbonic anhydrase inhibitors

Acidosis

• Severe renal disease

• Cirrhosis or other severe hepatic disease

CA inhibitors may contribute to

hyperammonemia (NH3) by reducing

production of NH4+, a main form of acid

excretion.

• Hypersensitivity to the drug or any component of the formulation

Loop diuretics that we need to know

•  Furosemide (sulfonamide)

• Bumetanide (sulfonamide)

•  Torsemide (sulfonylurea)

•  Ethacrynic acid (phenoxyacetic acid derivative)

Diuresis duration of furosemide

Diuresis duration oral ~6 h, IV ~2 h

Furosemide and torsemide uses

Furosemide-heart failure patients (Diuresis duration oral ~6 h, IV ~2 h)

Torsemide-refractory edema (Diuresis duration oral ~12 h)

Chlorthalidone Takeaway

Very long t½, long duration of

action provides smoother 24-hour blood pressure control.

Higher risk of hypokalemia than with hydrochlorothiazide

Thiazide diuretics are useful for

Primary hypertension

First line treatment for severe

edema/pulmonary edema

In a large vein, which layer is thickest and contains longitudinal smooth muscle?

Tunica adventitia. The tunica media is thinner and mainly circular smooth muscle.

A patient has a normal S1. Which mechanical event occurred immediately before this sound?

Atrioventricular valve closure.

When does S3 occur?

Rapid ventricular filling in early diastole.

What do pericytes do?

Wrap postcapillary venules/capillaries, are contractile, and can become endothelial or smooth muscle cells during vessel growth and wound healing.

Which of the following is the most likely mechanism for how aldosterone increases blood volume?

Insertion of sodium channels

What glomerular filtration barrier layer forms filtration slits?

Visceral epithelial layer → podocytes → foot processes/pedicels form filtration slits.

What features identify a lymphatic capillary?

Blind-ended + very permeable + incomplete basal lamina + takes up protein-rich interstitial fluid.

What are the key histologic features of Purkinje cells?

Large, pale, glycogen-rich cells with fewer myofibrils and few/no T-tubules.

After hemorrhage, GFR and tubular NaCl delivery fall. Which response is most likely?

Increased renin + afferent dilation.

Where do thiazides work, and what transporter do they block?

Distal convoluted tubule → block NCC (Na⁺/Cl⁻ cotransporter). Gitelman syndrome affects the same transporter.

What distinguishes a postcapillary venule from a muscular venule?

Postcapillary venule → no tunica media + pericytes. Muscular venule → 1–2 smooth muscle layers.

How does atrial histology differ from ventricular histology?

Atria have thinner myocardium and relatively thicker endocardium.

What does ANP do to GFR and Na⁺ reabsorption?

ANP → ↑ GFR + ↓ Na⁺ reabsorption → ↑ natriuresis/diuresis.

What represents true net renal acid excretion?

H⁺ leaving in urine as NH₄⁺ or bound to phosphate. Why: the proton actually leaves the body instead of being recycled.

Why can volume contraction maintain metabolic alkalosis?

↑ RAAS/aldosterone → ↑ renal H⁺ secretion. Why: preserving volume takes priority, so the kidney continues retaining Na⁺ and excreting H⁺.

Why are urinary buffers necessary for acid excretion?

Urine pH bottoms out around 4.4, so H⁺ must bind phosphate/NH₃ to allow continued acid excretion. Why: free H⁺ alone cannot carry enough acid.

What happens when H⁺ is excreted with phosphate?

New HCO₃⁻ is added to blood. Why: H⁺ actually leaves the body as titratable acid, so the bicarbonate formed intracellularly is a net gain.

What transporter changes occur in chronic respiratory acidosis?

↑ NHE3 and ↑ NBCe1. Why: this increases H⁺ secretion and HCO₃⁻ reclamation to compensate for elevated CO₂.

What proximal-tubule transporters increase in chronic respiratory acidosis?

↑ NHE3 and ↑ NBCe1. Why: this increases H⁺ secretion and returns more HCO₃⁻ to blood to compensate for high CO₂.

How does acidosis increase phosphate-buffered acid excretion?

↓ Na⁺-phosphate reabsorption → more luminal phosphate → more H⁺ excreted as H₂PO₄⁻. Why: phosphate acts as a urinary buffer.

How does the pulmonary circulation accommodate increased cardiac output during exercise?

Recruitment of previously closed vessels + distention of perfused vessels → accommodates ↑ flow with little increase in pulmonary resistance.

How does body habitus affect ECG amplitude?

Thin → larger amplitudes; obese → smaller amplitudes.