PHAR 753 Exam 1

Vasa recta is supplied by this arteriole

Efferent arteriole

Which nephron component performs the function of

filtration?

a) Glomerulus

b) Proximal convoluted tubule

c) Medulla

d) Thin descending Loop of Henle

a)

What is the term used to describe a substance

moving from a peritubular capillary into the renal

tubule?

a) Reabsorption

b) Excretion

c) Filtration

d) Secretion

d)

Ultrafiltrate

Small solutes less than

5k Daltons, can enter Bowman's space

Glomerular barrier that repels proteins

Basement membrane

Glomerular barrier that forms the filtration slit diaphragm

Podocytes

Amount of creatinine reabsorbed

0

Amount of glucose in urine

0

A patient presents with a 3-week history of frothy urine and

edema. A urine dipstick is positive for 4+ protein and a

follow-up urine protein creatinine ratio of 1000 mg/g. Where

is this patient most likely experiencing glomerular damage?

a) Bowman capsule

b) Afferent arteriole

c) Basement membrane

d) Juxtaglomerular cells

c)

Which of the following substances are expected to be found

in urine?

a) Glucose

b) Albumin

c) Creatinine

d) Hemoglobin

c)

Healthy GFR value

100-125 mL/min

eGFR

A population-based calculation using age, sex, & biomarker (serum creatinine or cystatin C)

mCrCl

Creatinine concentration measured from urine collected in 24 hours; known to overestimate GFR due to creatinine secretion

Serum Creatinine (sCr) elimination

Glomerular filtration (85-90%), tubular secretion (10-15%)

Serum Cystatin C elimination

Glomerular filtration (100%)

PCT reabsorption

All glucose, amino acids, Na+, Cl-, HCO3- (diffusion, active transport), most water (osmosis)

PCT secretion

H+, NH4+, creatinine, drug metabolites

Loop of Henle reabsorption (DTL)

Some water (osmosis, aquaporins)

Loop of Henle reabsorption (ATL)

Na+, Cl-

Loop of Henle reabsorption (TAL)

Na+, Cl-, K+

Loop of Henle secretion

None

DCT reabsorption

Na+, Cl-, HCO3- (active transport), water

DCT secretion

H+, K+, Na+, Cl-

Collecting duct reabsorption

Some water (osmosis), urea

Collecting duct secretion

None

Countercurrent multiplier (exchanger) actions

Preserving water, concentrating urine

Water in the DTL of the Loop of Henle is reabsorbed to the

Ascending vasa recta

Ions (Na+, Cl-, K+) in the TAL of the Loop of Henle are reabsorbed to the

Descending vasa recta

Macula densa

Specialized group

of sensory cells

lining the DCT that

sense flow rate

and Na+ levels

Na+ gradient in collecting duct is established by

Na+/K+ ATPase

Na+ reabsorption in collecting duct is enabled by

Epithelial Na+ channel (ENaC)

Water leaves the collecting duct through

Aquaporins

Aldosterone effect

Increased K+ excretion, increased Na+ reabsorption, and increased water reabsorption at the collecting duct

Aldosterone action

Binds to MR in the collecting duct and signals for more ENaC

and Na/K ATPase to be produced and inserted into membrane, increasing Na+ reabsorption, increasing water reabsorption,

increasing blood volume, causing increased MAP & GFR

Vasopressin (ADH) effect

Increases water reabsorption

Vasopressin (ADH) action

Binds to vasopressin receptor, stimulates aquaporins (AQP2)

Which section of the nephron is MOST responsible for the

reabsorption of water from the renal tubules?

a) Proximal convoluted tubule

b) Loop of Henle

c) Distal convoluted tubule

d) Collecting duct

a)

Which of the following is a critical component of the

countercurrent multiplier (exchanger) mechanism?

a) High water permeability in the thin ascending limb

b) Active sodium reabsorption in the thick ascending limb

c) High osmolality gradient in the cortex of the nephron

d) Macula densa sensing Na+ levels in the distal tubules

b)

Renal autoregulatory range

80-180 mmHg

Renal autoregulatory mechanisms

Myogenic response (stretch receptors in glomerulus causing vasoconstriction) and tubuloglomerular feedback

Nitric oxide

Vasodilation, increases RBF and GFR

Prostaglandins (PGE2, PGI2)

Vasodilation of afferent > efferent arteriole, increases RBF and GFR

Endothelin

Vasoconstriction, decreases RBF and GFR

Adenosine

Vasoconstriction of afferent arterioles, decreases RBF and GFR

Angiotensin 2

Vasoconstriction of efferent > afferent arterioles, decreases RBF and GFR (increases GFR in the short term)

Catecholamines (norepinephrine,

epinephrine)

Vasoconstriction of afferent >> efferent arterioles, decreases RBF and GFR

Natriuretic peptides

(ANP, BNP)

Vasodilates afferent arteriole, constricts efferent arteriole, increases RBF and GFR

Adenosine tubuloglomerular feedback

Released with increase in NaCl (macula densa), AA constriction/EA dilation, decrease RBF

Angiotensin 2 tubuloglomerular feedback

Released with decrease in NaCl from JG cells (macula densa), EA constriction, increase RBF

Angiotensin 2 full effects

Increase SNS, tubular Na+/Cl-/water reabsorption, K+ excretion, aldosterone release, arteriolar vasoconstriction, ADH release (from posterior lobe of pituitary gland)

RAAS key effects

Constrict EA, increase Na+ reabsorption

ADH key effects

Increase water and Na+ reabsorption

Natriuretic peptides (ANP/BNP) key effects

Counter RAAS and ADH, increase Na+ excretion

Angiotensin 2 released when

Decrease BP

ANP released when

Increase atrial pressure

Aldosterone released when

Decrease blood volume

ADH released when

Increase plasma osmolarity and decrease blood volume

RAAS overall

Increase BP, more water, more Na+, less K+

ADH mechanism

Released from posterior pituitary (hypothalamus). V1 constricts blood vessels, V2 causes water reabsorption (AQP), increasing arterial pressure

Which of the following best describes the relationship

between renal flow rate and mean arterial pressure (MAP)

within the autoregulatory zone?

a) Increased flow when MAP increases

b) Decreased flow when MAP decreases

c) Constant flow regardless of MAP changes

d) Variable impact depending on sympathetic nervous

system activity

c)

Which of the following will be released after a high

concentration of Na+ is sensed by the macula densa?

a) Renin

b) Adenosine

c) Angiotensin II

d) Aldosterone

b)

Based on your current knowledge of the RAAS system,

how do ACE inhibitors exert their effects on the renal

vasculature?

a) Constricts both afferent and efferent arterioles

b) Constricts afferent and dilates efferent arteriole

c) Dilates efferent and constrict afferent arteriole

d) Dilates both afferent and efferent arterioles

d)

Which hormone acts as a vasodilator in the kidney?

a) Angiotensin II

b) Antidiuretic hormone (ADH)

c) Atrial natriuretic peptide (ANP)

d) Nitric oxide

d)

Which hormone is most responsible for water reabsorption

in the collecting duct?

a) Aldosterone

b) Angiotensin II

c) Antidiuretic hormone (ADH)

d) Atrial natriuretic peptide (ANP)

c)

Erythropoiesis pathway

Decreased RBC, increased HIF, increased erythropoietin (kidneys), increased erythropoiesis, decreased HIF, decreased erythropoietin

High blood calcium

Thyroid gland releases calcitonin to inhibit osteoclast activity/decrease Ca2+ reabsorption

Low blood calcium

Parathyroid glands releases PTH to induce osteoclasts/increase Ca2+ reabsorption/increase vitamin D synthesis (kidneys)

ADH effects

Stimulates V2 receptors to increase aquaporin insertion into

membranes

Incrase permeability of collecting duct to reabsorb water

Angiotensin 2 effects

Increase aldosterone release from adrenal cortex

Increase Na+ reabsorption (and HCO3-) in PCT (NHE3)

Decrease GFR

ANP effects

Activates cGMP (potent vasodilator)

Increase GFR

Decrease tubular reabsorption of Na+ in collecting ducts

Decrease renin and aldosterone secretion

PTH effects

Decrease PO42- reabsorption in the PCT

Increase Ca2+ reabsorption in the DCT

Increase calcitriol synthesis

Percentage of Na+ removed at PCT

65%

Active transport, Na/H exchanger (NHE3), cotransporters, osmosis

Percentage of Na+ removed at the Loop of Henle (TAL)

20%

Na-K-2Cl cotransporter (NKCC2)

Percentage of Na+ removed at DCT

10%

Na-Cl cotransporter (NCC)

Percentage of Na+ removed at collecting duct

1-5%

Epithelial Na+ channels

(ENaC)

Drug classes acting on glomerulus

Methylxanthines

Drug classes acting on PCT

Methylxanthines, CAI

Drug classes acting on Loop of Henle

Osmotic diuretics (DTL), loop diuretics (TAL)

Drug classes acting on DCT

Thiazide(-like) diuretics

Drug classes acting on collecting duct

Potassium sparing diuretics, MR antagonists

CAI effect

Decrease bicarbonate reabsorption & alkalinization of urine

CAI use

Prevention of altitude sickness

Glaucoma (eye drops)

Uric acid & cystine kidney stones

Epilepsy

Refractory edema

Osmotic diuretic examples

IV: Mannitol, Glucose, Sorbitol, Urea

PO: Isosorbide, glycerol

Osmotic diuretic effect

Increase osmotic pressure to attract water as non-reabsorbable compounds in the lumen

Loop diuretic MOA

Inhibit NKCC2 (TAL, Loop of Henle)

Loop diuretic effect

Potent diuresis and decreased fluid retention

Loop diuretic typical onset

0.5-1hr

Which electrolyte-related adverse effect is most associated

with loop diuretics?

a) Hypokalemia

b) Hypermagnesemia

c) Hypernatremia

d) Hypercalcemia

a)

What is the primary mechanism of action of loop diuretics?

a) Competitive antagonism of aldosterone receptor

b) Inhibition of NKCC2 cotransporter

c) Inhibition of Na+ reabsorption in the distal convoluted

tubule

d) Increased osmotic pressure within the renal tubules in

the Loop of Henle

b)

Thiazide diuretic action

Inhibit tubular resorption of Na+ and Cl- in

the DCT, increasing excretion of water, Na+, Cl-, and K+

Dilate arterioles

Acute thiazide diuretic action

Decreased serum Na+

Decreased plasma volume

Decreased CO

Decreased BP

Increased TPR as a reflex

Chronic thiazide diuretic action

CO back to baseline

Decreased TRP

Plasma volume slightly below baseline

BP remains decreased

Thiazide diuretic effect

Acute diuresis/natriuresis (NCC inhibition, DCT) & systemic vasodilation

Thiazide diuretic dosing

Dose ceiling

Skipping multiple doses can exacerbate increased urination later

Thiazide diuretics, loop diuretics

A 35-year-old patient presents for a regular check-up. She has no concerns.

On examination, her BP is elevated (145/85). She is diagnosed with

hypertension and started on HCTZ. How does this agent work?

a) Inhibits reabsorption of sodium in the early distal convoluted tubule

b) Decreases net excretion of chloride, sodium, and potassium

c) Increases excretion of calcium

d) Inhibits reabsorption of sodium in the thick ascending limb of the Loop of

Henle

a)

Which statement correctly describes the long-term antihypertensive effects of

thiazide diuretics?

a) Increase total peripheral resistance

b) Decrease cardiac output

c) Decrease plasma volume

d) Promote systemic vasodilation

d)

K+-sparing diuretics MOA

Block epithelial sodium channels (ENaCs) in the collecting duct

MRA MOA

Competitively bind to

mineralocorticoid receptor to inhibit

aldosterone's effects in the collecting duct

K+-sparing diuretics effect

Inhibit Na+ reabsorption in collecting duct