PLE Physio Part 2

Which of the following substances or combinations of substances could be used to measure interstitial fluid volume? (A) Mannitol (B) D2O alone (C) Evans blue (D) Inulin and D2O (E) Inulin and radioactive albumin

(E) Inulin and radioactive albumin

If BP is high (e.g. 200mmHg), Macula Densa increases secretion of?

Adenosine Vasoconstricts AFFERENT arteriole → ↓ GFR back to normal (125ml/min)

Normal bowman's space oncotic pressure

0 mmHg dapat walang albumin in bowman's space

38/F decreased urine output. (+) ibuprofen use Labs: BUN: 49mg/dL Serum Na = 135 mmol/L Serum creatinine: 7.5mg/dL Urine Na = 33 mmol/L Urine creatinine = 90mg/dL What is her fractional Na excretion?

0.02 FE<1%: volume depletion FE>2%: acute renal failure

3 CANDIDATE GI HORMONES

1. Pancreatic Polypeptide - ↓ pancreatic HCO3- and enzymes 2. Enteroglucagon - Stimulates glycogenolysis and gluconeogenesis 3. GLP-1 - Stimulates insulin secretion

A patient is infused with para-aminohippuric acid (PAH) to measure renal blood flow (RBF). She has a urine flow rate of 1 mL/min, a plasma [PAH] of 1 mg/mL, a urine [PAH] of 600 mg/mL, and a hematocrit of 45%. What is her "effective" RBF? (A) 600 mL/min (B) 660 mL/min (C) 1091 mL/min (D) 1333 mL/min

1091 mL/min CPAH = UPAH × V/PPAH = 600 mL/min CPAH = RPF since clearance of PAH is used to estimate RPF RBF = RPF/ (1 - hematocrit) RBF = (6000mL/min)/ (1-0.45) RBF = 600mL/min/0.55 RBF = 1091 mL/min

total body water distribution

60% of BW: Water 40% of BW: ICF (15% interstitial, 5% plasma) 20% of BW: ECF

A person who takes an aspirin (salicylic acid) overdose is treated in the emergency room. The treatment produces a change in urine pH that increases the excretion of salicylic acid. What was the change in urine pH, and what is the mechanism of increased salicylic acid excretion? (A) Acidification, which converts salicylic acid to its HA form (B) Alkalinization, which converts salicylic acid to its A- form (C) Acidification, which converts salicylic acid to its A- form (D) Alkalinization, which converts salicylic acid to its HA form

Alkalinization, which converts salicylic acid to its A- form Here's a mnemonic - "do the opposite" rule: if you overdose with an ACIDIC drug (e.g. ASA), ALKALINIZE the urine so that the weak acid will be in its water-soluble (charged) form. If you overdose with an ALKALINE/BASIC drug (e.g., morphine), ACIDIFY the urine so that the weak base will once again be in its water-soluble (charged) form).

If BP is low (e.g. 80mmHg), Macula Densa increases secretion of?

Angiotensin II (via RAAS stimulation) Vasoconstricts EFFERENT Arteriole → ↑ GFR back to normal (125ml/min) Nitric Oxide Vasodilates AFFERENT Arteriole → ↑ GFR back to normal (125ml/min)

Cause of Hyponatremia in patient with Small Cell Lung CA

Arginine Vasopressin (SIADH)

Auerbach Plexus aka? location? acts on ____ for ____

Auerbach Plexus / Myenteric Plexus Location: between inner circular and outer longitudinal muscle layer (IC-OL) Actions: contraction of inner circular and outer longitudinal muscles for motility

____ and ____ increase when GFR decreases

BUN and Creatinine

In pre-renal azotemia (e.g. Hypovolemia), what happens to BUN/Crea ratio?

BUN increases more than creatinine and BUN/Crea ratio > 20:1

Ca Reabsorption increased by? decreased by?

Ca Reabsorption (-) Loop Diuretics (+) PTH (+) Thiazides

3 LAYERS/CHARGE AND FILTRATION BARRIERS OF THE GLOMERULUS

Capillary Endothelium Basement Membrane (main charge barrier) Podocytes

A man presents with hypertension and hypokalemia. Measurement of his arterial blood gases reveals a pH of 7.5 and a calculated HCO3- of 32 mEq/L. His serum cortisol and urinary vanillylmandelic acid (VMA) are normal, his serum aldosterone is increased, and his plasma renin activity is decreased. Which of the following is the most likely cause of his hypertension? (A) Cushing syndrome (B) Cushing disease (C) Conn syndrome (D) Renal artery stenosis (E) Pheochromocytoma

Conn syndrome (Primary aldosteronism)

2 types of nephrons? location? loops of henle? blood supply?

Cortical Nephron (75% of nephrons) located in renal cortex, with shorter Loops of Henle and with peritubular capillaries (has interstitial cells that will secrete EPO!) Juxtamedullary Nephrons (25% of nephrons) located in the corticomedullary junction, longer Loops of Henle and with Vasa Recta (for countercurrent exchanger!)

Creates "graded osmolarity" in renal medulla

Countercurrent Multiplier of Loop of Henle Maintained/preserved by Countercurrent exchanger of Vasa Recta

Hyperglycemia, muscle wasting, central obesity, round face, supraclavicular fat, buffalo hump, osteoporosis, striae, virilization and menstrual disorders in women, hypertension

Cushing Syndrome / Disease

Severe vasoconstriction of efferent arteriole will lead to?

Decreased GFR Will impede passage of protein to efferent arterioles so it's stuck on the glomerular capillary 1. increased capillary oncotic pressure 2. Gibbs Donnan Effect (negatively charged albumin will attract the positively charged Na towards it, drawing water with it)

increased free water clearance is a hallmark of what disease

Diabetes Insipidus

Which of the following would cause an increase in both glomerular filtration rate (GFR) and renal plasma flow (RPF)? (A) Hyperproteinemia (B) A ureteral stone (C) Dilation of the afferent arteriole (D) Dilation of the efferent arteriole (E) Constriction of the efferent arteriole

Dilation of the afferent arteriole

What 2 cells do aldosterone act on the nephrons?

Distal Tubule 1. Principal Cells Reabsorb: Na+ (and consequently water) Secrete: K+ 2. Intercalated Cells Reabsorb: K+ Secrete: H+ Net effect: Na absorbed K+ and H+ excreted!

Most common stimulus for GI peristalsis

Distention

One gram of mannitol was injected into a woman. After equilibration, a plasma sample had a mannitol concentration of 0.08 g/L. During the equilibration period, 20% of the injected mannitol was excreted in the urine. The subject's (A) extracellular fluid (ECF) volume is 1 L (B) intracellular fluid (ICF) volume is 1 L (C) ECF volume is 10 L (D) ICF volume is 10 L (E) interstitial volume is 12.5 L

ECF volume is 10 L ECF volume = amount of mannitol/concentration of mannitol = 1 g - 0.2 g/0.08 g/L = 10 L

aka "cortical diluting segment"

Early Distal Tubule (EDT) site of Macula Densa

Parasympathetic innervation to GIT is mediated by what nerves?

Esophagus to Upper Large Intestines: Vagus Nerve Lower Large Intestines to Anus: Pelvic Nerves

A patient arrives at the emergency room with low arterial pressure, reduced tissue turgor, and the following arterial blood values: pH = 7.69 [HCO3-] = 57 mEq/L PCO2 = 48 mm Hg Which of the following responses would also be expected to occur in this patient? (A) Hyperventilation (B) Decreased K+ secretion by the distal tubules (C) Increased ratio of H2PO4- to HPO4-2 in urine (D) Exchange of intracellular H+ for extra-cellular K+

Exchange of intracellular H+ for extra-cellular K+

Which of the following causes hyperkalemia? (A) Exercise (B) Alkalosis (C) Insulin injection (D) Decreased serum osmolarity (E) Treatment with β-agonists

Exercise Causes shift of K+ out of the cells (leading to hyperK) ACIDOSIS HYPEROSMOLAR EXERCISE CELL LYSIS

TRUE OR FALSE: Slow waves are true action potentials. Due to opening of what channels? Stimulated by what cells? Slowest frequency found at? Fastest at?

FALSE! Slow Waves ✓ Not true action potentials ✓ Due to cyclic opening of Ca2+ channels (depolarization) followed by opening of K+ channels (repolarization) ✓ Due to GI Pacemaker: Interstitial Cells of Cajal ✓ Slowest Frequency: Stomach (3/min) ✓ Fastest Frequency: Duodenum (12/min)

Filtration fraction equation

FF = GFR/RPF normally 20%

5 OFFICIAL GI HORMONES

GASTRIN - HCl CCK - think of fat, bile secretion and decreased gastric emptying SECRETIN - think of anti-HCl actions GIP - think increased insulin as a result of oral (not IV) glucose MOTILIN - think of fasting and increased GI motility to remove remnant food in the GI tract

NAGMA (Normal anion gap metabolic acidosis) aka Hyperchloremic Metabolic Acidosis with Normal Anion Gap

HARDUP Hyperalimentation Acetazolamide Renal tubular acidosis Diarrhea Uretero-enteric fistula Pancreatico-duodenal fistula

A patient has the following arterial blood values: pH = 7.52 PCO2 = 20 mm Hg [HCO3-] = 16 mEq/L Which of the following statements about this patient is most likely to be correct? (A) He is hypoventilating (B) He has decreased ionized [Ca2+] in blood (C) He has almost complete respiratory compensation (D) He has an acid-base disorder caused by overproduction of fixed acid (E) Appropriate renal compensation would cause his arterial [HCO3-] to increase

He has decreased ionized [Ca2+] in blood Remember trio of electrolytes mnemonic? Alkalosis will cause decreased plasma Ca2+

Most of the volatile acid entering the blood is buffered by?

Hemoglobin

CAUSES OF INCREASED DISTAL K SECRETION (6)

High K+ diet Hyperaldosteronism Alkalosis Thiazide Diuretics Loop Diuretics Luminal Anions via PRINCIPAL CELLS of distal tubule

clearance rate highest in what substance? lowest in?

Highest Clearance: PAH Lowest Clearance: Protein, Na, Glucose, amino Acids, HCO3- and Cl- PAH > K > inulin > urea > Na > glucose, amino acids and HCO3-

What will happen to the ff in patient lost in desert/with massive sweating? ICF Volume ICF Concentration ECF Volume ECF Concentration

ICF Volume - DECREASE ICF Concentration - INCREASE ECF Volume - DECREASE ECF Concentration - INCREASE ** you lose water >>> Na

What will happen to the ff in patient with excessive NaCl intake (drowning in seawater)? ICF Volume ICF Concentration ECF Volume ECF Concentration

ICF Volume - DECREASE ICF Concentration - INCREASE ECF Volume - INCREASE ECF Concentration - INCREASE

What will happen to the ff in patient with adrenal insufficiency? ICF Volume ICF Concentration ECF Volume ECF Concentration

ICF Volume - INCREASE ICF Concentration - DECREASE ECF Volume - DECREASE ECF Concentration - DECREASE ** you lose Na >>> water

What will happen to the ff in patient with SIADH? ICF Volume ICF Concentration ECF Volume ECF Concentration

ICF Volume - INCREASE ICF Concentration - DECREASE ECF Volume - INCREASE ECF Concentration - DECREASE

What will happen to the ff in patient with DIARRHEA ICF Volume ICF Concentration ECF Volume ECF Concentration

ICF Volume - NO CHANGE ICF Concentration - NO CHANGE ECF Volume - WILL DECREASE ECF Concentration - NO CHANGE

What will happen to the ff in patient infused with PNSS ICF Volume ICF Concentration ECF Volume ECF Concentration

ICF Volume - NO CHANGE ICF Concentration - NO CHANGE ECF Volume - WILL INCREASE ECF Concentration - NO CHANGE

Causes shift of K+ into the cells (leading to hypoK)

INSULIN BETA AGONIST

modified smooth muscles capable of phagocytosis

INTRAglomerular Mesangial Cells

Magnesium and calcium absorption

In the TAL of LH, Ca2+ and Mg2+ compete for reabsorption - Hypercalcemia causes hypomagnesemia - Hypocalcemia causes hypermagnesemia

Which of the following would produce an increase in the reabsorption of isosmotic fluid in the proximal tubule? (A) Increased filtration fraction (B) Extracellular fluid (ECF) volume expansion (C) Decreased peritubular capillary protein concentration (D) Increased peritubular capillary hydrostatic pressure (E) Oxygen deprivation

Increased filtration fraction

3 Muscle Layers of the Stomach

Inner Oblique, Middle Circular, Outer Longitudinal

increases rate of gastric emptying?

IntraGASTRIC volume (note: increasing the volume, fat content, acidity or osmolarity at the lumen of the SMALL INTESTINES inhibit gastric emptying)

Measures GFR

Inulin Filtered, but not reabsorbed nor secreted clearance = GFR others: creatinine

APPETITE/HUNGER CENTER

Lateral Hypothalamic Area OREXIGENIC NEURONS - GHRELIN Luh, GHREedy!

stimulates gastric contractions every 90 minutes to help clear stomach of residual food

MOTILIN

HAGMA (High anion gap metabolic acidosis)

MUDPILES Methanol Uremia DKA Paraldehyde, Propylene glycol Isoniazid, Iron, Infection Lactic acidosis Ethylene glycol Salicylates

Monitor Na+ concentration in the consequently, Blood Pressure)

Macula Densa in DISTAL convoluted tubule

only solute not mainly reabsorbed in the PCT

Magnesium is the only solute not mainly reabsorbed in the PCT. It is mainly reabsorbed in the TAL of LH.

Marker for ECF

Mannitol Inulin

Meissner Plexus aka? location? acts on ____ for ____

Meissner Plexus / Submucosal Plexus Location: between submucosa and inner circular muscle layer Actions: contraction of muscularis mucosa, for secretion

Composition of Myenteric Reflex

Muscles Upstream (nearer the mouth) will contract, Muscles Downstream (nearer the anus) will exhibit receptive relation

Measures renal plasma flow & renal blood flow

PAH (Para-aminohippurate) PAH-tapon: 100% filtered and secreted - lahat tinatapon sa ihi others: organic acids and bases

"workhorse" of the nephron

PROXIMAL convoluted tubule (+) microvilli, convolutions Most susceptible to hypoxia, toxins * coz super sipag, dapat madaming food!

Contractile Tissue in the GI tract is made up of Unitary Smooth Muscles EXCEPT these 3

Pharynx Upper 1/3 of Esophagus External Anal Sphincter

How will PTH affect phosphate excretion?

Phosphaturia (increased urinary PO4) and increased urinary cAMP ** Unreabsorbed PO4 serve as urinary buffer for H+

Myenteric Plexus is mainly excitatory EXCEPT for? (2)

Pyloric Sphincter (PS) Ileocecal Valve (ICV)

49/F vomiting shortly after eating has normal rate of liquid emptying but prolonged time for emptying of solids. Diagnosis?

Pyloric Stenosis

GIT Layer not seen in Esophagus

Serosa

2 GI PARACRINES

Somatostatin (somatoSTOPin) Histamine

Strongest Layer of the esophagus

Submucosa

Acidosis will lead to what 2 electrolyte imbalances?

TRIO OF ELECTROLYTES ↑H+ levels → HyperCalcemia & HyperKalemia

TRUE OR FALSE: Spike potentials are true action potentials.

TRUE True Action Potentials Depolarization: due to Calcium Influx Threshold: -40Mv

TUBULOGLOMERULAR FEEDBACK vs GLOMERULOTUBULAR BALANCEt

TUBULOGLOMERULAR FEEDBACK Macula Densa Feedback; For Autoregulation of GFR GLOMERULOTUBULAR BALANCE Percentage of solute reabsorbed is held constant; Buffers effect of drastic GFR changes on urine output

A 45-year-old woman develops severe diarrhea while on vacation. She has the following arterial blood values: pH = 7.25 PcO2 = 24 mm Hg [HCO3-] = 10 mEq/L Venous blood samples show decreased blood [K+] and a normal anion gap. Which of the following statements about this patient is correct? (A) She is hypoventilating (B) The decreased arterial [HCO3-] is a result of buffering of excess H+ by HCO3- (C) The decreased blood [K+] is a result of exchange of intracellular H+ for extracellular K+ (D) The decreased blood [K+] is a result of increased circulating levels of aldosterone (E) The decreased blood [K+] is a result of decreased circulating levels of antidiuretic hormone (ADH)

The decreased blood [K+] is a result of increased circulating levels of aldosterone

The following information was obtained in a 20-year-old college student who was participating in a research study in the Clinical Research Unit: Plasma: [Inulin] = 1 mg/mL [X] = 2 mg/mL Urine: [Inulin] = 150 mg/mL [X] = 100 mg/mL Urine flow rate = 1 mL/min Assuming that X is freely filtered, which of the following statements is most correct? (A) There is net secretion of X (B) There is net reabsorption of X (C) There is both reabsorption and secretion of X (D) The clearance of X could be used to measure the glomerular filtration rate (GFR) (E) The clearance of X is greater than the clearance of inulin

There is net reabsorption of X Cinulin = UinulinV/PinulinCinulin = (150mg/dL)(1mL/min)/(1mg/mL) Cinulin = 150mL/min Cx = UxV/PxCx = (100mg/mL) (1mL/min)/(2mg/ml) Cx = 50mL/min Cx < Cinulin Cx < GFR since Cinulin is used to estimate GFR X is therefore a substance that undergoes net reabsorption. Side Note: if X here is greater than GFR, there is net secretion. If X = GFR, then X is either inulin or creatinine.

aka the diluting segment of the nephron - why?frf

Thick Ascending Limb of LH (THAL) Permeable to: solutes (Na-K-2Cl symport) Impermeable to water

Time to transfer material from pylorus to ileocecal valve? Time to transfer material from ileocecal valve to colon?

Time to transfer material from pylorus to ileocecal valve: 3-5 hours Time to transfer material from ileocecal valve to colon: 8-15 hours

Marker for total body water

Tritiated water

3 NEUROCRINES

VIP * Enkephalins (met-enkephalin and leu-enkephalin) ** GRP (Bombesin) * VIP is the ultimate smooth muscle relaxant - it relaxes the LES, Orad Stomach, PS and ICV. Mnemonic: kapag VIP ang bisita, dapat chillax siya pagdating sa bahay nyo. VIP is a chillax substance - it provides smooth muscle relaxation. **Contracts LES, Pyloric Sphincter, Ileocecal Valve

Relaxation of the Lower Esophageal Sphincter (LES) due to what hormones

VIP and NO from inhibitory ganglionic neurons ** In Achalasia, esophageal myenteric plexus is deficient, NO and VIP is deficient (due to decreased expression of neuronal NO synthase) à no anterograde/receptive relaxation ahead of the stimulus

Facilitates Receptive Relaxation of Orad Stomach?

VIP, CCK reason why gastric pressure seldom rise above the levels that breach the LES even if stomach is filled with meal

Which of the following abolishes "receptive relaxation" of the stomach? (A) Parasympathetic stimulation (B) Sympathetic stimulation (C) Vagotomy (D) Administration of gastrin (E) Administration of vasoactive intestinal peptide (VIP)

Vagotomy Receptive relaxation of the orad stomach occurs using a vagovagal reflex. Vagotomy would prevent that.

Which of the following substances is released from neurons in the GI tract and produces smooth muscle relaxation? (A) Secretin (B) Gastrin (C) Cholecystokinin (CCK) (D) Vasoactive intestinal peptide

Vasoactive intestinal peptide

Effect on GFR, RPF, Filtration fraction of the ff: Vasoconstrict afferent Vasoconstrict efferent ↑ Plasma protein Ureteral stone

Vasoconstrict afferent: will ↓ Gc hydrostatic pressure Vasoconstrict efferent: will ↑ Gc hydrostatic pressure ↑ Plasma protein: will ↑ Gc oncotic pressure Ureteral stone: will ↑ Bs hydrostatic pressure

SATIETY CENTER

VentroMedial Hypothalamus Stimulates Anorexigenic Neurons: LEPTIN, INSULIN, GLP-1 thank you Very Much, Leptin

At plasma para-aminohippuric acid (PAH) concentrations below the transport maximum (Tm), PAH (A) reabsorption is not saturated (B) clearance equals inulin clearance (C) secretion rate equals PAH excretion rate (D) concentration in the renal vein is close to zero (E) concentration in the renal vein equals PAH concentration in the renal artery

concentration in the renal vein is close to zero PAH-tapon: 100% filtered and secreted - lahat tinatapon sa ihi PAH is supposed to be highly excreted since it is filtered, secreted and not reabsorbed. Since PAH concentration is still below Tm, it means we have not fully saturated the nephrons - PAH is still being excreted. Since it is still being excreted, little PAH can be found in the renal vein - almost all PAH goes to the urine.

3 things responsible for Corticopapillary Osmotic Gradient / Graded Osmolarity in the Renal Interstitium

countercurrent multiplier - LOOP OF HENLE countercurrent exchanger - VASA RECTA ADH simulation of UREA RECYCLING via UT1

MOA of motor paralysis in GBS

demyelination of Type A-Beta Fibers

Excretion formula

excretion = filtration - reabsorption + secretion

At plasma concentrations of glucose higher than occur at transport maximum (Tm), the (A) clearance of glucose is zero (B) excretion rate of glucose equals the filtration rate of glucose (C) reabsorption rate of glucose equals the filtration rate of glucose (D) excretion rate of glucose increases with increasing plasma glucose concentrations (E) renal vein glucose concentration equals the renal artery glucose concentration

excretion rate of glucose increases with increasing plasma glucose concentrations - 0-200: all are reabsorbed 200-375: splay > 375: transport maximum; ↑ plasma glucose, ↑ urine glucose Renal Threshold: plasma glucose 200mg/dL (some nephrons saturated) Renal Transport Maximum: plasma glucose > 375mg/dL (all nephrons saturated) Splay: between 200mg/dL - 375mg/dL (glucose excretion before complete saturation of all nephrons)

A negative free-water clearance (−CH2O) will occur in a person who (A) drinks 2 L of distilled water in 30 minutes (B) begins excreting large volumes of urine with an osmolarity of 100 mOsm/L after a severe head injury (C) is receiving lithium treatment for depression and has polyuria that is unresponsive to the administration of antidiuretic hormone (ADH) (D) has an oat cell carcinoma of the lung, and excretes urine with an osmolarity of 1000 mOsm/L

has an oat cell carcinoma of the lung, and excretes urine with an osmolarity of 1000 mOsm/L Since D is associated with SIADH which will cause a negative free- water clearance due to the high levels of ADH. If (-) ADH: Free Water excreted and CH2O is positive If (+) ADH: Free Water is NOT excreted (water is reabsorbed) and CH20 is negative

Cholecystokinin (CCK) has some gastrin-like properties because both CCK and gastrin (A) are released from G cells in the stomach (B) are released from I cells in the duodenum (C) are members of the secretin-homologous family (D) have five identical C-terminal amino acids (E) have 90% homology of their amino acids

have five identical C-terminal amino acids

Subjects A and B are 70-kg men. Subject A drinks 2 L of distilled water, and subject B drinks 2 L of isotonic NaCl. As a result of these ingestions, subject B will have a (A) greater change in intracellular fluid (ICF) volume (B) higher positive free-water clearance (CH2O) (C) greater change in plasma osmolarity (D) higher urine osmolarity (E) higher urine flow rate

higher urine osmolarity Subject A drinks water alone, subject B drinks water + salt. Therefore, subject B will excrete more salt compared to subject A, resulting in higher urine osmolarity.

3 main amino acids stimulating GASTRIN secretion

phenylalanine (F) tryptophan (W) methionine (M)

initiates a decrease in gastric emptying

hyperosmolality of duodenal contents

major extracellular buffer? major intracellular buffer?

major extracellular buffer is HCO3- major intracellular buffer is hemoglobin

Addison's disease

occurs when the adrenal glands do not produce enough of the hormones cortisol or aldosterone + Low weak androgen + Hyperpigmentation hypoNa hyperkalemia Metabolic acidosis

Slow waves in small intestinal smooth muscle cells are (A) action potentials (B) phasic contractions (C) tonic contractions (D) oscillating resting membrane potentials (E) oscillating release of cholecystokinin (CCK)

oscillating resting membrane potentials

Marker for plasma

radioactive iodinated serim albumin (RISA) evans blue

A woman has a plasma osmolarity of 300 mOsm/L and a urine osmolarity of 1200 mOsm/L. The correct diagnosis is (A) syndrome of inappropriate antidiuretic hormone (SIADH) (B) water deprivation (C) central diabetes insipidus (D) nephrogenic diabetes insipidus (E) drinking large volumes of distilled water

water deprivation presents with hypernatremia, polyuria, low urine Na, hypoosmolar urine: Diabetes Insipidus

ADH role in urea recycling

↑ ADH secretion → ↑ Water AND Urea reabsorption (via UT1 or urea transporter 1) → Low Urine Flow Rate Contributes to urea recycling and development of corticopapillary osmotic gradient. Urea is a solute that increases maximum urine osmolality (it doubles it).