Renal – Physio

Under normal physiological conditions, glucose is completely reabsorbed in the proximal convoluted tubule after being filtered at the glomerulus. Hence, its renal clearance is zero — none of it appears in the urine unless the plasma glucose level exceeds the renal threshold (~180 mg/dL).

Why others are wrong:
❌ Creatinine — slightly secreted, so its clearance is slightly greater than GFR.
❌ Inulin — freely filtered, neither reabsorbed nor secreted, so clearance equals GFR.
❌ PAH (para-aminohippuric acid) — actively secreted, so clearance equals renal plasma flow.
❌ Phenolphthalein — excreted by tubular secretion, not zero clearance.

The micturition reflex center is located in the sacral segments (S2–S4) of the spinal cord. These segments contain parasympathetic neurons that control detrusor muscle contraction and relaxation of the internal urethral sphincter, initiating urination when the bladder is full.

Why others are wrong:
❌ Kidney — involved in urine formation, not micturition control.
❌ Cerebrum — exerts voluntary control (deciding when to void), but not the reflex center.
❌ Urinary bladder — detects stretch but does not coordinate the reflex.
❌ Hypothalamus — influences autonomic tone but not directly involved in the micturition reflex.

In a healthy individual, around 15–20% of the effective renal plasma flow (ERPF) is filtered through the glomerulus into Bowman’s capsule — this is known as the filtration fraction (FF).

This fraction represents the portion of plasma that actually becomes glomerular filtrate, while the rest continues into the efferent arteriole to supply the renal tubules.

Formula:

Typical values:

So, about one-fifth of the plasma entering the glomerulus is filtered.

❌ Why the Other Options Are Wrong

• Less than 5%:
  Way too low — would indicate severe filtration impairment.

• Between 40 and 50%:
  Unrealistically high; kidneys would lose excessive plasma volume.

• Between 70 and 80%:
  Physiologically impossible; filtration this high would deplete plasma rapidly.

• Greater than 90%:
  Completely incompatible with life — no plasma would remain for renal perfusion

The juxtamedullary nephrons are primarily responsible for concentrating urine.
They make up about 15% of all nephrons, but their long loops of Henle, which extend deep into the renal medulla, are essential for establishing the osmotic gradient that drives water reabsorption under the influence of antidiuretic hormone (ADH).

Through the countercurrent multiplier (in the loop of Henle) and countercurrent exchanger (in the vasa recta), these nephrons allow the kidneys to produce hyperosmotic (concentrated) urine during dehydration or water conservation states.

❌ Why the Other Options Are Wrong

• Bowman’s capsule:
  Only collects filtrate — it has no role in water reabsorption or urine concentration.

• Superficial nephrons:
  Their loops of Henle are short and confined to the outer medulla, so they mainly dilute urine rather than concentrate it.

• The glomerulus:
  Involved in filtration, not concentration — it filters plasma but doesn’t alter osmolarity.

• The proximal tubule:
  Reabsorbs a large volume of water and solutes (≈65%), but this reabsorption is isotonic — it does not increase urine concentration relative to plasma.

The Na⁺–K⁺–2Cl⁻ cotransporter (NKCC2) in the thick ascending limb of the loop of Henle is a classic example of secondary active transport.
It uses the energy indirectly generated by the Na⁺/K⁺-ATPase on the basolateral membrane, which maintains a low intracellular Na⁺ concentration.

This Na⁺ gradient then drives Na⁺ to enter the cell from the tubular lumen — and in doing so, it brings K⁺ and 2Cl⁻ along with it via the NKCC2 cotransporter.
Even though ATP is not directly consumed by this cotransporter, its function depends on the ATP-driven sodium pump, hence the term secondary active transport.

❌ Why the Other Options Are Wrong

• Counter transport:
  Involves ions moving in opposite directions (e.g., Na⁺/Ca²⁺ exchanger), while NKCC2 moves ions in the same direction (symport).

• Facilitated diffusion:
  This is passive and driven solely by concentration gradients — NKCC2 requires an active sodium gradient.

• Passive transport:
  Doesn’t require energy — NKCC2 relies on energy indirectly via Na⁺/K⁺-ATPase activity.

• Primary active transport:
  Directly uses ATP (e.g., Na⁺/K⁺-ATPase). NKCC2 does not hydrolyze ATP itself, so it’s secondary active.

When the tubular fluid leaves the thick ascending limb of the loop of Henle and enters the collecting duct, it is hypotonic relative to plasma.

Here’s why:

• The thick ascending limb actively reabsorbs Na⁺, K⁺, and Cl⁻ via the Na⁺–K⁺–2Cl⁻ cotransporter, but it is impermeable to water.

• As solutes leave but water cannot follow, the tubular fluid becomes progressively dilute (hypotonic).

• By the time it reaches the distal convoluted tubule and collecting duct, its osmolarity is typically around 100 mOsm/L, much lower than plasma (~300 mOsm/L).

From this point onward, ADH (vasopressin) determines the final urine tonicity:

• With ADH: water is reabsorbed → urine becomes hypertonic.

• Without ADH: water stays → urine remains hypotonic.

❌ Why the Other Options Are Wrong

• Hypertonic:
  Occurs after ADH acts on the collecting ducts, not before it enters.

• Hypertonic or isotonic, but never hypotonic:
  Incorrect — urine is dilute (hypotonic) when entering the duct.

• Hypotonic or isotonic, but never hypertonic:
  Too broad; the entering filtrate is definitively hypotonic under normal conditions.

• Isotonic:
  The filtrate was isotonic only at the end of the proximal tubule, not at the entry to the collecting duct.

In the early part of the proximal convoluted tubule (PCT), about 90% of filtered glucose is reabsorbed by the Na⁺–Glucose co-transporter 2 (SGLT2) located on the apical (luminal) membrane of tubular epithelial cells.

How it works:

• SGLT2 couples 1 Na⁺ ion with 1 glucose molecule (1:1 ratio).

• It uses the Na⁺ gradient created by the Na⁺/K⁺-ATPase on the basolateral membrane — this is a form of secondary active transport.

• Once inside the cell, glucose diffuses into the peritubular capillaries via the GLUT2 transporter on the basolateral membrane.

In the late PCT, the remaining 10% of glucose is reclaimed by SGLT1, which is more efficient but has a lower capacity.

❌ Why the Other Options Are Wrong

• GLUT1:
  Found in late PCT (S3 segment) for basolateral glucose exit, not for luminal uptake.

• GLUT2:
  Basolateral transporter that facilitates glucose efflux into blood, not luminal entry.

• GLUT4:
  Insulin-dependent transporter found in muscle and adipose tissue, not in renal tubules.

• SGLT1:
  Active in the late PCT and reabsorbs the remaining ~10% of glucose, not the major portion.

The thin ascending limb of the loop of Henle is impermeable to water but allows passive diffusion of solutes (mainly Na⁺ and Cl⁻) into the medullary interstitium.

This occurs because:

• The concentration of solutes in the tubular fluid is high after the descending limb (which reabsorbs water).

• As the fluid ascends, NaCl diffuses out passively, but water cannot follow due to the wall’s impermeability to water.

• This process contributes to the hyperosmotic medulla, essential for urine concentration.

❌ Incorrect Options:

• Thick ascending limb: Impermeable to water, but solutes (Na⁺, K⁺, Cl⁻) move actively, not passively.

• Descending limb: Permeable to water, not solutes.

• Proximal convoluted tubule: Permeable to both water and solutes — most reabsorption occurs here.

• Distal convoluted tubule: Limited water permeability (depends on ADH) and active solute transport.

The sodium–hydrogen antiporters (Na⁺/H⁺ exchangers) are located in the apical membrane of the proximal convoluted tubule (PCT).
This antiporter plays a key role in acid–base balance and bicarbonate reabsorption:

• Na⁺ enters the tubular cell from the lumen in exchange for H⁺, which is secreted into the tubular fluid.

• The secreted H⁺ combines with filtered HCO₃⁻ to form H₂CO₃, which then dissociates into CO₂ + H₂O (via carbonic anhydrase).

• CO₂ diffuses back into the cell, where it reforms HCO₃⁻, which is transported into the blood.

This mechanism is secondary active transport, driven by the Na⁺ gradient established by the Na⁺/K⁺-ATPase on the basolateral membrane.

❌ Why the Other Options Are Wrong

• Collecting duct:
  H⁺ secretion here occurs via H⁺-ATPase pumps, not Na⁺/H⁺ exchangers.

• Distal convoluted tubule:
  Mainly uses Na⁺/Cl⁻ cotransporters, not Na⁺/H⁺ antiporters.

• Loop of Henle – thick segment:
  Uses the Na⁺–K⁺–2Cl⁻ cotransporter (NKCC2), not Na⁺/H⁺ exchange.

• Loop of Henle – thin segment:
  Has minimal active transport; solute movement is mostly passive diffusion.

To calculate renal clearance, we use the standard formula:

Where:

• U = concentration of substance in urine (mg/mL)

• V = urine flow rate (mL/min)

• P = plasma concentration (mg/mL)

Substitute the given values:

Since U = 0 mg/mL, no substance “x” is excreted in the urine — meaning it is either completely reabsorbed or not filtered at all.

❌ Why the Other Options Are Wrong

• 0.5, 1, 2, or 13.6 mL/min:
  These would only apply if the urinary concentration (U) were greater than zero. Here, since U = 0, all yield zero clearance.

When a substance’s clearance (C) is compared with the glomerular filtration rate (GFR):

• C = GFR: The substance is filtered only (no secretion or reabsorption) → e.g., inulin, creatinine (approx.).

• C < GFR: The substance is reabsorbed after filtration → e.g., glucose, amino acids.

• C > GFR: The substance is secreted into the tubule → e.g., PAH (para-aminohippuric acid), certain drugs.

In this case:

Because clearance exceeds GFR, it means additional drug is being secreted into the tubular lumen beyond what was filtered at the glomerulus.

❌ Why the Other Options Are Wrong

• No overall evaluation can be made:
  Incorrect — we can infer secretion based on clearance alone.

• Similar to amino acids:
  Amino acids are reabsorbed, giving C < GFR, not greater.

• Since clearance > GFR, the drug is likely reabsorbed:
  Opposite of the correct interpretation.

• TM (transport maximum) exceeded:
  TM applies to saturable reabsorptive transport, not to explain clearance > GFR.

The baby presents with signs of dehydration — lethargy, weakness, vomiting, diarrhea, and poor skin turgor (skin going back slowly after pinching).
This is a case of isotonic (fluid and electrolyte) dehydration, common in infants after gastrointestinal fluid loss.

The ideal IV fluid should replace both water and electrolytes, mimicking extracellular fluid composition.

Lactated Ringer’s solution (Ringer’s lactate) contains:

• Na⁺ = 130 mEq/L

• K⁺ = 4 mEq/L

• Ca²⁺ = 3 mEq/L

• Cl⁻ = 109 mEq/L

• Lactate = 28 mEq/L (converted to bicarbonate in the liver → helps correct acidosis)

This makes it the best choice for rehydrating a baby with dehydration due to diarrhea and vomiting.

❌ Why the Other Options Are Wrong

• Normal saline (0.9% NaCl):
  Can restore intravascular volume but lacks K⁺ and buffer, so it doesn’t correct metabolic acidosis that often accompanies diarrhea.

• Haemaccel:
  A colloid solution; used for hypovolemia or shock, not for simple dehydration.

• 5% dextrose solution:
  Provides free water, not electrolytes — can worsen hyponatremia in dehydrated infants.

• Hypertonic saline (3% NaCl):
  Used for severe hyponatremia, not for rehydration; can cause dangerous fluid shifts.

During acidosis, the blood pH drops (H⁺ concentration increases). To restore acid–base balance, the kidneys play a compensatory role by:
1️⃣ Increasing secretion of H⁺ ions into the tubular lumen (mainly in the proximal tubule, distal tubule, and collecting duct).
2️⃣ Reabsorbing filtered bicarbonate (HCO₃⁻) to conserve base.
3️⃣ Generating new bicarbonate ions through processes like ammonium (NH₄⁺) and phosphate buffering.

This renal compensation helps raise blood pH back toward normal over hours to days.

❌ Why the Other Options Are Wrong

• Secretion of HCO₃⁻:
  Would worsen acidosis — this happens during alkalosis, not acidosis.

• N₂ retention:
  Nitrogen gas isn’t regulated in acid–base balance.

• Secretion of Na⁺ ions:
  Sodium is reabsorbed, not secreted, especially when the body is trying to conserve volume.

• Secretion of K⁺ ions:
  H⁺ secretion actually tends to reduce K⁺ secretion; in acidosis, cells take up fewer K⁺ ions, often leading to hyperkalemia.

The proximal tubule is responsible for reabsorbing about 80–90% of filtered bicarbonate (HCO₃⁻).
If this reabsorption decreases — as in proximal renal tubular acidosis (Type II RTA) — the kidneys lose bicarbonate in urine, leading to:

• ↓ Plasma HCO₃⁻ concentration

• ↓ Blood pH
  → Resulting in metabolic acidosis

This is a primary loss of base, not an accumulation of acid, but the end effect is the same: blood becomes more acidic.

❌ Why the Other Options Are Wrong

• Metabolic alkalosis:
  Would occur if bicarbonate increased, not decreased.

• Hypochloremia:
  Not typically seen here; chloride may even rise as it’s reabsorbed to balance lost bicarbonate.

• Acidic urine:
  Initially urine is alkaline due to bicarbonate loss; later, when plasma bicarbonate falls, urine may become acidic — but the main systemic effect is acidosis.

• N₂ retention:
  Nitrogen gas isn’t related to acid–base handling.

Creatinine clearance is the most commonly used test to estimate the glomerular filtration rate (GFR) — the rate at which the kidneys filter plasma.

• It measures how efficiently creatinine, a muscle metabolism byproduct, is cleared from the blood into urine over time.

• GFR helps assess the stage of renal disease, monitor diabetic nephropathy, and guide drug dosage adjustments in renal failure.

❌ Why the Other Options Are Wrong:

Renal scan:

• Used mainly for visualizing renal perfusion, function asymmetry, or obstruction, not for calculating exact GFR.

• It provides a qualitative idea of renal function, not a precise numerical GFR.

Urinalysis:

• Checks for protein, glucose, blood, or infection in urine.

• It can indicate kidney damage, but not the filtration rate.

Intravenous pyelogram (IVP):

• An imaging technique to visualize urinary tract anatomy using contrast dye.

• Contraindicated in chronic kidney failure due to nephrotoxicity risk and does not assess GFR.

Serum pyruvate dehydrogenase:

• An enzyme in carbohydrate metabolism, unrelated to renal function or filtration capacity.

• Increased volume (polyuria):
  Due to osmotic diuresis — glucose pulls water into the tubular lumen.

• Increased specific gravity:
  Because of the presence of glucose and other solutes in urine, which makes it denser.

This combination is typical of uncontrolled diabetes mellitus, often accompanied by polydipsia and polyphagia.

❌ Why the Other Options Are Wrong:

Increased volume and decreased specific gravity:

• Seen in diabetes insipidus, not diabetes mellitus.

• In diabetes insipidus, there’s water loss without solute loss, so urine is dilute and of low specific gravity.

Decreased volume and increased specific gravity:

• Occurs in dehydration, where concentrated urine is formed due to water conservation.

Normal volume and decreased specific gravity / Normal volume and increased specific gravity:

• Both inconsistent with the osmotic diuresis typical of diabetes mellitus.

In an average 70 kg adult male, about 60% of body weight is water, distributed as:

• Intracellular fluid (ICF): ~40% of body weight (~28 L)

• Extracellular fluid (ECF): ~20% of body weight (~14 L)
   • Plasma: ~5% (~3.5 L)
   • Interstitial fluid: ~15% (~10.5 L)

💡 Mnemonic:

“60–40–20 rule” → 60% total body water, 40% inside cells, 20% outside.

During severe diarrhea, ECF volume decreases, leading to hypovolemia and electrolyte imbalance — hence why IV fluid replacement is critical.

❌ Why the Other Options Are Wrong:

10% / 20% / 30%:

• Far too low — would correspond only to single compartments, not total body water.

50%:

• Closer, but still underestimates the normal average for healthy adult males.

• Women typically have slightly less (~50%) due to higher fat content.

By the time the filtrate reaches the distal convoluted tubule → connecting tubule → collecting duct, it has passed through the thick ascending limb, which is impermeable to water but actively removes Na⁺, K⁺, and Cl⁻.

This makes the tubular fluid hypotonic before it enters the collecting duct — always.

Whether it becomes concentrated afterward depends on ADH, but entry fluid is always hypotonic.

✔ Why This Option Is Correct

Hypotonic only — ✅

• Thick ascending limb (TAL) removes solutes but keeps water inside → dilutes filtrate.

• DCT continues diluting effects.

• Therefore, filtrate arriving at collecting duct is hypotonic (~100 mOsm/L).

• ADH will later make it concentrated inside the collecting duct — but not before entry.

❌ Why the Other Options Are Incorrect

Hypertonic only — ❌

• Impossible.

• The TAL cannot concentrate filtrate (impermeable to water).

• Fluid entering CD is always dilute, not concentrated.

Hypertonic or isotonic, but never hypotonic — ❌

• Opposite of reality.

• The entire purpose of ascending limb is to make fluid less concentrated.

Isotonic, but never hypertonic — ❌

• The filtrate becomes isotonic at the end of PCT,

• But after ascending limb, it becomes hypotonic, not isotonic.

Isotonic only — ❌

• True only earlier in PCT, not at the entry to collecting duct.

Clearance (C) is calculated by:

C = (U × V) / P

Given:
U = 0.5 mg/ml
V = 2 ml/min
P = 1 mg/ml

Substitute:
C = (0.5 × 2) / 1
C = 1 ml/min

The micturition reflex (the basic spinal reflex for urination) is initiated by stretch receptors in the bladder wall, which activate parasympathetic neurons from S2–S4.

These sacral parasympathetic fibers cause:

• Detrusor muscle contraction

• Internal sphincter relaxation

This is the core initiator of the micturition reflex.

Higher centers only modulate the reflex, not initiate it.

Sacral parasympathetic neurons — S2–S4 — ✅

• They receive the stretch input from the bladder.

• They send the first efferent impulses that contract the detrusor muscle.

• This is the essential reflex arc that begins micturition.

❌ Why The Other Options Are Incorrect

Cortical micturition center — ❌

• Provides voluntary control, especially conscious inhibition.

• It modulates but does not initiate the reflex.

Pontine storage center — ❌

• Facilitates urine storage, not voiding.

• Inhibits sacral parasympathetics.

Pudendal motor neurons — ❌

• Somatic fibers (S2–S4) supplying external urethral sphincter.

• They maintain continence but do not initiate the micturition reflex.

Thoracolumbar sympathetic fibers — ❌

• Promote storage

  • Relax detrusor

  • Constrict internal sphincter

• Opposite of initiation.

https://www.jaypeedigital.com/book/9789352701148/chapter/ch20

In metabolic acidosis, the kidney must increase acid excretion and generate new bicarbonate.
It does so mainly by:

• ↑ NH₄⁺ excretion

• ↑ Titratable acid formation (H₂PO₄⁻)

• ↑ Glutamine metabolism → NH₄⁺ + new HCO₃⁻

• ↓ Urine pH

So the most characteristic response among the options is increased titratable acid formation.

✔ Why This Option Is Correct

Increased titratable acid formation — ✅

• Kidneys secrete more H⁺ into the lumen.

• This H⁺ binds urinary buffers like phosphate → titratable acids.

• This is a key mechanism for regenerating new bicarbonate during metabolic acidosis.

• Highly characteristic and always increased.

❌ Why The Other Options Are Incorrect

Decreased NH₄⁺ excretion — ❌

• WRONG direction.

• In acidosis, NH₄⁺ excretion increases, not decreases.

• Ammonium excretion is one of the most important acid-removal mechanisms.

Increased filtered bicarbonate load — ❌

• In metabolic acidosis, plasma HCO₃⁻ is low, so filtered load also decreases.

• The kidney instead creates new HCO₃⁻.

Increased urine pH — ❌

• Opposite of what happens.

• Urine becomes more acidic (LOW pH) due to increased H⁺ secretion.

Reduced glutamine metabolism — ❌

• In acidosis, glutamine metabolism increases to produce:

  • NH₄⁺ for excretion

  • New HCO₃⁻ for blood

• Reduced metabolism would worsen acidosis.

http://www.nephjc.com/dct

Parathyroid hormone (PTH) increases Ca²⁺ reabsorption mainly in the distal convoluted tubule (DCT) via:

• Upregulating TRPV5 Ca²⁺ channels

• Increasing calbindin

• Enhancing Na⁺/Ca²⁺ exchanger activity

This makes the DCT the primary PTH-regulated site of Ca²⁺ handling.

Distal convoluted tubule — ✅

• Strong PTH responsiveness

• Main regulated site for fine-tuning Ca²⁺ reabsorption

• Responsible for preventing urinary calcium loss

• Uses active transport, not just diffusion

❌ Why The Other Options Are Incorrect

Collecting duct — ❌

• Minimal Ca²⁺ handling

• Not responsive to PTH for calcium regulation

Proximal tubule — ❌

• Reabsorbs most Ca²⁺ (~65%),

• BUT this is passive and not controlled by PTH

• PTH inhibits phosphate here, not Ca²⁺

Thick ascending limb — ❌

• Reabsorbs ~25% Ca²⁺ via paracellular route

• Influenced by NKCC2 and lumen positivity,

• Not the primary PTH-regulated site

Thin descending limb — ❌

• Mainly permeable to water, not ions

• No major Ca²⁺ transport role

Along the Loop of Henle:

• Descending limb → permeable to water, NOT solutes

• Thin ascending limb → impermeable to water, solutes leave passively

• Thick ascending limb → impermeable to water, but solutes leave actively (NKCC2)

The question specifically states passive movement of Na⁺ and Cl⁻ → this uniquely matches the thin ascending limb.

✔ Why This Option Is Correct

Thin ascending limb — ✅

• Impermeable to water

• Passive NaCl diffusion into interstitium

• Helps build medullary osmotic gradient

• No active transport systems here

❌ Why The Other Options Are Incorrect

Descending limb loop of Henle — ❌

• Permeable to water, not to solutes

• Opposite of what the question states

Distal convoluted tubule — ❌

• Mostly active ion transport (NaCl cotransporter)

• Water permeability depends on ADH

• Not characteristic passive NaCl movement

Proximal convoluted tubule — ❌

• Highly permeable to water AND solutes

• Not selectively impermeable to water

Thick ascending limb loop of Henle — ❌

• Impermeable to water (correct)

• BUT Na⁺, K⁺, Cl⁻ leave actively via the NKCC2 transporter

• Not passive → does not match question

REABSORPTION & SECRETION IN LOOP OF HENLE

https://www.osmosis.org/learn/Proximal_convoluted_tubule

The proximal convoluted tubule (PCT) is the nephron’s main reabsorptive powerhouse.
It reabsorbs:

• 100% of glucose

• 100% of amino acids

• 65–70% of Na⁺ and water

• Most bicarbonate

This is the signature function of the PCT.

✔ Why This Option Is Correct

Reabsorption of filtered glucose and amino acids — ✅

• Occurs exclusively in the PCT

• Via SGLT2 (glucose) and various amino acid cotransporters

• Highly active, energy-dependent, and specific

• No other nephron segment performs this

❌ Why the Other Options Are Incorrect

Active secretion of H⁺ coupled to Cl⁻ reabsorption — ❌

• H⁺ secretion in the PCT is mostly linked to Na⁺/H⁺ antiport (NHE3)

• Cl⁻ reabsorption occurs, but not via a coupled H⁺ mechanism like in the DCT/CD

Active secretion of K⁺ into tubular lumen — ❌

• Happens in collecting duct (principal cells)

• Under control of aldosterone

• Not in the PCT

Passive reabsorption of NaCl driven by urea concentration — ❌

• Occurs mainly in the thin limbs of the loop of Henle

• NOT the PCT

• The PCT reabsorbs NaCl actively, not passively driven by urea.

Water reabsorption under the influence of ADH — ❌

• ADH acts on the late DCT and collecting duct

• Water reabsorption in PCT is obligatory, NOT ADH-dependent.

When the macula densa detects high Na⁺ and Cl⁻ in the distal tubule, it interprets this as GFR being too high.

To protect the nephron from excessive filtrate flow, it triggers tubuloglomerular feedback, resulting in:

• Adenosine release → Afferent arteriole constriction → ↓ GFR

This is the classical physiological response.

✔ Why This Option Is Correct

Increased adenosine release causing afferent constriction — ✅

• High NaCl = high flow → macula densa releases adenosine

• Adenosine acts on A1 receptors

• Causes afferent arteriole vasoconstriction

• Reduces GFR back toward normal

This is the hallmark of the tubuloglomerular feedback mechanism.

❌ Why The Other Options Are Incorrect

Decreased adenosine release causing afferent dilation — ❌

• Occurs when NaCl is low, not high.

• That situation aims to increase GFR, opposite of this question.

Decreased ATP release and increased GFR — ❌

• Low ATP occurs with low NaCl, not high.

• Increased GFR is opposite of the needed correction.

Increased NO release causing afferent dilation — ❌

• NO is released when NaCl is low, helping increase GFR.

• High NaCl → NO decreases.

Increased renin secretion and efferent constriction — ❌

• High NaCl inhibits renin, reducing RAAS activity.

• Renin increases only when NaCl is low.

The kidney autoregulates GFR between MAP 80–180 mmHg using:

1. 1. 1. Myogenic mechanism (afferent arteriole stretch response)

      2. Tubuloglomerular feedback

When MAP falls below ~70 mmHg, autoregulation fails because the afferent arteriole cannot dilate any further → GFR drops sharply.

This is the classic explanation.

✔ Why This Option Is Correct

Failure of myogenic reflex — ✅

1. 1. • Myogenic reflex keeps GFR stable only within its working range.

      • Below a critical MAP (≈70 mmHg), the afferent arteriole maxes out its dilation, and the mechanism fails.

      • Result → renal perfusion drops → GFR falls.

      • This is the primary physiological reason for the drop.

❌ Why The Other Options Are Incorrect

Decreased adenosine at macula densa — ❌

1. 1. • Decreased adenosine → afferent dilation → increases GFR.

      • Not responsible for the fall at low MAP.

Enhanced sympathetic outflow — ❌

1. 1. • Sympathetic activity can reduce GFR,

      • BUT the question asks why GFR falls when MAP drops below autoregulatory range → the core issue is loss of autoregulation, not sympathetic tone.

Increased prostaglandin E₂ synthesis — ❌

1. 1. • PGE₂ actually helps preserve GFR during low perfusion by dilating afferent arteriole.

      • So this would oppose the fall, not cause it.

Inhibition of NO release — ❌

1. 1. • Would reduce GFR, but this is not the mechanism involved in the autoregulatory lower limit.

      • Myogenic failure is the key.

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Glomerular Filtration

Urea transporters UT-A1 and UT-A3 are located in the inner medullary collecting duct (IMCD).
Here, ADH increases their activity, allowing large amounts of urea to leave the tubular fluid → contributing to the medullary osmotic gradient for urine concentration.

✔ Why This Option Is Correct

Inner medullary collecting duct — ✅

• Main site of urea reabsorption via UT-A1 and UT-A3

• Strongly stimulated by ADH, especially during dehydration

• Critical for creating a hyperosmotic medulla

❌ Why The Other Options Are Incorrect

Cortical collecting duct — ❌

• Very little urea reabsorption

• Has virtually no UT-A1 or UT-A3 activity

Distal convoluted tubule — ❌

• Does not handle urea reabsorption

• Focuses on Na⁺, Ca²⁺, and water handling (with hormonal control)

Thin ascending limb — ❌

• Permeable to NaCl, not urea

• Urea does not significantly move here

Thin descending limb — ❌

• Permeable to water, not to urea

• Passive water movement only

When efferent arteriolar resistance increases slightly (within physiological limits), blood backs up in the glomerular capillaries → increasing glomerular hydrostatic pressure.

This leads to:

• ↑ GFR

• ↓ RBF

• ↑ Filtration Fraction (GFR/RPF)

If efferent constriction becomes too strong, GFR will eventually fall — but the question clearly says within physiological limits, meaning the initial phase where GFR rises.

✔ Why This Option Is Correct

Increased GFR and filtration fraction — ✅

• Mild efferent constriction → ↑ pressure upstream → ↑ GFR

• RPF falls because resistance increased

• Since GFR rises and RPF falls → FF increases

• Textbook physiology pattern

❌ Why The Other Options Are Incorrect

Decreased GFR and filtration fraction — ❌

• Happens only with severe efferent constriction (not within normal limits).

• The question specifies physiological limits, so this is incorrect.

Decreased GFR, increased RBF — ❌

• Efferent constriction reduces RBF, not increases.

• GFR does not decrease in early stages.

Increased GFR, decreased RBF — ❌

• Only half correct

• Yes, RBF ↓

• But filtration fraction must increase, not be left unaddressed

• The option without FF cannot be correct.

No change in GFR — ❌

• Only occurs if autoregulation perfectly compensates, which does not apply here

• Efferent constriction clearly raises GFR early on.

Glomerular Filtration

1. CC BY: Attribution Licensed content. Edited Content. Provided by BCcampus. Located at https://opentextbc.ca/anatomyandphysiology/chapter/25-7-regulation-of-renal-blood-flow/ ↵

In severe dehydration, there is low plasma volume, leading to:

• ↓ renal perfusion

• ↓ renal blood flow

• ↓ glomerular hydrostatic pressure (Pᴳᶜ)

Since GFR is directly proportional to glomerular hydrostatic pressure, the fall in Pᴳᶜ is the main reason GFR drops.

✔ Why This Option Is Correct

Decreased glomerular hydrostatic pressure — ✅

• Severe dehydration → low circulating volume

• Afferent arteriole receives less blood → ↓ Pᴳᶜ

• This directly reduces GFR

• This is the major determinant in volume-depleted states (shock, dehydration)

❌ Why The Other Options Are Incorrect

Increased Bowman’s capsule pressure — ❌

• Occurs in urinary tract obstruction, not dehydration

• No obstruction is mentioned

Decreased plasma oncotic pressure — ❌

• Would increase GFR, not reduce it

• Seen in hypoalbuminemia, not dehydration

Decreased filtration coefficient — ❌

• Happens in diseases like glomerulonephritis, thickened basement membrane

• Not a feature of dehydration

Increased plasma proteins — ❌

• Dehydration concentrates plasma proteins → ↑ oncotic pressure

• This does oppose filtration but is not the MAIN determinant

• The primary cause is still low glomerular hydrostatic pressure

Glomerular Filtration

1. CC BY: Attribution Licensed Content. Edited content.  Provided by Lumen Learning. Located at https://courses.lumenlearning.com/cuny-kbcc-ap2/chapter/physiology-of-urine-formation/. ↵

A substance that is:

• Freely filtered

• Not reabsorbed

• Not secreted

…will appear in the urine only in proportion to how much is filtered at the glomerulus.

This is exactly the definition of a marker for GFR.
Classic example: inulin.

✔ Why This Option Is Correct

Glomerular filtration rate — ✅

• Because the substance’s urinary excretion = amount filtered

• No reabsorption or secretion changes the value

• So its clearance reflects pure filtration only

❌ Why The Other Options Are Incorrect

Renal blood flow — ❌

• Measured by PAH clearance, because PAH is filtered + secreted (almost completely removed)

Filtration fraction — ❌

• FF = GFR / RPF

• You need both GFR and RPF; this substance only gives GFR.

Renal plasma flow — ❌

• Requires a substance that is almost 100% cleared (PAH)

• Not one that is neither reabsorbed nor secreted.

Tubular reabsorption — ❌

• You cannot measure tubular reabsorption from a substance that is not reabsorbed at all.

Thiazide diuretics act specifically on the early distal convoluted tubule (DCT) and block the Na⁺–Cl⁻ cotransporter (NCC).
This reduces NaCl reabsorption → increases diuresis → lowers blood pressure.

Classic example: Hydrochlorothiazide.

✔ Why This Option Is Correct

Thiazide diuretic — ✅

• Site of action: early DCT

• Target: NCC (Na⁺–Cl⁻ cotransporter)

• Effects:

  • Increased Na⁺ and Cl⁻ excretion

  • Mild diuresis

  • Increased Ca²⁺ reabsorption (unique)

  • First-line for hypertension

This matches the question perfectly.

❌ Why The Other Options Are Incorrect

Aldosterone antagonist — ❌

• Acts in the collecting duct, not the DCT

• Blocks ENaC indirectly by blocking aldosterone

Carbonic anhydrase inhibitor — ❌

• Acts in the proximal tubule, not DCT

• Example: Acetazolamide

• Blocks bicarbonate reabsorption

Loop diuretic — ❌

• Acts in the thick ascending limb

• Blocks NKCC2 transporter

• Strongest diuretics, not the one described

Osmotic diuretic — ❌

• Acts mostly in PCT and descending limb

• Example: Mannitol

• Works by increasing tubular osmolarity, not by blocking transporters

https://cvpharmacology.com/diuretic/diuretics

The SGLT2 transporter in the early proximal convoluted tubule (PCT) is responsible for reabsorbing ~90% of filtered glucose.

A mutation → ↓ glucose reabsorption → glucose spills into urine, even if:

• Blood glucose is normal

• GFR is normal

This disorder is known as familial renal glucosuria.

✔ Why This Option Is Correct

Glucosuria with normal GFR — ✅

• SGLT2 mutation → failure to reabsorb glucose in PCT

• Filtration (GFR) stays normal

• Reabsorption drops → glucose appears in urine

• Blood glucose is normal

❌ Why The Other Options Are Incorrect

Glucosuria with low GFR — ❌

• Low GFR means less glucose filtered, which would reduce, not increase glucosuria.

Hyperglycemia without glucosuria — ❌

• This happens in poorly controlled diabetes, not SGLT2 mutation.

• Mutation causes renal glucosuria, not hyperglycemia.

Impaired secretion of glucose — ❌

• Glucose is never secreted by the kidney.

• Only filtered and reabsorbed.

Reduced renal plasma flow — ❌

• Unrelated to SGLT2 transporter.

• RPF is determined by renal blood flow, not glucose transporters.

The thick ascending limb (TAL) is the key generator of the medullary osmotic gradient.
It:

• Actively pumps Na⁺, K⁺, Cl⁻ out (NKCC2 transporter)

• Is impermeable to water

• Creates the hyperosmotic medulla needed for ADH to concentrate urine

If the TAL fails → medullary interstitial osmolarity drops → even with normal ADH, the collecting duct cannot reabsorb water → polyuria + dilute urine.

This is the classic mechanism of nephrogenic concentrating defect.

✔ Why This Option Is Correct

Thick ascending limb — ✅

• Main site of countercurrent multiplier

• Generates high medullary osmolarity

• Defect → low medullary osmolarity → no gradient → no water reabsorption even with ADH

• Leads to polyuria, hyposthenuria, inability to concentrate urine

Matches the clinical scenario perfectly.

❌ Why The Other Options Are Incorrect

Collecting duct — ❌

• ADH acts here, but question says ADH levels are normal.

• The problem is insufficient medullary gradient, not ADH unresponsiveness.

Descending limb of Henle’s loop — ❌

• Water-permeable segment

• Does not generate osmotic gradient

• Its failure wouldn’t markedly reduce medullary osmolarity

Distal convoluted tubule — ❌

• Handles NaCl and Ca²⁺ reabsorption

• Plays no major role in medullary gradient formation

Proximal convoluted tubule — ❌

• Reabsorbs most solutes and water

• Does not control the countercurrent multiplier

https://www.researchgate.net/figure/Mechanism-of-glucose-stimulated-insulin-secretion-in-pancreatic-b-cells-ATP-derived-from_fig1_301051919

After a potassium-rich meal, plasma K⁺ should rise — but it usually doesn’t, because the body has a rapid, immediate buffering system:

👉 Insulin drives K⁺ into cells within minutes.

This is the FASTEST mechanism for preventing dangerous hyperkalemia.
The kidney works later (hours), not within 30 minutes.

✔ Why This Option Is Correct

Rapid cellular uptake of K⁺ stimulated by insulin — ✅

• Eating triggers insulin release.

• Insulin stimulates Na⁺–K⁺ ATPase in muscle & liver → K⁺ shifts into cells.

• This prevents any spike in plasma K⁺.

• This is the primary and immediate response after a meal.

❌ Why The Other Options Are Incorrect

Elevated K⁺ filtration due to increased GFR — ❌

• GFR does not significantly increase after a meal.

• And filtration alone cannot prevent hyperkalemia.

Enhanced distal tubular K⁺ secretion — ❌

• This depends on aldosterone, which takes hours to act.

• Not immediate.

Increased Na⁺–K⁺ ATPase inhibition in muscle cells — ❌

• Insulin actually stimulates, not inhibits, Na⁺–K⁺ ATPase.

• Inhibition would worsen hyperkalemia.

Increased renal excretion via aldosterone — ❌

• Aldosterone secretion and action takes 1–3 hours.

• Not responsible for the early (30-minute) regulation.

Acute blood loss → low blood pressure (80/60) → activates sympathetic nervous system → at the kidney this causes:

• Vasoconstriction of renal vessels → ↓ renal blood flow (RBF)

• Stimulation of β₁ receptors on JG cells → ↑ renin release → activates RAAS to help restore BP

So in shock/hemorrhage: low RBF + high renin is the classic combo.

✔ Why This Option Is Correct

Decreased renal blood flow and increased renin release — ✅

• Sympathetic activation → afferent & efferent constriction → ↓ RBF

• β₁ stimulation on juxtaglomerular cells → renin secretion ↑

• Renin → angiotensin II → vasoconstriction + aldosterone → Na⁺ and water retention

• All of this is the body’s attempt to restore BP and circulating volume

Matches the scenario perfectly.

❌ Why The Other Options Are Incorrect

Decreased GFR and decreased renin release — ❌

• GFR may indeed fall,

• But renin will increase, not decrease, in hemorrhage.

• Sympathetic activity + low perfusion pressure both stimulate renin.

Increased GFR and decreased afferent tone — ❌

• In shock, afferent tone is increased (constriction), not decreased.

• GFR tends to fall, not rise.

Increased renal blood flow and reduced sodium reabsorption — ❌

• This would happen in a high-volume or vasodilated state, not in acute blood loss.

• In hemorrhage: RBF falls, and Na⁺ is retained, not wasted.

Reduced renal vascular resistance and elevated urine flow — ❌

• Sympathetic tone actually increases renal vascular resistance.

• Urine flow typically falls sharply in hypovolemia/shock.

In chronic respiratory acidosis, CO₂ is persistently elevated.
The kidney compensates by:

• Increasing H⁺ secretion

• Increasing HCO₃⁻ reabsorption

• Increasing ammonium (NH₄⁺) production

• Increasing titratable acid formation

This restores pH toward normal.

✔ Why This Option Is Correct

Increased H⁺ secretion and HCO₃⁻ reabsorption — ✅

• More H⁺ secreted into the tubules → binds buffers (phosphate, NH₃)

• More new HCO₃⁻ generated and added back to blood

• This is the classic renal compensation for chronic respiratory acidosis

• Occurs over 2–5 days during chronic states

❌ Why the Other Options Are Incorrect

Decreased H⁺ secretion and Cl⁻ excretion — ❌

• Opposite of what happens

• In acidosis, H⁺ secretion increases, not decreases

Decreased tubular glutamine activity — ❌

• Glutamine metabolism increases → generates NH₄⁺ + new HCO₃⁻

• Decreased activity would worsen acidosis

Increased phosphate buffering in plasma — ❌

• Buffering happens in urine, not plasma

• Plasma phosphate buffering changes minimally

• Kidney increases urinary titratable acid, not plasma phosphate

Reduced ammonium production — ❌

• NH₄⁺ production increases drastically

• Essential for removing excess acid

In hemorrhagic shock, renal perfusion pressure drops.
Normally, this would ↓ GFR — but angiotensin II saves the day.

Angiotensin II has a stronger constricting effect on the efferent arteriole than the afferent, which:

• Increases glomerular hydrostatic pressure

• Helps maintain GFR near normal despite low renal blood flow

This is the key mechanism that preserves filtration during low perfusion states.

✔ Why This Option Is Correct

Preferential efferent arteriole constriction — ✅

• Angiotensin II acts more intensely on efferent > afferent

• Efferent constriction → raises pressure in glomerular capillaries

• Helps maintain GFR even when renal blood flow is low

• Classic mechanism in volume depletion and shock

❌ Why the Other Options Are Incorrect

Decreasing glomerular oncotic pressure — ❌

• Ang II does not affect plasma protein concentration

• Oncotic pressure typically increases in low-flow states, which would reduce GFR

Dilating afferent arterioles — ❌

• Angiotensin II does not dilate afferent arterioles

• If anything, it mildly constricts them

• Prostaglandins—not Ang II—help dilate the afferent arteriole during shock

Increasing mesangial surface area — ❌

• Ang II actually contracts mesangial cells, which reduces filtration area

• This action slightly lowers GFR, not maintains it

Suppressing proximal Na⁺ reabsorption — ❌

• Ang II increases, not suppresses, proximal Na⁺ reabsorption

• This effect helps volume recovery, not GFR maintenance

https://www.researchgate.net/figure/Glomerulus-with-afferent-and-efferent-arteriole-In-the-presence-of-a-reduced-cardiac_fig1_11270958

The vasa recta are the countercurrent exchangers of the kidney medulla.
They must have slow blood flow to preserve the medullary osmotic gradient.

👉 If vasa recta blood flow doubles (too fast) → solutes (NaCl, urea) are washed out from the medulla →
🔻 Medullary hyperosmolarity falls
🔻 Collecting duct has less gradient to pull water out (even with ADH)
🔻 Urine becomes less concentrated

So: more flow = more washout = less concentration.

✔ Why This Option Is Correct

Dissipation of medullary gradient with reduced urine concentration — ✅

• Faster vasa recta flow → solutes carried away quickly

• Medulla becomes less hyperosmotic

• Collecting duct cannot reabsorb as much water → dilute urine

• Classic “washout” phenomenon

❌ Why The Other Options Are Incorrect

Decreased washout of interstitial urea — ❌

• Doubling blood flow would increase, not decrease, washout.

• So this is the opposite of what happens.

Enhanced countercurrent exchange and solute trapping — ❌

• Countercurrent exchange works best with slow flow.

• High flow disrupts it → less solute trapping, not more.

Higher urea recycling efficiency — ❌

• Increased flow reduces time for urea to equilibrate → less recycling, more washout.

Increased osmolarity of descending limb fluid — ❌

• With loss of medullary gradient, the descending limb fluid becomes less concentrated, not more.

The Na⁺–K⁺–2Cl⁻ (NKCC2) cotransporter in the thick ascending limb uses the Na⁺ gradient created by the basolateral Na⁺/K⁺ ATPase to pull K⁺ and Cl⁻ into the cell.

Since it depends on the energy of another pump (Na⁺/K⁺ ATPase), NOT ATP directly, it is a secondary active transporter.

✔ Why This Option Is Correct

Secondary active transport — ✅

• NKCC2 does not use ATP directly.

• It relies on the Na⁺ gradient (created by Na⁺/K⁺ ATPase) → indirect energy use.

• Classic example of symport-type secondary active transport.

❌ Why The Other Options Are Incorrect

Counter transport — ❌

• Countertransporters move solutes in opposite directions (antiport).

• NKCC2 moves three solutes together in the same direction → symport, not antiport.

Facilitated diffusion — ❌

• Facilitated diffusion is passive and only uses concentration gradients.

• NKCC2 requires the Na⁺ gradient supplied by active pumping → not pure diffusion.

Passive transport — ❌

• NKCC2 moves ions against some electrochemical gradients; cannot be passive.

• Requires energy indirectly via Na⁺ gradient.

Primary active transport — ❌

• Primary transporters (like Na⁺/K⁺ ATPase) directly hydrolyze ATP.

• NKCC2 does not use ATP directly → so it is NOT primary.

https://triyambak.org/free-resources/csir-net-life-sciences/pointer/5529

In the proximal convoluted tubule (PCT):

• Water and Na⁺ are reabsorbed very early and proportionally

• Glucose and amino acids are reabsorbed completely (100%)

• Cl⁻ reabsorption lags behind early in the PCT, so its concentration in the tubular fluid increases

By the end of the PCT, Cl⁻ becomes more concentrated than at the beginning.

This is why Cl⁻ is the ONLY substance that increases in concentration across the PCT.

✔ Why This Option Is Correct

Chloride — ✅

• Early PCT: Na⁺ and water removed rapidly → Cl⁻ left behind

• Cl⁻ concentration rises because it is reabsorbed later in the PCT

• Therefore its tubular concentration is higher at the end than at the start

This is a classic physiology fact.

❌ Why The Other Options Are Incorrect

Amino acids — ❌

• 100% reabsorbed in the first part of the PCT

• None should remain by the end

Calcium — ❌

• Reabsorbed passively with Na⁺ and water

• Does not accumulate in tubular fluid

Glucose — ❌

• Completely reabsorbed in early PCT (SGLT2, then SGLT1)

• Zero at the end, unless TM is exceeded (diabetes)

Sodium — ❌

• Reabsorbed in proportion to water (isosmotic reabsorption)

• Concentration stays nearly the same, not higher

Polyuria with low urine osmolarity means the kidneys are failing to concentrate urine.
The only hormone responsible for concentrating urine is ADH (vasopressin).

If ADH is not released, the collecting ducts become impermeable to water, causing:

• Large volumes of dilute urine

• Excessive thirst (polydipsia)

• Low urine osmolarity

This is classic central diabetes insipidus.

✔ Why This Option Is Correct

Impaired release of antidiuretic hormone — ✅

• ADH makes collecting ducts water-permeable

• Without it → water cannot be reabsorbed

• Result → very dilute urine + high volume (polyuria)

• Blood osmolarity rises → excessive thirst

Matches the clinical picture perfectly.

❌ Why The Other Options Are Incorrect

Excessive release of aldosterone — ❌

• Aldosterone increases Na⁺ reabsorption, not water permeability

• It does not cause massively dilute urine

• Instead, it reduces urine volume slightly

Increased reabsorption of Na⁺ in proximal tubule — ❌

• This would not cause low urine osmolarity

• PCT water reabsorption is obligatory, so osmolarity stays the same

Reduced secretion of renin — ❌

• Affects blood pressure and Na⁺ balance

• Not directly linked to dilute polyuria

Inadequate glomerular filtration rate — ❌

• Low GFR would decrease urine output, not increase it

• Polyuria cannot occur with low GFR

Paradoxical aciduria occurs when the extracellular fluid (ECF) becomes alkaline while urine remains acidic.
This typically happens in states such as severe vomiting with hypochloremic, hypokalemic metabolic alkalosis.

• The body loses gastric HCl → ECF becomes alkaline.

• At the same time, due to potassium depletion, the kidneys conserve Na⁺ by exchanging it with H⁺ instead of K⁺, leading to acidic urine despite systemic alkalosis.

Thus, it is called “paradoxical” because the urine acidity is the opposite of what you would expect in systemic alkalosis.

Why the Other Options Are Wrong

Glucosuria ❌

• Refers to excretion of glucose in urine (commonly seen in uncontrolled diabetes mellitus).

• Has no connection with ECF alkalinity or paradoxical urine acidity.

Phenylketonuria ❌

• A metabolic disorder due to deficiency of phenylalanine hydroxylase, leading to accumulation of phenylalanine and its metabolites.

• It manifests with mental retardation and seizures if untreated, not with paradoxical aciduria.

Ketonuria ❌

• Excretion of ketone bodies in urine, usually seen in diabetic ketoacidosis or prolonged starvation.

• This leads to systemic acidosis, not alkalosis.

Amino aciduria ❌

• Refers to abnormal excretion of amino acids in urine (e.g., cystinuria, Hartnup disease).

• Has no relation to paradoxical ECF/urine acid-base differences.

In hemorrhagic hypovolemic shock, the primary goal is to rapidly restore intravascular volume and oxygen-carrying capacity to prevent organ failure and death. While crystalloids like Ringer’s lactate are common, there is a strong physiological argument for initiating therapy with a colloid like Haemaccel (a gelatin-based plasma expander) in an emergency setting.

• Superior Volume Expansion: Haemaccel is a colloid, meaning it contains large molecules that cannot easily leak out of the capillaries. This creates an oncotic pressure that draws fluid into the bloodstream. Compared to crystalloids (e.g., Ringer’s lactate), which distribute quickly throughout the extracellular space, a much smaller volume of Haemaccel is required to achieve the same hemodynamic effect (e.g., raising blood pressure). This is a critical advantage in emergency situations where rapid stabilization is paramount.
• Longer Intravascular Retention: Because of its larger molecular size, Haemaccel remains in the intravascular space longer than crystalloids. This provides more sustained perfusion pressure to vital organs like the brain and heart while awaiting definitive treatment (e.g., surgery to control bleeding).
• Iso-oncotic and Isotonic: Haemaccel is formulated to have an oncotic pressure similar to plasma, making it an effective plasma volume expander without causing significant fluid shifts between compartments.
• Carrier for Calcium: Unlike other colloids like albumin or starches, Haemaccel contains calcium ions. In a massive transfusion scenario where citrate-containing blood products are used, the calcium in Haemaccel can help mitigate the risk of citrate toxicity and hypocalcemia.

Why the Other Options Are Less Suitable:

1. Ringer’s lactate: This is a crystalloid.
   • Why it’s inferior: It rapidly equilibrates throughout the extracellular space; only about 25% of the infused volume remains in the intravascular compartment. This necessitates administering 3-4 times the volume to achieve the same effect as a colloid, increasing the risk of tissue edema (e.g., pulmonary edema, cerebral edema) and abdominal compartment syndrome.
2. Albumin: This is a human blood-derived colloid.
   • Why it’s not the best initial choice: It is significantly more expensive and a limited resource compared to synthetic colloids like Haemaccel. It offers no proven mortality benefit in trauma resuscitation and carries a theoretical risk of disease transmission, however small.
3. Amino acid solution: This is a nutritional supplement, not a resuscitation fluid.
   • Why it’s incorrect: It is designed for parenteral nutrition to provide nitrogen. It is hypertonic and would cause dangerous fluid shifts, worsening the patient’s metabolic state. It has no role in emergency volume resuscitation.
4. 5% dextrose water: This is a hypotonic fluid.
   • Why it’s dangerous: D5W is contraindicated in shock. The dextrose is metabolized, leaving free water that distributes evenly across all body compartments. Less than 10% stays in the blood vessels, diluting electrolytes and critically worsening hypovoleemia and hyponatremia.

When severe dehydration occurs, plasma osmolality rises because water is lost in greater proportion than solutes. The body’s key corrective mechanism is via ADH (vasopressin):

• Osmoreceptors in the hypothalamus sense the increased osmolality.

• They stimulate ADH release from the posterior pituitary.

• ADH acts on collecting ducts of the kidney, inserting aquaporin-2 channels, which increases water reabsorption.

• This dilutes the plasma, lowering osmolality back toward normal.

This mechanism works rapidly and is the primary regulator of water balance.

Why the Other Options Are Wrong

Angiotensin-II ❌

• Important in volume depletion and blood pressure regulation.

• Causes vasoconstriction and stimulates aldosterone release, but does not directly correct osmolality.

Aldosterone ❌

• Increases sodium reabsorption in the distal nephron.

• Helps expand extracellular fluid volume but affects Na⁺ balance more than water/osmolality.

Increased intake of glucose ❌

• Glucose intake does not correct dehydration-driven hyperosmolality; in fact, excess glucose can worsen osmotic load.

Increase in protein intake ❌

• Increases urea production, which may affect renal medullary concentration but is not the main corrective mechanism for plasma osmolality.

In acute hyperkalemia, the kidneys attempt to excrete excess K⁺.

• To maintain electroneutrality during increased K⁺ secretion in the distal nephron, H⁺ secretion is reduced.

• As a result, H⁺ is retained in the body, leading to acidosis.

This explains why hyperkalemia is often associated with a tendency toward metabolic acidosis.

Why the Other Options Are Wrong

Increased secretion of H⁺ ❌

• Actually, the opposite occurs. During hyperkalemia, H⁺ secretion decreases, leading to retention of H⁺.

Alkalosis ❌

• If H⁺ were excessively excreted, alkalosis would develop.

• But in hyperkalemia, reduced H⁺ secretion leads to acidosis, not alkalosis.

Increased secretion of HCO₃⁻ ❌

• The kidney does not excrete bicarbonate in this scenario.

• In fact, bicarbonate handling is not the primary compensatory mechanism here.

Increased secretion of Na⁺ ❌

• Sodium is usually reabsorbed, not secreted, in distal tubules.

• Its reabsorption is often coupled with K⁺ and H⁺ secretion, but Na⁺ secretion is not the corrective response to hyperkalemia.

The most sensitive indicator of glomerular function is glomerular filtration rate (GFR). Since we cannot measure GFR directly in routine clinical practice, we use markers:

• Creatinine clearance is the best practical and sensitive indicator of GFR because:

  • Creatinine is produced at a fairly constant rate from muscle metabolism.

  • It is freely filtered by the glomerulus.

  • Only minimally secreted by tubules (slight overestimation, but still very close to true GFR).

Thus, creatinine clearance reflects GFR more accurately than serum levels of urea or creatinine.

Why the Other Options Are Wrong

Serum ammonia ❌

• Reflects liver function, not kidney filtration.

• Relevant in hepatic encephalopathy, not in glomerular assessment.

Serum creatinine ❌

• Commonly used, but it only rises after significant GFR decline (>50%).

• Less sensitive than creatinine clearance for early changes.

Serum urea ❌

• Affected by diet, hydration, GI bleeding, and catabolic states.

• Not a reliable or sensitive marker of GFR alone.

Urea clearance ❌

• Less accurate because urea is not only filtered but also reabsorbed in tubules.

• Underestimates GFR compared to creatinine clearance.

Amino acids and glucose are freely filtered at the glomerulus.

• Under normal physiological conditions, they are completely reabsorbed in the proximal tubule via specific transporters.

• As a result, they do not appear in urine in healthy individuals.

• If transporters are saturated (e.g., diabetes mellitus for glucose → glucosuria; aminoacidurias like cystinuria), these substances spill into urine.

Why the Other Options Are Wrong

Electrolytes ❌

• Freely filtered but not fully reabsorbed.

• Sodium, potassium, chloride, and bicarbonate are reabsorbed to varying degrees, but some amount is always excreted to maintain homeostasis.

Bases ❌

• Many weak bases are filtered and may undergo tubular secretion or partial reabsorption depending on pH.

• They are not completely reabsorbed.

Inulin ❌

• Freely filtered but neither reabsorbed nor secreted.

• 100% excreted in urine, which is why it’s the gold standard for measuring GFR.

Creatinine ❌

• Freely filtered and also slightly secreted by tubules.

• This causes creatinine clearance to slightly overestimate GFR.

• It is not completely reabsorbed like glucose or amino acids.

Creatinine is:

• Freely filtered at the glomerulus.

• Not reabsorbed by the renal tubules.

• Additionally, a small amount is secreted from the peritubular capillaries into the tubule.

Because of this, the amount of creatinine in urine slightly overestimates the true GFR. That’s why creatinine clearance is a close but not perfect measure of glomerular filtration rate.

Why the Other Options Are Wrong

Organic acids and bases ❌

• Many (e.g., PAH, drugs) are filtered and secreted, but they are not physiologic markers of GFR.

• They are handled differently depending on transporters and pH.

Electrolytes ❌

• Freely filtered but also largely reabsorbed (e.g., sodium, potassium, chloride).

• They are not completely excreted or primarily secreted.

Amino acids and glucose ❌

• Freely filtered but completely reabsorbed under normal conditions, so none is excreted.

• They are not secreted into tubules.

Inulin ❌

• Freely filtered but neither reabsorbed nor secreted.

• It is excreted in exactly the amount filtered, which makes it the gold standard for measuring GFR.

Inulin is the classic example of a substance that:

• Is freely filtered at the glomerulus.

• Is neither reabsorbed nor secreted by the renal tubules.

• Therefore, the amount excreted in urine = amount filtered at the glomerulus.

Because of these properties, inulin clearance is the gold standard for measuring GFR (glomerular filtration rate).

Why the Other Options Are Wrong

Glucose ❌

• Freely filtered, but under normal conditions it is completely reabsorbed in the proximal tubule.

• It only appears in urine when plasma levels exceed the transport maximum (e.g., diabetes mellitus → glucosuria).

Electrolytes ❌

• Freely filtered, but then undergo variable reabsorption and secretion to maintain homeostasis.

• Their excretion ≠ filtration rate.

Creatinine ❌

• Freely filtered but also slightly secreted by the tubules.

• Excretion is slightly greater than the filtration rate, making creatinine clearance slightly overestimate true GFR.

Amino acids ❌

• Freely filtered but completely reabsorbed under normal conditions.

• No excretion in healthy individuals.

Renin is an enzyme crucial in the renin–angiotensin–aldosterone system (RAAS).

• It is secreted by the juxtaglomerular (JG) cells, which are modified smooth muscle cells located in the wall of the afferent arteriole near its entry into the glomerulus.

• Stimuli for renin release include:

  • ↓ Renal perfusion pressure (sensed in afferent arteriole)

  • ↓ Sodium chloride delivery to macula densa (in distal tubule)

  • Sympathetic stimulation via β₁-adrenergic receptors

• Renin converts angiotensinogen → angiotensin I, eventually leading to angiotensin II and aldosterone release, increasing BP and sodium retention.

Why the Other Options Are Wrong

Interstitial kidney cells ❌

• These cells produce erythropoietin (EPO), not renin.

Parietal epithelial cells ❌

• Line Bowman’s capsule.

• Provide structural support; no role in RAAS or enzyme secretion.

Brush border cells ❌

• Found in the proximal tubule; specialized for absorption due to microvilli.

• Do not secrete renin.

Glomerulus parietal cells ❌

• Same as parietal epithelial cells; not involved in renin secretion.

Let’s recall the forces governing glomerular filtration (Starling’s forces):

• Favors filtration (↑ GFR):

  • Glomerular capillary hydrostatic pressure (PGC) → pushes fluid out into Bowman’s space.

• Opposes filtration (↓ GFR):

  • Bowman’s capsule hydrostatic pressure (PBC) → resists fluid entry.

  • Glomerular capillary plasma oncotic pressure (πGC) → pulls fluid back into the capillaries.

When glomerular capillary oncotic pressure increases (e.g., due to more plasma proteins), it exerts a stronger pull on water back into the capillaries, thereby decreasing GFR.

Why the Other Options Are Wrong

Glomerular capillary hydrostatic pressure ❌

• An increase would actually increase GFR because more pressure pushes fluid out.

Bowman’s capsule plasma oncotic pressure ❌

• Plasma proteins are absent in Bowman’s capsule under normal conditions.

• So this force is not physiologically significant.

Peritubular capillary hydrostatic pressure ❌

• This affects reabsorption in peritubular capillaries, not glomerular filtration.

• Changes here don’t directly alter GFR.

None of these ❌

• Incorrect, because one of the listed factors (glomerular oncotic pressure) clearly decreases GFR when increased.

The counter-current multiplier mechanism is essential for the kidney’s ability to produce concentrated urine.

• The Loop of Henle, particularly in juxtamedullary nephrons, is the key structure.

• The descending limb is permeable to water but not to solutes → water leaves, filtrate becomes concentrated.

• The ascending limb is impermeable to water but actively pumps out Na⁺, K⁺, and Cl⁻ → diluting the filtrate but increasing medullary interstitial osmolarity.

• This creates the osmotic gradient in the medulla, which is then utilized by ADH in the collecting ducts to reabsorb water.

Why the Other Options Are Wrong

Proximal convoluted tubules ❌

• Major site of reabsorption (≈65% of filtrate, including glucose, amino acids, Na⁺, and water).

• Not directly involved in counter-current multiplication.

Vasa recta ❌

• Involved in the counter-current exchanger, not multiplier.

• Maintains the osmotic gradient by preventing washout of solutes.

Glomerulus ❌

• Site of filtration, not concentration mechanisms.

Peritubular arteries ❌

• Supply cortical nephrons and help in reabsorption, but they don’t play a role in counter-current multiplication.

In end-stage renal disease (ESRD), anemia develops because diseased kidneys cannot produce sufficient erythropoietin (EPO), the hormone that stimulates red blood cell production in the bone marrow.

• Giving exogenous erythropoietin corrects anemia by increasing RBC production.

• However, a known side effect is increased blood pressure (hypertension).

  • Mechanism: Increased hematocrit → higher blood viscosity + possible vascular endothelial effects of EPO → rise in blood pressure.

Thus, in ESRD patients treated with EPO, hypertension is a frequent complication to monitor.

Why the Other Options Are Wrong

Decreased blood volume ❌

• EPO increases RBC mass, which increases blood volume/viscosity, not decreases it.

Decreased blood pressure ❌

• The opposite occurs; EPO often raises blood pressure.

Induces hypoxia ❌

• EPO improves oxygen-carrying capacity by raising hemoglobin and hematocrit.

• It corrects hypoxia rather than inducing it.

Decreased erythrocyte production ❌

• Exogenous EPO directly increases RBC production in bone marrow, not decreases it.

Why “Phosphate” is Correct:

Upon re-evaluation, the most abundant and physiologically relevant buffer in the proximal tubular fluid is phosphate (HPO₄²⁻/H₂PO₄⁻). Here’s why:

1. High Concentration and Availability:
   • Phosphate is freely filtered at the glomerulus and is present in the proximal tubule at a concentration of ~1-2 mM, which is significant compared to other non-bicarbonate buffers.
   • While bicarbonate is filtered at a higher initial concentration (~24 mEq/L), it is rapidly reabsorbed (80-90% in the proximal tubule), leaving phosphate as the dominant buffer later in the proximal tubule after bicarbonate depletion.
2. Role as a Titratable Acid:
   • Phosphate serves as a key titratable acid buffer, accepting H⁺ ions to form H₂PO₄⁻, which is excreted in urine. This process is critical for acid-base balance.
   • Its pKa (~6.8) is close to the urine pH range, making it highly effective for buffering in the tubular fluid.
3. Physiological Importance in Proximal Tubule:
   • Phosphate buffering is especially important in the late proximal tubule, where bicarbonate concentration has decreased due to reabsorption, and ammonia synthesis is still ramping up.
   • It works in concert with ammonia to excrete acid and maintain pH homeostasis.

Why the Other Options Are Incorrect:

1. Bicarbonate:
   • Although bicarbonate is filtered abundantly, it is rapidly reabsorbed in the early proximal tubule. By the time the fluid reaches the mid to late proximal tubule, bicarbonate levels are significantly reduced, making it less available for buffering in those segments.
2. Ammonia (NH₃):
   • Ammonia is synthesized in the proximal tubule (from glutamine) and is a crucial buffer for distal acid excretion. However, it is not present in the initial filtrate and is secreted into the lumen later, so it is not the most abundant buffer initially.
3. Lactate:
   • Lactate is a metabolic byproduct and is not a primary buffer for urinary pH. It is reabsorbed or metabolized rather than used for buffering H⁺ ions.
4. Protein:
   • Proteins are excluded from the filtrate under normal conditions due to the glomerular filtration barrier. Proteinuria indicates pathology, and filtered proteins do not contribute to buffering in the tubular fluid.

The principle mechanism of H⁺ secretion in the proximal convoluted tubule (PCT) is the sodium–hydrogen exchanger (NHE3) located in the luminal (apical) membrane.

• Here, Na⁺ moves into the tubular cell (down its electrochemical gradient) while H⁺ is secreted into the tubular lumen.

• The secreted H⁺ combines with filtered HCO₃⁻ → forming H₂CO₃, which is broken down by carbonic anhydrase to CO₂ and H₂O.

• CO₂ diffuses back into the cell, recombines to form HCO₃⁻, and is reabsorbed into blood.

👉 This is essential for bicarbonate reabsorption and acid–base balance.

Why the Other Options Are Wrong

H-ATPase ❌

• Important in distal nephron (collecting ducts) for H⁺ secretion, especially in intercalated cells.

• Not the main mechanism in the proximal tubule.

Na-H symport ❌

• Symport would move both Na⁺ and H⁺ in the same direction, which does not occur here.

• The mechanism is antiport (exchange), not symport.

H-Ca exchanger ❌

• No physiological exchanger of this type exists in renal tubular transport.

H-HCO₃⁻-ATPase ❌

• No such pump; HCO₃⁻ is not directly secreted into the lumen but reabsorbed indirectly.

Why “150 ml – 200 ml” is Correct:

The micturition reflex is a spinal cord reflex that facilitates emptying of the urinary bladder. It is initiated by stretch receptors in the bladder wall.

• Physiological Threshold: As the bladder fills with urine, its walls distend. This stretch is detected by mechanoreceptors (baroreceptors) within the detrusor muscle.
• Firing Threshold: These receptors begin to send afferent signals via the pelvic nerves to the sacral spinal cord (S2-S4) when the bladder volume reaches approximately 150 – 200 mL.
• Reflex Arc: At this volume, the signals are strong enough to initiate the reflex arc. The spinal cord integrates this information and sends parasympathetic efferent signals back via the pelvic nerves, causing contraction of the detrusor muscle (the bladder’s muscular wall) and relaxation of the internal urethral sphincter.
• Voluntary Control: It is crucial to understand that in adults, this simple reflex is overridden by voluntary control from the brain (the pontine micturition center) until a socially convenient time is found. The first sensation of bladder filling is typically felt around 150 mL, and a strong desire to void occurs around 400-500 mL.

Therefore, while we can consciously suppress it, the reflex itself is initiated at the 150-200 mL volume range.

Why the Other Options Are Incorrect:

1. 100 ml – 150 ml: Incorrect. While some initial stretch might be detected, the afferent signals are not yet powerful enough to trigger the reflex arc. This is generally below the threshold for initiating the reflex.
2. 250 ml – 300 ml: Incorrect. This is above the initiation threshold. By this volume, the reflex is already active and is likely producing a noticeable urge to void. This range is often associated with the normal desire to empty the bladder.
3. 300 ml – 400 ml: Incorrect. This represents a strong desire to void. The reflex is not being initiated at this point; it has been active for some time and is now generating significant signals that are harder to ignore voluntarily.
4. 450 ml – 500 ml: Incorrect. This is approaching the maximum functional capacity of the bladder (which is typically 500-600 mL). At this volume, the stretch receptor firing is intense, and pain or severe discomfort may be experienced. The reflex is not initiated here; it is in a state of powerful, often involuntary, activation.

High protein intake and increased blood glucose both cause an increase in the filtered load of solutes (amino acids and glucose).

• In the proximal convoluted tubule (PCT), glucose and amino acids are reabsorbed through Na⁺-coupled cotransporters (secondary active transport).

• When more glucose and amino acids are filtered, more sodium is reabsorbed along with them.

• This phenomenon is known as glomerulotubular balance.

Thus, the net dietary effect is increased sodium reabsorption in the PCT.

Why the Other Options Are Wrong

Increase Bowman’s capsule hydrostatic pressure ❌

• Hydrostatic pressure in Bowman’s capsule is mainly affected by obstruction (e.g., stones).

• Protein or glucose intake does not significantly alter it.

Increase afferent arteriolar constriction ❌

• Would reduce GFR.

• In high protein intake, there is actually afferent arteriolar dilation (via tubuloglomerular feedback) to maintain high GFR, not constriction.

Increase efferent arteriolar constriction ❌

• Angiotensin II can constrict efferent arterioles to maintain GFR, but this is not the primary effect of protein or glucose intake.

Increase glomerular colloid oncotic pressure ❌

• This depends on plasma protein concentration and filtration fraction, not dietary protein/glucose directly.

• Creatinine is an endogenous substance produced at a fairly constant rate from muscle metabolism.

• It is freely filtered at the glomerulus, not reabsorbed, and only minimally secreted.

• Therefore, creatinine clearance is commonly used as a practical measure of glomerular filtration rate (GFR) in clinical practice.

• Although it slightly overestimates GFR (because of tubular secretion), it is reliable, easy to measure, and does not require infusion of external substances.

Why the Other Options Are Wrong

Urea ❌

• Freely filtered but also reabsorbed significantly.

• Clearance of urea underestimates GFR, so it is not an accurate test of renal function.

Para-amino hippuric acid (PAH) ❌

• Used to measure renal plasma flow (RPF), not GFR.

• Because it is both filtered and actively secreted, almost all PAH is cleared from renal plasma in one pass.

Potassium ions ❌

• Renal handling of K⁺ involves filtration, reabsorption, and secretion.

• Clearance is variable and depends on dietary intake and hormonal regulation (aldosterone).

• Not used to assess renal function.

Inulin ❌

• Gold standard for measuring GFR because it is freely filtered, not reabsorbed, not secreted.

• However, it must be given exogenously by IV infusion, so it is impractical for routine clinical use.

In metabolic acidosis, the kidneys play a vital role in restoring acid–base balance:

• They increase secretion of H⁺ ions into the tubular fluid, mainly in the proximal tubule, distal tubule, and collecting ducts.

• This is coupled with:

  • Reabsorption and generation of new HCO₃⁻, which is returned to the blood.

  • Buffering of secreted H⁺ by phosphate and ammonia in the tubular fluid, allowing excretion as titratable acid and NH₄⁺.

This helps eliminate excess acid and raise blood pH back toward normal.

Why the Other Options Are Wrong

Secretion of Na⁺ ions ❌

• Sodium is generally reabsorbed, not secreted, especially during acidosis.

• Na⁺ reabsorption is coupled with H⁺ secretion (via Na⁺–H⁺ exchanger).

Secretion of HCO₃⁻ ❌

• The kidneys retain and regenerate bicarbonate during acidosis.

• They secrete HCO₃⁻ only in alkalosis.

Secretion of K⁺ ions ❌

• Potassium secretion is primarily regulated by aldosterone, not directly by acid–base status.

• In acidosis, K⁺ secretion is often reduced (leading to hyperkalemia).

Urea retention ❌

• Urea handling is linked to water balance and ADH, not acid–base correction.

In metabolic alkalosis, the blood has excess bicarbonate (HCO₃⁻) and a higher than normal pH. To compensate:

• The kidneys reduce H⁺ secretion and instead increase secretion (excretion) of HCO₃⁻ into the tubular fluid.

• This helps lower plasma bicarbonate levels, allowing the pH to return toward normal.

• At the same time, less bicarbonate is reabsorbed in the proximal tubule.

Why the Other Options Are Wrong

N₂-retention ❌

• Nitrogen retention (e.g., in the form of urea) is not a mechanism for acid–base balance.

Secretion of H⁺ ions ❌

• Increased H⁺ secretion occurs in acidosis, not alkalosis.

• In alkalosis, H⁺ secretion is actually decreased.

Secretion of K⁺ ions ❌

• Potassium secretion is mainly controlled by aldosterone.

• In alkalosis, cells may take up K⁺ (leading to hypokalemia), but this is not the primary renal response.

Secretion of Na⁺ ions ❌

• Sodium is almost always reabsorbed, not secreted.

• It plays a supportive role in bicarbonate and H⁺ handling but is not secreted to correct alkalosis.