Renal – 2025

https://www.kenhub.com/en/library/anatomy/renal-pelvis

The renal pelvis is the funnel-shaped upper expansion of the ureter. It collects urine from the major calyces and narrows down to continue as the ureter.

🧠 Why This Option Is Correct

Ureter — ✅

• The renal pelvis directly tapers into the ureter at the hilum.

• This is the structure that carries urine from the kidney to the bladder.

• In renal stones, this is exactly where obstruction often occurs at the ureteropelvic junction (UPJ).

❌ Why the Other Options Are Incorrect

Renal pyramid — ❌

• This is a medullary structure containing loops of Henle and collecting ducts.

• It drains into the minor calyx, not into the pelvis.

• It is deep inside the kidney, nowhere near the direct continuation.

Renal column — ❌

• This is simply cortical tissue between pyramids.

• It transports NO urine and connects to NO collecting system.

• It is supportive tissue, not part of the drainage pathway.

Major calyx — ❌

• The major calyx drains into the renal pelvis, but it does not continue from it.

• Instead, multiple major calyces unite to form the pelvis — not the other way around.

Minor calyx — ❌

• This is the first site that collects urine from renal papillae.

• Minor → Major → Pelvis → Ureter

• So it is two steps upstream from the renal pelvis, not continuous after it.

The ureter has three natural constrictions where stones commonly get stuck:

1. Ureteropelvic junction (UPJ) – between renal pelvis & ureter

2. Pelvic brim – where ureter crosses the external iliac artery

3. Ureterovesical junction (UVJ) – where ureter enters bladder wall (Narrowest)

The narrowest and therefore most common site of obstruction → UVJ

Where the ureter enters the wall of urinary bladder — ✅

• This is the ureterovesical junction (UVJ).

• It is the tightest constriction of the ureter.

• Most stones that reach this far tend to get lodged here.

• Classic presentation: pain radiating to the groin, due to involvement of L1–L2 dermatomes.

❌ Why The Other Options Are Incorrect

Apex of renal pyramid — ❌

• This is where collecting ducts open into the minor calyx.

• It is not a constriction of the ureter.

• Stones don’t lodge here; they lodge in calyces or ureter.

In between renal artery and renal vein — ❌

• No such anatomical constriction exists here.

• The artery and vein do not sandwich the ureter.

When ureter crosses the external iliac artery — ❌

• This is a real constriction and stone can lodge here,
  BUT → it’s not the most likely site.

• The pelvic brim is the second most common location.

Between renal pelvis and major calyces — ❌

• This is NOT a ureteric constriction.

• This area is part of the collecting system, not the ureter’s diameter changes.

• The actual constriction is between renal pelvis and ureter (UPJ), not major calyces.

7 55-year-old man with right lower quadrant pain

By OpenStax College – Anatomy & Physiology, Connexions Web site. http://cnx.org/content/col11496/1.6/, Jun 19, 2013., CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=30148537

Blood reaches the renal cortex through a branching sequence:
Renal → Segmental → Interlobar → Arcuate → Interlobular → Afferent arteriole → Glomerulus

The interlobular arteries run through the cortex and give rise to afferent arterioles, which directly supply the glomeruli of the cortex.

✔ Why This Option Is Correct

Interlobular arteries — ✅

• These are the final arterial branches before the afferent arterioles.

• They run upward into the cortex between the lobules.

• They directly supply cortical tissue, especially the glomeruli.

❌ Why The Other Options Are Incorrect

Segmental arteries — ❌

• These supply the renal sinus / major regions, not the cortex.

• They do not reach the cortex directly.

Interlobar arteries — ❌

• These run between renal pyramids (in the medulla).

• They only reach the bases of the pyramids, not the cortex.

Arcuate arteries — ❌

• These arch along the corticomedullary junction.

• They give rise to interlobular arteries but do not directly enter the cortex themselves.

Renal artery — ❌

• This is the main supply entering the kidney.

• It branches multiple times before anything reaches the cortex.

Lymphatic drainage of the urinary bladder depends on the region involved:

• Superior bladder → External iliac nodes

• Inferior bladder (neck, trigone) → Internal iliac nodes

• Posterior bladder → May drain to common iliac nodes

• Very advanced disease → Para-aortic nodes

• Superficial inguinal nodes → only perineal skin, glans, distal urethra — not bladder

Since this patient has a superior bladder carcinoma, the first lymph nodes involved are external iliac nodes.

✔ Why This Option Is Correct

External iliac lymph nodes — ✅

• Drain superior portions of the bladder.

• Located along the external iliac vessels.

• Most common first site of metastasis in superior bladder cancers.

❌ Why the Other Options Are Incorrect

Superficial inguinal lymph nodes — ❌

• Drain external genitalia, perineum, lower abdominal wall.

• Do NOT drain any part of the bladder.

Internal iliac lymph nodes — ❌

• Drain inferior bladder (neck, trigone).

• Not the primary drainage for the superior part.

Common iliac lymph nodes — ❌

• Receive lymph after external or internal iliac nodes.

• Involvement occurs later, not first.

Para-aortic (lumbar) lymph nodes — ❌

• Very advanced spread — kidneys, testes drain here, not bladder initially.

• Not the first station for bladder cancer metastasis.

Renal columns (Columns of Bertin) are extensions of the renal cortex that project downward between adjacent medullary pyramids.
They provide support and contain interlobar vessels.

✔ Why This Option Is Correct

Cortical substance that extends into the medulla — ✅

• Renal columns are made of cortical tissue, not medulla.

• They dip between the pyramids, reaching toward the renal sinus.

• Contain interlobar arteries & veins.

❌ Why The Other Options Are Incorrect

Marks the beginning of a nephron — ❌

• Nephrons begin in the cortex at the renal corpuscle.

• The renal column does not mark a starting point for nephrons.

Medullary substance that extends into the cortex — ❌

• This is the opposite of what happens.

• Medulla → pyramids

• Cortex → columns

Renal columns are cortex extending down, not medulla moving up.

Nephrons that are drained by a common collecting duct — ❌

• That describes a renal lobule, not a renal column.

• Lobules revolve around a collecting duct → very different structure.

Convoluted parts of renal tubules — ❌

• PCT and DCT are convoluted parts, but they are located within the cortex, not isolated in renal columns.

• Renal columns are structural supports, not tubular segments.

The membranous urethra is the shortest, narrowest, least dilatable part of the male urethra. It passes through the external urethral sphincter, making catheterization difficult and commonly causing resistance + pain.

✔ Why This Option Is Correct

Membranous urethra — ✅

• Shortest (≈1 cm) and narrowest segment

• Surrounded by the external urethral sphincter (voluntary muscle)

• Least distensible part → exactly matches “short, non-dilatable segment”

• Common site of resistance during catheterization

• Trauma here can cause extravasation into the deep perineal pouch

❌ Why The Other Options Are Incorrect

Prostatic urethra — ❌

• It is the widest and most dilatable segment.

• Surrounded by prostate, not the external sphincter.

• Catheter usually passes easily through this region.

Penile (spongy) urethra — ❌

• Longest part and very distensible due to corpus spongiosum.

• Resistance here is uncommon unless strictures are present.

Fossa terminalis (navicular fossa) — ❌

• Slight natural narrowing but located at the glans, not deep pelvic area.

• Resistance here causes discomfort at the tip, not deep pain.

Internal urethral sphincter — ❌

• Located at the neck of the bladder and composed of smooth muscle.

• It is not the narrowest region and does not cause this typical resistance.

• Also, internal sphincter is not part of the urethra itself.

The narrowest part of the ureter is the ureterovesical junction (UVJ) — where the ureter pierces the wall of the urinary bladder.
This is the most common site where stones get lodged.

The CT level of ischial spine corresponds to the pelvis, close to the bladder entry—matching UVJ obstruction.

✔ Why This Option Is Correct

Ureterovesical junction (pass through bladder wall) — ✅

• Narrowest point of the entire ureter.

• Stones most frequently get stuck here.

• Located near the ischial spine level on imaging.

• Pain may radiate into groin due to L1–L2 segments.

❌ Why The Other Options Are Incorrect

Pelviureteric junction — ❌

• This is a constriction, but not the narrowest.

• Located near the kidney, not at ischial spine level.

At pelvic brim — ❌

• Second potential constriction where ureter crosses external iliac artery.

• Still not the narrowest.

Ureter is pierced by ductus deferens — ❌

• This is simply where the ductus crosses the ureter (“water under the bridge”).

• NOT a constriction.

• Not relevant to stone impaction.

Opening in trigone — ❌

• This refers to the ureteral opening inside the bladder, after the UVJ.

• Stones rarely lodge here since they must already pass the tight UVJ.

The urinary bladder develops mainly from the vesical part of the urogenital sinus, which arises after the cloaca is divided by the urorectal septum.

This part forms almost the entire bladder, except the trigone region (which is mesonephric duct–derived initially but gets overgrown).

Urogenital sinus (vesical part) — ✅

• Forms most of the urinary bladder (epithelium + mucosa).

• Specifically, the superior and main body of the bladder.

• Smooth muscle of the bladder wall forms from splanchnic mesoderm, but the epithelium is from the urogenital sinus.

❌ Why The Other Options Are Incorrect

Mesonephric duct — ❌

• Only contributes temporarily to the trigone region.

• Later, trigone becomes overgrown by endoderm of the urogenital sinus.

• It does NOT form the whole bladder.

Metanephric blastema — ❌

• This forms nephrons of the definitive kidney, not the bladder.

• No part of the bladder is derived from this tissue.

Cloacal membrane — ❌

• This is merely the membrane covering the cloaca (ectoderm + endoderm).

• It ruptures to create openings but does not form the bladder itself.

Allantois — ❌

• The allantois becomes the urachus, then the median umbilical ligament.

• Only forms the apex of the bladder’s fibrous connection, not the bladder body.

A horseshoe kidney forms when the lower poles of the kidneys fuse.
During ascent, the fused kidney gets trapped under the inferior mesenteric artery, preventing it from reaching its normal lumbar position.

✔ Why This Option Is Correct

Inferior mesenteric artery — ✅

• The IMA arises at L3, exactly where the fused lower poles of a horseshoe kidney get blocked.

• This is the classic and most tested cause of failed kidney ascent.

• As a result, the kidney remains low in the abdomen, usually around L3–L5.

❌ Why the Other Options Are Incorrect

Inferior vena cava — ❌

• Lies to the right of the aorta and does not obstruct midline ascent.

• No classical association with horseshoe kidney.

Superior mesenteric artery — ❌

• Originates much higher (L1).

• By the time the kidney reaches this level, the ascent would already have been blocked earlier if fused.

Aortic bifurcation — ❌

• Occurs at L4, below the IMA.

• The kidney would already have been blocked earlier at the IMA — this is too low to be responsible.

Median sacral artery — ❌

• Arises at the posterior aspect of the aortic bifurcation.

• Too small and too low to impede ascent.

Image Reference :- https://www.mayoclinic.org/diseases-conditions/bladder-exstrophy/symptoms-causes/syc-20391299

When the urethra opens on the dorsal surface AND the bladder is exposed/protruding onto the abdominal wall, this combination strongly indicates bladder exstrophy — a severe defect of the ventral body wall + pelvic region caused by abnormal closure of the anterior abdominal wall and failure of mesoderm migration.

Epispadias is part of bladder exstrophy, but when the bladder is open externally, the diagnosis becomes exstrophy of the bladder.

Exstrophy of bladder — ✅

• Caused by failure of the lateral body wall folds to close properly.

• Characterized by:

  • Dorsal opening of urethra (epispadias)

  • Exposure of bladder mucosa on the abdominal wall

• This is the classical presentation described in the question.

❌ Why the Other Options Are Incorrect

Hypospadias — ❌

• Urethral opening is on the ventral (underside) of penis.

• No bladder involvement.

• Opposite orientation from what is described.

Epispadias — ❌

• Urethral opening is on the dorsal surface, correct

• BUT there is no protruding bladder in isolated epispadias.

• When bladder protrudes → it is not just epispadias anymore → it is bladder exstrophy.

Exstrophy of cloaca — ❌

• More severe than bladder exstrophy.

• Includes imperforate anus, omphalocele-like defects, and exposure of both urinary & intestinal mucosa.

• Not described here.

Undescended testes — ❌

• Completely unrelated to bladder or urethral opening defects.

• No genital surface malformation of this type.

Bilateral renal agenesis → complete absence of both kidneys, causing severe oligohydramnios, which leads to Potter sequence:

• Respiratory distress (lung hypoplasia)

• Flattened facial features (“Potter facies”)

• Limb deformities

This is a classic presentation.

✔ Why This Option Is Correct

Bilateral renal agenesis — ✅

• No kidneys → almost no fetal urine → severe oligohydramnios

• Oligohydramnios causes lung hypoplasia, leading to respiratory distress.

• Characteristic flattened face, low-set ears, limb deformities = Potter sequence.

• Always associated with very poor prognosis.

❌ Why The Other Options Are Incorrect

Renal hypoplasia — ❌

• Kidneys are small but present.

• Does not cause complete absence of urine → oligohydramnios would not be severe enough to produce classic Potter features.

Polycystic kidney disease — ❌

• Kidneys are enlarged with cysts, not absent.

• Oligohydramnios may occur in autosomal recessive PKD, but kidneys are visible on ultrasound.

Ectopic kidney — ❌

• Kidney(s) are present but misplaced (pelvic kidney).

• Amniotic fluid remains normal.

• No facial or pulmonary abnormalities.

Hydronephrosis — ❌

• Kidney is present but dilated.

• Does NOT cause severe oligohydramnios unless bilateral and extreme — still kidneys visible.

https://www.histology.leeds.ac.uk/urinary/bladder.php

An organ with transitional epithelium (urothelium) + a thick muscle coat + highly folded lumen is characteristic of the urinary bladder, especially when empty.

The folds (rugae) allow distension as it fills.

✔ Why This Option Is Correct

Urinary bladder — ✅

• Lined by transitional epithelium

• Has very thick smooth muscle layer (detrusor muscle)

• Highly folded lumen when empty → hallmarks of urinary bladder histology

• The organ’s function requires extreme expansion and contraction.

❌ Why The Other Options Are Incorrect

Kidney — ❌

• Lined mostly by simple cuboidal epithelium (tubules).

• No transitional epithelium lining large cavities.

• Cortical/medullary patterns—not thick smooth muscle walls.

Ureter — ❌

• Does have transitional epithelium,

• BUT muscle layer is moderately thick, not as massive as the bladder.

• Lumen is less folded and usually appears star-shaped.

Urethra — ❌

• Epithelium varies:

  • Transitional → pseudostratified columnar → stratified squamous.

• Does not have such a thick smooth muscle coat.

• Folds not as prominent and lumen shape is irregular.

Nephron — ❌

• Microscopic unit, not a gross organ.

• Lined by various epithelium types (simple squamous, cuboidal).

• No transitional epithelium + no thick muscular wall.

https://medcell.org/histology/urinary_system_lab/collecting_ducts.php

https://histology.siu.edu/crr/RN009b.htm

1. Histological Appearance (Cuboidal with Distinct Boundaries)

• Cell Shape: The collecting duct is lined by simple cuboidal epithelium (which can become columnar in the deeper medullary regions).

• Tight Junctions (Distinct Borders): Under light microscopy, the cells of the collecting duct (specifically the Principal Cells) are often described as having distinct cell boundaries. This is a key differentiator from the convoluted tubules (PCT and DCT), where the extensive interdigitations of the lateral membranes make the cell borders appear indistinct or absent. These distinct boundaries correspond to the tight junctions that are crucial for the duct’s regulated permeability.

• Cytoplasm: The cytoplasm is typically pale-staining (clear) compared to the eosinophilic (pink) cytoplasm of the proximal and distal tubules.

2. Physiological Function (Urine Concentration)

• The question specifies a “region responsible for urine concentration.” While the Loop of Henle creates the hyperosmotic gradient, the Collecting Duct is the site where the final concentration of urine actually occurs.

• Under the influence of ADH (Vasopressin), aquaporins are inserted into the apical membranes of these cells, allowing water to be reabsorbed into the hypertonic medullary interstitium, thus concentrating the urine.

Why the other options are unlikely

• Proximal Convoluted Tubule (PCT):

  • Histology: While cuboidal, these cells have a prominent brush border (microvilli) which fills the lumen, and the cell boundaries are indistinct due to basolateral interdigitations.

  • Junctions: The tight junctions here are actually “leaky” to allow paracellular transport of water and ions.

  • Function: Responsible for bulk reabsorption (isomotic), not the final concentration of urine.

• Loop of Henle (Thick Ascending Limb):

  • Histology: Cuboidal cells with indistinct borders (similar to DCT).

  • Function: This is known as the “Diluting Segment.” Although it creates the medullary gradient necessary for concentration, the fluid leaving this segment is actually hypotonic (dilute) because it actively pumps out salts while being impermeable to water.

  • Junctions: It does have very tight junctions (to maintain water impermeability), but the “diluting” function and indistinct borders usually make it a less likely answer than the CD for this specific description.

• Distal Convoluted Tubule (DCT):

  • Location: Located in the cortex, not the medullary region primarily associated with the concentration gradient.

  • Histology: Cuboidal cells with no brush border, but cytoplasm is eosinophilic and borders are less distinct than in the collecting duct.

• Bowman’s Capsule:

  • Histology: The parietal layer is simple squamous epithelium, not cuboidal. The visceral layer consists of podocytes.

Summary Table

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.

1. CC BY-SA: Attribution-ShareAlike Liscenced content. Edited Content. Provided by Wikimedia Commons. Located at https://commons.wikimedia.org/wiki/File:2108_Capillary_Exchange.jpg ↵
2.  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/. ↵

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.

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

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

https://radiopaedia.org/cases/monosodium-urate-crystals-in-tophaceous-gout

Gout is fundamentally caused by elevated uric acid levels (hyperuricemia), which leads to precipitation of monosodium urate (MSU) crystals in joints and tissues.

These crystals trigger neutrophilic inflammation, producing the classic painful gout attack.

This precipitation—not purine accumulation itself—is the primary biochemical event.

✔ Why This Option Is Correct

Precipitation of monosodium urate crystals — ✅

• Hyperuricemia → urate becomes supersaturated

• MSU crystals form in cooler joints (e.g., big toe)

• Crystals activate NLRP3 inflammasome → IL-1β release → inflammation

• This is the defining biochemical step of gout

❌ Why the Other Options Are Incorrect

Accumulation of purine nucleotides — ❌

• Purine breakdown leads to uric acid

• But nucleotides do not accumulate in joints

• They do not cause inflammation

Overproduction of xanthine oxidase — ❌

• Gout is caused by overproduction of uric acid, not overproduction of the enzyme

• And many gout cases are due to underexcretion, not overproduction

Dehydration leading to high blood viscosity — ❌

• Dehydration may raise uric acid temporarily

• But it is not the primary biochemical trigger for gout attacks

Accumulation of pyrimidine nucleotides — ❌

• Pyrimidine metabolism does not produce uric acid

• Irrelevant to gout

https://www.medboundtimes.com/medicine/lesch-nyhan-syndrome-self-mutilation-disorder

This child has Lesch–Nyhan syndrome, a classic condition due to:

👉 HGPRT deficiency → purine salvage failure → ↑ uric acid

Key clinical clues:

• Self-mutilation (lip and finger biting)

• Aggression + involuntary movements

• Hyperuricemia

• Orange “sand-like” urate crystals in diaper

• Neurologic dysfunction + developmental delay

These all point directly to HGPRT deficiency.

✔ Why HGPRT Deficiency Is Correct

HGPRT normally salvages:

• Hypoxanthine → IMP

• Guanine → GMP

Without it:

• Both are shunted into uric acid production

• Causes gout-like crystals and severe neurobehavioral symptoms

Perfect match.

❌ Why the Other Options Are Incorrect

Adenosine deaminase — ❌

• Causes SCID (Severe Combined Immunodeficiency)

• No self-mutilation or hyperuricemia

• Completely different presentation

Dihydrofolate reductase — ❌

• Target of methotrexate

• Not related to uric acid metabolism

• No neurologic or behavioral symptoms

PRPP synthetase — ❌

• Overactivity causes gout

• But not self-mutilation or severe neurologic disease

• Not consistent with this case

Xanthine oxidase — ❌

• Deficiency decreases uric acid

• Would NOT cause hyperuricemia or crystals

• The opposite of this case

Acute gout results from hyperuricemia, either due to:

• Overproduction of uric acid, or

• Underexcretion of uric acid

Among the given choices, the metabolic defect most classically associated with increased uric acid production is a deficiency (partial or complete) of HGPRT, the key enzyme of the purine salvage pathway.

Even partial HGPRT deficiency (unlike the severe Lesch–Nyhan syndrome) can lead to adult-onset gout.

✔ Why This Option Is Correct

Hypoxanthine–guanine phosphoribosyl transferase (HGPRT) deficiency — ✅

• HGPRT salvages hypoxanthine → IMP and guanine → GMP

• When HGPRT is reduced or absent:

  • Purines cannot be salvaged

  • PRPP accumulates

  • De novo purine synthesis increases

  • Excess purines → excess uric acid

Even mild/partial deficiency predisposes adults to gout, especially after triggers like red meat and alcohol.

❌ Why the Other Options Are Incorrect

Adenosine deaminase deficiency — ❌

• Causes SCID (Severe Combined Immunodeficiency)

• No link to gout or uric acid overproduction

CPS-II deficiency — ❌

• Involved in pyrimidine synthesis

• Deficiency causes orotic aciduria, not gout

Glucose-6-phosphatase deficiency — ❌

• Causes Von Gierke disease

• Leads to hyperuricemia, BUT presents in infancy with severe hypoglycemia, lactic acidosis

• Not consistent with a healthy 45-year-old who develops gout after dietary triggers

Xanthine oxidase overactivity — ❌

• Not a known primary cause of gout

• If anything, XO inhibition (e.g., allopurinol) is a treatment for gout

• Overactivity rarely mentioned as a natural genetic defect

When food intake is very low for several days, the body shifts to fat breakdown for energy.
This leads to:

• ↑ free fatty acid oxidation

• ↑ ketone body production (acetoacetate + β-hydroxybutyrate)

• Ketones spill into urine → positive dipstick

This is called starvation ketosis, and it occurs with normal or low-normal glucose, exactly as in this case (glucose = 70 mg/dL).

✔ Why This Option Is Correct

Prolonged starvation — ✅

• Low caloric intake for 5 days → glycogen depleted

• Body switches to lipolysis + ketogenesis

• Ketones appear in urine

• Normal glucose level rules out diabetes

• Perfectly matches the scenario

❌ Why the Other Options Are Incorrect

Diabetic ketoacidosis — ❌

• Characterized by high glucose (usually >250 mg/dL)

• She has normal glucose (70 mg/dL)

• No dehydration/severe symptoms like Kussmaul breathing

False positive due to vitamin C — ❌

• Vitamin C causes false negatives, not positives

• No sign she took high-dose vitamin C

Heavy protein intake — ❌

• Heavy protein intake does not cause significant ketonuria

• She is eating less, not more

Renal tubular acidosis — ❌

• Causes acidic blood, electrolyte issues, and no ketones

• Urine dipstick ketones are not a feature

Normal urine is mostly water (~95%) and about 5% solutes, including urea, creatinine, uric acid, ions, and trace substances.
The values in the question (water 1.1 L, solids 60 g, SG 1.018, pH ~6) all fall within the normal physiological range.

✔ Why This Option Is Correct

Water comprises approximately 95% of normal urine volume — ✅

• Normal urine output: ~1–2 L/day

• Water content ≈95%

• Solids ≈5% (urea being the major one)
  This matches the given data almost exactly.

❌ Why the Other Options Are Incorrect

Absence of solids is expected in normal urine — ❌

• Completely incorrect

• Urine must contain solutes (urea, uric acid, creatinine, electrolytes)

Normal urine contains >90% solids and <10% water — ❌

• Opposite of reality

• Solids are ~5% max

pH of normal urine must always be exactly 7.0 — ❌

• Normal urine pH varies 4.5–8.0, typically around 6.0

• It is rarely neutral at exactly 7.0

Specific gravity of normal urine should be less than 1.005 — ❌

• SG <1.005 = very dilute urine (e.g., diabetes insipidus)

• Normal SG = 1.010–1.025

• The value 1.018 in the question is normal

https://themedicalbiochemistrypage.org/nucleotides-biosynthesis-catabolism/

The question describes a cytosolic enzyme that uses:

• Glutamine

• CO₂

• ATP
  to make carbamoyl phosphate

…AND operates best at a slightly elevated (more alkaline) intracellular pH.

This profile matches CPS-II, the committed step of pyrimidine synthesis.

✔ Why the Regulation Is UTP Feedback Inhibition

In normal cells:

• CPS-II is inhibited by UTP (end-product feedback)

• Activated by PRPP

• Located in the cytosol

Tumor cells often show overactive CPS-II, accelerating pyrimidine synthesis to support rapid DNA replication.

❌ Why the Other Options Are Incorrect

Aspartate transcarbamoylase — inhibited by ATP ❌

• ATCase is a bacterial enzyme (classic allosteric enzyme example)

• In humans, regulation occurs at CPS-II, not at ATCase

• ATP activates it (not inhibits)

CPS-I — activated by N-acetylglutamate ❌

• Located in the mitochondria, not cytosol

• Uses NH₃, not glutamine

• Part of urea cycle, not nucleotide synthesis

• Activated by N-acetylglutamate, but does NOT fit the tumor cell description

CTP synthase — inhibited by UMP ❌

• Converts UTP → CTP

• Does not produce carbamoyl phosphate

• Not the rate-limiting step in pyrimidine synthesis

OMP decarboxylase — inhibited by CTP ❌

• This enzyme converts OMP → UMP

• Does not use glutamine or produce carbamoyl phosphate

• Not regulated by CTP

In Crossed fused ectopia, the kidneys are fused into a single mass, but they maintain their original vascular and collecting structures. This explains why you see:

• A single fused renal mass: The two kidneys have joined together on one side of the abdomen.

• Two separate ureters: Each original kidney has its own ureter. Crucially, the ureter from the ectopic kidney typically crosses the midline to enter the bladder at its intended, normal location.

Comparison of Options

A child developing facial puffiness + hematuria + RBC casts 2 weeks after a sore throat points strongly toward:

👉 Post-streptococcal glomerulonephritis (PSGN)

The hallmark mechanism:
Circulating immune complexes (streptococcal antigen–antibody complexes) deposit in the glomerulus, activating complement → inflammation → RBC casts + mild proteinuria.

✔ Why This Option Is Correct

Circulating immune complex deposition — ✅

• Classic mechanism in PSGN

• Deposition occurs in the subepithelial “hump-like” pattern

• Leads to complement activation (↓ C3)

• Produces RBC casts and cola-colored urine

This perfectly matches the vignette.

❌ Why The Other Options Are Incorrect

Anti-GBM antibody formation — ❌

• Seen in Goodpasture syndrome

• Causes hematuria + hemoptysis (lung involvement)

• Not triggered by strep throat

• Not typical in children

Complement deficiency — ❌

• Increases risk of Neisseria infections

• Not related to post-infectious glomerulonephritis mechanism

Amyloid deposition — ❌

• Causes nephrotic syndrome, NOT hematuria with RBC casts

• Occurs in adults with chronic inflammation/malignancy

Podocyte injury — ❌

• Causes minimal change disease, leading to massive proteinuria, NOT RBC casts

• Hematuria is not characteristic

Post-Infectious Glomerulonephritis (GN)

The combination of:

• Uniform thickening of the glomerular basement membrane

• “Spike and dome” appearance on silver stain

• Granular IgG + C3 deposition

…is classic and pathognomonic for membranous nephropathy.

It is the most common cause of nephrotic syndrome in adults.

✔ Why This Option Is Correct

Membranous nephropathy — ✅

• Caused by subepithelial immune complex deposition

• New basement membrane is laid down around these deposits → spikes

• Immune complexes form domes

• Immunofluorescence shows granular (“lumpy-bumpy”) IgG & C3

• Produces heavy proteinuria (nephrotic)

Fits the biopsy perfectly.

❌ Why the Other Options Are Incorrect

Post-streptococcal glomerulonephritis — ❌

• Shows subepithelial humps, not spike and dome

• IF: granular IgG + C3, but histology lacks uniform thickening

Lupus nephritis — ❌

• IF shows full-house pattern (IgG, IgM, IgA, C3, C1q)

• Histology varies by class; spike and dome is NOT classic

Minimal Change Disease — ❌

• Light microscopy: normal

• EM: podocyte foot process effacement

• No immune deposits, no spikes, no thickening

Focal segmental glomerulonephritis — ❌

Membranous Nephropathy

This is diabetic nephropathy with Kimmelstiel–Wilson nodules (nodular glomerulosclerosis).
The core mechanism in diabetes:

• Chronic hyperglycemia → non-enzymatic glycosylation of proteins

• Glycosylation of glomerular basement membrane (GBM) →

  • Initially → increased permeability → proteinuria

  • Later → GBM thickening + mesangial expansion → nodular sclerosis

So the best explanation is:

Non-enzymatic glycosylation causing increased basement membrane permeability

❌ Why the Other Options Are Incorrect

Deposition of immune complexes along the GBM

• Seen in membranous nephropathy, some lupus cases

• Would give granular IgG/C3, not specifically Kimmelstiel–Wilson nodules.

Deposition of amyloid fibrils derived from serum amyloid A

• That’s AA amyloidosis, can cause nephrotic syndrome

• Biopsy shows Congo red–positive, apple-green birefringence, not KW nodules.

Complement-mediated mesangial injury

• More typical of MPGN or some IgA nephropathies

• Doesn’t explain diabetic nodular sclerosis.

Autoantibody-induced mesangial proliferation

• Think lupus nephritis (immune complex & “full-house” IF)

• Not the classic lesion of diabetes.

Diabetic Nephropathy

https://www.webmd.com/skin-problems-and-treatments/henoch-schonlein-purpura-causes-symptoms-treatment

This is IgA nephropathy (Berger disease) — the classic features:

• Hematuria 1–2 days after a URI

• Mesangial proliferation

• IgA deposits on IF

• Normal renal function between episodes

IgA nephropathy is essentially the renal-limited form of Henoch–Schönlein purpura (HSP).

✔ Why This Option Is Correct

It represents a localized form of Henoch–Schönlein purpura — ✅

• HSP = systemic IgA vasculitis (skin, GI, joints + kidneys)

• IgA nephropathy = kidney-only involvement

• Same pathology: mesangial IgA immune complexes

Hence: IgA nephropathy = renal-limited HSP.

❌ Why The Other Options Are Incorrect

It commonly leads to crescent formation within days — ❌

• Crescents = rapidly progressive GN (RPGN)

• IgA nephropathy usually has a benign, recurrent course

• Crescents may occur rarely but NOT within days

It is due to anti-GBM antibody deposition — ❌

• That is Goodpasture syndrome

• IF would show linear IgG, not granular IgA

It is associated with severe proteinuria (>3.5 g/day) — ❌

• That describes nephrotic syndrome

• IgA nephropathy → usually hematuria ± mild proteinuria, not massive protein loss

It usually follows streptococcal infection by 2–3 weeks — ❌

• That is post-streptococcal GN

• IgA nephropathy flares within 1–2 days, not weeks

Both cystitis (lower UTI) and pyelonephritis (upper UTI) can show:

• Fever

• Pyuria

• Positive nitrites

• Positive urine culture

• Bacteriuria

But WBC casts indicate that inflammation is inside the kidney tubules, meaning upper urinary tract involvement → acute pyelonephritis.

✔ Why This Option Is Correct

Presence of WBC casts — ✅

• Casts are formed in renal tubules, not the bladder

• Only pyelonephritis causes WBCs to enter tubules and form casts

• Pathognomonic for upper UTI

❌ Why the Other Options Are Incorrect

Positive urine culture — ❌

• Seen in both cystitis and pyelonephritis

• Not specific

Pyuria — ❌

• Pus cells appear in both

• Indicates infection but not location

Bacteriuria — ❌

• Common to all UTIs

• No localization value

Fever with chills — ❌

• More severe in pyelonephritis, but can occur mildly in cystitis

• Not definitive

An elderly male with:

• Urinary hesitancy

• Nocturia

• High post-void residual urine

• Bilateral hydronephrosis

…strongly points toward outlet obstruction at the prostate → classic BPH.

This causes chronic bladder outlet obstruction → back pressure → bilateral hydronephrosis.

✔ Why This Option Is Correct

Benign prostatic hyperplasia — ✅

• Most common cause of obstructive uropathy in elderly men

• Leads to:

  • Weak stream

  • Hesitancy

  • Nocturia

  • Incomplete emptying (↑ post-void residual)

  • Bilateral hydronephrosis from chronic obstruction

• Fits the patient perfectly

❌ Why the Other Options Are Incorrect

Ureteric stone — ❌

• Causes unilateral hydronephrosis (unless bilateral stones, which is rare)

• Does not cause high post-void residual urine

Urethral stricture — ❌

• Can cause obstruction, but commonly in younger men

• Usually associated with trauma or infection history

• Not the most likely in a 68-year-old with BPH symptoms

Neurogenic bladder — ❌

• Would cause retention + hydronephrosis, but patient would typically have:

  • Diabetes

  • Spinal cord injury

  • MS

  • Parkinsonism

• And nocturia + hesitancy classically point to BPH, not neurogenic dysfunction

Posterior urethral valves — ❌

• Occurs only in male infants

• Not seen in elderly men

She has:

• Bilateral hydronephrosis

• No stones

• A pelvic mass infiltrating the cervix and lower ureters

• Gradual rise in creatinine + dull flank pain

This is classic chronic obstructive uropathy due to extrinsic compression of both ureters by a malignant pelvic mass (very likely cervical carcinoma).

Obstruction → urine cannot drain →
🔺 Increased pressure in pelvis & calyces
🔺 Compression of renal cortex
🔻 Progressive atrophy of renal parenchyma and ↓ GFR

That’s exactly what the last option states.

❌ Why the Other Options Are Incorrect

• Acute tubular necrosis due to ischemia

  • Would be acute, with hypotension/shock, toxins, etc.

  • Not a slow, structural back-pressure problem.

• Immune-mediated interstitial inflammation

  • Describes interstitial nephritis (often drug-induced, allergic, autoimmune).

  • Would show fever, rash, eosinophilia—not bilateral hydronephrosis from a pelvic mass.

• Glomerular immune complex deposition

  • Seen in glomerulonephritis (PSGN, lupus, IgA nephropathy etc.)

  • Would give hematuria, RBC casts, proteinuria—not hydronephrosis.

• Bacterial invasion causing abscess formation

  • That’s acute pyelonephritis / renal abscess.

  • Would present with fever, chills, CVA tenderness, pyuria—not chronic, silent back-pressure with a pelvic mass.

Obstruction and obstructive nephropathy

Chronic NSAID (ibuprofen) use +

• Sterile pyuria

• Eosinophils in urine

• Mild proteinuria

• Normal-sized kidneys, no obstruction

…is classic for drug-induced acute interstitial nephritis (AIN) — usually an immune-mediated hypersensitivity reaction involving the renal interstitium.

✔ Why This Option Is Correct

Immune-mediated hypersensitivity reaction affecting interstitium — ✅

• Many drugs (NSAIDs, antibiotics like methicillin, PPIs) can trigger type IV hypersensitivity in the kidney.

• This targets the interstitium and tubules, not primarily the glomeruli.

• Hallmarks:

  • Eosinophiluria

  • Sterile pyuria

  • Mild proteinuria

  • Rising creatinine

This matches the vignette perfectly.

❌ Why The Other Options Are Incorrect

Glomerular necrosis due to inhibition of oxidative phosphorylation — ❌

• This sounds like a toxin/poison effect (e.g., heavy metals)

• Would cause severe glomerular damage, often heavy proteinuria or hematuria

• Not the typical pattern for ibuprofen use with eosinophils in urine

Direct immune complex deposition with complement activation — ❌

• That describes immune complex glomerulonephritis (e.g., lupus, PSGN).

• You’d expect RBC casts, hematuria, more significant proteinuria, not just sterile pyuria with eosinophils.

Ischemic cortical necrosis from severe hypotension — ❌

• Requires massive shock, obstetric catastrophe, DIC, etc.

• Would cause acute renal failure with very sick patient, not this slower, drug-related picture.

Acute bacterial infection ascending from lower urinary tract — ❌

• That’s pyelonephritis, which would show:

  • Fever, chills

  • Flank tenderness

  • Positive urine culture

• Our patient has sterile pyuria, not infectious.

A renal transplant patient who develops symptoms 2–6 weeks after surgery with:

• Fever

• Tenderness over graft

• Rising creatinine

• Lymphocytic infiltration of interstitium + tubules

• Endothelial inflammation (“endothelialitis”)

…is showing the classic picture of acute T-cell–mediated (cellular) rejection.

This is the most common rejection in the first few weeks.

✔ Why This Option Is Correct

Acute cellular rejection — mediated by T lymphocytes — ✅

• Occurs days to weeks after transplant (here: 3 weeks)

• Histology:

  • Dense lymphocytic infiltrate in interstitium

  • Tubulitis (lymphocytes invading tubules)

  • Endothelialitis (lymphocytes under endothelium)

• Mediated by host CD8⁺ and CD4⁺ T cells reacting to donor MHC

• Treatable with steroids and immunosuppression escalation

Matches perfectly.

❌ Why the Other Options Are Incorrect

Hyperacute rejection due to preformed antibodies — ❌

• Occurs within minutes to hours, not 3 weeks

• Caused by preformed anti-donor Abs

• Characterized by thrombosis, fibrinoid necrosis, not lymphocytic infiltrates

Chronic antibody-mediated rejection — ❌

• Occurs over months to years

• Shows fibrosis, vascular thickening, transplant glomerulopathy

• Not acute lymphocytic interstitial infiltration

Acute antibody-mediated rejection due to ABO mismatch — ❌

• Occurs early, often days, and involves neutrophils + complement (C4d positivity)

• More vascular, less interstitial/tubular lymphocytes

• ABO mismatch usually causes hyperacute events, not this picture

Drug-induced nephrotoxicity — ❌

• e.g., calcineurin inhibitors → causes arteriolar hyalinosis & striped fibrosis, not T-cell infiltration

• No fever or graft tenderness typically

https://webpath.med.utah.edu/RENAHTML/RENAL107.html

A blood pressure of 220/130 mmHg with:

• Headache

• Blurred vision

• Rising creatinine

• Hematuria

…is classic for malignant hypertension.

The renal lesion most strongly associated with malignant hypertension is:

👉 Hyperplastic arteriolosclerosis (“onion-skinning”)

This results from severe, rapidly progressive blood pressure elevation causing concentric, laminated smooth muscle proliferation in arterioles.

✔ Why This Option Is Correct

Onion-skin hyperplastic arteriolosclerosis — ✅

• Seen in malignant hypertension

• Arterioles show concentric laminated (“onion-skin”) thickening

• Leads to ischemia, acute kidney injury, hematuria

• Fits the clinical picture perfectly

❌ Why the Other Options Are Incorrect

Hyaline arteriolosclerosis — ❌

• Seen in benign hypertension and long-standing diabetes

• Slow process, not associated with BP crisis or acute renal injury

Necrotizing granulomatous vasculitis — ❌

• Seen in Wegener (GPA)

• Respiratory + kidney involvement

• Not associated with hypertensive emergency

Necrotizing glomerulonephritis — ❌

• Seen in RPGN, Goodpasture, ANCA-associated diseases

• Not primarily caused by severe hypertension

• Doesn’t produce “onion-skin” arterioles

Lipid-laden macrophage infiltration — ❌

• Seen in xanthogranulomatous pyelonephritis

• Chronic obstruction + infection

• Not related to malignant hypertension

https://www.pathologyoutlines.com/topic/kidneychronicpyelo.html

Long-standing vesicoureteral reflux → reflux nephropathy, a form of chronic pyelonephritis.
This leads to:

• Asymmetric, irregular scarring

• Blunted calyces

• Tubular atrophy with thyroidisation (tubules filled with colloid-like casts)

• Interstitial fibrosis + chronic inflammatory cells

This is the classic hallmark.

✔ Why This Option Is Correct

Interstitial fibrosis with thyroidisation of tubules — ✅

• Tubules become dilated and atrophic

• Filled with eosinophilic, colloid-like casts → “thyroid-like” appearance

• Interstitium shows fibrosis + chronic inflammatory infiltrate

• This is pathognomonic for chronic pyelonephritis

Fits the entire clinical scenario.

❌ Why the Other Options Are Incorrect

Diffuse glomerular sclerosis only — ❌

• Glomeruli may scar late, but this is not the primary lesion

• Tubulointerstitium is the main site of injury in chronic pyelonephritis

Diffuse fibrosis with neutrophilic infiltration — ❌

• Neutrophils = acute pyelonephritis

• Chronic disease shows lymphocytes, plasma cells, not neutrophils

Neutrophilic infiltration of glomeruli — ❌

• Glomerular neutrophils suggest acute GN, not pyelonephritis

Granulomatous inflammation — ❌

• Seen in TB, sarcoidosis, fungal infections

• Not a feature of chronic pyelonephritis