Renal – 2022

• Renal calculi are crystalline concretions formed in the kidneys from calcium oxalate, phosphate, uric acid, or cystine.

• Most contain calcium, making them radio-opaque on plain X-rays.

• They typically appear as white opacities in the region of the kidney, ureter, or bladder.

• Associated symptoms include loin pain, hematuria, and urinary obstruction.

• Hence, in this patient’s KUB X-ray, the opaque shadow in the renal calyces represents a renal stone.

❌ Why the Other Options Are Wrong:

Slough off renal papillae:

• Seen in papillary necrosis (e.g., diabetes, analgesic nephropathy); may appear as filling defects on IVP, but not radio-opaque on plain X-ray.

Gravels filtered from glomeruli:

• Glomeruli don’t “filter gravels”; stones form distally in tubules/collecting system, not at glomeruli.

Necrosis with dystrophic calcification:

• May cause calcification but is diffuse and irregular, not a discrete stone shadow in calyces.

Proteins:

• Organic materials (like proteins) are radiolucent, hence invisible on X-ray.

• When renal calculi (kidney stones) obstruct the urinary tract, urine cannot drain freely.

• This leads to hydronephrosis — dilation of the renal pelvis and calyces.

• The stretching of the renal capsule causes a dull, constant, aching pain in the loin (flank region).

• If obstruction becomes complete or infection supervenes, the pain may become sharp and colicky.

Thus, while the stone is the underlying cause, the immediate mechanism producing the dull ache is back pressure from retained urine.

❌ Why the Other Options Are Wrong:

Infection:
⚠️ May cause fever and tenderness, but typically gives sharp or burning pain, not a dull ache.

Obstruction to the flow of urine:
⚠️ True in general, but the pain mechanism specifically comes from back pressure, not just the presence of obstruction.

Renal calculi:
⚠️ The primary cause, but the question asks for the mechanism of dull pain — that’s due to back pressure.

Stenosis of renal artery:
❌ Causes ischemic nephropathy and hypertension, not dull loin pain.

• When the stone moves or causes acute obstruction, the pain becomes sharp and colicky (renal colic).

• When it’s partially obstructing or stationary, the pain is dull and persistent, due to pressure buildup rather than spasm.

• The renal calyces, renal pelvis, ureters, and urinary bladder are all lined by transitional epithelium, also called urothelium.

• This specialized epithelium:

  • Is stratified, but the surface cells (umbrella cells) can change shape depending on bladder fullness.

  • Provides a watertight barrier and resists urine toxicity.

  • Allows distension without tearing or losing integrity.

❌ Why the Other Options Are Wrong:

Simple columnar:

• Found in gastrointestinal tract, not urinary passages.

Simple cuboidal:

• Lines renal tubules (PCT, DCT), not the collecting ducts or calyces.

Pseudostratified columnar:

• Common in respiratory tract and male reproductive tract, not in urinary pathways.

Stratified columnar:

• Rare; occurs in some ducts (e.g., salivary glands), not in the kidney.

• The creatinine clearance test estimates the glomerular filtration rate (GFR) — the most comprehensive indicator of overall kidney function.

• It measures how efficiently creatinine (a constant by-product of muscle metabolism) is cleared from blood into urine.

• The test requires 24-hour urine collection and plasma creatinine measurement to calculate Creatinine Clearance

• This gives a direct estimate of GFR, helping evaluate both kidneys’ performance and any damage caused by obstruction or infection.

❌ Why the Other Options Are Wrong:

Urine D/R (detailed report):

• Checks for protein, blood, pus cells, crystals, etc.

• Useful for infection or hematuria, but not for functional assessment.

X-ray KUB:

• Provides anatomical information (stones, calcifications), not kidney function.

Urea, creatinine, electrolytes:

• Reflect biochemical changes in blood but cannot measure GFR precisely — a rise in serum creatinine only appears after significant nephron loss.

Urine acidification test:

• Assesses tubular function, not overall glomerular function.

• MCUG (also called Voiding Cystourethrogram) is the gold standard test to confirm vesico-ureteric reflux.

• The procedure involves:

  1. Filling the bladder with a radiopaque contrast through a catheter.

  2. Taking X-rays during filling and voiding.

  3. Observing for retrograde flow of contrast from the bladder into the ureters or kidneys.

• It also helps detect posterior urethral valves and other structural abnormalities of the bladder outlet — important in male toddlers.

❌ Why the Other Options Are Wrong:

CT Urography:

• ❌ High radiation exposure and not routinely used in children; poor sensitivity for reflux.

Intravenous urography (IVU):

• ❌ Outdated for VUR; mainly shows anatomy, not functional reflux.

MR Urography:

• ⚠️ Can show urinary tract anatomy without radiation but is less practical and not the investigation of choice for reflux detection in toddlers.

Ultrasound bladder with pre and post-void volumes:

• ⚠️ Useful for assessing residual urine or hydronephrosis, but cannot detect reflux.

• The kidneys produce erythropoietin, which stimulates erythropoiesis in the bone marrow.

• In CKD, damaged renal tissue cannot produce enough EPO → reduced RBC production → normocytic, normochromic anemia.

• This type of anemia causes fatigue, pallor, and dyspnea, commonly seen in long-term renal failure.

• Treatment involves recombinant EPO therapy along with iron supplementation if needed.

❌ Why the Other Options Are Wrong:

Hypokalemia:

• CKD usually leads to hyperkalemia due to decreased excretion of potassium.

Hypophosphatemia:

• CKD causes hyperphosphatemia because phosphate is not adequately excreted.

Hypercalcemia:

• CKD often leads to hypocalcemia, not hypercalcemia, because of low vitamin D activation and high phosphate levels.

Hypomagnesemia:

• CKD leads to hypermagnesemia, as magnesium excretion also decreases.

• Pre-renal acute kidney failure occurs when there is a drop in blood flow to the kidneys, leading to reduced glomerular filtration rate (GFR).

• Profuse diarrhea causes severe fluid and electrolyte loss, resulting in hypovolemia and decreased renal perfusion.

• If uncorrected, this can progress to ischemic injury and acute tubular necrosis (ATN).

• It is reversible if treated early by restoring fluid balance.

❌ Why the Other Options Are Wrong:

Nephrotic syndrome:

• ⚠️ Primarily a glomerular disease causing protein loss, not a perfusion issue — classified as renal (intrinsic).

Prostatic hypertrophy:

• 🚫 Causes urinary outflow obstruction, leading to post-renal failure.

Cancer of prostate:

• 🚫 Also causes post-renal failure through obstruction of the urethra.

Acute glomerulonephritis:

• 🚫 A renal (intrinsic) cause — inflammation within the glomeruli impairs filtration directly.

• The pH indicates whether the blood is acidic (<7.35) or alkaline (>7.45).

• Once pH is known, the next steps are:

  1. Determine if it’s acidosis or alkalosis (based on pH).

  2. Look at PCO₂ → if it changes in the same direction as pH, it’s respiratory.

  3. Look at HCO₃⁻ → if it changes in the opposite direction to pH, it’s metabolic.

  4. Calculate anion gap or delta–delta only after the primary disorder is identified.

So in this COPD patient, the ABG shows respiratory acidosis, but the first thing to check is the pH to confirm acidemia before determining the cause.

❌ Why the Other Options Are Wrong:

Anion gap:

• Used only for metabolic acidosis to identify the cause — not the first step.

Delta–delta gap:

• Used in mixed metabolic disorders, much later in interpretation.

HCO₃⁻ level:

• Evaluated after pH and PCO₂ to decide if it’s metabolic or compensatory.

PCO₂:

• Important for determining respiratory involvement, but only after pH is assessed.

• The kidneys are highly sensitive to blood volume and pressure.

• In severe dehydration, renal perfusion falls sharply, leading to pre-renal acute kidney injury (AKI).

• The glomeruli cannot filter blood adequately, resulting in decreased urine output (oliguria or anuria).

• If uncorrected, this may progress to acute tubular necrosis and permanent kidney damage.

❌ Why the Other Options Are Wrong:

Liver:

• Has dual blood supply (hepatic artery + portal vein) — remains functional longer even in hypovolemia.

Lungs:

• Usually remain functional unless dehydration leads to severe shock or multi-organ failure.

Pancreas:

• Not directly affected early; ischemia may occur only in prolonged shock.

Eyes:

• May appear sunken in dehydration, but visual function remains intact.

• Severe dehydration leads to hypovolemia, hypotension, and impaired consciousness.

• Since the patient is semi-conscious, oral fluids are unsafe (risk of aspiration) and ineffective.

• IV fluid therapy (e.g., Ringer’s lactate or normal saline) is the first line of management to restore:

  • Circulating volume

  • Electrolyte balance

  • Blood pressure

  • Renal perfusion

Once stable, oral rehydration and further management (antibiotics if indicated) can follow.

❌ Why the Other Options Are Wrong:

IV antibiotics:
❌ Not the first priority. Infection may be present, but immediate correction of shock and dehydration takes precedence.

Oral fluid replacement:
❌ Contraindicated in semi-conscious patients due to risk of aspiration. Suitable only for mild to moderate dehydration in alert patients.

Oral antibiotics:
❌ Not useful in acute management; hydration comes first. Antibiotics are only given if bacterial infection is confirmed or strongly suspected (e.g., cholera, dysentery).

KYB diet (Keep Your Balance / light diet):
❌ Dietary changes are not part of emergency stabilization and only apply later during recovery.

• Patients and families have the right to seek another specialist’s opinion if they doubt a diagnosis or prognosis.

• The doctor’s duty is to respect and facilitate this choice — not to react defensively.

• Supporting a second opinion builds trust, ensures informed decision-making, and aligns with ethical principles of autonomy and beneficence.

❌ Why the Other Options Are Wrong:

Discharge the patient immediately:
❌ Unethical and unprofessional — patients must not be abandoned, especially when critically ill.

Facilitate by counselling:
⚠️ Partially correct, but the core duty here is to support the right to a second opinion, not just offer counselling.

Offer palliative care:
⚠️ Important in advanced cancer, but that comes after the family accepts the diagnosis; this option ignores their current request for another opinion.

Offer psychoeducation:
⚠️ Helpful, but secondary. The ethical issue here is respecting the right to seek another medical opinion, not just providing information.

An authorized person or someone who needs to know patient information is:

• Directly involved in the patient’s care, and

• Requires the information to provide safe, effective, and coordinated treatment.

For example, a nurse, doctor, psychologist, or social worker involved in the same patient’s case can access relevant information as part of multidisciplinary care.

❌ Why the Other Options Are Wrong:

A senior worker not involved in supporting the individual:

• ❌ Hierarchical seniority doesn’t justify access. Only those involved in the patient’s care may know details.

A member of the family of the individual that you support:

• ❌ Not automatically authorized unless the patient consents or the person is a legal guardian (e.g., in minors or incapacitated adults).

A colleague who is not involved in supporting care:

• ❌ Curiosity or general discussion does not justify information sharing; this violates confidentiality.

Another health personnel from another team providing support to another individual:

• ❌ Not relevant to this patient’s care; sharing information here is a breach of confidentiality.

• A cross-sectional study (also called a prevalence study) measures both the presence of disease (outcome) and exposure factors at the same time in a defined population.

• It is ideal for assessing the burden of disease (like diabetes) in a community — in this case, Karachi.

• It helps public health authorities plan interventions and allocate resources.

Example:
Surveying a random sample of adults in Karachi, measuring their fasting glucose levels, and recording how many have diabetes — all done once — gives prevalence data.

❌ Why the Other Options Are Wrong:

Cohort study:

• Follows disease-free individuals over time to determine incidence (new cases), not prevalence.

Case control study:

• Starts with cases (diseased) and controls (non-diseased) and looks backward for exposures — used for studying risk factors, not prevalence.

Experimental study:

• Involves intervention (e.g., new drug trial), not just observation of existing conditions.

Case series:

• Describes a group of patients with a known disease; no comparison group or population-based prevalence estimation.

• Matching of ABO blood group and major HLA (human leukocyte antigen) types is crucial for reducing rejection risk.

• However, minor histocompatibility antigens — though they can contribute to mild rejection — are not required to be matched, as they don’t cause severe immune reactions.

• Even with optimal matching, lifelong immunosuppressive therapy is necessary to maintain graft tolerance.

❌ Why the Other Options Are Wrong:

ABO compatibility between donor and recipient is a must:
❌ Usually true and preferred, but not an absolute requirement anymore — ABO-incompatible transplants are possible with plasmapheresis and immunosuppressive conditioning, especially in living donors.

Allergen test is performed on potential recipient:
❌ Irrelevant — allergies don’t determine transplant compatibility; HLA typing and crossmatching do.

HLA compatibility is sometimes not required:
❌ Incorrect — HLA matching is always assessed (especially for living donors), though not necessarily perfect; better matching means better long-term graft survival.

Immunosuppressant drugs are prescribed to selective transplant patients:
❌ Wrong — all transplant recipients require lifelong immunosuppive therapy (e.g., tacrolimus, cyclosporine, steroids, mycophenolate).

• XGP has no association with viral infections — especially not Polyomavirus.

• It’s purely bacterial and obstructive in nature, resulting from long-standing infection and poor drainage.

• Microscopically, there are foamy (lipid-laden) macrophages, plasma cells, lymphocytes, and multinucleated giant cells.

• Grossly, the kidney shows yellow-orange nodules, often mimicking renal cell carcinoma on imaging or at surgery.

❌ Why the Other Options Are Correct (and thus not the answer):

Accumulation of foamy macrophages with plasma cells, lymphocytes, giant cells:
✅ True — classic histological hallmark of XGP.

Grossly resembles Renal cell carcinoma:
✅ True — both show yellow nodules; differentiation requires histology.

Rare form of Chronic Pyelonephritis:
✅ True — XGP is an uncommon chronic suppurative infection.

Shows large yellow-orange nodules:
✅ True — due to lipid-laden macrophages, giving a characteristic yellow hue.

• Nephrotic syndrome primarily involves damage to podocytes, which allows protein (not blood) to leak into urine.

• The hallmark features are:

  • Heavy proteinuria (>3.5 g/day)

  • Hypoalbuminemia

  • Edema

  • Hyperlipidemia and lipiduria

  • Decreased plasma colloid osmotic pressure (due to low plasma proteins)

• Hematuria (blood in urine), on the other hand, is a feature of nephritic syndrome, which involves inflammatory glomerular injury (e.g., post-streptococcal GN, IgA nephropathy).

❌ Why the Other Options Are Wrong:

Heavy proteinuria:
✅ Defining feature of nephrotic syndrome — due to glomerular capillary leak.

Selective proteinuria:
✅ Often seen in minimal change disease, a cause of nephrotic syndrome, where mainly albumin is lost.

Hypoalbuminemia:
✅ Result of excessive urinary protein loss.

Decreased plasma colloid osmotic pressure:
✅ Caused by low serum albumin → leads to edema formation.

Anti-GBM antibody–induced GN is a type of rapidly progressive glomerulonephritis (RPGN) characterized histologically by:

• Crescent formation in Bowman’s space (due to proliferation of parietal epithelial cells and macrophage infiltration).

• Linear IgG deposition on immunofluorescence along the GBM.

• Rapid loss of renal function, often progressing to renal failure within weeks.

Hence, it is classified under crescentic nephropathy — a hallmark of RPGN Type I (anti-GBM disease).

❌ Why the Other Options Are Wrong:

Proliferative nephropathy:

• General term for increased cellularity; not specific to anti-GBM disease.

Membranous nephropathy:

• Due to subepithelial immune complex deposits causing spike and dome pattern, not linear IgG deposition.

Membranoproliferative nephropathy (MPGN):

• Involves immune complex deposition in both mesangium and subendothelial regions — “tram-track” appearance — unrelated to anti-GBM antibodies.

Mesangioproliferative nephropathy:

• Features mesangial hypercellularity, commonly linked to IgA nephropathy, not anti-GBM antibodies.

FSGS is not an immune complex–mediated disease, so IgA deposition is not a feature.

• On immunofluorescence, FSGS may show nonspecific trapping of IgM and C3 in sclerotic segments — but not IgA.

• The hallmark lesion is segmental sclerosis and hyalinosis involving some glomeruli, with podocyte effacement visible on electron microscopy.

• Clinically, it presents with proteinuria (often nephrotic range), edema, and hypoalbuminemia.

❌ Why the Other Options Are Wrong:

Nephrotic syndrome:

• ✅ Common presentation of FSGS.

• Especially in adults and in secondary causes (HIV, obesity, heroin use).

Some of the glomeruli are normal:

• ✅ True — “focal” means only a subset of glomeruli are affected.

Some of the glomeruli are sclerosed:

• ✅ True — “segmental sclerosis” defines the disease histologically.

IgM deposition on immunofluorescence:

• ✅ Commonly seen as trapped IgM and complement (C3) in sclerotic regions.

• E. coli accounts for ~80–85% of community-acquired UTIs.

• It possesses fimbriae (pili) that help it adhere to the uroepithelium and resist flushing during urination.

• Commonly causes cystitis (burning micturition, frequency, urgency) and sometimes pyelonephritis.

• Risk factors include female sex, sexual activity, pregnancy, and diabetes.

❌ Why the Other Options Are Wrong:

Klebsiella:

• Can cause UTIs, but is more often hospital-acquired.

• Often seen in catheterized or immunocompromised patients.

Proteus:

• Known for urease production, leading to alkaline urine and struvite stones, but again more common in complicated or recurrent UTIs.

Staphylococcus saprophyticus:

• Second most common cause of UTI in sexually active young women, but far less frequent overall compared to E. coli.

Streptococcus faecalis (Enterococcus faecalis):

• Common in hospital-acquired or post-instrumentation UTIs, not typically in community settings.

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.

• 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.

Folate (in its active form, tetrahydrofolate — THF) donates one-carbon units during the synthesis of purine rings.

• Specifically, N¹⁰-formyl-THF contributes carbon atoms at positions C₂ and C₈ of the purine structure.

• Without folate, purine synthesis — and thus DNA and RNA production — slows dramatically, leading to megaloblastic anemia due to impaired cell division.

❌ Why the Other Options Are Wrong:

Thiamine (Vitamin B₁):

• Functions as thiamine pyrophosphate (TPP) in carbohydrate metabolism (e.g., pyruvate dehydrogenase, α-ketoglutarate dehydrogenase).

• Plays no role in purine synthesis.

Biotin:

• Acts as a CO₂ carrier in carboxylation reactions (e.g., acetyl-CoA carboxylase, pyruvate carboxylase).

• Not involved in transferring one-carbon units for purines.

Flavin (Vitamin B₂):

• Component of FAD/FMN, coenzymes for oxidation-reduction reactions.

• Does not donate carbon groups for nucleotide synthesis.

Caltrate:

• A calcium supplement, unrelated to metabolic cofactors or nucleotide biosynthesis.

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.

All the listed conditions — urine retention, chronic cystitis, anemia, obstructing gastric ulcers, and alkaline therapy — contribute to a rise in systemic or urinary pH, leading to a state of alkalosis (excess alkalinity).

Mechanisms:

• Urine retention & chronic cystitis: allow bacterial decomposition of urea → ammonia formation, which makes the urine alkaline.

• Obstructing gastric ulcers: cause loss of gastric acid (HCl) through vomiting → increased blood bicarbonate → metabolic alkalosis.

• Alkaline therapy: direct intake of bicarbonate or antacids → increases systemic alkalinity.

• Anemia may occur secondarily (e.g., from chronic gastric loss) but isn’t the direct cause — it’s part of the overall systemic disturbance.

Hence, collectively these conditions point toward excess alkalinity (alkalosis).

❌ Why the Other Options Are Wrong

• Excess acidity: opposite effect — would occur in metabolic acidosis.

• Retention of acid metabolites: linked to renal failure or poor perfusion, not to these conditions.

• Raised pCO₂: seen in respiratory acidosis, not relevant here.

• Raised specific gravity: depends on dehydration, not acid–base status.

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.

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 patient’s description — sudden, intensely painful swelling of the big toe (podagra) with needle-shaped urate crystals in the synovial fluid — is classic for gout.
Although most gout is acquired (due to excess uric acid production or decreased excretion), an enzyme deficiency in purine metabolism can predispose to hyperuricemia.

The key enzyme here is HGPRT (Hypoxanthine-Guanine Phosphoribosyltransferase), part of the purine salvage pathway, which normally salvages hypoxanthine and guanine back to IMP and GMP using PRPP.

When HGPRT is deficient or partially defective, the salvage pathway fails → PRPP accumulates → de novo purine synthesis increases → excess uric acid production → gout.

Partial deficiency = Kelley–Seegmiller syndrome (adult gout).
Complete deficiency = Lesch–Nyhan syndrome (neurobehavioral issues + self-mutilation).

❌ Why the Other Options Are Wrong

• Alkaline phosphatase, PRPP:
  Alkaline phosphatase isn’t involved in purine metabolism; PRPP is a substrate, not an enzyme.

• Adenosine deaminase + HGPRT:
  ADA deficiency → SCID, not gout.

• HGPRT + PRPP:
  PRPP (phosphoribosyl pyrophosphate) isn’t an enzyme, so this combination is invalid.

• Phosphoribosyl pyrophosphate:
  It’s a substrate synthesized by PRPP synthetase — overactivity of PRPP synthetase may cause gout, but deficiency does not.

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.

This presentation describes orotic aciduria, a rare autosomal recessive disorder caused by a deficiency of uridine monophosphate (UMP) synthase — an enzyme complex that catalyzes the final two steps of de novo pyrimidine synthesis:

1️⃣ Orotate phosphoribosyltransferase (OPRTase) converts orotic acid → orotidine monophosphate (OMP).
2️⃣ OMP decarboxylase then converts OMP → uridine monophosphate (UMP).

When this enzyme is deficient, orotic acid accumulates in the urine, and pyrimidine nucleotides (especially UMP) are deficient. This leads to megaloblastic anemia and growth retardation, because DNA synthesis is impaired.

Treatment: Administration of uridine bypasses the enzyme block — it gets converted to UMP, replenishing pyrimidine pools, correcting the anemia, and alleviating symptoms.

❌ Why the Other Options Are Wrong

• Adenine & Guanine:
  Purine bases — supplementing them won’t fix a pyrimidine synthesis defect.

• Hypoxanthine:
  Also a purine precursor; relevant to Lesch–Nyhan syndrome, not orotic aciduria.

• Thymidine:
  A pyrimidine nucleoside but downstream of UMP — it cannot substitute for the missing UMP synthase function.

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.

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.

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.

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.

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.

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.

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.

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.

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

In females, the entire urethra develops from the pelvic part of the urogenital sinus.
During embryogenesis, the urogenital sinus divides into three regions:

1️⃣ Vesical part → forms most of the urinary bladder (except trigone).
2️⃣ Pelvic part → gives rise to the entire female urethra and lower part of the vagina.
3️⃣ Phallic part → contributes to the vestibule of the vagina in females (the external opening area).

Hence, the pelvic part is responsible for forming the tubular urethra extending from the bladder to the vestibule.

❌ Why the Other Options Are Wrong

• Tip:
  There’s no “tip” region in the urogenital sinus; this option is a distractor.

• Vesical part:
  Forms the bladder, not the urethra.

• Phallic part:
  Forms the vestibule of the vagina, not the urethra itself.

• Widest part:
  Anatomically imprecise — the sinus isn’t divided by width but by embryological regions (vesical, pelvic, phallic).

The visceral layer of Bowman’s capsule is formed by podocytes — specialized epithelial cells with a stellate (star-shaped) body. Each podocyte gives off primary processes that branch into numerous secondary foot processes (pedicels), which interdigitate with neighboring cells to form filtration slits. These slits are bridged by a thin slit diaphragm, a key part of the glomerular filtration barrier.

Podocytes play a vital role in maintaining selective filtration and preventing protein loss in urine. Injury to podocytes (e.g., in minimal change disease or diabetic nephropathy) leads to proteinuria.

❌ Why the Other Options Are Wrong

• Brushed cells:
  Found in the proximal convoluted tubule, not in Bowman’s capsule. Their brush border (microvilli) increases surface area for reabsorption.

• Endothelium:
  Lines the glomerular capillaries, not Bowman’s capsule. It is fenestrated, forming part of the filtration barrier but not the visceral layer.

• Mesangial cells:
  Located between glomerular capillaries; they provide structural support, secrete matrix and cytokines, and have phagocytic properties — but they don’t form the capsule lining.

• Simple cuboidal cells:
  These line tubular structures like the PCT and DCT, not the visceral layer of Bowman’s capsule.

The renal filtration barrier is a highly specialized tri-layered structure designed to selectively filter blood plasma while retaining cells and large proteins. It ensures that essential molecules like glucose and amino acids can pass through while keeping albumin and blood cells inside the circulation.

It consists of three key components (from inside to outside):
1️⃣ Fenestrated endothelium of glomerular capillaries — allows plasma through but blocks blood cells.
2️⃣ Glomerular basement membrane (basal lamina) — acts as a size and charge barrier.
3️⃣ Podocyte foot processes with slit diaphragms — fine-tune filtration selectivity at the outermost layer.

There is no continuous epithelium in this barrier — the endothelium is fenestrated specifically to allow ultrafiltration.

❌ Why the Other Options Are Wrong

• Podocytes:
  These form the visceral layer of Bowman’s capsule and create slit diaphragms between foot processes — a crucial part of the filtration barrier.

• Fenestrated endothelium of glomerular capillaries:
  The first filtration layer. Its pores (~70–100 nm) allow water and solutes but not cells to pass through.

• Basal lamina (glomerular basement membrane):
  The shared basement membrane between endothelium and podocytes, rich in type IV collagen and heparan sulfate, providing both mechanical strength and charge selectivity.

• Endothelial cells:
  They line the glomerular capillaries and contribute to the fenestrations forming part of the barrier.

An ectopic ureter is a congenital anomaly in which the ureter does not open into the urinary bladder at its normal site (the trigone).
In females, it may open into the vagina, urethra, or vestibule, leading to continuous dribbling of urine despite normal voiding — exactly as described here.

Why others are wrong:
❌ Autosomal recessive polycystic kidney disease — causes cystic renal enlargement and renal failure, not dribbling of urine.
❌ Ectopic kidney — refers to abnormal position of the kidney, not abnormal ureteric drainage.
❌ Ectopic bladder — incorrect term; the bladder itself is not misplaced here.
❌ Supernumerary kidney — extra kidney present, but ureteral opening remains normal.

The proximal part of the ureter receives its blood supply from the renal artery, which gives off small ureteric branches as it descends from the renal pelvis.
The blood supply to the ureter is segmental and varies along its length:

• Upper (proximal) part: from the renal artery

• Middle part: from the gonadal (testicular/ovarian) and abdominal aorta branches

• Lower part: from the superior vesical artery (branch of the internal iliac artery)

Why others are wrong:
❌ Suprarenal artery — supplies the adrenal gland, not the ureter.
❌ Gonadal artery — supplies the middle part, not proximal.
❌ Cystic artery — supplies the gallbladder, unrelated to ureter.
❌ Common iliac artery — gives no direct ureteric branches; lower ureter is supplied by internal iliac branches.

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.

From outside to inside, the coverings of the kidney are arranged as follows:

1️⃣ Paranephric (pararenal) fat — outermost layer, between posterior abdominal wall and renal fascia.
2️⃣ Renal fascia (Gerota’s fascia) — encloses kidney and adrenal gland; anchors them in place.
3️⃣ Perinephric (perirenal) fat — surrounds kidney and adrenal gland within the fascia, acting as cushioning.
4️⃣ Renal capsule — tough fibrous covering tightly adherent to kidney surface.

Why others are wrong:
❌ Other options mix up the order — particularly confusing paranephric and perinephric layers.

Renal columns of Bertin are extensions of cortical tissue that project between the renal pyramids into the medulla. They contain interlobar blood vessels and help separate adjacent pyramids, providing structural support for the renal cortex and medulla.

Why others are wrong:
❌ Marks beginning of nephron — the nephron begins at the renal corpuscle, not in the renal columns.
❌ Medullary substance that extends into cortex — reversed; it’s the cortex extending into the medulla.
❌ Nephrons that are drained by a common collecting duct — describes the organization within a renal lobule, not the columns.
❌ Convoluted parts of renal tubules — these are located in the renal cortex, not in the renal columns.