MICROBIOLOGGY AND LAB ANALYSIS
A 25-year-old non-pregnant woman with a history of vesicoureteric reflux and recurrent urinary tract infections presents with a 3-day history of dysuria, urinary frequency, urgency and suprapubic pain. An MSU specimen is collected before antibiotics are started.
Urine dipstick
Urine culture
Question 1.1: What is the most likely diagnosis?
Question 1.2: Which two dipstick findings support a urinary tract infection?
Question 1.3: Is this UTI likely to be complicated or uncomplicated?
Answers:
Question: Which cells in the kidney produce renin?
Juxtaglomerular cells
Question: What three processes are involved in drug elimination by the kidneys?
Question: Why do immune-mediated glomerular diseases occur? Name the three main causes.
Answer:
Immune-mediated glomerular diseases occur when the immune system mistakenly causes damage to the glomeruli, the filtering units of the kidney. In most cases, the injury is caused by immune complexes, complement activation, and type III hypersensitivity reactions which occur as a result of the first two.
Question: A patient with liver failure develops confusion due to high ammonia levels. Why?
Answer:
Ammonia depletes α-ketoglutarate. α-ketoglutarate is a key intermediate in the Krebs cycle so depletion in it will lead to Krebs cycle impairment, reducing ATP produced, affecting the brain and causing confusion.
A 25-year-old non-pregnant woman with a history of vesicoureteric reflux and recurrent urinary tract infections presents with a 3-day history of dysuria, urinary frequency, urgency and suprapubic pain. An MSU specimen is collected before antibiotics are started.
Urine dipstick
Urine culture
Question: Give two reasons why a urine dipstick test might produce a false negative nitrite test.
Answer:
Question: How can you distinguish the distal convoluted tubule from the proximal convoluted tubule under the microscope?
Answer (Any of each):
Question: What class of drugs often require a higher dose in patients with renal failure?
Answer:
Loop diuretics
Question: What are the characteristic findings on Electron Microscopy and Immunofluorescence for Acute Post-Infectious Glomerulonephritis (APGN)?
Answer:
EM: Large, subepithelial electron-dense "humps". IF: Granular "starry sky" deposits of IgG and C3 along capillary walls and mesangium.
Question 1.1: Where do the major nitrogenous waste products come from?
Question 1.2: Which nitrogenous waste product is the biggest indicator of GFR: Urea or Creatinine? Why? List factors of each marker
Answer 1.1:
Answer 1.2:
Creatinine
Urea
Question: Why are ASOT and anti-DNase B titres useful in diagnosing acute post-streptococcal glomerulonephritis even though they do not diagnose active infection?
Answer:
These antibody tests provide evidence of a recent streptococcal infection, which is necessary because APSGN develops after the infection has resolved. They support the diagnosis but do not indicate that bacteria are still present.
Question: Starting at the renal artery, describe the complete pathway of blood until it leaves the kidney via the renal vein.
Renal artery → Segmental arteries → Interlobar arteries → Arcuate arteries → Interlobular arteries → Afferent arteriole → Glomerulus → Efferent arteriole → Peritubular capillaries (or vasa recta) → Interlobular veins → Arcuate veins → Interlobar veins → Renal vein.
Question: What is aciclovir nephrotoxicity caused by?
Answer:
By crystals
Aciclovir nephrotoxicity is caused by precipitation of aciclovir crystals in the renal tubules, resulting in crystal-induced obstructive nephropathy (acute kidney injury).
Question: Which specific cell types proliferate to form the crescents in Rapidly Progressive Glomerulonephritis (RPGN)?
Answer:
Parietal epithelial cells of Bowman's capsule and infiltrating monocytes/macrophages.
Question: Why can a patient with severe heart failure develop acute kidney injury even though the kidneys are receiving more total body fluid than normal?
Question 1.1: Why is acute post-streptococcal glomerulonephritis considered an immune-mediated disease rather than a direct bacterial infection of the kidney?
Question 1.2: Explain why serum C3 is decreased in acute post-streptococcal glomerulonephritis and describe its clinical significance.
Answer 1.1:
The kidneys are damaged by immune complex deposition and complement activation rather than by direct invasion of the kidney by streptococci. By the time nephritis develops, the original infection has usually resolved.
Answer 1.2:
C3 is decreased because it is consumed during activation of the alternative complement pathway by immune complexes. A low C3 level supports the diagnosis of APSGN and usually returns to normal within 6–8 weeks.
Question 1.1: What two structures form the permanent kidney?
Question 1.2: Why does a horseshoe kidney remain lower than normal?
Answer 1.1:
The ureteric bud and metanephric mesenchyme.
Answer 1.2:
Its fused lower poles become trapped beneath the inferior mesenteric artery.
Describe how the kidneys maintain fluid and electrolyte homeostasis. In your answer, explain the role of glomerular filtration, tubular reabsorption, tubular secretion, and hormonal regulation (ADH and aldosterone).
The kidneys maintain fluid and electrolyte homeostasis by regulating the volume and composition of the extracellular fluid.
The nephron performs four basic processes:
Hormones regulate the final composition of urine:
Through these mechanisms, the kidneys regulate extracellular fluid volume, osmolarity, electrolyte concentrations, and blood pressure.
Question: How do the macroscopic renal scars of Chronic Pyelonephritis differ from typical vascular scars?
Answer:
Chronic pyelonephritis scars are coarse, irregular, asymmetric scars that directly overlie blunted or deformed calyces (vascular scars are typically V-shaped, superficial, and do not deform the underlying calyces).
During sepsis, patients often develop acute kidney injury even when there is no obstruction or direct damage to the kidneys. Explain the mechanisms responsible.
Question: The urine culture reports pure bacterial growth (<10⁴ CFU/mL). Is this result clinically significant? Explain your answer and state the next appropriate step.
Answer:
This is likely clinically significant. Although bacteriuria of <10⁴ is typically considered insignificant in a properly collected MSU, urine culture results should always be interpreted in conjunction with the patient's clinical presentation and other lab findings. In this case, the presence of 3+ leucocytes on dipstick and the absence of squamous epithelial cells on urine microscopy support a true urinary tract infection rather than contamination.
A 28-week premature infant is born with bilateral renal agenesis. Explain, with precise reference to developmental timing, tissue interactions, and sequential kidney systems, why this condition is incompatible with extrauterine life
Bilateral renal agenesis results from failure of reciprocal induction between the ureteric bud and metanephric mesenchyme during the 5th week of embryonic development, preventing formation of the permanent kidneys. Although the pronephros and mesonephros develop earlier, they are either non-functional or only transiently functional and cannot support postnatal life. Absence of metanephric kidneys prevents fetal urine production from approximately 9–10 weeks, causing severe oligohydramnios, which leads to pulmonary hypoplasia (Potter sequence). Consequently, the infant is born without functional kidneys and with severely underdeveloped lungs, making extrauterine life incompatible with survival.
A patient with chronic kidney disease presents with fluid overload, hyperkalaemia, metabolic acidosis, and hypertension. Using your knowledge of renal physiology, explain how impaired kidney function leads to each of these abnormalities.
Chronic kidney disease causes a progressive loss of functioning nephrons, reducing the kidneys' ability to regulate fluid, electrolytes, and acid-base balance.
1. Fluid overload
Reduced GFR decreases filtration of sodium and water. Excess sodium and water are retained, expanding extracellular fluid volume and causing peripheral oedema and pulmonary oedema.
2. Hyperkalaemia
Normally, potassium is secreted by principal cells in the distal tubule and collecting duct. In CKD, reduced nephron number and decreased tubular secretion result in potassium retention, leading to hyperkalaemia, which increases the risk of life-threatening cardiac arrhythmias.
3. Metabolic acidosis
The kidneys are unable to:
As a result, acid accumulates and plasma bicarbonate falls, producing metabolic acidosis.
4. Hypertension
Reduced sodium and water excretion causes expansion of blood volume. In addition, impaired renal perfusion activates the renin–angiotensin–aldosterone system (RAAS), producing vasoconstriction and further sodium retention, increasing blood pressure.
Overall physiological consequence
Loss of nephron function impairs the kidneys' ability to:
This explains why patients with CKD commonly present with fluid overload, hyperkalaemia, metabolic acidosis, hypertension, and eventually uraemia.
A 58-year-old man develops acute kidney injury (AKI) following severe dehydration from gastroenteritis. Two days later, he has reduced urine output, ankle oedema, and a blood pressure of 165/95 mmHg.
His blood tests show:
Using your knowledge of renal physiology, explain the mechanisms responsible for each of the patient's clinical signs and biochemical abnormalities. In your answer, relate your explanation to the effects of reduced glomerular filtration rate (GFR) and impaired kidney function.
Acute kidney injury causes a reduced glomerular filtration rate (GFR) and impaired tubular function, resulting in:
Overall: Reduced GFR and impaired tubular function prevent the kidneys from maintaining normal fluid, electrolyte, and acid–base homeostasi
Question: A patient with nephrotic syndrome has massive proteinuria, oedema, and hyperlipidaemia. Explain how damage to podocytes eventually leads to each of these findings.
Massive Proteinuria (Protein in Urine)
Oedema (Severe Swelling)
Hyperlipidaemia (High Blood Cholesterol/Lipids)