Congenital renal disorders: Pathology review

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Congenital renal disorders: Pathology review

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Development of the renal system
Ureter, bladder and urethra histology
Kidney histology
Renal system anatomy and physiology
Body fluid compartments
Hydration
Movement of water between body compartments
Horseshoe kidney
Renal agenesis
Potter sequence
Posterior urethral valves
Multicystic dysplastic kidney
Polycystic kidney disease
Vesicoureteral reflux
Alport syndrome
Urinary incontinence
Urinary incontinence: Pathology review
Neurogenic bladder
Bladder exstrophy
Antidiuretic hormone
Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Diabetes insipidus and SIADH: Pathology review
Diabetes insipidus
Nephrotic syndromes: Pathology review
Nephritic and nephrotic syndromes: Clinical
Nephritic syndromes: Pathology review
Minimal change disease
Hydronephrosis
Glomerular filtration
Measuring renal plasma flow and renal blood flow
Renal clearance
TF/Px ratio and TF/Pinulin
Regulation of renal blood flow
Sodium homeostasis
Kidney countercurrent multiplication
Urea recycling
Tubular reabsorption and secretion
Tubular reabsorption and secretion of weak acids and bases
Tubular secretion of PAH
Tubular reabsorption of glucose
Distal convoluted tubule
Loop of Henle
Proximal convoluted tubule
Renin-angiotensin-aldosterone system
Free water clearance
Amyloidosis
IgA nephropathy (NORD)
Poststreptococcal glomerulonephritis
Rapidly progressive glomerulonephritis
Lupus nephritis
Potassium homeostasis
Hypophosphatemia
Hyperphosphatemia
Hypermagnesemia
Hypomagnesemia
Hypocalcemia
Hypercalcemia
Hyperkalemia
Hypokalemia
Hyponatremia
Hypernatremia
Phosphate, calcium and magnesium homeostasis
The role of the kidney in acid-base balance
Acid-base disturbances: Pathology review
Physiologic pH and buffers
Renal tubular acidosis
Renal tubular acidosis: Pathology review
Metabolic acidosis
Metabolic and respiratory acidosis: Clinical
Respiratory acidosis
Metabolic alkalosis
Plasma anion gap
Respiratory alkalosis
Metabolic and respiratory alkalosis: Clinical
Acid-base map and compensatory mechanisms
Ornithine transcarbamylase deficiency
Kidney stones: Pathology review
Nitrogen and urea cycle
Goodpasture syndrome
Erythropoietin
Vitamin D
Kidney stones
ACE inhibitors, ARBs and direct renin inhibitors
Kidney stones: Clinical
Hypokalemia: Clinical
Renal tubular defects: Pathology review
Urinary tract infections: Clinical
Urinary tract infections: Pathology review
Lower urinary tract infection
Proteus mirabilis
Staphylococcus saprophyticus
Enterobacter
Klebsiella pneumoniae
Serratia marcescens
Pseudomonas aeruginosa
Renal artery stenosis
Thiazide and thiazide-like diuretics
Carbonic anhydrase inhibitors
Osmotic diuretics
Loop diuretics
Potassium sparing diuretics
Acute kidney injury: Clinical
Renal azotemia
Postrenal azotemia
Prerenal azotemia
Chronic kidney disease
Acute tubular necrosis
Renal papillary necrosis
Medullary cystic kidney disease
Chronic kidney disease: Clinical
Congenital renal disorders: Pathology review
Medullary sponge kidney
Chronic pyelonephritis
Acute pyelonephritis
Neisseria gonorrhoeae
Chlamydia trachomatis
Urethritis
Prostatitis
Schistosomes
Hemolytic-uremic syndrome
Thrombotic thrombocytopenic purpura
Renal cortical necrosis
Renal cell carcinoma
Angiomyolipoma
WAGR syndrome
Nephroblastoma (Wilms tumor)
Non-urothelial bladder cancers
Transitional cell carcinoma
Electrolyte disturbances: Pathology review
Renal failure: Pathology review
Renal and urinary tract masses: Pathology review
Transplant rejection
Graft-versus-host disease
Non-corticosteroid immunosuppressants and immunotherapies
Hypertension
BK virus (Hemorrhagic cystitis)

Assessments

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Questions

USMLE® Step 1 style questions USMLE

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A 25-year-old female comes to the primary care physician for a follow-up appointment. The patient is currently asymptomatic and denies increased urinary frequency or dysuria. However, she has had multiple urinary tract infections during the past year, each of which resolved with antibiotic therapy. Additionally, the patient has had 3 episodes of calcium oxalate nephrolithiasis treated with conservative measures. She is sexually active, in a monogamous relationship, and uses condoms consistently. Temperature is 37.0°C (98.6°F), pulse is 65/min, and blood pressure is 120/80 mmHg. Physical examination shows no abnormalities. Urinalysis and IV pyelography are obtained and the results are shown below:  
 
 Urine  
 Color  Yellow 
 Clarity  Clear 
 Erythrocytes  8/hpf 
 Leukocytes  2/hpf 
 pH   5.5 
 Nitrates  Negative 
 Glucose   Negative 
 Protein  Negative 
 Bacteria   None 
 Sediment   None 


Image reproduced from Radiopedia  
Which of the following is the most likely underlying cause of this patient condition?  

Transcript

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Two people came to the Nephrology ward one day.

The first is 29 year old Dan, who presents with hypertension, gross hematuria, and flank pain.

Dan’s family history showed that his grandmother died of a berry aneurysm.

Next is 35 year old Heather.

She doesn’t present have any symptoms, but she has been referred to the nephrology clinic because her primary care doctor discovered that she her kidneys have a “weird shape” on an abdominal x-ray.

Both individuals underwent abdominal ultrasound.

Dan had many cysts of different sizes on both kidneys, while Heather’s kidneys are located lower than normal and appear fused together.

Both Dan and Heather have congenital renal disorders.

The renal system starts developing during week 4 of intrauterine life.

It comes from the mesoderm, which is one of the three primitive germinal layers.

More specifically, it develops from a portion of the mesoderm called the intermediate mesoderm.

The intermediate mesoderm on either side of the embryo condenses to form a cylindrical structure called the urogenital ridge, and a portion of the urogenital ridge called the nephrogenic cord gives rise to urinary structures.

During renal development, the nephrogenic cord gives rise to three sets of structures: the nonfunctional pronephros in the embryo’s head region which regresses by the end of week 4.

Then, the mesonephros forms, appears in the thoracic and upper lumbar region and acts as temporary kidneys until they regress in week 12.

Finally the metanephros develops in the pelvic region, and it forms the permanent kidneys.

Ok, the metanephros sprout small buds called the ureteric buds.

At the same time, the intermediate mesoderm gives rise to another tissue called the metanephric blastema.

The blastema release growth factors that stimulates the ureteric bud to become the ureter, the renal pelvis, the renal calyces, and the collecting ducts.

Meanwhile, the ureteric bud release growth factors that cause the metanephric blastema to develop into nephrons.

At around week 20, the metanephric kidneys take over urine production, this becomes the major source of amniotic fluid.

As they continue to grow, they move up from the pelvis to reach their adult position.

Okay, so if there’s a problem during the development of the kidneys we can get oligohydramnios, or a deficiency of amniotic fluid.

As a result, a number of things can happen leading to the so called Potter sequence.

With less amniotic fluid, there’s pulmonary hypoplasia.

Not only that though, with less amniotic fluid, there’s less space in the amniotic sac, and so the fetus is literally compressed into a smaller space, which causes developmental abnormalities like a flattened face, wrinkly skin, low-set ears, as well as limb abnormalities like clubbed feet.

Some renal conditions make it impossible for urine to be excreted, in which case there will also be renal failure in utero.

Okay, now, one high yield fact is remembering the specifics for Potter sequence.

We have a mnemonic for that: P is for Pulmonary hypoplasia, O is for oligohydramnios, first T is for Twisted face, second T is for Twisted skin, E is for extremity defects and R is for renal failure.

Okay, let’s now let’s talk about each of the congenital renal disorders.

To make things easier, we can split them into cystic and non-cystic disorders.

The first cystic congenital renal disorders is polycystic kidney disease.

Based on the the inheritance pattern, this can further be split into autosomal recessive polycystic kidney disease or ARPKD, and autosomal dominant polycystic kidney disease or ADPKD.

With ARPKD, someone inherits a mutation on both copies of the PKHD1 gene, which codes for the fibrocystin protein.

Fibrocystin is found in the collecting ducts, as well as in the epithelial cells of the hepatic bile duct.

The lack of fibrocystin leads to cystic dilation of the collecting ducts in both kidneys.

Individuals with ARPKD can develop Potter sequence in utero, and the most common cause of death in these individuals is pulmonary hypoplasia.

If they don’t develop Potter sequence, then after birth, they develop progressive renal failure and systemic hypertension.

The liver is also affected and they can have congenital hepatic fibrosis which leads to portal hypertension.

Autosomal dominant polycystic kidney disease, or ADPKD, is more common and symptoms usually develop in adulthood.

ADPKD is an inherited genetic disorder mostly caused by mutations in the PKD1 gene, but mutations can also happen in the PKD2 gene. Now, PKD1 and PKD2 code for the polycystin 1 and polycystin 2 proteins, respectively.

In the nephron, polycystin 1 and 2 inhibit cell growth and proliferation through signaling pathways that’s not well understood.

Now, a person who develops ADPKD would have inherited a single mutation in PKD1 or PKD2.

This leaves one functional copy of the gene in every cell, which allows for the production of polycystin 1 or polycystin 2.

However, there is something called the “second hit” theory.

This means that a random mutation can occur in the remaining good copy of the gene later in life.

This disrupts the regulation of renal cell growth and proliferation, leading to cyst formation.

Overtime, these cysts will fill with fluid and enlarge, causing damage to the surrounding tissue, hypertension, and flank pain.

Eventually this will cause kidney damage.

Now, if there’s hypertension and signs of kidney damage like proteinuria, the best treatment is with ACE inhibitors or ARBs.

Now, it’s important to remember ADPKD affects other organ systems too!

Individuals can have cysts pop up in the liver too, which will lead to liver failure.

They are also more likely to develop berry aneurysms in the cerebral arteries, usually in the Circle of Willis.

These can rupture and cause subarachnoid hemorrhage.

Some individuals may also present mitral valve prolapse or diverticulosis.

For you tests, some clinical clues that should make you think of ADPKD include flank pain, hematuria, hypertension and a family history of sudden death due to aneurysms.

Sources

  1. "Robbins Basic Pathology" Elsevier (2017)
  2. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
  3. "Practical Renal Pathology, A Diagnostic Approach E-Book" Elsevier Health Sciences (2012)
  4. "Campbell-Walsh Urology" Elsevier Health Sciences (2015)
  5. "Ultrasonography of the Kidney: A Pictorial Review" Diagnostics (2015)
  6. "Renal Cystic Diseases" Advances in Anatomic Pathology (2006)
  7. "Kallmann syndrome: phenotype and genotype of hypogonadotropic hypogonadism" Metabolism (2018)