Congenital Anomalies, Cystic Diseases of the Kidney and Hereditary Nephritis- Dr. Trif (Final Exam)

Terms in this set (35)

What are the 3 sequential developmental phases to form the urogenital system?
1) Pronephros: arises at 3 wks as segmental collections of mesoderm in the cervical region. Attached to paired pronephric ducts. It is nonfunctional in humans and undergoes regression at 4 wks.
2) Mesonephros: begins to develop as pronephros degenerates. Consists of glomeruli and mesonephric tubules which open into paired mesonephric (Wolffian) ducts, which are continuations of the pronephric ducts. It forms elongated interim kidneys that produce little, if any, urine in humans and undergoes regression at 5 weeks.
3) Metanephros: the permanent kidneys begin to develop as the mesanephros degenerates. Result from interaction b/w ureteric bud, a diverticulum from the mesonephric duct, and the metanephric mesenchyme (metanephric blastema). The collecting tubules, collecting ducts, calyces, renal pelvis and the ureter are all derived from ureteric bud. The collecting tubules induce the surrounding mesenchyme to grow and become tubules that form parts of the nephron: glomerulus, Bowman's capsule, convoluted tubules and the loop of Henle.
Ascent of the kidneys
At 5-6 weeks the mature kidneys lie in the pelvis with their hilus directed anteriorly. With continued growth and elongation of the embryo, the kidneys move upward and eventually lie in a retroperitoneal position in the abdomen rotated so that the hilus face antero-medially. As the kidneys ascend, new blood vessels arise sequentially from the iliac artery, the distal aorta and finally, the upper abdominal aorta.
What is renal agenesis?
Failure of one or both kidneys to develop, usually due to ureteric bud degeneration and/or failure to reach the metanephric blastema.
1) Unilateral: more common, and compatible w/ life--> existing kidney undergoes compensatory hypertrophy
2) Bilateral: babies afflicted die shortly after birth. One of the causes of reduced formation of amniotic fluid (oligohydramnios) and is associated with Potter Syndrome.
What is Potter Syndrome (sequence)?
1) Potter facies- flattened nose, recessed chin, prominent epicanthal folds, and low set abnormal ears
2) Pulmonary hypoplasia
3) Other malformations including skeletal (sirenomelia=mermaid syndrome), opthalmologic, abdominal and CV
4) Assoc. with bilateral agenesis
What is renal hypoplasia?
Condition in which there is a reduction in renal mass and # of nephrons, usually unilateral. When bilateral, kidneys are functional for 5-10 yrs. Constitute 20% of juvenile population on dialysis.
What is oligomeganephronia?
Small kidneys with exceptionally hypertrophied nephrons.
What is renal dysplasia?
A defect in nephrogenesis that produces abnormal cells and tissues. These kidneys contain islands of undifferentiated mesenchyme, primitive glomeruli and tubules and sometimes cartilage. From abnormal development of the renal vasculature, renal tubules, collecting ducts or the drainage apparatus-->cystic tissue occurs inversely proportional to amt of fibrous tissue.
Kidneys vary from very small to very large.
When bilateral, renal function is severely affected resulting in oligohydramnios and Potter syndrome. Renal dysplasia represents a continuum b/w renal aplasia and multi cystic dysplastic kidneys.
What is renal duplication?
If 2 ureteric buds arise from the mesonephric duct, or if a single bud divides into 2 branches before it enters the metanephric blastema, a duplication occurs.
1) Complete: two separate ureters drain separate parts of the kidney, usually upper pole and lower pole. The lower pole ureter is at increased risk of reflux.
2) Partial: two ureters join before reaching the bladder
What are ectopic kidneys?
When one or both kidneys fail to ascend to their retroperitoneal location. The most common form is the pelvic kidney.
When both kidneys fail to ascend, they fuse due to limited space in the pelvic cavity, causing fusion anomalies.
What is a horseshoe kidney?
The MC fusion anomaly. Partial fusion at one of the poles (usually the lower poles) form a horseshoe that is unable to ascend bc it is blocked by the inferior mesenteric artery.
What is a crossed fused renal ectopia?
2nd MC fusion anomaly that occurs when the renal parenchyma of both kidneys ends up on the same side of the vertebral column. One of the ureters crosses the midline to enter the bladder on the opposite side.
What is a pancake kidney?
Fused pelvic kidney. Total fusion of the two kidneys results in a pancake like structure.
What arterial abnormalities can occur in the developing kidneys?
As the kidneys ascend, they receive branches sequentially from the iliac artery, distal aorta and finally the abdominal aorta. With the exception of the abdominal branches (the renal arteries) all other branches usually undergo recession. However, some can persists as accessory renal arteries. When multiple arteries occur, each artery supplies a distinct segment of the kidney. Since there is no collateral circulation, occlusion of one artery will result in infarction but will be limited to the assoc. segment.
What venous abnormalities occur in the developing kidneys?
Multiple renal veins may also occur, but unlike the arteries, they interconnect in the kidney. If one renal vein becomes occluded, the other veins will continue drainage.
What is hydronephrosis?
During development, the uretero-pelvic junction may become malformed or have abnormal peristalsis, so that urine flow is obstructed. This results in pooling of fetal urine within the pelvis.
Mild--> children usually have no symptoms. Condition may disappear within 1st year of life
Moderate--> usually maintain normal kidney function and may improve with time
Severe--> damage to normal kidney fxn can occur, but effects may take months or years to occur.
What are renal cysts?
Epithelial lined cavities filled with fluid. They develop mainly from renal tubular elements.
What are simple (solitary) cysts?
Single or multiple cysts found at the outer cortex. They are common, being found in about half of those >50 yo. Typically asymptomatic but can become infected. It is important to differentiate them from malignancy, abscesses or polycystic kidney disease.
What is Multicystic dysplastic kidney?
Aka cystic renal dysplasia, Potter Type II.
Although, relatively rare, it is the MC cystic disorder in children and is a frequent cause, second only to hydronephrosis, of an abdominal mass in the neonate. There is a sporadic inheritance pattern.
What is the clinical appearance of multi cystic dysplastic kidney?
a) unilateral abdominal mass is MC finding
b) bilateral abdominal mass may occur
c) renal failure
d) may present with oligohydramnios and Potter syndrome
Gross: kidney resembles a bunch of grapes with a mass of cysts filled with clear fluid. Usually there is associated ureteral atresia.
Micro: similar to that of renal dysplasia, but with numerous large epithelial lines cysts. The inter-cystic tissue is the same with islands of undifferentiated mesenchyme, primitive glomeruli, tubules and sometimes cartilage.
There is a continuum from renal aplasia to renal dysplasia to multi cystic dysplastic kidney.
What are polycystic kidney diseases?
Inherited multi-sustemic disorders characterized in the kidney by multiple bilateral cysts of varying sizes.
What is Autosomal Dominant Polycystic Kidney Disease?
Aka adult polycystic kidney disease or Potter Type III
1/1,000 adults
Genetics:
a) PKD 1 locus on chromosome 16 (85-90% of cases)
b) PKD 2 locus on chromosome 4 (10-15% of cases)
c) There may be other loci for this disease since in some cases no linkage to either PKD1 or PKD2 has been reported
Clinical: may be asymptomatic until middle age, palpable bilateral abdominal masses, lumbar pain, renal infections, hematuria, HTN, nephrolithiasis, progressive renal failure
Gross: massively enlarged kidneys with large cysts filled w/ serous, turbid or hemorrhagic fluid.
Micro: multiple epithelial lined cysts, adjacent nephrons in various stages of degeneration
What are the associated manifestations with PKD and what is the prognosis?
-Liver cysts in 40-60% of cases
-Lung, spleen and pancreatic cysts
-*Berry aneurysms in the Circle of Willis
-Mitral valve prolapse, aortic aneurysms, aortic valve abnormalities*
Prognosis:
-Pts w/ PKD2 mutation have a slower progression of the disease and a longer life expectancy than those with mutated PKD1. Renal failure ultimately occurs in both cases in those that survive the related conditions.
What is autosomal recessive polycystic kidney disease?
Aka: Infantile PKD, Potter Type I
Rare (1/10,000)
Linked to mutations in the PKHD1 locus on chromosome 6.
Clinical manifestations depend on the age at which the disease occurs:
1) Perinatal: severe form, MC, usually ends in death shortly after birth as a result of pulmonary hypoplasia secondary to the effects of renal dysfunction and oligohydramnios (Potter syndrome)
2) Infantile: less severe form is characterized mainly by HTN and progressive renal failure
3) Juvenile: least severe is dominated by hepatic related conditions. Renal involvement continues, but at a slower rate eventually leading to renal failure. Cirrhosis--> portal HTN; splenomegaly
What is the pathology of infantile PKD?
Gross: kidneys, in contrast to those in ADPKD, are smooth and enlarged. Dilated elongated cystic channels can be observed in cut sections that are oriented in a radial fashion with their long axis at right angles to the capsule.
Micro: Cysts in the kidney have a uniform cuboidal lining w/ a cylindrical or saccular dilation of the collecting tubules. Cysts are present in the liver along with portal fibrosis (congenital hepatic fibrosis)
Prognosis: In those who survive past the perinatal period, morbidity and mortality are mainly related to severe HTN, renal failure and portal HTN secondary to hepatic fibrosis
What is medullary sponge kidney?
Genetic component.
Clinical: usually asymptomatic w/ normal renal function; some pts dev. hematuria, renal stone development and/or infections.
Gross: superficially normal that reveal dilated papillary ducts and small cysts in the medulla in cut section giving it a sponge-like character
Micro: Cystic dilation of the collecting tubules in one or more renal pyramids in one or both kidneys. These cysts frequently contain calculi.
Prognosis: Normal life expectancy in vast majority. Few cases with renal failure.
What is Nephronophthisis?
Aka Medullary Cystic Disease Complex
A group of rare progressive renal disorders occurring mostly in children characterized by cystic involvement of the medulla--> tubulointerstitial damage is the common denominator in all forms.
4 variants of the disease complex:
1) Non-familial or sporadic (20%)
2) Familial juvenile nephronophthisis (40-50%)- autosomal recessive
3) Renal-retinal dysplasia (15%)- autosomal recessive, assoc with retina degeneration
4) Adult onset medullary cystic disease (15%)- autosomal dominant
Genetics and clinical signs of nephronophthisis?
Mutations involving 3 gene loci: NPH1, NPH2, and NPH3 w/ recessive transmission are involved in the juvenile form.
Clinical: progressive symmetrical destruction of the kidneys mainly involving the tubules--> anemia, polyuria, polydipsia and progressive renal failure.
Pathology of medullary cystic disease complex?
Gross: kidneys are small with a granular surface. Cut sections show cysts in the medulla especially at the portico-medullary junction
Micro: Cysts are lined by squamous or cuboidal epithelium and are surrounded by inflammatory cells or fibrous tissue. Atrophy and thickening of the BM of the proximal and distal tubules is observed together with interstitial fibrosis.
Onset: in the juvenile forms, kidney failure develops anywhere from 3-19 years. Adult forms develop between 20-70 years.
What is acquired cystic disease?
Patients who have received prolonged dialysis will often develop multiple cortical and medullary cysts. Many of the pts will be asymptomatic, but occasionally hematuria occurs as cysts bleed. Pts with acquired cystic disease are at increased risk of developing RCC.
What is hereditary nephritis?
A group of inherited renal diseases involving glomerular injury.
Alport syndrome is the MC.
What is Alport syndrome?
The MC hereditary nephritis characterized by renal, cochlear and ocular involvement.
Mutations in the type IV collagen genes (COL4A5, COL4A3, COL4A4)
a) X-linked (80%)- COL4A5
b) Autosomal recessive (15%)
c) Autosomal dominant (5%)
d) Sporadic cases
What are the clinical findings of Alport syndrome?
Clinical: Chronic hematuria begins in infancy in males with X-linked form.
Cochlear signs: 80% of males will develop deafness affecting both ears at some point in their lives. Females may develop deafness, but less frequently and later in life.
Ocular: 15% of male pts will develop defects affecting both eyes (Anterior lenticonus, cataracts, blindness)
Prognosis: females are usually asymptomatic, while males develop symptoms at ages 5-20 and renal failure between ages 20-50.
What are the pathological findings of Alport Syndrome?
Gross: kidneys appear normal throughout most of the course of the disease
Micro: Early changes only seen with EM; diffuse glomerular BM (GBM) thinning; interstitial foam cells.
Fully dev. disease: areas of thickening alternating with thinning of the GMB
Splitting of the lamina densa into lemma w/ surrounding lucent areas, like a basket weave appearance.
LM of fully developed disease:
*1) Focal segmental and global glomerulosclerosis
2) Vascular sclerosis
3) Tubular atrophy
4) Interstitial fibrosis*
Immunohistochemistry: in X-linked form there is a lack of alpha3, alpha4, and alpha5 collagen in the GBM and TBM
What is Fabry disease?
A deficiency of lysomsomal α-galactosidase A*; X-linked recessive syndrome.
All the lesions are generated by an accumulation of globotriaosyl ceramide and other glycosphingolipids in the endothelium of the brain, heart, skin, kidneys.
Clinical: Children (avg. age 10) may experience episodic pain in hands and feet; recurrent fever; hyperhidrosis; heat and cold intolerance. Angiokeratoma skin tumors.
Dx is usually delayed until avg. age 30.
Progressive vascular insufficiency, then renal, cerebral and cardiac infarcts. Corneal and lenticular opacities, hearing loss and tinnitus, GI problems.
Prognosis: Die in early adulthood from vascular complications: renal insufficiency, cardiac dysfunction, CVD. Avg. age of death is 41.
What is the pathology of Fabry Disease?
Gross: kidneys appear normal during early years and become shrunken with advanced disease
Micro: Glycosphingolipid deposits are found in the glomerular, vascular and interstitial cells. Tubular involvement is primarily in the DCTs and loops of Henle. Glomeruli present with adundant podocyte inclusions (foamy podocyte cytoplasm) and segmental sclerosis. Tubular epithelial cells and interstitial macrophages present inclusions staining with silver. There are also cytoplasmic inclusions in SM cells of arteries.
With progressing disease, intimal thickening and degenerative glomerular and tubular changes are evident.
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