Flashcards in Week 3 Deck (12)
What are potential clinical manifestations of a nephrotic syndrome and what are their causes?
Edema – increased loss of albumin in the urine leads to reduced plasma oncotic pressure, resulting in decreased capillary absorption of fluid from the interstitial spaces
Hypercoagulability – due loss of antithrombin III in the urine
Increased infection susceptibility – due to loss of immunoglobulins in the urine
Hyperlipidemia – believed to be due to increased hepatic biosynthetic activity that occurs in response to reduced plasma protein levels, leading to increased lipoprotein synthesis; also may be due to impaired lipoprotein clearance
What are the three major causes of primary nephrotic syndrome, and how do their appearances differ on biopsy?
Minimal change disease – shows minimal change on light microscopy; shows podocyte foot process effacement on electron microscopy
Focal segmental glomerulosclerosis (FSGS) – shows sclerosis affecting portions of some glomeruli; electron microscopy shows loss of foot processes and podocyte detachment
Membranous nephropathy – light microscopy shows thickening of the glomerular basement membrane; electron microscopy shows subepithelial deposits and classically described as having a “spike-and-dome” appearance
How can Goodpasture Syndrome, pauci-immune glomerulonephritis, and immune complex-mediated glomerulonephritis be differentiated on renal biopsy?
Pauci-immune glomerulonephritis will not show significant staining on immunofluorescence microscopy due to the absence of immune complexes; it is instead typically diagnosed via serum measurements of anti-neutrophil cytoplasmic antibodies (ANCAs).
Goodpasture syndrome will show a linear staining pattern on immunofluorescence microscopy, as it is characterized by the presence of anti-GBM antibodies that directly attach to the GBM (a type II hypersensitivity).
Immune complex-mediated glomerulonephritis, such as that caused by lupus nephritis or post-streptococcal glomerulonephritis, will show a spotty/speckled pattern on immunofluorescence microscopy, which reflects the spotty deposition of antibody-antigen complexes in the glomerulus (a type III hypersensitivity).
What urinary finding suggests that hematuria originates from the glomerulus and not a more distal site?
Red blood cell casts
What two mechanisms prevent cells and proteins from being filtered in the glomerulus in a healthy kidney?
Size barrier: The fenestrations of the glomerular endothelium as well as the filtration slits of the podocyte foot processes form a size barrier that restricts filtration of substances greater than ~5-6 nm in size.
Charge barrier: The glomerular basement membrane has anionic glycosaminoglycans associated that serve to restrict filtration of negatively-charged substances, such as albumin.
Why is the kidney particularly susceptible to damage from thrombotic microangiopathies? What are potential protective mechanisms present in the kidney to prevent this damage?
The kidney has several features that make it vulnerable to TMA damage, including a high level of exposure to toxins/immune components due to high blood flow, high glomerular blood pressure, the presence of fenestrations in the vascular endothelium, and potential exposure of the highly thrombogenic glomerular basement membrane in the event of endothelial damage.
Protective mechanisms include the abundant presence of VEGF and complement inhibiting factors in the glomerulus as well as the presence of the protease ADAMTS13, which breaks down multimers of von Willebrand factor.
What does hypernatremia suggest about the patient’s water balance? What are potential causes?
Hypernatremia is generally indicative of increased serum tonicity caused by a negative water balance (water loss is greater than water intake). Causes can be categorized as being due to hypertonic intake or degree of water loss.
Non-Polyuric: Can be caused by an inability to consume water when serum osmolarity is high (common in elderly patients with difficulty independently drinking when thirsty); osmotic diarrhea, in which large amounts of free water are lost, can be another cause. These causes can be thought of as the kidneys doing everything right, but lack of water intake as well as ongoing water losses result in hypernatremia.
Polyuric: Commonly caused by diabetes insipidus, where water is not being appropriately reabsorbed in the kidney.
Hypertonic Na Gain: Caused by disorders that lead to excess sodium retention, including primary hyperaldosteronism. This is a much less common reason for hypernatremia.
What genetic polymorphism commonly found in individuals of African descent is associated with an increased risk of chronic and end stage kidney disease? Why does this polymorphism persist in the population?
The G1 and G2 alleles of the APOL1 gene are high-risk variants for kidney disease commonly found in individuals of African descent. They persist in the population because heterozygosity of these alleles provides a survival advantage against African trypanosomiasis (African sleeping sickness), creating a selective pressure for their preservation.
What extrarenal manifestations are common in patients who have autosomal dominant polycystic kidney disease?
Mitral valve prolapse, cerebral berry aneurysms, and hepatic cysts are common extrarenal findings in ADPKD.
How do mutations in the PKD genes lead to the findings observed in autosomal dominant polycystic kidney disease?
It is believed that mutations in the PKD genes lead to abnormal cell-cell and cell-matrix interactions that result in an abnormal extracellular matrix, alteration of cell growth patterns, and increased fluid secretion.
How do loop and thiazide diuretics affect calcium reabsorption? What is the mechanism of this effect?
Loop diuretics decrease calcium reabsorption (and thus increase the risk for calcium-based kidney stones). This occurs because, normally, the Na-K-2Cl transporter helps to establish an electrical gradient between the tubule of the loop of Henle and the peritubular capillaries, providing a driving force for the paracellular reabsorption of calcium. By inhibiting the Na-K-2Cl transporter, loop diuretics abolish this electrical gradient and thus reduce calcium reabsorption.
Thiazide diuretics increase calcium reabsorption (and can thus be used as a treatment for calcium-based kidney stones). This occurs because, by inhibiting the Na-Cl transporter in the distal convoluted tubule, the intracellular Na concentration decreases. This in turn drives an increase in activity of the Na-Ca exchanger on the basolateral surface of the cell, pushing more calcium into the peritubular capillaries. This reduces the intracellular calcium concentration , creating a driving force for the reabsorption of calcium from the tubular lumen.