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Nephrotic and Nephritic Syndrome | Causes Symptoms & Treatment🩺

Dr. Najeeb Lectures・60 minutes read

The lecture series on phrenology will delve into renal system pathologies, specifically focusing on glomerular injuries such as glomerulonephritis, highlighting how these conditions lead to proteinuria and complications like edema and chronic renal failure. As glomerular damage progresses, it causes significant alterations in protein levels and renal function, ultimately resulting in severe clinical manifestations such as hypertension, oliguria, and uremia.

Insights

  • The lecture series will delve into the renal system's pathology, particularly focusing on glomerular injuries like glomerulonephritis, highlighting the importance of understanding the structure and function of nephrons, which are vital for kidney filtration, with each kidney containing around 1.2 million nephrons.
  • The glomerulus is a complex structure essential for filtration, composed of various components including the afferent and efferent arterioles, the glomerular basement membrane, and podocytes that create filtration slits. These features allow for selective filtration of substances based on size and charge, with healthy kidneys preventing protein leakage into urine.
  • Heavy proteinuria, defined as protein loss exceeding 3.5 grams per day, is a hallmark of nephrotic syndrome, which can lead to serious complications such as hypoalbuminemia, edema, and increased risk of infections and thrombosis due to the loss of essential proteins, demonstrating the critical impact of glomerular damage on overall health.
  • The transition from nephrotic to nephritic syndrome signifies a progression in renal injury, marked by symptoms like hematuria and oliguria, indicating a shift in the underlying pathology and emphasizing the need for careful monitoring and management of kidney health to prevent irreversible damage.

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Recent questions

  • What is nephrotic syndrome?

    Nephrotic syndrome is a kidney disorder characterized by heavy proteinuria, hypoalbuminemia, generalized edema, and hyperlipidemia. It results from significant damage to the glomeruli, which are the filtering units of the kidneys. In nephrotic syndrome, the glomerular filtration barrier becomes compromised, allowing large amounts of protein, particularly albumin, to leak into the urine. This loss of protein leads to low levels of albumin in the blood, causing fluid to accumulate in tissues, resulting in edema. Additionally, the liver attempts to compensate for the low protein levels by increasing protein synthesis, which can lead to elevated lipid levels in the blood, known as hyperlipidemia. Patients may also experience lipiduria, where lipids appear in the urine, giving it a frothy appearance. The condition can lead to various complications, including increased risk of infections and thrombosis due to the loss of important proteins that help maintain immune function and blood clotting.

  • How does edema form in nephrotic syndrome?

    Edema in nephrotic syndrome forms primarily due to the loss of plasma proteins, particularly albumin, which is crucial for maintaining osmotic pressure in the blood vessels. When the levels of these proteins drop, the osmotic pressure decreases, allowing fluid to leak from the blood vessels into the interstitial spaces, leading to fluid accumulation. This process is exacerbated by the kidneys' retention of sodium and water in response to low blood volume, which further dilutes the remaining proteins in circulation. The resulting imbalance between hydrostatic pressure, which pushes fluid out of the vessels, and oncotic pressure, which pulls fluid back in, leads to generalized edema. In nephrotic syndrome, this fluid accumulation is often most noticeable around the eyes (periorbital edema) and can spread throughout the body. The condition can also be classified into pitting and non-pitting edema, depending on how easily the fluid can be displaced by pressure.

  • What causes heavy proteinuria?

    Heavy proteinuria, defined as the loss of more than 3.5 grams of protein in urine per day, is primarily caused by damage to the glomeruli, the filtering units of the kidneys. In nephrotic syndrome, this damage can result from various underlying conditions, such as minimal change disease, focal segmental glomerulosclerosis, or membranous nephropathy. The glomerular filtration barrier, which normally prevents large proteins from passing into the urine, becomes compromised, allowing proteins like albumin and globulin to leak through. Initially, proteinuria may be selective, with only albumin present, but as the condition progresses, it can become non-selective, leading to the loss of a broader range of proteins. The severity of proteinuria is indicative of the extent of glomerular injury, and significant protein loss can lead to further complications, including hypoalbuminemia and edema.

  • What is the role of the kidneys in fluid balance?

    The kidneys play a crucial role in maintaining fluid balance in the body by regulating the volume and composition of blood. They filter blood through the glomeruli, where waste products and excess substances are removed, while reabsorbing essential nutrients and water back into the bloodstream. The kidneys respond to changes in blood volume and pressure by adjusting the reabsorption of sodium and water in the renal tubules. In conditions like nephrotic syndrome, where there is significant protein loss and reduced blood volume, the kidneys may retain more sodium and water to compensate, which can lead to fluid overload and edema. Additionally, the kidneys produce hormones such as renin, which activates the renin-angiotensin-aldosterone system (RAAS), further influencing fluid retention and blood pressure regulation. This intricate balance is vital for maintaining homeostasis and ensuring that the body's tissues receive adequate hydration and nutrients.

  • What are the complications of nephrotic syndrome?

    Nephrotic syndrome can lead to several serious complications due to the significant loss of proteins and the resulting physiological imbalances. One major complication is an increased risk of infections, as the loss of complement proteins in urine impairs the immune response, particularly against encapsulated bacteria. Patients may also experience thrombosis due to the loss of anticoagulant proteins like antithrombin III, which can lead to blood clot formation. Additionally, the condition can result in iron deficiency anemia due to the loss of transferrin, a protein responsible for iron transport. The persistent heavy proteinuria and hypoalbuminemia can lead to severe edema, impacting the patient's quality of life. Furthermore, chronic nephrotic syndrome can progress to chronic renal failure, characterized by irreversible damage to the kidneys and a decline in their ability to filter waste products from the blood. This progression underscores the importance of careful management and monitoring of patients with nephrotic syndrome to mitigate these risks.

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Summary

00:00

Understanding Glomerular Pathologies and Proteinuria

  • The lecture series on phrenology will focus on the pathology of the renal system, specifically glomerular injuries, including glomerulonephritis and glomerular pathologies.
  • Each kidney contains approximately 1.2 million nephrons, totaling about 2 to 2.5 million nephrons across both kidneys, which are essential for filtration.
  • The glomerulus consists of an afferent arteriole bringing blood in, an efferent arteriole taking blood out, a glomerular basement membrane, Bowman's capsule, and mesangial connective tissue.
  • The filtration membrane in the glomerulus has three components: endothelial cells, the basement membrane, and epithelial cells, with endothelial cells featuring fenestrations (pores) sized 70-200 nanometers.
  • Epithelial cells, specifically podocytes, have filtration slits between their foot processes, which are about 20-30 nanometers wide, allowing selective filtration based on size and charge.
  • Plasma proteins, such as albumin, are normally repelled by the negatively charged filtration membrane, preventing their leakage into urine under healthy conditions.
  • In cases of mild glomerular injury (grade one), only small molecules like albumin may leak into urine, resulting in a condition known as selective proteinuria.
  • With more severe injury (grade two), both albumin and globulin can leak, leading to non-selective proteinuria, while severe injury (grade three) results in significant protein loss exceeding 3.5 grams per day.
  • The liver can produce 10-12 grams of plasma proteins daily, but when proteinuria exceeds 3.5 grams, it cannot compensate adequately, leading to hypoalbuminemia and other complications.
  • The proximal convoluted tubules play a crucial role in reabsorbing proteins that leak into the urine, and significant losses occur due to catabolism of these proteins, further complicating the patient's condition.

20:06

Understanding Heavy Proteinuria and Edema Formation

  • Heavy proteinuria is defined as protein loss in urine exceeding 3.5 grams, leading to conditions such as hyperproteinuria and hypovolemia, which can result in generalized edema, particularly around the eyes (periorbital edema) and later spreading throughout the body.
  • The glomerular structure damage causes proteins to leak into Bowman's space, with a total protein loss of 14 grams, where 5 grams appear in urine and 9 grams are catabolized in the proximal convoluted tubule.
  • Plasma proteins, including albumin and globulin, are crucial for maintaining osmotic pressure in the circulatory system; a decrease in these proteins leads to reduced osmotic pressure, allowing excess fluid to leak into interstitial spaces.
  • Normal osmotic pressure in the capillaries is approximately 27 mmHg, while hydrostatic pressure varies from 40 mmHg at the arterial end to about 15 mmHg at the venous end, facilitating fluid exchange between blood and tissues.
  • Edema formation occurs when osmotic pressure drops significantly due to low plasma protein levels, resulting in fluid accumulation in interstitial spaces, which is termed generalized edema or anasarca.
  • The mechanism of edema is influenced by the loose connective tissue around the eyes, allowing for easier fluid accumulation without significant pressure buildup, leading to early swelling in the periorbital region.
  • Edema can be classified as pitting or non-pitting; pitting edema occurs when fluid can be displaced by pressure, while non-pitting edema is characterized by fluid tightly held by proteins, making it resistant to displacement.
  • In cases of increased hydrostatic pressure, such as in patient A, fluid leaks excessively due to high pressure, while in patient B, reduced oncotic pressure leads to normal fluid filtration but inadequate protein drainage, resulting in edema.
  • Lymphatic obstruction, as seen in patient C, prevents the drainage of proteins, leading to fluid accumulation and non-pitting edema, which can occur in conditions like advanced breast cancer.
  • Patients with heavy proteinuria experience reduced blood volume due to fluid loss to interstitial spaces, which can further complicate their renal function and exacerbate edema.

38:53

Understanding Nephrotic Syndrome and Its Complications

  • Renal perfusion decreases, leading to increased renin production, activating the renin-angiotensin-aldosterone system (RAAS) as a compensatory mechanism in patients with kidney issues.
  • The RAAS causes angiotensinogen to convert into angiotensin I, which is then converted to angiotensin II in the lungs, resulting in vasoconstriction and increased hydrostatic pressure, contributing to edema.
  • Angiotensin II stimulates the adrenal cortex to release aldosterone, promoting sodium and water reabsorption in the kidneys, which further increases blood volume but exacerbates edema due to low protein levels in circulation.
  • The kidneys' retention of sodium and water leads to dilution of blood proteins, causing hyperosmolarity, which triggers osmoreceptors in the hypothalamus to release antidiuretic hormone (ADH) that retains more water, worsening edema.
  • The liver attempts to compensate for low protein levels by increasing protein synthesis, resulting in excessive production of lipoproteins, leading to hyperlipidemia characterized by elevated LDL, VLDL, and triglycerides.
  • Patients with nephrotic syndrome may experience lipiduria, where lipids leak into urine, causing the urine to appear frothy and indicating significant kidney damage.
  • Nephrotic syndrome is defined by heavy proteinuria (≥3.5 grams per day), hypoalbuminemia, generalized edema, hyperlipidemia, and lipiduria, indicating severe glomerular damage.
  • Chronic nephrotic syndrome can lead to iron deficiency anemia due to the loss of transferrin, a protein responsible for iron transport, and increased risk of thrombosis due to loss of anticoagulant proteins like antithrombin III.
  • Patients with nephrotic syndrome are at higher risk for infections due to the loss of complement proteins in urine, which impairs the immune response, particularly against encapsulated bacteria like pneumococcus.
  • The clinical presentation of nephrotic syndrome includes frothy urine due to high protein levels, significant edema, and potential complications such as thrombosis and infections, necessitating careful management and monitoring.

57:42

Glomerular Damage and Proteinuria Insights

  • Patient number one presented with non-selective proteinuria and albuminuria, while the second patient had non-selective proteinuria but below nephrotic range levels. The third patient exhibited heavy proteinuria characteristic of nephrotic syndrome.
  • Patient number four experienced severe renal injury, leading to inflammatory lesions in the glomeruli, which became infiltrated with neutrophils and macrophages, indicating a significant inflammatory response.
  • The distinction between selective and non-selective proteinuria is crucial; selective proteinuria involves increased pore numbers without size increase, leading to albuminuria below 3.5 grams, while non-selective proteinuria involves both increased pore numbers and sizes, resulting in higher protein loss.
  • In cases of nephrotic syndrome, heavy proteinuria is observed, which may initially be selective but can progress to non-selective as the condition worsens, particularly in minimal change disease where cytokines neutralize negative charges in the glomerular basement membrane.
  • Severe renal injury can lead to significant loss of all plasma proteins, including albumin and globulin, resulting in a clinical picture of albuminuria, non-selective proteinuria, and hematuria, indicating serious glomerular damage.
  • Hematuria can be differentiated based on the morphology of red blood cells (RBCs); dysmorphic RBCs with star-shaped edges suggest glomerular origin, while normal RBCs may indicate other sources of bleeding.
  • The presence of RBC casts in urine signifies severe glomerular injury, where RBCs become compressed and form casts due to obstruction in the tubular system, indicating a critical condition.
  • Inflammatory damage to the glomeruli can lead to reduced glomerular filtration rate (GFR), resulting in oliguria (urine output less than 400 ml in 24 hours) and decreased proteinuria due to diminished filtration capacity.
  • As GFR decreases, waste products like urea and creatinine accumulate in the blood, leading to a condition known as azotemia, characterized by elevated blood urea nitrogen (BUN) and creatinine levels.
  • The transition from nephrotic to nephritic syndrome occurs as renal injury progresses, marked by the development of hypertension, oliguria, hematuria with dysmorphic RBCs, and RBC casts, indicating a shift in the underlying pathology of glomerular damage.

01:18:11

Kidney Injury and Its Progressive Consequences

  • Fibrin molecules accumulate in response to severe injury, stimulating epithelial cell growth and attracting macrophages to the injury site, which enhances local healing processes.
  • The presence of macrophages and activated platelets leads to the production of various growth factors, including those from platelets and macrophages, which promote the proliferation of epithelial cells in the affected area.
  • As epithelial cells proliferate, they form cellular crescents, which can lead to conditions such as crescentic glomerulonephritis, resulting in rapidly progressive loss of kidney function due to obstruction in the glomerular layer.
  • Patients with this condition may experience acute renal failure characterized by elevated levels of urea and creatinine in the blood, leading to symptoms of uremia, which is a severe disturbance in blood chemistry due to renal dysfunction.
  • Uremia is defined as the clinical syndrome that arises when renal dysfunction leads to significant biochemical disturbances, resulting in multiple clinical features of renal failure, distinguishing it from azotemia, which indicates only biochemical abnormalities without clinical symptoms.
  • Chronic renal failure can develop from prolonged glomerular injury, where inflammatory cells produce growth factors that activate fibroblasts, leading to collagen deposition and irreversible damage to the glomeruli.
  • The progression from acute to chronic renal failure can occur without clear initial symptoms, and patients may present with chronic renal failure due to previously undiagnosed mild injuries that have led to significant fibrotic changes in the kidney over time.
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