Renal Dysfunctions PKD and Nephrotic and Nephritic Syndromes Flashcards
What are renal cysts? What is the difference between a simple and a complex renal cyst?
- sacs of fluid that can form on the kidney
- Simple: thin walled and the fluid is watery, caused by: injury, dysregulation of cell growth or possible ischemia; hardly any symptoms
- Complex: usually thicker and contain a more dense substance that may include blood, necrotic tissue, calcification, connective tissue, or tumor tissue (seen w/ kidney cancer)
What is PKD? What are the two inheritable types? What are the genes and gene products involved?
- Polycystic Kidney Disease: heritable form of cyst development on the kidney
- Two Types:
1. autosomal dominant PKD (ADPKD): genes-> PKD1(85%), PKD2(15%)
2. autosomal recessive PKD (ARPKD): gene-> PKHD1
Symptoms of PKD
-family history for the condition, blood in the urine, cyst infection, multiple cysts visible on scans, extra-large kidneys and renal failure
autosomal dominant PKD (ADPKD)
- Most common inherited kidney disease. Affects both kidneys and can cause cysts in other organs as well including the liver, pancreas, colon, seminal vesicles and cerebral vessels
- symptoms aren’t shown until 4th or 5th decade
- fine until something comes in to damage healthy allele (cancer, radiation)
Explain the function as we know it for polycystin I, polycystin II and fibrocystin
- Polycystin I: protein product of PKD1 gene
- Polycystin II: protein product of PKD2 gene
- Both found surrounding primary cilium. Primary cilium helps with cell proliferation and growth. It also works with calcium entering the cell (inhibits cell growth)-> mutation in genes mean unregulated cell proliferation and growth-> cysts - Fibrocystin: PKHD1 (same function above)
Explain the mechanism of how increased cAMP can increase the size of cysts
- Cl- crosses the apical side via the CFTR channel
- The opening of CFTR is facilitated by cAMP
- Cl- is negative and draws Na+ to the fluid in the lumen
- Buildup of NaCl draws a lot of water to the inside of the lumen
- increased growth and division of nephron epithelial cells, and extra sodium, chloride and water entering the lumen=development of cysts
-V2 receptors increase cAMP
Why does someone with PKD need to drink a lot of water? Explain.
keep the osmolality of their plasma down because increased osmolality stimulates hypothalamus cells to raise ADH levels. ADH will bind and stimulate V2 receptors.
Why should someone with PKD avoid caffeinated beverages.
caffeine inhibits phosphodiesterase(breaks down cAMP) therefore increasing cAMP.
Why is ACE inhibitors and Angiotensin II inhibitors are often used for PKD
more effective in lowering urine protein excretion. They also reduce blood pressure
Autosomal recessive polycystic kidney disease (ARPKD)
- involve a mutation in a gene called PKHD1 (stands for Polycystic Kidney and Hepatic Disease 1)
- gene codes for a transmembrane protein called fibrocystin
- It is rare for someone to develop PKD with the PKHD1 gene. If someone inherits 2 genes with PKHD1 then they will develop ARPKD early in life
- manifestations: bilateral impaired lung development, flank masses, liver fibrosis, hypertension and renal failure can be noted even at birth
- 75% infants die
- If survive, kidney transplant recommended.
Review the structural components of the glomerulus
Glomerular capillaries are made up of endothelial barriers which are supported by a basement membrane and podocytes(visceral).
What is the pressure generally found in the glomerular capillaries?
Glomerular capillaries have a pressure around 55mmHg
Explain how fenestrae, basement membrane and podocytes function to create a filtration membrane
- Fenestrae: small pores in the endothelium of the glomerular capillaries
- Podocytes: make filtration slits. negatively charged.
- basement membrane: negatively charged
- albumin and other plasma proteins are also negative so they don’t get filtered. Blood and platelets are too big to get filtered
What are mesangial cells and what do they do?
- contract or relax to help regulate the flow of blood through the glomerular capillaries
- extraglomerular mesangial cells: between efferent and afferent arterioles.
What is the juxtaglomerular apparatus and what does it do?
made up of macula densa cells (apart of DCT) and granular cells. These cells communicate with each other to regulate the release of renin. Renin is then released by granular cells in times of low BP
What is nephrotic syndrome and what are the symptoms and signs?
- occurs when there is injury and damage to the podocytes and even the basement membrane, but the endothelial cells are relatively intact
- froth occurs in the urine
Describe the mechanisms of how nephrotic syndrome causes these manifestations
- The negative charges around the fenestrae are diminished causing plasma proteins to be filtered out
- selective proteinuria: mostly just albumin in the urine
- non-selective proteinuria: other proteins in the urine besides just albumin
- loss of albumin can lead to a decrease in blood oncotic pressure and a resulting movement of fluid to the interstitial spaces occurs
Why does someone with nephrotic syndrome have increased blood pressure?
- loss of albumin = decrease in blood oncotic pressure
- water leaves vascular system and enters the interstitial spaces = drop in blood volume
- R.A.A.S stimulated
- sodium and water retention from R.A.A.S causes increase in blood pressure
Why does someone with nephrotic syndrome have an increased risk of DVTs?
Because antithrombin III (anticoagulant) sits right next to the fenestrae and gets filtered with the plasma proteins with nephrotic syndrome. If the liver can not produce what is lost, the Deep vein thrombosis
Why does someone with nephrotic syndrome often have a poor lipid profile that can cause high risk for cardiovascular disease?
Because there is a loss of plasma proteins in the filtration, the liver attempts to make more. But it makes lipoproteins instead and causes hyperlipidemia. This increases risk for cardiovascular disease.
What is Minimal Change Disease?
- causes by a random loss of podocytes-> leads to a lot of edema
- mostly in children
- Under immunofluorescence, immunoglobulins and complement deposits found
- immunoglobin complexes damage podocytes which leads to increased permeability of the filtration membrane and proteins are lost
- Tx: corticosteroids
How does Diabetic Nephropathy lead to nephrotic manifestations?
- High blood sugar can cause excessive glucose to be filtered
- glucose gets deposited into the basement membrane causing it to thicken
- filtration becomes more permeable-> albumin can be filtered
- hardening of the glomerulus occurs-> leads to obliteration
- inflammatory response may arise that leads to nephritic syndrome and ultimately very low GFR that induces end stage renal disease
What is Nephritic Syndrome? How does this syndrome occur?
-significant inflammatory processes in the glomerulus as well as RBCs, WBCs and platelets in the urine
What are the classic manifestations Nephritic syndrome?
- Hematuria: blood in the urine and dysmorphic RBC’s
- RBC casts: stacks of RBCs that are moving together in a large bundle
- Proteinuria: protein in urine but not as much as nephrotic syndrome
- Oliguria: drop in urine output because of decrease in GFR
- Hypertension: occurs because of the excessive response to a low GFR
