Pathoma Chapter 12 Flashcards
1
Q
What is horseshoe kidney?
A
- Conjoined kidneys usually connected at the lower pole
- Most common congenital renal anomly
- Most commonly located in the lower abdomen
- Horseshoe kidney gets caught on the inferior mesenteric artery root during its ascent from the pelvis to the abdomen
2
Q
What is the difference between unilateral and bilateral renal agenesis?
A
- renal agnesis = absent kidney formation
- Unilateral agenesis leads to hypertrophy of the existing kidney
- One kidney now has to do the work of two kidneys
- Functions fine until later in life
- Hyperfiltration increases risk of renal failure later in life
- Bilateral Agenesis leads to oligohydramnios (not enough amnitic fluid is produced) with lung hypoplasia, flat face with low set ears and developmental defects of the extremities (Potter’s Sequence)
- Incompatabile with life
3
Q
What is Potter’s Sequence?
A
- Due to Oligohydramnios: not enough amniotic fluid is produced
- Lung Dysplasia (lungs don’t develop properly)
- When the lung develops, one way that it grows is by stretch
- Breathing in and out amniotic fluid streches the lung
- If not enough amniotic fluid, lung can’t develop
- Flat face with low set ears
- no amniotic fluid means face will get pressed up against the wall of the uterus causing flat face with low set ears
- Limb Deformaties
- limbs are also pressued up against mom so they develop abnormally
4
Q
What is dysplastic kidney disease?
A
- Noninherited
- Congenital malformation of the renal parenchyma characterized by cysts and abnormal tissue
- Usually unilateral
- When bilateral, must be distinguished from inherited polycystic kidney disease
5
Q
What is Polycystic Kidney Disease? What are the two different versions?
A
- Inherited defect leading to bilateral enlarged kidneys with cysts in the renal cortex and medulla
- Autosomal recessive form presents in infants as worsening renal failure and hypertension
- Newborns may present with Potter sequence
- Kidneys are not working properly so not producing enough amniotic fluid
- Newborns may present with Potter sequence
- Autosomal dominant form presents in young adults as hypertension (due to increased renin), hematuria, and worsening kidney failure
- Due to mutation in the APKD1 or APKD2 gene
- Cysts develop over time
- Associated with berry aneurysms, hepatic cysts and mitral valve prolapse
- If have family history of renal disease and there is death occuring b/c of renal disease or brain hemorrhage, think autosomal dominant polycystic kidney disease
6
Q
What is Medullary Cystic Kidney Disease?
A
- Inherited: autosomal dominant
- Defect leading to cysts in the medullary collecting ducts
- Parenchymal fibrosis results in shrunken kidneys and worsening renal failure
7
Q
What is acute renal failure?
A
- acute, severe decrease in renal function (develops in days)
- Hallmark is azotemia (increase in waste products in the blood: increased BUN and creatinine)
- Often with Oliguria: low production of urine
- 3 types: prerenal, postrenal and intrarenal azotemia
8
Q
What is prerenal azotemia?
A
- Due to increased blood flow to the kidneys
- Ex. Cardiac Failure
- Decreased blood flow results in decreased GFR, azotemia and oliguria
- Reabsorption of fluid and BUN ensues (serum BUN:Cr ratio >15)
- Because there is low blood flow to the kidney, the renin/angiotensin system will be activated and aldosterone will cause reabsorption of sodium and water
- B.c of water reabsorption, more BUN will be reabsorbed
- Tubular function remains intact (fraction excretion of sodium [FANa] <1% and urinary osmalility is [osm] > 500
- tubules can absorb sodium and concentrate urine still
9
Q
What is postrenal azotemia?
A
- Due to obstruction of the urinary tract downstream of the kidney
- Have back pressure which will decrease glomerular pressure
- Decreased outflow results in decreased GFR, azotemia and oliguria
- During early stage of obstruction, increased tubular pressure forces BUN into the blood (serum BUN:Cr >15)
- Tubular Function remains intact (FENa <1% and urine osm >500)
- With longstanding obstruction, tubular damage ensues resulting in:
- decreased reabsorption of BUN (serum BUN:Cr <1)
- decreased reabsorption of sodium (FENa >2)
- inability to concentrate urine (urine osm <500)
10
Q
What is Acute Tubular Necrosis?
A
- Injury and necrosis of tubular epithelial cells
- Most common cause of acute renal failure
- Intrarenal azotemia
- Necrotic cells plug tubules and the obstruction causes a decrease in the GFR
- It causes backpressure and backpressure counteracts glomerular pressure
- Brown, granular casts are seen in the urine
- Dysfunctional tubular epithelium results in decreased reabsorption of BUN (serum BUN/Cr <15), decreased reabsorption of sodium (FENa >2%) and inability to concentrate urine (urine osm <500)
11
Q
What are the two causes of Acute Tubular Necrosis? What can prevent chemotherapy induced Acute Tubular Necrosis?
A
- Ischemia
- decreased blood supply resulting in necrosis of tubules
- often preceded by prerenal azotemia
- If bloodflow remains low for an extended period of time, can become ischemic
- proximal tubule and medullary segment of the thick ascending limb are particularly susceptible to ischemic damage
- Nephrotoxic
- Toxic agents result in necrosis of tubules
- Proximal tubule is particularly susceptible
- Causes include aminoglycosides (most common), heavy metals (lead), myoglobinuria (crush injury to muscle), ethylene glycol (associated with oxalate crystals in urine), radiocontrast dye, and urate (ex. tumor lysis syndrome)
- Hydration and allopurinol are used prior to initiation of chemotherapy to decrease risk of urate-induced Acute Tubular Necrosis
- Toxic agents result in necrosis of tubules
12
Q
What are the clinical features of Acute Tubular Necrosis? How do you treat it?
A
- Oliguria with brown, granular casts
- Elevated BUN and creatinine
- low GFR means you can’t filter out BUN and Cr
- Hyperkalemia (due to decreased renal excretion) with metabolic acidosis
- Metabolic acidosis is due to the fact that you have a decrease in excretion of organic acids
- will have increased anion gap
- Reversible but often requires supportive dialysis since electrolyte imablances can be fatal
- Oliguria can persist for 2-3 weeks before recovery
- tubular cells (stable cells) take time to reenter the cell cycle and regenerate
13
Q
What are the brown, granular casts found in Acute Tubular Necrosis?
A
- Epithelial cells die, sloth off and obstruct the the tubule
- Dead epithelial cells then get casted in the shape of the tubule
- See dead endothelial cells making up the cast in the urine
- Looks brown and granular because cells are dead
14
Q
What is Acute Interstitial Nephritis?
A
- Drug-induced hypersentivity involving the interstitum and tubules results in acute renal failure (intrarenal azotemia)
- Causes include NSAIDS, penicillin, and diuretics
- Presents as oliguria, fever, and rash days to weeks after strating a drug
- Eosinophils may be seen in urine
- Resolves with cessation of drug
- May progress to renal papillary necrosis
15
Q
What is Renal Papillary Necrosis?
A
- Necrosis of renal papillae
- Presents with gross hematuria and flank pain
- Causes include:
- Chronic analgesic abuse (long term phenacetin or aspirin use)
- Diabetes Mellitus
- Sickle Cell trait or disease
- Severe Acute Pyelonephritis
16
Q
What is nephrotic syndrome?
A
- Glomerular disorders characterized by proteinuria (>3.5 g/day) resulting in:
- Hypoalbuminemia: pitting edema
- Hypogammaglobulinemia: increased risk of infection
- Hypercoagualable state: due to loss of antithrombin III
- Antithrombin III breaks up thrombin and other coagulation factors so you can’t produce thrombin
- Hyperlipidemia and hypercholesterolemia: may result in fatty casts in urine
- loss of protein causes blood to be tthin so liver reacts by putting excess fat in the blood to beef it up
17
Q
What is Minimal Change Disease (MCD)?
A
- Most common cause of nephrotic syndrome in children
- Usually idiopathic but may be associated with Hodgkins lymphoma
- Normal glomeruli on H&E stain
- lipid may be seen in the proximal tubule
- Effacement of foot process on eletron microscopy
- in MCD, you lose the foot processes on the glomerular filtration barrier
- No immune complex deposits; negative immunofluorescence
- Selective proteinuria
- change is so minimal that only protein lost is albumin
- Excellent response to steroids (damage is mediated by cytokines from T cells)
18
Q
What is the relationship between Minimal Change Disease and Hodgkins Lymphoma?
A
- in MCD, you lose the foot processes on the glomerular filtration barrier
- cytokines damage the foot processes
- In Hodkins lymphoma, get massive production of cytokines by Reed-Sternberg cells
- Cytokines can attack the kidney and knock out podocytes
19
Q
What is Focal Segmental Glomerulosclerosis?
A
- Most common cause of nephrotic syndrome in Hispanics and African Americans
- Usually idiopathic but can be associated with HIV, heroin use, and sickle cell disease
- Focal (some glomeruli) and segmental (involving only part of the glomerulus) sclerosis is seen on H&E staining
- not all glomeruli are affected
- glomeruli that are affected have only part of it not working
- Effacement of foot processes on EM (flattened podocytes)
- No immune deposits; negative IF
- Poor response to steroids
- Progresses to chronic renal failure
- Patient with Minimal Change Disease that do not respond to steroids progress to Focal Segmental Glomerulosclerosis
20
Q
What does mebranous mean in terms of renal pathology?
A
- thickening of the membrane due to immune complex desposition
21
Q
What is Mebranous Nephropathy?
A
- Most common cause of nephrotic syndrome in Caucausian adults
- May be associated with Hep B or C, solid tumors, SLE or drugs (NSAIDS and penicillamine)
- immune complex deposition forms under podocyte or subepithelial
- Due to immune complex deposition
- Get granular immunoflorescence
- subepithelial deposits with spike dome appearance on EM
- Poor response to steroids
- Progresses to chronic renal failure
22
Q
Why does Membranous Nephropathy have a spike and dome appearance on EM?
A
- immune complex deposition forms under podocyte or on subepithelial cell
- podocyte responds by trying to lay down additional basement membrane
- generate a dome over the deposit
- in between the deposits, end up creating spikes
23
Q
What causes Membranoproliferative Glomerulonephritis?
A
- get immune complex deposition under the endothelium or under the basement membrane
- the mesangial cell that is holding the capillary together will notice the immune complex deposit and will proliferate its cytoplasm to cut through the deposit
- creates a tram track appearance b/c splits deposit in half
24
Q
What is Membranoproliferative Glomerulonephritis and what are the two subtypes?
A
- thick glomerular basement membrane formation with tram track appeance due to immune complex deposition
- Granular immunoflorence
- Divied into two suptypes based on location of the deposits
- Type I: subendothelial
- Associated with Hep B and Hep C
- more associated with Tram Tracks
- Type II: dense deposit disease
- intramembranous
- Associated with C3 nephritic factor
- Autoantibody that stabilizes C3 convertase, leading to overactivation of complement, inflammation and low levels of circulating C3)
- Type I: subendothelial
- Poor response to steroids
- Progresses to chronic renal failure
25
Q
What is the effect of Diabetes Mellitus on the kidneys? How can progression to kidney failure be slowed down?
A
- High serum glucose leads to nonenzymatic glycoslylation of the vascular membrane resulting in hyaline arteriolosclerosis
- when you stick sugar on the basement membrane without the use of enzyme, thats nonenzymatic glycosylation: basement membrane becomes leaky and protein leaks into wall of blood vessel causing hyaline arteriosclerosis
- hyaline arteriolosclerosis causes thickening of the blood vessel wall which causes a decrease in the size of the lumen
- Glomerular effererent arteriole is more affected than the afferent arteriole, leading to high glomerular pressure
- Hyperfiltration injury leads to microalbuminuria
- Eventually progresses to nephrotic syndorme
- characterized by sclerosis of the mesangium with formation of Kimmelstiel-Wilson nodules
- ACE inhibitors slow progression of hyperfiltration-induced damage
- Angiotension II squeezes on efferent arteriole
- If you stop that from happening, have less squeezing down on efferent arteriole thus slowing down progression
26
Q
How does systemic amyloidoisis affect the kidneys?
A
- Kidney is te most commonly involved organ in systemic amyloidosis
- Amyloid deposits in the mesangium, resulting in nephrotic syndrome
- Characterized by apple-green birefringence under polarized light after staining with Congo red
27
Q
What is nephritic syndrome?
A
- Glomerular disorders characterized by glomerular inflammation and bleeding
- Limiting proteinuria (<3.5 g/day)
- Oliguria and azotemia
- Salt retention with periorbital edema and hypertension
- RBC casts and dysmorphic RBCs in urine
- Biopsy reveals hyperceulluar, inflammed glomeruli
- immune complexes cause the inflammation
- immune complex deposition activates complement
- C5a attracts neutrophils which mediate damage
28
Q
What type of casts are found with nephritic syndromes and why?
A
- glomerulus is bleeding so have RBCs going into the tubules
- the RBCs get casted in the shape of the tubule and are urinated out as a square cast of RBCs
29
Q
What is Poststreptococcal Glomerulonephritis (PSGN)? How does it present and how is it treated?
A
- Nephritic syndrome that arises after group A beta hemolytic streptococcal infection of the skin or pharynx
- occurs with nephritogenic strains: strain carrying M protein virulence factor
- May occur after infection with nonstreptococcal organisms as well
- Presents 2-3 weeks after infection as hematuria (cola-colored urine), oliguria, hypertension and periorbital edema
- Usually seen in children but may occur in adults
- Mediated by immune complex deposition: immune complexes start subendothelial and work their way up and pile up in subepithelial
- Deposits will eventually pass their way through
- Treatment is supportive
- Children rarely progress to renal failure
- Some adults develop rapidly progressive glomerulonephritis (RPGN)
30
Q
What are the histological findings associated with Poststreptococcal Glomerulonephritis (PSGN)?
A
- Hypercellular, inflammed glomeruli on H&E
- Mediated by immune complex deposition (granular immunoflorescence)
- Subepithelial humps on EM
