Diseases Flashcards
Nephrogenic Diabetes Insipidus
Kidneys are unable to conserve water
Due to: lack of response of collecting ducts to ADH
Unresponsive to injected ADH
Neurogenic Diabetes insipidus
Kidneys unable to conserve water
Due to: lack of production or release of ADH
responsive to injected ADH
Syndrome of Inappropriate ADH
Excessive water retention
Hyponatremia with continued urinary Na+ secretion
Urine osmolarity > serum osmolarity
Body responds to water retention with decreased aldosterone (hyponateremia) to maintain near-normal volume status
Can lead to cerebral edema and seizures
Correct slowly to prevent central pontine meylinolysis
Causes: ectopic ADH (small cell lung cancer)
CNS disorders/head trauma
Pulmonary disease
Drugs
Treatment: fluid restriction, IV hypertonic saline, conivaptan, tolvaptan, demeclocycline
Autosomal Dominant Polycystic Kidney Disease
Due to PKD1 gene mutations on Chromosome 16 (most)
PKD2 gene mutations on chromosome 4
Requires second hit genetic mutation
Both involed in tubular cell proliferation and fluid secretion
Both regulate nephron epithelial cell developent and apoptosis, vascular development in kidneys, liver brain, heart and pancrease
Cysts develop in collecting ducts most
Cysts: thickens and changes of adhesion of basement membrane
epithelial cell proliferation stimulated by increased ICF
increased cAMP leads to increased CL channel and increased aquaporin channel conductance in apical membrane leading to fluid accumulation
Presents with: flank pain, hematuira, hypertension urinary infection and progressive renal failure
Death from chronic kidney disease or hypertension (atrophy and fibrosis of renal parenchyma)
Associated with berry aneurysms, mitral valve prolapse, benign hepatic cysts
Pre-renal azotemia
Functional response to renal hypoperfusion not associated with renal injury
Can lead to irreversible renal injury
Response to Volume Depletion (trying to maintain GFR)
Decreased renal perfusion leads to activation of SNS and RAAS
Increased AII levels leads to vasoconstriction of efferent arteriole
Increased AII levels and Increased SNS lead to increased proximal tubular Na+ and H2O absorption
Decreased renal perfusion also leads to aldosterone and ADH secretion leading to increased Na+, BUN and water reabsorption
LABS: Increased BUN:creatinine ratio (Increased BUN reabsorption due to Increased Na and H2O reabsorption) greater than 20
Increased Urine osmolality (Increased Na and H2O reabsorption)
higher than 500
Decreased urinary Na+ and FeNa (Increased Na reabosption)
less than 20 and less than 1%
Causes: hypovolemia, Decreased perceived blood volume (CHF, Cirrhosis, nephrotic syndrome), intrarenal vasoconstriction (NSAIDS, hepatorenal syndrome)
Post-renal Acute Kidney injury
Obstruction of urinary collecting system
Patients with normal renal function and 2 kidneys you need bilateral obstruction of urinary tracts
Causes: prostate disease, retroperitoneal and pelvic malignancies, bladder or pelvic disease, neurogenic bladder, ureteral obstruction-stones, clots papillary necrsosis
Rapidly and fully reversible if diagnosed early
Urine osmolarity less than 350
Urine Na+ greater than 40
FeNa greater than 1% if mild, greater than 2% if severe
BUN/Cr greater than 15
Acute tubular necrosis
Ischemic or Nephrotoxic (7-21 day duration)
Drugs that cause ATN: aminoglycosides, radiocontrast, lead and cisplatin
Risk factors: pre-existing CKD, atherosclerosis, Diabetes, poor nutrional status, cardiac surgery and AAA repair
Denuding of epithelial cells (proximal tubules and thick ascending loop of Henle), loss of brush border enzyme
Occlusion of lumens by cellular debris and casts
Presents: 3 stages
1. inciting event
2. maintenance phase: oliguric; lasts 1-3 weeks, risk of hyperkalemia (arrythmias), metabolic acidosis (retention of H+ anions)
increased ECF-weight gain, edema, pulmonary vascular congestion
Decreased Na and Ca
Increased PO4 and Mg
3. Recovery phase-polyuric; BUN and creatinine fall, risk of hypokalemic
Tubular re-epithelization and regain renal function
Dramatically decreased GFR
Dirty or muddy brown casts
Specific gravity is low
Una is high
Ischemic event: proximal tubule and thick ascending limb most susceptible
Nephrotoxic event: proximal tubule most susceptible
Treatment: maintain perfusion pressure in glomerulus
Correct electrolyte and metabolic disturbances
Dialysis if indicated
Acute intersitial nephritis
Drug induced intersitial nephritis or Hypersensitivity nephritis
Not dose related-immune reaction related
Significant edema and mononuclear (lymphocytic and macrophage) infiltration in intersitium
Glomerulus spared
Serum IgE and eosinophilslevels elevated
Clinical triad: fever, eosinophilia and rash with renal dysfunction
CVA tenderness
not painful urination
UA: pyruia, WBC casts, little proteinuria, RBCs and eosinophilia
Common drugs (15 days after): penicillins, cephalosporins, sulfonamides, phenytoin, rifampin, diuretics
Months after NSAIDs
Drugs act as hapten inducing hypersensitivity
Treatment: remove offending drug +/- steroids
Acute Pyelonephritis
Acute supourative inflammation of kidney
Affects intersitium, tubules and renal pelvis
Caused by: vesicouretral reflux, UTI and hematogenous spread to kidney
Hallmarks: interstitial suppurative inflammation
Intratubular aggregates of PMNs
Can result in tubular necrosis
Complications include papillary necrosis, pyonephrosis, perinephric abscess
UA: WBCs, WBC casts, mild proteinuria
Presents as fever, dysuria, costovertebral angle tenderness, nausea and vomiting
Non pathogenic flora prevent colonization by pathogenic strains
Papillary Necrosis
necrosis of tips or distal 2/3 of pyramids-gray white or yellow of tips
Due to poor blood supply to papilla versus the rest of the kidney
usually chronic and bilateral
Presents with: colicky flank pain gross hematuria, proteinuria
Acute: sloughing of necrotic tissue and diagnosis made by finding tissue in urine
Associated with:
urinary tract obstruction,
analgesic abuse (phenacetin acetominphen derivative)-decreased prostaglandin synthesis inhibits renal flow,
sickle cell anemia and trait: obstruction of small kidney vessels
pyelonephritis: edematous insterstitium compresses medullary vasculature
diabetes mellitus: non-enzymatic glycosylation leads to vascular damage that compromises renal vasculature
Vascular Disease: instrinsic injury to the kidney
Large vessel disease: renal thromboembolism, renal artery dissection, renal vein thrombosis
Results in renal infarction
Presents with flank pain, hematuria, increased LDH
Needs to be bilateral to cause increased creatinine
Renal atheroembolism
“cholesterol emboli syndrome”
Spontaneous or iatrogenic showering of cholesterol crystals from atheromatous plaques
Onset can be days to weeks after procedure
Emboli result in skin, GI, renal, cutaneous hepatic abnormalities
Clinical: purple mesh rash or blue toes
Can have eosinophilia, eosinophiluria, decreased complement
Treatment is supportive
Intratubular obstruction
Light chains in myeloma Calcium in hypercalcemia Uric acid in tumor lysis syndrome (treat with by alkalanizing urine) Acyclovir crystals Myoglobin in rhabodmylolysis
Rhabodmyolysis
Causes: cocaine, seizures, statin drugs, crush injuries
Injury to tubules: direct tubular toxicity at acidic pH
Vasoconstriction
Diabetic Nephropathy
#1 cause of ESRD Patients with GFR 25-50% greater than normal are more likely to get DM renal disease
Earliest clinical finding is microalbuminuria
Once dipstick is + for protenuria there is already a 30-50% decline in GFR
End stage renal disease
Progressive loss of kidney function is the result of the compensatory glomerular hemodynamic changes in response to nephron loss
-remaining nephrons are injured as a result of the compensatory mechanisms that take place in response to an injured nephron
Kidney adapts by increasing the filtration rate in remaining nephrons
Initially helps but results in long term damage
Mechanisms: loss or renal mass leads to hemodynamic adaptation, single nephron hyperfiltration, activation of RAAS, systemic hypertension, and hyperlipidemia
leads to increased inflammation and oxidative stress: up-regulation of TGF-B, EGF, VEGF, IGF-1, and PDGF
Decrease in NO
Results in: mesangial cell and podocyte atrophy/apoptosis
Endothelial cells decreasing NO production
Tubular epithelial cells: hypertrophy/atrophy, cytokine and chemokine production
Interstitial cells: infiltration and proliferation
All lead to matrix elaboration causing glomerulosclerosis and intersitial fibrosis.
Slowing progresssion: treatmetn of HTN, reduction of proteinuria, improve glycemic control
Anemia as complication of CKD
Main factor: Inability to produce enough erythropoietin
Other factors:
Decreased responsiveness to erythorpoietin
Decreased RBC lifespan
Fe deficiency, B12 deficiency, or folate deficiency
Chronic infection or inflammation
Hct begins to fall when GFR is 30% of normal or when creatinine is between 2 and 4
Normochromic, normocytic anemia
Causes: fatigue, impaired sleep, impaired cognitive function
Directly related to development of LVH
Treat with erythropoietin
Renal osteodystrophy as complication of CKD
alterations in bone morphology and bone pathology associated with CKD
Asymptomatic to bone pain to pathologic fractures
Subtypes:
- osteitis fibrosa cystica: increased bone turnover, end result of secondary hyperparathyroidism
- adynamic bone disease: excess suppression of PTH, main lesion in dialysis patients
- osteomalacia: low bone turnover,
- Mixed uremic osteodystrophy
Renal osteodystrophy: Secondary Hyperparathyroidism
Phosphate retention when GFR falls
Uremia
Signs and symptoms of advanced kidney failure
Indicates need for dialysis
Mechanisms:
1. Altered fluid and electrolyte excretion
Little to no urine excretion
Stage 3 and beyond there is decreased H+ excretion leading to chronic metabolic acidosis -treated with bicarbonate or lead to worse bone disease or muscle breakdown
2. accumulation of uremic toxins (decreased excretion of organic solutes)
Uremic encephalopathy: insomnia, altered cognitive function, confusion, hiccups, anxiety, depression. May lead to seizures, coma or death
Peripheral neuropathy: restless or burning legs/feet
GI symptoms: anorexia, nausea, vomiting, breath smells funny (uremic fetor)
Hematologic: anemia, impaired WBC and immune function, abnormal platelet (bruising)
Dermatologic: uremic frost, pruritis, ecchymosis
Cardiac: uremic pericarditis
3. decreased renal hormone synthesis
(decreased renin, decreased calcitriol, decreased erythorpoietin)
Nephritic Syndrome
Inflammatory process
Hematuria and RBC casts in urine
Associated with azotemia, oliguria, hypertension and proteniuria
Acute Proliferative Glomerulonephritis
Ex: post streptococcal glomerulonephritis
1-4 weeks after group A beta-hemolytic streptococal infection of the skin or pharynx
Coca-Cola Colored urine (hematuria)-dysmorphic RBCs and RBC casts
Periorbial edema
Increase in ASO titers, anti DNAase B and anti cationic proteinase
Decreased C3 in serum
Primarily affects children-recover completely
Pathogenesis: immune complex mediated
LM: hypercelular, enlarged glomeruli many neutrophils and monocytes
IF: granular lumpy bumpy due to IgG, IgM and C3 deposition along GBM and mesangium
EM: subepithileal hump-like immune complex deposits
Type III hypersensitivity
Resolves spontaneously
Rapidly progressive Glomerulonephritis
Severe and rapidly progressive glomerular injury
Oliguria, azotemia, hematuria and variable proteinuria found
Untreated leads to death within weeks or months
LM: Crescents: breaks in GBM leads to leaks of fibrinogen converted to fibrin. IgG and C3b also present.
Parietal epithelial cells proliferate and fill up Bowman’s space
Monocytes and macrophages migrate to urinary space
IF: Type I-linear (anti-GBM)
Type II-Immune complex-granular
Type III-Pauci immune-Little to no deposition
EM: severe injury with GBM break
Immune complex deposits
RPGN Type I
Anti-GBM disease
Goodpastures syndrome: RPGN plus pulmonary hemorrhage
Ab to type IV collagen in GBM cross reacts with pulmonary alveolar basement membranes (hemoptysis)
Linear glomerular basement membrane deposits of IgG and C3
Treatment: plasmapheresis, cytotoxic therapy
RPGN Type II
Immune complex
idiopathic, post infectious(Strep gomerulonephritis) , lupus nephritis, Henoch-Shonlein purpura (IgA nephropathy)
Lumpy-bumpy granular pattern on IF
Plasmapheresis does not help
RPGN Type III
ANCA associated
Patietns have circulating anti-neutrophil cytoplasmic Ab in blood
part of systemic vasculitis:
Wegener graulomatosis-C-ANCA test positive
Microscopic polyagniitis: P-ANCA test positive
NO IgG or complement deposits on BM
Patients present with renal failure, pulmonary symptoms (cough, dyspnea, hemoptysis) and upper respiratory tract symptoms (epitaxis, mucosal ulceration, chronic sinnusitis)
Treatment: cyclophosphamide therapy
High incidence of irreversible renal failure
Nephrotic Syndrome
Massive proteinuria
Leakage from damaged GBM, increased permeability to plasma proteins
Hypoalbuminemia
Generalized edema (oncotic pressure change)
Sodium and water retention (perceived loss of water)
Hyperlipidemia-liver compensates by increasing lipid synthesis
Hypercoagulability-thromboembolism due to loss of AT III in urine
Vulnerable to infection (loss of Igs)
Fatty casts
Membranous Glomerulopathy
Idiopathic
Secondary to: drugs (penicillamine, captopril, gold, NSAIDs) lung and colon cancer, melanoa, SLE, hep B and C, syphilis, scistosomiasis, and malaria
Slowly progressive course
LM: diffuse capillary and GBM thickening (no increase in cellularity)
looks thick and fuzzy or spiked
IF: granular deposits of IgG along the GBM (dot to dot)
EM: Diffuse subepithileal immune-complex deposits (IgG and C3) -spikes and domes
Poor response to steroid therapy and may progress to chronic renal disease
Minimal Change disease
Most common in children
May be triggered by recent infection, immunization, or immune stimulus or Hodgkin lymphoma
LM and IF: normal
EM: foot processes of epithelial cells are flattened/effaced
(podocytes)
Albuminuria
Responds well to steroids
Focal Segemental Glomerulosclerosis
Most common cause of nephrotic syndrome in adults in the US
Idiopathic
Secondary: HIV, heroin addiction, sickle cell disease, morbid obesity, interferon treatment, adaptive response from other renal diseases
Inherited forms
LM: focal=some glomeruli, segmental=part of the glomerulus, sclerosis=scarring
Segmental sclerosis and hyalinosis
IF: negative
EM: effacement of foot processes (similar to minimal change disease)
most progress to renal failure; recurs in kidney transplants
Variable response to steroids
Type I: Membranoproliferative Glomerulonephritis
Slowly progressive, unremitting course can remit in kidney transplants
Can present with nephritic or nephrotic syndrome
LM: hypercellular
Mesangial proliferation gives lobular appearance
Wire-loop local accumulations of subendothelial deposits
Thickening and duplication GBM-tram-track double contour GBM pattern
IF: C3 granular pattern
sometimes deposits of C1q and C4
EM: Subendothelial deposits (BAD)
Associated with HBV, HCV, or idiopathic
Secondary to SLE
Nephrotic and nephritic
Type II: membranoproliferative Glomerulonephritis
Slowly progressive, unremitting course can remit in kidney transplants
Can present with nephritic or nephrotic syndrome
Intramembranous deposits
LM: hypercellular
Mesangial proliferation gives lobular appearance
Wire-loop local accumulations of subendothelial deposits
Thickening and duplication GBM-tram-track double contour GBM pattern
IF: C3 irregular granular or linear foci in GBM and in mesagnial rings (intramembranous dense deposits)
EM: Ribbon like dense deposits in the basement membrane
Associated with C3 nephritic factor (stabilizes C3 convertase and decreases serum C3 levels)
Secondary to SLE
Nephrotic and nephritic
IgA nephropathy (Berger disease)
Most common type of GN worldwide
Recurrent gross or microscopic EPISODIC hematuria with RBC casts , mild proteinuria
LM: mesangial proliferation
IF: IgA immune complex deposits in mesangium
EM: Immune complex deposits in mesangium
Pathogenesis: increased IgA synthesis in response to environmental agents, flares after infection (URI) or gastroenteritis
Slowly progressive
Can recur after transplants
Henoch Schonlein Purpura
Variant IgA nephropathy with systemic symptoms
Tetrad: skin purpura (arms legs and buttocks), abdominal pain or intestinal bleeding, intussecpetion, arthralgias (necrotizing vasculitis of dermal vessels and subepidermal hemorrhage), nephritic syndrome
Common in children
Secondary to: liver disease and gluten enteropathy/celiac disease
Alport Syndrome
Defective GBM type IV collagen synthesis-thinning and splitting of GBM
Hematuria, Chronic renal failure, nerve deafness, eye defects
X-linked recessive
Presents with hematuria, progresses to proteinuria and overt renal failure
EM: basket weave-thinning and splitting of GBM
Thin Basement membrane disease (benign familial hematuria)
Defective collagen type IV
NO deafness or eye abnormalities
Most patietns heterozygous
Renal function normal/prognosis excellent
Kidney biopsy: diffuse thinning of the GBM on EM
