March 18 - Renal Flashcards
Anatomy of ureters
Pass posterior to gonadal vessels, anterior to common and internal iliac arteries
Acute tubular necrosis: three phases
- Initiation: ischemic injury to renal tubules
- Maintenance: decreased urine output resulting in fluid overload. Increase in Cr/BUN. Hyperkalemia.
- Recovery: Increase in urine output with vigorous diuresis. Can decrease electrolyte levels - most serious is hypokalemia. See muddy brown casts
Progression of ATN
Severe hyperperfusion plus toxicity lead to ischemia, which leads to infarction and necrosis. Kidney cells slough off yielding muddy brown casts.
Causes of ATN
- Sepsis and hypoperfusion
2. Drugs - aminoglycosides, cisplatin, amphotericin B
Lbas in ATN: BUN:Cr, urine Osm, FeNa, urine sediment, urine sodium
BUN:Cr is 10:1 indicating damage to renal tubules. Initially may be 20:1 because to start the patient is in pre-renal azotemia that then progresses to ATN.
Urine Osm low - very dilute urine, can’t concentrate, less than 350
FeNa is >1% as can’t reabsorb sodium
Urine sediment shows muddy brown casts
Urine sodium high, over 40
Eosinophils in parasitic defense
Th2 and mast cells produce IL-5 which stimulates eosinophils.
When parasite invades, gets coated by IgG and IgE. Antibodies bind Fc receptors on eosinophil surface, the eosinophil degranulates and releases major basic protein. Form of antibody-dependent cell-mediated cytotoxicity.
Acute hemolytic transfusion reaction: pathogenesis
Antibody mediated hypersensitivey (type II). IgM binds leading to complement-mediated cell lysis
Vasopressin and urea
Vasopressin activates urea transporters in medullary collecting duct, increasing urea reabsorption and decreasing urea clearance. Increase in urea reabsorption increases medullary osmotic gradient, further increasing water reabsorption
Creatinine, para-amino hippuric acid, and inulin handling in kidney
Creatinine freely filtered by glomerulus. Small amount secreted by proximal tubule.
PAH filtered by glomerulus and then compleletly secreted by the proximal tubules with no significant reabsorption. Amount excreted is greater than amount filtered.
Inulin is filtered with no net secretion or absorption. Thus filtration=excretion and it is good for measuring GFR
Kidney med associated with ototoxicity
Loop diuretics
Sodium and potassium concentrationin prox tubule
No change in concentration along proximal nephron because reabsorbed euqlally with water
Bicarb handling in nephron
Actively reabsorbed in proximal tubule due to carbonic anhydrase. Thus, bicarb concentration decreases as move through nephron.
Bicarb is filtered by glomerulus and present in tubular fluid. H+ is actively secreted by Na+/H+ antiporter and primary active transport. H+ and HCO3- bind in the tubular fluid yielding H2CO3. Carbonic anhydrase in apica membrane converts to H2O and CO2. CO2 freely crosses into tubular epithelial cell where it reforms bicarb and H+. H+ is transported by mechansisms above to tubular fluid. Bicarb reabsorbed into blood across basolateral membrane by Na+-bicarb cotransport and cl- bicarb countertransport
Fetal hydronephrosis: three causes
Kinking/narrowing at ureteropelvic junction: most common cause of obstructive unilateral hydronephrosis.
Posterior urethral valves: most common cause of bilateral obstructive hydronephrosis in boys
Vesicoureteral reflux: incomplete closure at VU junction. Causes uni or bilateral non-obstructive hydronephrosis
Tubular fluid osmolarity throughout regions of nephron
Proximal tubule: isotonic with plasma (around 300 mOsm) because water reabsorbd along with electrolytes
Descending loop: becomes hypertonic (over 300) because water reabsorbed but impermeable to solutes
Ascending loop: becomes hypotonic (less than 300) because solutes but not water reabsorbed
Distal tubule: stays hypotonic (less than 300) because solutes but not water reabsorbed; where most dilute
Collecting duct: in presence of ADH, highly permeable to water and becomes hypertonic
Description of Bence Jones proteins in multiple myeloma
Large glassy casts that stain intensely eosinophilic
Causes of acute interstitial nephritis
Most commonly drug induced. Can also be due to infection or autoimmune disease
Crescents in RPGN
Proliferated glomeruluar parietal cells + macrophges/monocytes + fibrin
Calculation of clearance
CL = urine concentration x urine flow / plasma concentration
Foscarnet: MOA, Use, toxicity
MOA: pyrophosphate analog. Viral polymearase inhibitor, HIV RT inhibitor. No activation by viral kinase
Use: gancyclovir-resistant CMV, acyclovir-resistant HSV
Toxicity: nephrotoxicity with electrolyte abnormalities (hypocalcemia and hypomagnesemia) that can lead to seizures
Cidofovir: MOA, use , toxicity
MOA: inhibits viral DNA polymerase, no activation by viral kinase required
Use: Resistant CMV retinitis, acyclovir resistant HSV
Toxicity: nephtotoxicity
Calculating RPF and RBP
RPF = PAH clearance = urine PAH x urine flow rate / plasma PAH
Divide by 1-HCT to get renal blood flow
Calculating GFR
GFR = inulin clearance = urine inulin - urine flow rate / plasma inulin
Uric acid crystals: where forma nd why
Precipitate in distal tubules and collecting duct where pH is the lowest
Hemolytic uremic syndrome pathogenesis and how to distinguish from henloch shonlein pupora
Toxins injure the endothelium leading to platelet activation, microthrombi formation and thrombocyptoneia. Red cells get sheared leading to formation of schistocytes and microangiopathic hemolytic anemia
In HSP platelet count is normal and palpable purpora are present
Chlorthalidone
Thiazide diuretic. More potent than other thiazides but more associated electrolyte abnormalities (greater risk of hypokalemia and metabolic alkalosis)
Severe hypokalemia presentation
Muscle weakness, cramps, rhabdo
Poor prognostic factors for PSGN
Increased age, pre-existing renal disease
Phenylephrine
Alpha agonist
Oxybutynin
Antimuscarnic used for urge incontinence
Imipramine
TCAD
Anatomy and function of JG apparatus
Consists of macula densa + JG cells
Macula densa: cells in distal tubule that monitor salt content and distal flow rate and transmit info to JG cells and regulate dilation/constriction of afferent arteriole. Increased Na+ delivery to distal tubule signals high filtration and causes macula densa to decrease NO synthase in the afferent, decreasing GFR. Decreased Na+ delivery to distal tubule causes macula densa to increase NO synthase in the afferent, increasing GFR
JG cells: modified smoth muscle cells in wall of afferent arteriole that secrete renin via granules when stimulated by macula densa
Effect of long term renal artery stenosis on JG apparatus
Causes hypertropha and hyperplasia of JG apparatus
Membranous vs membranoproliferative glomerulonephritis
Membramous is the most common cause of nephrotic syndrome in adults. Uniform, diffuse thickening of glomerular capillary wall without hypercellularity. On EM irregular dense deposits that resembles spikes on silver staining. On IF, IgG and C3 immune complex deposits
Membranoproliferative: large hypercellular glomeruli - membranous thickening plus hypercellularity
Minimal change disease: pathophysiology
Cytokine damage to podocyte foot processes. Can be idiopathic or associated with the large amounts of cytokines release in Hodkin lymphoma
FSGS: population, pathology
Population: Hispanics and african americans. Can be idiopathic or associated with HIV, heroin, sickle cell disease
Pathology: Foot process effacement, segmental collagen deposition in some of glomeruli. No immune complex deposits
Membranous nephropathy: population
Caucasian adults. Usually idiopathic but can be associated with SLE, cancer, hepatitis B or C
Reason for low Ca++ in CKD
Decreased active vitamin D results in decreased Ca++ absorption
Phosphate retention results in increased serum phosphate which binds free serum Ca++, exacerbating hypocalcemia
Acetazolimide: MOA and adverse effect
MOA: carbonic anhydrase inhibitor in proximal tubule
Adverse effect: Metabolic alkalosis due to decreased bicarb reabsorption
ENaC blockers
Amiloride and triamterene. Can cause metabolic acidosis
Clear cell carcinoma
Most common form of RCC. Cells contian intracellular glycogen and lipids
Renal compensation for metabolic acidosis
1) increasing bicarb reabsorption
2) increasing H+ secretion
3) increasing acid buffer secretion: HPO4-2 and NH3. NH3 is the major mechanism as kidney can increase its production in chronic acidosis
EFfects of angiotensin II
Increases aldosterone
Causes vasoconstriction
Selective proteinuria
Albumin loss with minimal loss of more bulky proteins. Occurs because albumin small enough to fit through slits and is mostly excluded by charge.
Drug-induced AIN: presentation, labs, pathology, mechanism
Presentation: fever, rash, acute renal failure after starting new drug
Labs: Can see elevated eosinophils and IgE
Pathology: Edema and mononucleuar infiltrate in interstitium
Mechanism: IgE mediated or type IV depending on drug
Horseshoe kidney
Inferior poles fail to separate. When kidneys try to ascend, get stuck on IMA.
Kidney drug associated with hyperglycemia
Thiazides
Renal papillary necrosis: causes, pathology, presentation
Causes
- sickle cell trait/disease: sickled cells obstruct small kidney vessels leading to ischemia
- NSAIDS: constriction of afferent arteriole leads to renal hypoperfusion
- diabetes: renal vasculopathy leads to hypoperfusion
- pyelonephritis: edema compresses medullary vasculature leading to ischemia
Pathology
- macro: gray white or yellow necrosis of distal renal pyramides
- micro: coagulative necrosis
Presentation
- dark or bloody urine
- flank pain
- urinary obstruction
ACE inhibitors and renal failure
For patients with renovascular HTN, ACEIs can precipitate renal failure because they need ang II to constrict the efferent to maintain their GFR
Potassium citrate
Given to prevent kidney stones. Increasing urinary citrate binds free Ca++ and decreases stone formation
Nodular glomerulosclerosis: pathophys and pathology
Most commonly due to diabetes. GBM thickening and mesangial matrix deposition. Appears as nodules in the peripheral mesangium. Eosinophilic and PAS positive. Causes nephrotic syndrome.
ACEIs in pregnancy
Contraindicated because can cause renal agenesis
Metabolic alkalosis due to vomiting
Lose H+ and Cl- in vomit. Metabolic alkalosis with low urine Cl-, corrects with isotnoic saline
Metabolic alkalosis due to diuretics
Increased distal NaCl delivery + hypovolemia leads to increased aldosterone production and increased Na+ reabsorption in the collecting duct while K+ and H+ keep being lost. Leads to metabolic alkalosis.
Ongling use: high urine Cl-
Stopped: low urine Cl-
Corrects with isotonic saline
Metabolic alkalosis due to excess mineralocorticoids
Increased Na+ reabsorption with increased K+ and H+ loss leads to metabolic alkalosis. Causes expansion of extracellular fluid and HTN. High urine Cl-. Not corrected with isotonic saline. Aldo still being made
Acute tubular necrosis: pathology
Proximal tubular cell ballooning and vacuolar degeneration
Renal clear cell carcinoma vs renal oncocytoma
RCC originates from proximal renal tubules
Oncocytoma: rare tumor arises from collecting duct cells
Mannitol: MOA, use, ADRs
MOA: osmotic diuretic
Use: Manage cerebral edema and ICP
ADRs: pulmonary edema, volume depletion, hypernatremia
