Renal & Electrolytes UWorld Flashcards
Why are patients on thiazides more likely to become hyponatremic compared to those taking loop diuretics?
The loop diuretics prevent reabsorption of salt in the ascending loop of Henle and disrupt the normal corticomedullary gradient. This results in significant water and salt loss. Thiazides do not affect the corticomedullary gradient and patients respond more to increased vasopressin levels, retain more water and are at higher risk of hyponatremia.
Light microscopy, electron microscopy and immunofluorescence in patients with post-strep glomerulonephritis?
LM = hypercellularity EM = sub-epithelial humps IF = lumpy-bumpy IgG, IgM and C3 deposits
Layers of the anterior abdominal wall
Skin Camper's fascia Scarpa's fascia External oblique Internal oblique Transversus abdominis Transversalis fascia Extraperitoneal fat Peritoneum
A) Substances that are freely filtered by the glomerulus without absorption or secretion?
B) Substances with net reabsorption?
C) Substances with net secretion?
A) Manitol and inulin
B) Glucose, Na and BUN
C) PAH and creatinine
Where is BUN reabsorbed and secreted in the nephron?
Reabsorbed: PCT & medullary collecting duct
Secreted: thin loop of Henle
What is used to calculate renal plasma flow?
PAH. It is freely filtered, more is secreted than is filtered and not reabsorbed.
Congenital abnormalities that can result from failure of the urachus to obliterate?
Patent urachus = attachment of bladder to umbilical cord
Vesicourachal diverticulum = asymptomatic out pouching at the apex of the bladder
Urachal sinus = failure to close the distal urachus resulting in recurrent infections
Urachal cyst = fluid filled cyst between the two obliterated ends of the urachus between the navel and bladder
Baby with meconium coming from his belly button
Persistent vitelline duct (yolk sac). Partially obliterated vitelline duct results in a Meckel diverticulum.
Most common viral cause of acute hemorrhagic cystitis in children
Adenovirus
2nd most common cause of UTI in sexually active women
S. saprophyticus
Hyper acute, acute and chronic kidney transplant characteristics
Hyperacute: preformed antibodies, within minutes to hours
Acute: C4b deposition, PMNs, lymphs and vasculitis less than 6 months after transplant
Chronic: vascular wall thickening, fibrosis and atrophy months to years after transplant
Drugs for renal transplant patients that can cause renal arterial hyalinization, tubular vacuolization and reduced renal blood flow.
Calcineurin inhibitors: tacrolimus and cyclosporine
Embryonic kidney development
Pronephros: forms and completely regresses by 5 weeks
Mesonephros: gives rise to the vas deferens, epididymus and Gartner’s ducts in women.
Metanephric diverticulum: ureteric bud sprouts off mesonephros. It penetrates into the sacral intermediate mesoderm and induces surrounding tissue to differentiate into the metanephric mesoderm (blastema). The metanephric blastema then causes the ureteric bud to differentiate into the collecting system.
Metanephric blastema: gives rise to the glomerulus, PCT and DCT.
Content inside granules of eosinophils
Major basic protein
Causes of metabolic alkalosis that are saline responsive?
What types are not saline responsive?
Saline-responsive: vomiting/NG (low urine Cl) and prior diuretic use (high urine Cl) deplete the body of Cl-. This prevents HCO3- excretion and promotes H+ excretion.
Saline-non-responsive: Bartter, Gitleman and excess mineralocorticoid receptor stimuli
What enzyme is critical for DNA synthesis in bacteria and is involved in the incorporation of uracil into DNA?
Primase. It synthesizes the RNA primers at the replication fork that are necessary before DNA polymerase III can continue replication away from the replication fork.
Enzyme that repairs single-stranded breaks in DNA
Ligase
Enzyme that is primarily responsible for synthesis of the daughter strands in DNA replication
DNA polymerase III
Enzyme that is responsible for replacement of RNA primers with DNA bases
DNA polymerase I has 5’->3’ exonuclease activity that allows it to remove the RNA bases and replace them with DNA bases
What allows DNA polymerase I and III to repair mismatched bases in newly formed daughter strands?
3’->5’ exonuclease proofreading function
Enzymes involved in unwinding DNA during replication
Helicase unwinds it at the replication fork, topoisomerase II relieves the downstream tension secondary to unwinding the double helix
Why must you be cautious when prescribing ACE-I to patients with renal artery stenosis?
ATII is necessary to maintain renal perfusion pressure. When ATII is blocked, renal perfusion pressure can drop and the patient can develop acute kidney injury.
Mechanism of Henoch-Schoelin purpura
Post-infectious IgA immune complexes result in leukocytoclastic vasculitis and deposit in vessel walls (palpable purpura), GI tract (hematochezia), kidneys (IgA nephropathy) and joints (arthralgia).
Taking what class of drugs would decrease the response of your patient to loop diuretics?
NSAIDs. Loops also increase prostaglandin release, dilating blood vessels and increasing drug delivery to the target site. NSAIDs inhibit prostaglandin synthesis and limit this effect.
How does the tonicity of tubular fluid change as you progress through the nephron?
PCT: isotonic because water is passively reabsorbed
Descending loop of Henle: hypertonic due to its impermeability to Na+, but permeability to H2O and hypertonicity of medulla
Ascending loop of Henle: becomes hypotonic due to impermeability to H2O, but transport of Na, K and Cl out of tubule.
DCT: lower water permeability generally means hypotonic fluid, however, this region is dependent on vasopressin
CD: hypertonic in presence of ADH due to increased H2O permeability, hypotonic in absence of ADH due to decreased H2O permeability
Substances that can be used to calculate GFR and renal plasma flow (RPF)?
GFR = inulin and creatinine RPF = PAH
Clearance = [urine] x (flow rate/[plasma])
How to calculate filtration fraction. Normal value?
GFR/RPF. Normal value ~ 20%.
How does diabetic nephropathy occur?
1st morphologic changes = GBM thickening and mesangial matrix deposition
1st clinical changes = upregulation of heparinase, degradation of heparin sulfate in GBM, proteinuria and increased GFR
In later stages Kimmelstein-Wilson nodules form, GFR drops dramatically and patients develop nephrotic syndrome
Triggers of minimal change disease and characteristic EM findings?
Immunization, bee stings and allergies can cause. EM shows podocyte foot process effacement.
Membranoproliferative glomerulonephritis LM and EM findings
LM = hypercellularity EM = splitting of GBM due to sub endothelial immune complex deposition
Membranous nephropathy EM findings
Sub epithelial spikes
Post-strep GN LM, EM and IF findings
LM = diffuse hypercellularity. EM = Sub epithelial humps composed of IgG and C3 that luminesce on IF
Causes of secondary hyperaldosteronism
Anything that elevates renin: reninomas, renal artery stenosis, diuretics and malignant hypertension.
BPH treatment
alpha-1 blockers to relax smooth muscle in bladder neck
5-alpha-reductase inhibitors to prevent hormone-mediated hyperplasia by inhibiting conversion of testosterone to dihydrotestosterone
Why give thiazides to patients with recurrent Ca-based stones
Inhibition of the apical Na/Cl cotransporter in the DCT results in decreased intracellular Na, then activation of the basal 3Na/Ca transport, then Ca leaves the tubular cell and increased amounts of Ca are absorbed into the tubular cell from the tubular lumen, thus decreasing tubular [Ca].
Hypovolemia from diuretics increases Na and H2O reabsorption in the PCT. This also increases paracellular reabsorption of Ca.
Regions of the nephron particularly susceptible to ischemic injury?
PCT and ascending loop of Henle because the participate in high levels of active transport requiring ATP. The medulla is also susceptible due to low blood supply compared to the rest of the kidney.
Mechanism of calcineurin inhibitor toxicity
They cause dose dependent vasoconstriction and tubular damage, resulting in hypertension and acute kidney injury. This can be precipitated by patients drinking grapefruit juice because CYP3A is inhibited by grapefruit juice and calcineurin inhibitor levels rise.
Rule of thumb in predicting GFR from serum creatinine?
Every time the creatinine doubles, cut the GFR in half. Note however, that large GFR losses above 60% will result in a relatively unchanged creatinine.
Disease to think about in a patient with bilateral renal angiomyolipomas.
Tuberous sclerosis. Look for seizures and mental retardation due to cortical tubers and subependymal hamartomas. There may also be associated ash-leaf patches on the skin, cardiac rhabdomyomas and facial angiofibromas.
NF1
AD mutation on chromosome 17 with neurofibromas, optic gliomas, pigmented iris nodules (Lisch nodules) and café-au-lait spots
NF2
Bilateral acoustic neuromas, gliomas, meningiomas and ependymomas of the spinal cord.
Von-Hippel Lindau
Bilateral renal cell carcinoma, cerebellar hemangioblastomas, liver cysts and retinal hemorrhages from AD mutation in the tumor suppressor VHL gene on chromosome 3p.
Facial port wine stain and leptomeningeal capillary venous malformation
Sturge-Weber syndrome
Risks for nephrolithiasis
Hyperparathyroidism - hypercalciuria
Crohn’s - hyperoxaluria
Distal RTA - hypocitraturia
Gout - hyperuricosuria
Effect of stimulation of the muscarinic receptors
M1 stimulation - Gq activation -> memory formation and increased cognition
M2 stimulation - Gi activation -> decreased HR and atrial contractility
M3 stimulation - Gq activation -> bronchoconstriction, detrusor contraction, miosis, accommodation, peristalsis, increased secretions and increased sweat
Oxybutinin mechanism of action
M3 antagonism -> decreased Gq activation -> decreased IP3 and DAG -> decreased Ca release and decreased detrusor muscle contraction
Origination of clear cell renal carcinoma
Tubular epithelial cells
Region of the nephron that absorbs the most water
PCT absorbs ~ 60% passively
Pauci-immune glomerulonephritis
Granulomatosis with polyangiitis (Wegener’s): there is renal damage without anti-GBM antibodies or immune complex deposition, only c-ANCA.
Portion of the nephron most prone to develop uric acid crystals
DCT and CD because they are the most acidic portions of the nephron.. Uric acid is typically soluble at physiologic pH, but precipitates when the pH becomes acidic.
Why are thiazides not as effective as loops
Not as much Na reaches the DCT where thiazides act
Tmax of PAH
It is freely filtered by the glomerulus, so there is no Tmax there; however, it is actively secreted in the PCT, and that Tmax is ~80mg/min.
Why are patients taking Foscarnet at increased risk for seizures?
It causes hypomagnesemia, reduces PTH and chelates Ca, causing hypocalcemia.
Sofosbuvir
Inhibits NS5B (an RNA-dependent RNA polymerase) needed for HCV replication
Conditions associated with renal papillary necrosis
Sickle cell disease, NSAIDs, DM and pyelonephritis all result in ischemia and papillary necrosis
Major source and effects of IL-2
SOURCE: T-cells T-cell growth (autocrine via IL-2 receptor) and IFN-gamma secretion B-cell division Helper T-cell growth and differentiation Monocyte and NK cell activation
Major source and effects of IL-1
SOURCE: macrophages
Increases PMN and macrophage migration
Increases acute phase reactants -> fever & shock
Major source and effects of IL-3
SOURCE: T-cells
Increased hematopoiesis
Major source and effects of IL-4
SOURCE: Th2 cells
Increased Th2 differentiation
B cell growth and IgE class switching
Major source and effects of IL-5
SOURCE: Th2 cells
Differentiation to eosinophils
IgA class switching
Major source and effects of IL-6
SOURCE: macrophages
Increases T and B cell growth
Increases osteoclast activity
Increases acute phase reactants and fever
Major source and effects of IL-8
SOURCE: macrophages and T-cells
PMN activation and chemotaxis
Major source and effects of IL-10
SOURCE: Th2 cells
Decreased Th1 differentiation, decreased cell-mediated immunity and APC activity
Increased B-cell function
Major source and effects of IL-12
SOURCE: macrophages
Increase Th1 differentiation
Increased NK and CD8+ T-cell activity
Sirolimus mechanism of action
Binds FK-506 binding protein, which inhibits mTOR. This prevents IL-2 signal transduction and limits G1 to S phase progression of developing lymphocytes
Mycophenylate mechanism of action
Reversibly inhibits inosine monophosphate dehydrogenase, reducing proliferation of activated lymphocytes
Proximal and distal ureteral blood supply
Proximal = renal artery Distal = superior vesical artery
Proteins found in the urine of patients with tubulointerstitial nephritis
Ig and beta2-microglobulin are filtered by the glomerulus, but reabsorbed in the PCT. When the PCT is damaged, these show up in the urine.
How does pyruvate’s destination vary depending on O2 content?
Low O2: lactate dehydrogenase converts pyruvate to lactate in order to regenerated NAD+ from NADH.
Adequate O2: pyruvate dehydrogenase converts pyruvate to acetyl CoA, which enters the Krebs cycle and goes on to oxidative phosphorylation
Enzyme that converts phosphoenolpyruvate to pyruvate
Pyruvate kinase
Enzyme that converts pyruvate to oxaloacetate
Pyruvate carboxylase
Enzyme that converts 2-phosphoglycerate to phosphoenolpyruvate
Enolase
Urodynamic studies in a patient with urge incontinence and MS
Bladder hypertonia due to lack of upper motor neuron inhibitory signaling
Risk for hyperuricosuria
Myeloproliferative disease, Lesch-Nyhan, gout and tumor lysis syndrome. Uric acid stones also serve as a nidus for precipitation of calcium stones.
Risk for hyperoxaluria
Low Ca absorption seen in Crohn’s, high oxalate diet (chocolate, nuts, spinach) and ethylene glycol poisoning
Majority of K+ reabsorption in nephron
~65% in PCT
~25% in thick ascending loop of Henle
alpha-intercalated cells: reabsorb K+ in periods of hypokalemia via H+/K+ ATPase
principal cells: secrete K+ in periods of hyperkalemia via Na+/K+ pumps
What makes up the crescents in patients with RPGN?
Fibrin, macrophages, monocytes and glomerular parietal cells.
3 ways the kidney tries to overcome a respiratory acidosis
Increased HCO3- reabsorption in the PCT via increased CA activity
Increased H+ secretion in PCT Na/H anti port, and alpha-intercalated cell H+ ATPase and H+/K+ ATPase
Increased Gln metabolism to increase NH3 production in PCT. NH3 sequesters H+ and is excreted as NH4 without significantly lowering the urine pH. HPO4 can also sequester H+, but to a lesser degree than NH3.
Antibodies associated with anti-phospholipid antibody syndrome
Anti-beta-glycoprotein I and anti-cardiolipin antibody
Labs seen in post-strep GN
Anti-DNAase, anti-streptolysin O and low C3
Why patients with CHF are at increased risk for hyponatremia?
They have a low effective intravascular circulating volume. This results in increased ADH release and plasma dilution.
Major side effect of using mannitol in a patient with elevated ICP
Pulmonary edema from rapid intravascular fluid expansion and increased vascular hydrostatic pressure.
Lithium’s effect on the kidney
Antagonizes vasopressin in the collecting duct and causes nephrogenic DI
Type I, II and III RPGN
Type I: anti-GBM disease
Type II: immune complex disease (SLE)
Type III: pauci-immune (Wegener’s, microscopic polyangiitis)
Major antigen in pathogenesis of idiopathic membranous nephropathy?
Phospholipase A2-receptor (PLA2R), it is present in the glomerular podocytes and IgG4 antibodies develop against it.
Characteristics of TTP-HUS
Fever, neurologic symptoms, renal failure, anemia and thrombocytopenia in the setting of a GI illness. Symptoms are a consequence of platelet activation, microvascular thrombi, microangiopathic hemolytic anemia (schistocytes) and thrombocytopenia. Note that the aPTT and PT will be normal (unlike DIC).
DKA treatment
Insulin: allows cells to use glucose for fuel and decreases ketogenesis, decreasing metabolic acidosis. This will also result in increased HCO3- levels and intracellular shift of K+ and need for K+ supplementation.
Normal saline: rehydrates the patient and normalizes serum [Na]
Common cause of membranous nephropathy?
Hep B, hep C, malaria, syphilis, penicillamine, gold, NSAIDs and systemic diseases.
Innervation of the external urethral sphincter
Pudendal nerve
Octahedron, envelope-like crystals that form at a lower pH and are radiopaque,
Ca-oxalate, most common
Elongated, wedge-shaped crystals that form crystals at a higher pH and are radiopaque
Ca-phosphate
Rectangular coffin-lid prism crystals that form at a higher pH and are radiopaque
Mg-NH4-PO4 (struvite). Associated with UTI bugs that have urease
Yellow, red or brown rhomboid-shaped crystals that form at a lower pH and are radiolucent
Uric acid crystals
Flat, yellow and hexagonal crystals that form at a lower pH and are radiopaque
Cysteine crystals that form due to AR mutation in defective “COLA” (cysteine, ornithine, lysine and arginine) transport across intestinal and renal tubular epithelium.
Net excretion rate
Total filtration rate - tubular reabsorption rate
TFR = GFR x [substance x in plasma] GFR = inulin clearance
beta-blocker effect on RAAS
Inhibit renin release by blocking beta-1 stimulation
