Renal and Urinary Systems Flashcards
DDX for WBC casts?
Pyelonephritis
Acute intersitial nephritis
DDx for muddy brown casts?
Acute tubular necrosis
Can be caused by ischemic AKI or nephrotoxic AKI (antibiotics, radiocontrast agents, NSAIDs, poisons, myoglobinuria, hemoglobinuria, chemotherapy, AL in MM)
Metabolic derangements in AKI
Hyperkalemia
Anion gap metabolic acidosis
Hypocalcemia
Hyponatremia
Hyperphosphatemia
Hyperuricemia
Metabolic derangements in CKD
Hyperkalemia
Hypermagnesemia
Hyperphosphatemia (decreased GFR → decreased excretion)
Metabolic acidosis
Hypocalcemia (decreased 1,25-OH vitamin D)
Side effects of ACEI
ACEIs dilate afferent arteriole
Hyperkalemia (↓ aldosterone)
Angioedema, cough (↓ breakdown of bradykinin)
Absolute indications for dialysis
AEIOU:
Acidosis
Electrolyte abnormalities
Intoxications
Overload, hypervolemic
Uremia based on clinical presentation (e.g. AMS, pericarditis)
Minimal change disease
Most common in children
May present as nephrotic syndrome
A/w lymphomas
Microscopy: no changes on light microscopy, foot process fusion
Tx: 4-8 weeks of steroids
Focal segmental glomerulosclerosis (FSGS)
Nephrotic
More common in Blacks
Microscopy: focal segmental sclerosis, foot process fusion
No immunofluorescence
A/w HIV, heroin use, sickle cell disease
Does not respond well to steroids
Membranous nephropathy
Nephrotic
IgG4 antibodies to phospholipase A2 receptor
LM: thick glomerular basement membrane without an increase in cellularity
IF: granular deposits of IgG and C3 along glomerular basement membrane
EM: “spike and dome” apperance with subepithelial deposits
A/w: Hep B, Hep C, SLE
Does not respond well to steroids
Post-infectious glomerulonephritis
Nephritis 10-21 days following URI or skin infection; abx treatment of the infection does not decrease risk of post-infectious glomerulonephritis
LM: enlarged and hypercellular glomeruli
IF: “lumpy-bumpy” granular deposits of IgG, IgM and C3 –> low C3 complement
EM: subepithelial immune complex humps
Elevated anti-streptolysin O and/or anti-DNAse B
Adult onset is poor prognostic factor
IgA nephropathy (Berger disease)
Nephritis 5 days following URI or gastroenteritis
IF: grandular deposits of IgA in mesangium
Normal complements
a/w Henoch-Schonlein purpura
Prostate cancer
Risk factors include age, African American race, high-fat diet, FHx, exposure to herbicides and pesticides
Mostly adenocarcinoma, starts at periphery
Mostly asymptomatic but can cause obstruction in late phase
Likes to metastasize to bone (pelvis, vertebral bodies, long bones in the legs)
Tx: radiation + androgen deprivation OR prostatectomy OR orchiectomy, antiandrogens, leuprolide, GnRH antagonists
Describe the embryology of the kidneys?
Derived from intermediate mesoderm
Pronephros forms in week 4 and degenerates into:
Mesonephros for the first trimester and converts into:
Metanephros which is permanent (appears in week 5 and continues to develop until weeks 32-36). Glomerular filtration starts at 12 weeks but excretion of waste still handled by the placenta. Nephron formation is complete at term.
- Ureteric bud branches from the mesonephric duct to form the ureter, pelvises, calyces, and collecting ducts
- Metanephric mesoderm forms glomerulus through distal convoluted tubules
As the kidney ascends, it’s blood supply changes from internal illiac to inferior mesenteric to renal arteries
Mesonephric/Wolffian duct becomes vas deferens
Describe the embryology of the adrenal glands?
Cortex = intermediate mesoderm
Medulla = neural crest
How are the left and right gonadal veins different?
Left gonadal vein drains into the left renal vein
Right gonadal vein drains into the IVC
How do you calculate renal clearance (i.e. effective renal plasma flow)?
Clearance (mL/min) = (Urine concentration x urine flow rate)/plasma concentration
Renal blood flow = Renal plasma flow/(1-Hct)
*You can estimate GFR using inulin or creatinine because amount filtered = amount excreted
*You can estimate effective renal plasma flow using para-aminohippuric acid because amount excreted > amount filtered
How does the histology vary between the proximal and distal convoluted tubules?
Both are made of simple cuboidal cells but proximal convoluted tubules have a brushed border while distal convolutued tubules don’t but have buldging apical nuclei
What is the difference between dark and light cells in collecting duct?
Dark/intercalating cells are darker-staining, more common in the cortex, and maintains acid-base balance
Light/principle cells are light-staining and moderate water resorption (ADH sensitive, lots of aquaporins)
How do you calculate plasma osmolarity?
Posm = 2Na+ + Glucose/18 + BUN/2.8
What is Hartnup disease?
Autosomal recessive deficiency in neutral amino acid transporters in the proximal renal tubule
S&S: neutral aminoaciduria, pellagra-like symptoms (dermatitis, diarrhea, depression 2/2 lack of tryptophan or nicotinic acid)
Tx: high-protein diet, nicotinic acid
Describe the physiology of water regulation in the body?
Plasma osmolarity is sensed by osmoreceptors in the hypothalamus and effective circulating volume is sensed by baroreceptors in the carotid sinus and the aortic arch.
An increased in Posm or decreased in ECV stimulates thirst and release of ADH from the posterior pituitary. ADH binds to V2 receptors in principle/light cells of the collecting duct –> phosphorylation of aquaporin 2 –> insertion of channel into apical membrane
Describe the physiology of sodium regulation in the body?
Excess sodium increases plasma osmolarity which increases effective circulating volume which is sensed by baroreceptors (heart) and the macula densa (kidney). Regulation is controlled by RAAS, sympathetic nervous system, and natriuretic peptides (works opposite of RAAS).
Proximal tubule: sodium-coupled cotransporters and exchangers
Thick ascending limb: Na-K-2Cl cotransporter
Distal convoluted tubule: Na-Cl co transporter
Collecting duct principle cells: ENac (upregulated in response to aldosterone)
Describe the physiology of potassium regulation in the body?
Increased K+ stimulates increases in insulin and epinephrine which drives K+ into cells. High extracellular K+ activates the Na/K ATPase in renal tubular cells –> increased intracellular K+ –> increased efflux of K+ into tubular fluid. High K+ also stimulates aldosterone secretion which increases K+ excretion in the kidneys by increasing expression of apical K+ channels.
How is calcium and phosphate handled in the kidneys?
Calcium passively diffuses through tight junctions in the proximal convoluted tubules. PTH increases synthesis of calcium transporters increasing calcium reabsorption thus decreasing excretion. PTH reduces the transport maximum of the phosphate transporter increasing excretion of phosphate.
What is different about the handling of magnesium in the kidneys?
Unlike other substances that are mostly reabsorped in the proximal convoluted tubule, most magnesium (70%) is reabsorped in the loop of Henle.
What stimulates release of renin from juxtaglomerular cells?
Renin secretion is induced by low BP, low Na+ delivery to macula densa of distal convoluted tubule, or increased sympathetic tone at β1 receptors (β-blockers decrease renin thus decrease BP).
How do you calculate filtration fraction?
FF= GFR/RPF
How does afferent or efferent constriction change GFR, RBP, or FF?
Afferent arteriole constriction (i.e. NSAIDs) → decreased renal plasma flow → decreased capillary hydrostatic pressure → decreased GFR; RPF and GFR both decrease so FF unchanged
Efferent arteriole constriction (i.e. RAAS activation) → increased capillary hydrostatic pressure → increased GFR + decreased RPF → increased FF
What is the blood supply to the ureters?
Proximal part → renal artery
Distal part → superior vesicle artery
Inbetween → anatamosis from gondal, common and internal iliac, aorta, and uterine arteries
How do you calculate net filtration pressure?
Net filtration pressure = K (hydrostatic pressure of glomerular capillaries - hydrostatic pressure of Bowman’s space) - (oncotic pressure of glomerular capillaries - oncotic pressure of Bowman’s space)
Furosemide
Sulfonamide loop diuretic: inhibits Na-K-2Cl symporters in the thick ascending limb of the loop of Henle → increased Na and Cl excretion → increased water excretion
Loop diuretics also stimulate renal prostaglandins which dilate the afferent arteriole → increased renal blood flow → increased GFR → increased drug delivery
Concurrent use of NSAIDs will blunt diuretic response
Indicated for edematous states, HTN, hypercalciuria (Loops loose calcium)
SA: ototoxicity, hypokalemia, dehydration, sulfa allergies, interstitial nephritis, gout
Spironolactone
Competitive aldosterone receptor antagonist in the cortical collecting tubule (K+ sparing diuretic)
Indicated for hyperaldosteronism, K+ depletion, CHF (proven to reduce mortality)
SA: hyperkalemia → arrhythmias, endocrine effects such as gynecomastia, antiandrogen effects
Anti-glomerular basement membrane disease
Presents as nephritic syndrome
Anti-glomerular basement membrane antibodies target type IV collagen → linear deposits of IgG and C3 along the glomerular basement membrane → crescents
Antibodies may also cross-react with type IV collagen in pulmonary basement membrane causing pulmonary hemorrhage and hemoptysis (renal and lung involvement = Goodpasture syndrome)
Eplerenone
Competitive aldosterone receptor antagonist in the cortical collecting tubule (K+ sparing diuretic)
Indicated for hyperaldosteronism, K+ depletion, CHF (proven to reduce mortality)
SA: hyperkalemia → arrhythmias; fewer side effects than spironolactone
Triamterene
Na+ channel blockers in the cortical collecting tubule (K+ sparing diuretic)
Indicated for hyperaldosteronism, K+ depletion, CHF
SA: hyperkalemia → arrhythmias
Amiloride
Na+ channel blockers in the cortical collecting tubule (K+ sparing diuretic)
Indicated for hyperaldosteronism, K+ depletion, CHF
SA: hyperkalemia → arrhythmias
Mannitol
Osmotic diuretic → increased tubular fluid osmolarity → increased urine flow → decreased intracranial/intraocular pressure
Indicated for drug overdose, increased intracranial/intraocular pressure
SA: pulmonary edema, dehydration
Contraindicated in anuria, CHF
Acetazolamide
Carbonic anhydrase inhibitor → NaHCO3 diuresis and decreased total body HCO3- stores
Indicated for glaucoma, urinary alkalinization, metabolic alkalosis, altitute sickness, pseudotumor cerebri
SA: hyperchloremic metabolic acidosis, paresthesias, NH3 toxicity, sulfa allergy
Ethnacrynic acid
Phenoxyacetic acid loop diuretic: inhibits Na-K-2Cl symporters in the thick ascending limb of the loop of Henle → increased Na and Cl excretion → increased water excretion
Loop diuretics also stimulate renal prostaglandins which dilate the afferent arteriole → increased renal blood flow → increased GFR → increased drug delivery
Concurrent use of NSAIDs will blunt diuretic response
Indicated for edematous states, HTN, hypercalcemia
SA: ototoxicity, hypokalemia, dehydration, slfa allergies, interstitial nephritis, hyperuricemia → don’t use with gout
Hydrochlorothiazide
Thiazide diuretic: inhibits NaCl reabsorption in early distal tubule → decreased diluting capacity of the nephron; decreased calcium excretion
Indicated for HTN, CHF, idiopathic hypercalciuria, nephrogenic DI, osteoporosis
SA: hypokalemic metabolic alkalosis, hyponatremia, hyperglycemia, hyperlipidemia, hyperuricemia, hypercalcemia, sulfa allergy
Captopril
ACE inhibitor → decreased angiotensin II → dilation of efferent arteriole → decreased GFR
Indicated for HTN, CHF, proteinuria, diabeic nephropathy, prevention of unfavorable remodeling as a result of chronic HTN or MI
SA: cough (ACEI prevent inactivation of bradykinin), angioedema, teratogen, increased creatinine due to decreased GFR, hyperkalemia, hypotension
Contraindicated in bilateral renal stenosis (further decrease in GFR → renal failure)
-sartans
Angiotensin II receptor blockers (ARBs)
Decreased risk of cough or angioedema because it does not increase bradykinin
How do diuretics affect serum calcium concentration?
Loop diuretics can cause hypocalcemia → hypercalciuria (Loops Loose calcium).
Thiazide diuretics can cause hypercalcemia → hypocalciuria
How do diuretics affect serum potassium concentration?
Serum potassium increases with K+ sparing diuretics and decreases with loop and thiazide diuretics.
What effects do diuretics have on acid-base status?
Carbonic anhydrase inhibitors and K+ sparing diruetics may cause acidemia.
Loop and thiazide diuretics may cause alkalemia.
Fanconi syndrome
Reabsorptive defect in proximal convoluted tubule → increased excretion of amino acids, glucose, HCO3- (proximal renal tubular acidosis), PO43-
Bartter syndrome
Reabsorptive defect in the thick ascending loop of Henle (Na/K/2Cl cotransporter) → hypokalemia, metabolic alkalosis with hypercalciuria
Gitelman syndrome
Reabsorptive defect of NaCl in distal convoluted tubule → hypokalemia, metabolic alkalosis without hypercalciuria
Liddle syndrome
Increased activity of ENac channels in collecting duct → increased sodium reabsorption → HTN, hypokalemia, metabolic alkalosis, decreased aldosterone
Autosomal dominant
Tx: amiloride
Causes of respiratory acidosis?
Hypoventilation from airway obstruction, lung disease, opioids, weakening of respiratory muscles
Causes of metabolic acidosis?
Anion-gap metabolic acidosis:
MUDPILES
Methanol
Uremia
Diabetic ketoacidosis
Propylene glycol
Iron/Isoniazid
Lactic acidosis
Ethylene glycol
Salicylates
Non-anion gap metabolic acidosis:
HARDASS
Hyperalimentation
Addison disease
Renal tubular acidosis
Diarrhea
Acetazolamide
Spironolactone
Saline infusion
Causes of respiratory alkalosis?
Hyperventilation from hysteria, hypoxemia, salicylates, tumor, PE
Causes of metabolic alkalosis?
Loop diuretics (volume contraction → increased angiotensin II → increased Na+/H+ exchange in proximal tubule → increased HCO3- reabsorption), vomiting (removal of HCl from body), antacid use, hyperaldosteronism (increased H+ excretion)
Minimal change disease
Most common cause of nephrotic syndrome in children; inciting event (URI, immunization, insect bite) → podocyte damage and decreased anionic properties of GBM → selective loss of albumin
No changes visible by microscopy
No IF
EM: effacement of foot processes
A/w Hodgkin lymphoma
Responds well to steroids
Membranoproliferative glomerulonephritis
May be nephritic or nephrotic
Type I - subendothelial immune complex deposits with granular IF; “tram-track” appearance due to GBM splitting; a/w Hep B, Hep C
Type II - intramembranous dense immune complex deposits; decreased C3
Diabetic glomerulonephropathy
Nephrotic
Mesangial expansion, GBM thickening (nonenzymatic glycosylation), eosinophilic nodular glomerulosclerosis (Kimmelsteil-Wilson lesion)
Alport syndrome
X-linked mutation in type IV collagen → thinning and splitting of GBM
a/w glomerulonephritis, deafness, and eye problems (less common)
Diffuse proliferative glomerulonephritis
Nephritic or nephrotic
a/w SLE and MPGN
LM: “wire-looping” of capillaries
IF: granular IgG and C3 subendothelial and intramembranous deposits
What effects do ACEI and NSAIDS have on glomerular arterioles?
ACEI dilate efferent arterioles
NSAIDs constrict afferent arterioles (by peventing dilation by prostaglandins)
Using them together can greatly drop GFR causing acute renal failure
Granulomatosis with polyangiitis (Wegener)
Small vessel vasculitis affecting the nasopharynx, lungs, and kidneys
PR3-ANCA/c-ANCA
No immunoglobulin or complement deposits
Microscopic polyangiitis
MPO-ANCA/p-ANCA
No immunoglobulin or complement deposits
Torsemide
Sulfonamide loop diuretic: inhibits Na-K-2Cl symporters in the thick ascending limb of the loop of Henle → increased Na and Cl excretion → increased water excretion
Loop diuretics also stimulate renal prostaglandins which dilate the afferent arteriole → increased renal blood flow → increased GFR → increased drug delivery
Concurrent use of NSAIDs will blunt diuretic response
Indicated for edematous states, HTN, hypercalcemia
SA: ototoxicity, hypokalemia, dehydration, slfa allergies, interstitial nephritis, gout
Chlorthalidone
Thiazide diuretic: inhibits NaCl reabsorption in early distal tubule → decreased diluting capacity of the nephron; decreased calcium excretion
Indicated for HTN, CHF, idiopathic hypercalciuria, nephrogenic DI, osteoporosis
SA: hypokalemic metabolic alkalosis, hyponatremia, hyperglycemia, hyperlipidemia, hyperuricemia, hypercalcemia, sulfa allergy
Bumetanide
Sulfonamide loop diuretic: inhibits Na-K-2Cl symporters in the thick ascending limb of the loop of Henle → increased Na and Cl excretion → increased water excretion
Loop diuretics also stimulate renal prostaglandins which dilate the afferent arteriole → increased renal blood flow → increased GFR → increased drug delivery
Concurrent use of NSAIDs will blunt diuretic response
Indicated for edematous states, HTN, hypercalcemia when furosemide is ineffective
SA: ototoxicity, hypokalemia, dehydration, slfa allergies, interstitial nephritis, gout
Fibromuscular dysplasia
Hypertension in women aged 20-30
Renal arteries look like a “string-of-pearls” on imaging
Metolazone
Thiazide-like diuretic
