UWORLD - RENAL & GENITOURINARY

Mixed acid base disorders involve 2+ primary disturbances. It either has a very abnormal pH or a near normal pH due to significant abnormalities in both HCO3= and PaCO2. Step by step approach...

1. evaluate pH 2. identify primary process - bicarbonate and respiratory. The parameter shifted in the direction that explains the pH disturbance explains the primary disturbance (if pH is low and bicarbonate is also low - then it is the primary). 3. Then determine the compensation. Metabolic disturbances should quickly be compensated via alveolar ventilation changes. You should develop respiratory alkalosis with a low bicarbonate. If you have elevated PaCO2 - it is a mixed disturbance and a second primary disturbance. Then, explain why. Sepsis is a common cause of mixed disturbance. Lactic acidosis in respiratory can cause metabolic acidosis, but you can get respiratory muscle fatigue from high ventilatory demand can cause respiratory failure and the respiratory acidosis, for example.

Drug induced Rhabdomyolysis

Direct myotoxicity: statins, colchicine, ethanol, cocaine Vasoconstrictive: cocaine, amphetamines Prolonged immobilization: ethanol, opioids, benzodiazepines.

Patient with persistent proteinuria (moderately increased albuminuria - albumin:creatinine ratio of 30:300mg/g). Start screening at diagnosis of type 2 DM and after 5 years of diagnosing type I. Look for diabetic nephropathy (hyper filtration injury) in patients with long standing diabetes and poorly controlled HTN. In renal artery stenosis, you get poorly controlled HTN but persistent proteinuria is an UNCOMMON finding. Compare the two.

Acute interstitial nephritis: acutely elevated Cr, pyuria (eosinophilia) and white cell casts in urine. Patient can also have dark urine and mild proteinuria. Non-renal presentation? fever, maculopapular rash, and renal failure.

Membranoproliferative glomerulonephritis is unique because it is caused by activation of alternative complement pathway. Dense intramembranous deposits that stain for C3 is a characteristic microscopic finding.

Anti-GBM - Goodpastures Circulating immune complexes - Immune complex mediated glomerlonephropathies such as SLE, PSGN, etc. Cell mediated - important in idiopathic crescentic glomerulonephritis Nonimmunologic damage - diabetic nephropathy, hypertensive nephropathy

Acute kidney rejection: T-cell mediated, occurs within 6 months of transplant. Asymptomatic rise in serum creatinine. Renal biopsy: lymphocytic infiltration of the intima. Treatment: High dose IV glucocorticoids.

BK Virus activation: results from excessive immunosuppression in renal allograft recipients and leads to tubulointerstitial nephritis. Asymptomatic rise in creatinine as well but renal biopsy reveals intranuclear inclusions and a mixed lymphocytic and neutrophilic infiltrate.

Cardiovascular risk factors in ESRD patients

CKD is an independent RF for CVD, likely due to renal dysfunction or renal replacement therapy. Metabolic abnormalities such as hyperphosphatemia and increased calcium (given to correct hyperphosphatemia) can result in arterial deposition of calcium. Uremia causes oxidative stress which also accelerates atherogenesis.

Painful skin lesions in a patient who has ESRD is actually due to hyperphosphatemia. Calciphylaxis (characterized as systemic arteriolar calcification) will happen in ESRD patients on hemodialysis, or in those with kidney transplants. The lesions are plaques and nodules that can be violaceous or purpuric. It is more common in areas of adiposity. In contrast to atherosclerotic ischemia, it usually has intact peripheral pulses. Labs and workup?

Calciphylaxis labs: High PTH, high phosphate Hypercalcemia and elevated calcium-phosphate product increases the risk, although normal serum calcium levels do not rule out calciphylaxis because tissue calcium concentrations may be much higher due to local inflammatory changes. Also known as calcific uremic arteriolopathy.

Acute Ureterilithiasis causes severe flank pain, vomiting and hematuria. Acute obstruction of the ureter at the vesico-ureteral junction causes pain that radiates to the groin or inner thigh. What type of stone is most common?

Calcium Oxalate (radio-opaque) Serum calcium usually normal. RFs: dehydration, excess sodium or oxalate in diet, obesity, hyperparathyroidism, malabsorption disorders (Crohn's, bowel resection).

Best next step in diagnosing a patients acid-base status?

Calculate PLASMA anion gap

Hypotonic hyponatremia can occur due to SIADH - medications that cause it? & What are the lab findings?

Carbamezepine, SSRIs, NSAIDs

Contrast induced nephropathy causes an acute rise in creatinine within 24-48 hours.

Causes ATN (cytotoxicity) and Pre-Renal AKI (vasoconstriction)

Uncomplicated cystitis (dysuria, urinary frequency, suprapubic tenderness) suggests uncomplicated cystitis. Can treat with clinical diagnosis and no urinalysis etc. Give oral fluoroquinolone or nitrofurantoin or fosfomycin. Severe cases may require IV broad spectrum antibiotics such as ceftriaxone.

Complicated cystitis refers to presence of RFs that increase risk of treatment failure. These include diabetes, CKD, pregnancy, immunocompromised state, urinary tract obstruction, hospital acquired infection or infection associated with procedure (cystoscopy) or indwelling foreign body (Catheter, stent). These patients should have urine culture prior to therapy.

How do you prevent calcium stones?

Dietary recommendations for patients with renal calculi are: Increased fluid intake Decreased Sodium Intake Normal Dietary Calcium intake

HIV associated nephropathy

Direct infection of renal epithelial cells by HIV. presents with heavy proteinuria, rapidly progressive renal failure and edema. Most common in Africans with HIV (possibly due to APOL1 gene that confers resistance to trypanosomiasis but increases suceptibility too HIVAN. BK virus induced nephropathy causes progressive renal failure but is characterized by an interstitial nephritis with hematuria, pyuria, and white cell casts. Primary membranes nephropathy causes nephrotic syndrome and slow progressive CKD, but most have normal Cr on presentation. Secondary membranoius nephropathy is associated with Hepatitis B and C, not HIV.

A urine osmolality of <100 mOsm/kg suggests primary polydipsia or malnutrition (beer potomania). More common in patients with psychiatric conditions, possibly due to a central defect in thirst regulation.

Diabetes inspidus (central or nephrogenic) is due to decreased ADH action -> decreased water reabsorption, water loss with polyuria, and dilute urine. Patients typically develop hypernatremia.

Lithium induced nephrogenic diabetes insipidus results from lithium accumulation in the collecting ducts -> ADH resistance and impaired renal water absorption.

Diabetes inspidus is a leading cause of hypernatremia. It usually presents with severe polyuria and mild hypernatremia. DI can be complete (urine osmolality <300mOsm, often less than 100), or partial (300-600mOsm/kg). SERUM OSMOLALITY IS ELEVATED IN BOTH TYPES

Angiotensin II blockade in early diabetic nephropathy helps to reduce glomerular hyperfiltration that is due to hormonal renal afferent vasodilation and efferent vasoconstriction. Consequent increase in glomerular hydrostatic pressure sitmulates glomerular capillary sclerosis and facilitates gradual progression of DN. ACE inhibitors and angiotensin II receptor blockers decrease efferent vasoconstriction to slow progression.

Diabetic nephropathy presentation: Nocturia, dribbling, weak urinary stream (similar to BPH/obstructive uropathy). However, an elevated protein urine and elevated creatinine gives suspicion for diabetic nephropathy in a diabetic (long standing - 5-10 years). (microangiopathy - that predominantly affects glomeruli)

Mixed cryoglobulinemia is a vasculitis with immune complex deposition in small and medium sized vessels. patients typically have palpable purpura on their lower extremities, peripheral neuropathy, liver involvement, arthralgia, and systemic symptoms (fatigue, weakness). Up to 60% develop renal disease, most commonly glomerulonephritis (manifests as HTN, RF, proteinuria, hematuria, and RBC casts on microscopy. Strong association with hepatitis C, HIV, Hep B, autoimmune diseases, and lymphoproliferative disorders.

Diagnosis? Assay for cryoglobulins (Immunoglobulins that precipitate in colder temperatures) that classically contain RF (IgM against IgG and polyclonal IgG. *Compare to AA amyloidosis nephritis in RF Tissue biopsy: small vessel leukocytoclastic vasculitis. Tx underlying disease.

Patients with COPD often have chronic CO2 retention, resulting in respiratory acidosis and compensatory metabolic alkalosis. Diuretics to treat cor pulmonale symptoms should be used cautiously as they reduce CO and cause pre-renal AKI.

Diuretics can cause hypokalemia and metabolic alkalosis

Severe hypercalcemia can be due to an underlying malignancy. Patients are usually volume depleted due to polyuria and decreased oral intake. Initially -> volume repletion and calcitonin to inhibit bone resorption. Bisphosphonates can further reduce calcium and are given after the initial saline administration.

Diuretics can worsen it. Multiple myeloma can also cause severe hypercalcemia with pancytopenia.

Pre-Renal azotemia/AKI is characterized by....

Elevated creatinine elevated BUN with BUN:Cr >20 Elevated anion gap metabolic acidosis (may or may not be present; usually due to uremia) If caused by diuretics, K+ may be normal because diuretics cause hypokalemia and AKI would negate that.

Envelope shaped crystals are seen in what toxicities?

Ethylene glycol (antifreeze) ingestion - metabolic acidosis with anion gap (complication - acute renal failure) Methanol ingestion as well (complication - antifreeze)

What stimulates ADH secretion?

Exercise associated hyponatremia usually occurs due to ingesting large amounts of hypotonic fluid during and immediately following prolonged exercise. It can cause SIADH, because they develop a temporary inability to excrete appropriately dilute urine (osmolality remains >100mOsm/kg H2O) - consistent with an excess of ADH. In these individuals, excessive ADH is triggered by non osmotic stimuli (exertion, pain, hypoglycemia, nausea) that occur during intense exercise.

Primary renal causes of Nephrotic Syndrome

FSGS is the most cause of nephrotic syndrome in adults in the US, especially in African Americans. If no known amyloidosis or diabetes, most likely etiology of nephropathy is primary renal disease!

Asymptoamtic hypercalcemia, normal renal function, normal-high PTH level and low urinary calcium secretion?

Familial hypocalciuric hypercalcemia. Benign AD disorder. In FHH, higher calcium levels are required to suppress PTH. Concurrently, defective CaSR leads to increased reabsorption of calcium in the renal tubules. In the evaluation of hypercalcemia, an elevated (or inappropriately normal) PTH level suggests either primary hyperparathyroidism or FHH. However, patients with primary hyperparathyroidism have increased urinary calcium secretion due to excessive mobilization of calcium from bones, whereas patients with FHH usually have very low urinary calcium levels (typically <100mg/24hr) Urine calcium excretion can be more precisely assessed using the urine calcium/creatinine clearance ratio (UCCR).

Renal Cell Carcinoma

Flank pain, hematuria, palpable abdominal renal mass Scrotal varicoceles (left sided) Paraneoplastic syndromes (anemia, erythrocytosis) Thrombocytosis Fever Hypercalcemia Cachexia

Postictal lactic acidosis (due to skeletal muscle hypoxia and impaired hepatic lactic acid uptake) commonly occurs allowing a tonic-clonic seizure. it is a transient anion gap metabolic acidosis that resolves without treatment within 90 minutes following resolution of seizure activity. If not resolved -> investigate other causes (intoxication, sepsis).

Give sodium bicarbonate in severe acute metabolic acidosis with pH 7.1. Administration of sodium bicarbonate may cause myocardial depression and increased lactic acid production, therefore the relatively small benefits in patients with pH >7.1 do not typically outweigh the risks.

RTA is a group of disorders characterized by non-anion gap metabolic acidosis. Cortical collecting tubule is the site for H+ and K+ exretion, which is regulated by aldosterone. Impaired function due to aldosterone deficiency will cause these 2 to retain and is called hyperkalemic RTA (or type 4 RTA)

Hyperkalemic RTA is commonly seen in elderly patients due to poorly controlled diabetes -> damage to the JG apparatus -> hyporeninemic hypoaldosteronism

Side effects of loop diuretics?

Hypokalemia Metabolic Alkalosis Pre-renal kidney injury

Chronic alcoholism - most common electrolyte abnormality and what is so difficult about it?

Hypomagnesemia. Hypomagnesemia that occurs with hypokalemia is a well known cause of refractory hypokalemia that won't correct with potassium. Intracellular magnesium is thought to inhibit K+ secretion by renal outer medullary potassium channels (ROMK). Must restore magnesium first to see K+ levels correct.

Lupus Nephritis

Immune complexes of dsDNA and ant dsDNA antibodies deposit in mesangoum/subendothelial space -> trigger of complement -> lowering C3-C4. Can also deposit in sub epithelial space, causing nephrotic syndrome. May see eosinophil casts as part of WBC casts.

Orthostatic hypotension with abnormal serum and urine chemistries (hyponatremia, hypokalemia, hypochloremia, and increased urinary sodium and potassium). Diuretic Abuse vs Self induced vomiting?

In self induced vomiting - urinary sodium will be low as the kidneys try to conserve water by maximally resorbing sodium and water. Urinary sodium is high in diuretic abuse. Serum chloride is low in both disorders. Both can be seen in patients trying to lose weight.

Causes of hypokalemia

Intracellular entry (with insulin, beta adrenergic agents, hematopoiesis) GI losses Renal K+ wasting (hyperaldosteronism, diuretics)

Anion Gap Metabolic Acidosis - Alkalosis with a primary decrease in HCO3 (<24). Due to non-chlorinated acids in the serum Na - (HCO3 + Cl) M/C Causes are MUDPILES

Lactic acidosis (lactate) Ketoacidosis Methanol/formaldehyde Ethylene glycol (glycolic and oxalic acid) Salicylate poisoning Uremia

Acute Interstitial Nephritis - what causes it?

Medications such as sulfonamides, penciillins, cephalosporins, trimethoprim, rifampin, NSAIDs and diuretic. Other medications include phenytoin and allopurinol. Less commonly, infectious agents can cause it too (legionella, mycobacterium tuberculosis and streptococcus).

Vomiting and NG suctioning causes loss of hydrogen, chloride and potassium ions. This leads to...

Metabolic Alkalosis Hypochloremia Hypokalemia. Bicarbonate is only elevated because of hydrogen loss and RAAS activation! Small anion gap can occur due to akalemia causing albumin to release hydrogen ions, which results in an increased anionic charge of albumin and a higher anion gap. Give isotonic NaCl Saline and K+

Rhabdomyolysis can occur from prolonged immobilization (i.e. patients on opioids or benzos). They may have ischemic compression of dependent areas of skeletal muscle (mottled skin over back, buttocks and posterior thighs). AKI in rhabdomyolysis predominantly occurs due to decreased renal perfusion (intravascular volume depletion from shifting fluid into damaged muscle tissue) and direct renal tubular toxicity of heme pigments, which are contained in myoglobin proteins released from lysed muscle cells. It presents with dark urine, blood on urinalysis with no RBCs on urine microscopy, and AKI. An increase in serum creatinine is often delayed from presentation but can become profound.

Next best step? Monitor with serial... Treatment?

Leukocyte esterase: signify significant pyuria. Nitrites: signifies presence of enterobacteriae. Positive for esterase and nitrites in UTI, pyelonephritis (flank pain + fever)... Dipsticks reduce necessity for urine culture, however, patients with positive dipsticks still should have urine culture done...Workup of a UTI?

Next best step? Do you diagnose further or just treat?

Hyperkalemia that occurs out of proportion to renal dysfunction and non-anion gap metabolic acidosis indicate a renal tubular disorder i.e. renal tubular acidosis. What are some causes of normal anion gap metabolic alkalosis? Also, you do not need pH to determine acid/base. Low bicarbonate + electrolyte abnormalities - you know there is an acidosis

Normal anion gap metabolic alkalosis Diarrhea Fistulas Carbonic anhydrase inhibitors Renal tubular acidosis Ureteral diversion (i.e. ileal loo

Nephrotic syndrome does not need an elevated creatinine. Edema, hypoalbuminemia and urinary protein >3.5g/day suffices. Low plasma oncotic pressure due to hypoalbuminiemia increases hepatic lipoprotein synthesis -> increase in serum cholesterol and triglyceride levels. Patients can also be hypercoaguable due to loss of antithrombin III.

Other complications of nephrotic syndrome: Protein malnutrition, iron resistant microcytic hypo chromic anemia, increased susceptibility to infection, and vitamin D deficiency due to urinary excretion of cholecalciferol binding protein, decreased thyroxin levels due to loss of thyroxine binding globulin and.

A serum BUN:Cr ratio is typically 10-15 in acute tubular necrosis, in contrast to pre-renal azotemia it is >20. Other findings in ATN are: Urine osmolality 300-350 (never <300). Urine Na >20 mEq/L FeNa >2%

Prolonged hypotension from any cause can lead to ATN. Muddy brown casts are nonspecific but very sensitive.

Hepatorenal syndrome occurs in patients with liver failure. It is due to renal hypo perfusion from splanchnic dilation. Patient won't respond to fluids or blood transfusion.

Patients have acute renal failure (creatinine >1.5mg/dL) with a very low urine sodium (<10mEq/L) with no casts, RBCs or protein in urine. Renal vein thrombosis is more likely in patients with hyperocoaguability, trauma, or nephrotic syndrome, or severe dehydration. They present with abdominal pain and hematuria.

Occlusion of the left renal vein causes markedly increased GFR and causes hematuria and left sided flank pain. Because the left gonadal vein drains into the left renal vein, obstruction also causes left gonadal vein dilatation. RFs: nephrotic syndrome (especially membranous nephropathy), renal malignancy and trauma.

Patients with RVT & AKI should have urgent clot removal (thrombolysis). Otherwise, anticoagulation alone is appropriate.

Glomerular Hemturia vs Nonglomerular

RBC casts or dysmorphic RBCs -> glomerulonephritis

Renal artery stenosis is most often seen in patients with diffuse atherosclerosis (PVD etc.) and results in renovascular hypertension - the most common, correctable cause of secondary HTN. Limiting blood flow to the poststenotic kidney causes RAAS activation. It improves RBF and GFR but worsens sodium retention, volume expansion, vasoconstriction and HTN. Give ACEIs and ARBs due to their ability to reduce angiotensin II. Patients on these meds with RAS are less likely to develop MI - but higher risk of AKI so must monitor accordingly. Additionally, add aggressive RF reduction (ASA, diabetes, hyperlipidemia control, smoking cessation) to prevent CVD.

Renal artery stunting or surgical revascularization is reserved for patients with resistant HTN or recurrent flash pulmonary edema and/or refractory HF due to severe hypertension!

What does hyperventilation do to calcium homeostasis?

Respiratory alkalosis causes elevations in blood pH which decreases serum ionized calcium by dissociation of hydrogen ions bound to albumin. This causes increased calcium binding -> decreases serum ionized calcium. Lowering pH causes an increase of H+ ions bound to calcium leading to increase in serum ionized calcium. Note: only ionized calcium is active calcium.

Differential diagnosis of metabolic alkalosis - Saline responsive

Saline responsive metabolic alkalosis is commonly due to loss of gastric secretions (self induced vomiting, spontaneous vomiting or NG suctioning). Patients typically develop volume depletion (hypotension, orthostasis) and low serum Cl due to chloride loss in secretions. ECF loss stimulates renal mineralocorticoids -> increased Na and Cl resorption (low urinary Cl), and H+ and K+ secretion. Prior diuretics reduce chloride as well, but current use raises urine chloride. Low serum chloride also impairs renal HCO3- excretion and further worsens the alkalosis. Corrects with isotonic saline and restores both ECF and chloride.

Hyperkalemia warrants an ECG. Patients then need to be evaluated for acute treatable secondary causes (uncontrolled hyperglycemia, medications...). Patients should then have a review of recent/current medications as they frequently can cause hyperkalemia.

The most common causes of hyperkalemia include acute or chronic CKD. Common offending medications include nonselective beta-adrenergic blockers, potassium sparing diuretics (triamterene), ACE inhibitors, Angiotensin II receptor blockers, and NSAIDs.

First line treatments for urgency incontinence are bladder training and pelvic floor muscle exercises. Nonresponders can use an antimuscarinic agent (oxybutynin) to decrease detrusor activity and increase bladder capacity by reducing ACh activity.

Vaginal pessary is for symptomatic organ prolapse and stress incontinence when surgical correction (midurethral sling surgery) fails or is contraindicated. A pessary can reduce urine loss in patients with stress incontinence by increasing bladder outlet resistance.

Hypovolemia or decreased perfusion stimulates RAAS to improve intravascular volume, GFR and BP. Renin converts angiotensinogen to Angiotensin I, which is then converted to Angiotensin II by ACE...this causes...

Vasoconstriction: increased efferent and systemic artiolar resistance to improve GFR and BP Sodium and Water resorption: direct effect on the proximal tubule to reabsorb sodium Aldosterone secretion: increases sodium and water resorption in distal tubule Activated by: acute gallstone pancreatitis (vomiting), anything reducing oral intake, increasing vomiting or diarrhea etc.

Simple renal cysts found on imaging DO NOT require further follow-up normally, because they are benign lesions. They usually do not cause symptoms such as flank pain, HTN, hematuria etc. What qualities found on imaging, however, will raise suspicion for possibility of malignancy?

multilocular mass, irregular walls, thickened septum and contrast enhancement