UWorld 1 Flashcards
How does the kidney compensate for respiratory alkalosis?
The kidneys retain H ions and excrete increased amounts of bicarb in an attempt to normalize the serum pH. The increased bicarb in the urine increases urine pH
Renal transplant dysfunction in early postop period
Manifests as oliguria, HTN, and increased Cr/BUN. It can be explained by a number of causes:
1) Ureteral obstruction - renal US would show this as dilated calyces
2) Acute rejection - bx of transplant shows heavy lymphocyte infiltration and vascular involvement with swelling of the intima. Normal serum cyclosporine. Transplant feel tender. Tx is IV steroids.
3) Cyclosporine toxicity - No graft tenderness. The transplant’s function is usually restored when the dose of cyclosporine is decreased.
4) Vascular obstruction
5) Acute tubular necrosis - give IV diuretics
MRI and renal bx can be employed in conducted the ddx.
Normal acid-base status
1) pH 7.35-7.45
2) HCO3 22-28
3) PaCO2 33-45
DKA on ABG
Anion gap metabolic acidosis with low PH, low bicarb and compensatory (respiratory compensation) fall in PaCO2 due to Kussmaul breathing via chemoreceptor response (rapid, deep breathing/hyperventilation).
Typical symptoms of DKA (very brief)
Usually in type 1 DM. Polyuria, polydipsia, nausea, vomiting and abdominal pain that may mimic a surgical abdomen.
When should metformin be avoided?
Do not give to acutely ill patients with acute renal failure, liver failure or sepsis. These all increase risk of lactic acidosis.
What is one feared renal complication of cocaine overdose?
Nearly 20% of cocaine overdoses are complicated by rhabdo (marked elevations in serum CPK, high K, urine dipstick positive for blood but no RBCs on microscope - this is due to myoglobin in urine). CPK levels above 20000 is associated with acute renal tubular necrosis due to myoglobinuria.
Risk of rhabdo-induced renal failure is decreased with aggressive hydration. Mannitol and urine alkalinization may also help.
Rifampin urine changes
Rifampin causes red to orange discoloration of body fluids including urine, saliva, sweat and tears. It can also cause discoloration of soft contact lenses.
Get a UA. Absence of significant changes on UA (proteinuria, hematuria, and sterile pyuria) essentially rules out renal TB or TB-associated glomerulopathy) - remember they may have TB if they are on rifampin to begin with so the UA is just making sure there isn’t some TB complication.
First generation H1 antihistamines
Diphenhydramine, chlorpheniramine, hydroxysine. They all also have significant anticholinergic effects (at muscarinic receptors of the parasympathetic nervous system), which can manifest as dryness of eyes, dryness of the oral mucosa and respiratory passages, or urinary retention.
Urinary retention caused by anticholinergic agents results from failure of detrussor muscle contraction and (to lesser extent) impaired bladder sphincter relaxation, both of which are controlled by parasympathetic input from the pelvic splanchnic nerves.
Elderly men, who are likely to have some degree of underlying urinary obstruction due to BPH are at increased risk of developing urinary retention due to anticholinergic agents.
Most common causes of respiratory acidosis
Usually caused by respiratory suppression.
1) Narcotic OD
2) Neuro diseases causing airway muscle weakness
3) COPD
Classic causes of metabolic acidosis
MUDPILES (anion gap)
1) Methanol
2) Uremia
3) DKA
4) Paraldehyde
5) INH
6) Lactic acidosis
7) Ethylene glycol
8) Salicylates
Non-anion gap
1) Diarrhea
2) RTA
Most common causes of metabolic alkalosis
1) Vomiting
2) Hyperaldosteronism
3) Volume contraction
Common causes of respiratory alkalosis
Hyperventilation due to:
1) Pneumonia
2) High altitude
3) Salicylate intox
Brief overview of metabolic alkalosis
Causes: Saline responsive 1) Vomiting 2) Gastric suctioning 3) Diuretics 4) Laxative abuse 5) Decreased oral fluid intake (volume depletion)
Saline resistant
1) Primary hyperaldosteronism
2) Cushing’s Syndrome
3) Severe hypoK (less than 2)
Clinical presentation
1) Volume depletion - easy fatigability, postural dizziness, muscle cramps
2) HypoK - muscle weakness, arrhythmias
3) Urine Chloride - less than 20 is saline responsive. More than 20 is saline resistant.
Tx
1) Treat underlying cause to reverse generation phase in all cases
2) Saline-responsive: Also give NS to correct maintenance phase
Metabolic alkalosis pathophys
MA is due to an underlying disorder producing excess bicarb (generation phase) combined with a process preventing renal bicarb excretion (maintenance phase). MA is further classified as saline responsive or resistant. The generation phase in saline responsive form can be due to urinary or GI Hydrogen loss (diuretics, vomit) or decreased oral intake. Maintenance phase (hypovolemia) prevents the normal kidney from excreting the excess bicarb in the urine.
The kidneys perceive a decreased effective arterial blood volume from the underlying etiology (vomiting with volume depletion) and increase renin and aldosterone release. This leads to sodium reabsorption, K excretion, and H excretion. There is also decreased HCO3 excretion.
If the history cannot reveal the cause of the MA, urine Cl can help. Saline-resistant MA has excess mineralocorticoid causing H and K loss and increased Na retention leading to increased extracellular volume. The kidneys respond by excreting both Na and Cl to result in high urine Cl
Saline-responsive MA has low serum Cl due to hypovolemia and hypochloremia.
Treatment for both types focuses on the underlying cause to reverse generation and increase renal bicarbonate excretion. In saline responsive MA, saline restores arterial volume, corrects hypochloremia and increases urinary bicarb excretion
Membranoproliferative glomerulonephritis (type 2)
Nephrotic range proteinuria and hematuria. Dense intramembranous deposits that stain for C3 is characteristic.
It is caused by IgG antibodies (this is unique) called C3 nephritic factor directed against C3 convertase of the alternate complement pathway. These antibodies reacting with C3 convertase lead to persistent complement activation and kidney damage.
Note: This glomerulonephritis is NOT caused by circulating immune complexes. Those are SLE, PSGN, etc.
What drugs can stimulate hypothalamic ADH production and cause SIADH?
1) Carbamazepine
2) Cyclophosphamide
3) SSRIs like fluoxetine
Glomerular vs non-glomerular causes of hematuria
Glomerular
1) Microscopic is more than gross hematuria
2) Causes include glomerulonephritis and basement membrane disorders (Alport)
3) Presents with nonspecific or no symptoms. Can have nephritic syndrome (HTN, oliguria, elevated Cr)
4) UA shows blood AND protein. RBC casts, dysmorphic RBCs
Non-glomerular (more common)
1) Gross is more than microscopic hematuria
2) Can be caused by kidney stones. Cancer (renal cell, prostate). PCKD. Infections (cystitis). Papillary necrosis. Renal infarction.
3) Presents with dysuria or symptoms of urinary obstruction (flank pain, renal or ureteral colic, anuria)
4) UA shows blood but NO protein. Normal appearing RBCs.
Proteinuria and transient gross hematuria following acute pharyngitis.
Think IgA nephropathy. This is the most common GN in adults. It is typified by hematuria starting within 5 days of an URI or pharyngeal illness. AKA synpharyngitic GN.
Causes of papillary necrosis
This is sloughing of renal papilla. A rare cause of non-glomerular hematuria. May be seen with long term acetaminophen abuse but not with light-intermittent use.
NSAID is the trick.
1) NSAIDs
2) Sickle Cell Disease
3) Analgesic abuse
4) Infection (pyelonephritis)
5) Diabetes mellitus
Tubular origins of hematuria
Acute tubular necrosis is characterized by acute azotemia following a hypotensive or nephrotoxic injury. Patients may have dark or cola urine, but significant hematuria is uncommon.
Tubulointerstitial nephritis causes microscopic hematuria associated with elevated Cr and variable proteinuria. Most commonly linked with certain meds like ABx, NSAIDs and diuretics.
SIADH very brief clinical markers
Hypotonic hyponatremia with euvolemia.
Low plasma osmolality (less than 280) with high urine osmolality (more than 100-150) is diagnostic.
Preferred modality for diagnosing a ureteral stone
Ultrasound or noncontrast CT (US is preferred, esp in patients with a low likelihood of an alternative diagnosis and who are pregnant)
Renal side effect of amitriptyline
Urinary retention (anticholinergic properties). Treat acute urinary retention by stopping offending agent and performing urinary cath.
Bedside US or bladder scan can help in dx by showing post void residual of more than 50cc.
Indications for cystoscopy (6)
1) Gross hematuria with no evidence of glomerular disease or infection
2) Microscopic hematuria with no evidence of glomerular disease or infection but increased risk for malignancy (smoking**, painters, metal workers, chronic cystitis, cyclophosphamide, pelvic radiation exposure)
3) Recurrent UTIs
4) Obstructive symptoms with suspicion for stricture, stone
5) Irritative symptoms without urinary infection
6) Abnormal bladder imaging or urine cytology
Most important risk factor for bladder cancer
Smoking. Smokers have higher risk than nonsmokers even 20 years after quitting.
Probably BPH but risk factors for bladder cancer
Get cystoscopy first then start treatment for BPH if negative. Treatment is alpha antagonists (terazosin, tamsulosin) with or without 5-alpha reductase inhibitors (finasteride)
BPH vs Prostate cancer
BPH - symmetrically enlarged, smooth, no nodules. Age over 50. Central portion (transitional zone). May have elevated PSA.
Cancer - asymmetric enlargement, firm, nodules. These findings prompt a biopsy. Age over 40. African American. Usually lateral lobes but can be anywhere. Markedly elevated PSA.
Chronic alcoholics present with what kinds of electrolyte abnormalities?
1) HypoK
2) HypoMg
3) HypoP
HypoMg causes refractory hypoK - therefore, it is important to correct Mg along with K levels to correct lyte issues.
Risk factors for Acute Urinary Retention
1) Men (rarely happens in women)
2) Advanced age (33% of men over 80 will develop AUR)
3) History of BPH
4) History of neuro disease (mild cognitive impairment)
5) Surgery (esp abdominal, pelvic, and joint replacement)
Also look out for things like opioids or anticholinergics.
AUR diagnosis
Bladder US shows at least 300mL of urine. Tx is with Foley. UA should be collected to rule out UTI
Sometimes, like with obesity, ascites, or tissue edema, bladder US is rendered inaccurate. In these cases, Foley is diagnostic and therapeutic.
2 treatment options for ESRD
Transplant or Dialysis. If both options are available then transplant is better.
Advantages and disadvantages of transplant vs dialysis
Advantages
1) Better survival and QoL
2) Anemia, bone disease, and HTN persist in spite of dialysis. These are better controlled with transplant.
3) Transplant patients have a return to normal endocrine, sexual and repro functions, and enhanced energy levels. Returning to fulltime employment and more strenuous physical activity is possible
4) In diabetics, autonomic neuropathy persists or worsens after dialysis. It stabilizes or improves with transplant
5) Expected survival after transplant is 95% at 1 year and 88% at 5 years.
Disadvantages
1) Trouble finding donor (living related donor has least graft rejection and best graft survival)
2) Surgical risk
3) Side effects of immunosuppression
What is the most common cause of abnormal hemostasis in patients with Chronic Renal Failure?
Platelet dysfunction. PT, PTT, platelet count normal. BT prolonged.
Abnormal hemostasis is common manifestation seen in patients with CRF. Abnormal bleeding and bruising are characteristic of uremic coagulopathy. Now, ecchymoses and epistaxis are the only major bleeding manifestations seen due to the advent of dialysis. However, GI bleeding, hemopericardium, subdural hematoma and bleeding from surgical or invasive sites can still occur due to uremic coagulopathy.
The major defect involves platelet-vessel wall and platelet-platelet interaction. Several uremic toxinc have been implicated in the pathogenesis of platelet dysfunction seen in CRF. The main one is guanidinosuccinic acid. aPTT, PT and thrombin times (TT) are normal. Bleeding time is reflective of platelet dysfunction, and is usually prolonged. The platelet count is normal, but there is platelet dysfunction that causes bleeding.
Desmopression (DDAVP), cryopreciptate and conjugated estrogens have been used to correct the coagulaopthy in uremic patients. DDAVP increases the release of factor 8:vWF multimers from endothelial storage sites. DDAVP is usually tx of choice
Platelet transfusion is not indicated bc the transfused platelets quickly become inactive.
Cystinuria
A group of disorders characterized by impaired amino acid transport and several modes of inheritance. The problem lies with the defective transport* of dibasic amino acids (cystine, ornithine, lysine, arginine - COLA) by the brush borders of renal tubular and intestinal epithelial cells. Cystine is poorly soluble in water. This leads to formation of hard, radioopaque renal stones.
Clues are history of recurrent stones since childhood, positive family history, typical hexagonal crystals on UA, and positive urinary cyanide nitroprusside test.
Urinary cyanide nitroprusside test can detect elevated cystine levels which can help confirm the dx. It is especially useful in detecting homozygotes. It is a qualitative screening measure.
Unfavorable metabolic side effects of thiazide diuretics (chlorthalidone, HCTZ)
1) Hyperglycemia (seen more in patients with DM and metabolic syndrome)
2) Increased LDL and triglycerides
3) Hyperuricemia
4) HypoNa
5) HypoK
6) HypoMg
7) HyperCa
These effects are dose-dependent. Seen more with chlorthalidone than HCTZ. BUT, chlorthalidone is still the preferred drug in the class based on results of ALLHAT trial. Chlorthalidone was associated with overall decrease in CV mortality comparable to that seen with ACEIs and dihydropyridine CCBs.
Renal involvement of SLE
Glomerulonephritis - renal failure with RBC casts, proteinuria, HTN and low complement.
Immune complexes composed of dsDNA and anti-dsDNA antibodies deposit in the mesangium and/or subendothelial space. The immune complexes trigger an intense inflammatory reaction with activation of the complement system. This lowers C3 and C4 levels!!!
Immune complexes may also deposit in the subepithelial space and cause membranous glomerulonephritis, presenting with nephrotic syndrome without hypocomplementemia.
Nephrotic Syndrome (main diagnostic features)
1) Proteinuria (more than 3-3.5 g/d - this is most important)
2) Hypoalbuminemia
3) Edema
4) Hyperlipidemia and lipiduria
What is the basic pathophys of Nephrotic Syndrome? Also, list the associated diseases (most common ones)
Basic pathology is altered permeability of the glomerular membrane for proteins. Diseases most commonly causing nephrotic syndrome are:
1) minimal change disease (kids)
2) membranous glomerulopathy (adults)
3) mesangial proliferative glomerulonephritis
4) membranoproliferative glomerulonephritis
5) focal segmental glomerulosclerosis
What causes the hypercoagulation that is often seen as a complication of nephrotic syndrome?
NS is frequently complicated by hypercoagulation, thus raising risk for thromboembolic complications. This is caused by:
1) increased urinary loss of antithrombin 3
2) altered levels of proteins C and S
3) increased platelet aggregation
4) hyperfibrinogenemia due to increased hepatic synthesis
5) impaired fibrinolysis.
Renal vein thrombosis is the most common manifestation of coagulopathy (ESP with membranous glomerulopathy), but arterial thrombosis and PE can also occur.
Coagulopathy is less common but more severe in kids
Complications of Nephrotic Syndrome
1) Protein malnutrition
2) Iron-resistant microcytic hypochromic anemia due to transferrin loss
3) Vit D deficiency due to increased urinary excretion of cholecalciferol-binding protein
4) Decreased thyroxin level due to loss of thyroxine-binding protein
5) Increased susceptibility to infection
Meds that can cause hyperK (7 groups)
1) Nonselective B blockers - Interferes with beta-2-mediated intracellular K uptake
2) ACE, ARB, K sparing diuretics (amiloride) - Inhibition of aldosterone or the ENaC channel
3) Digitalis - Inhibition of the Na-K-ATP pump
4) Cyclosporine - Blocks aldosterone activity
5) Heparin - Blocks aldosterone production
6) NSAIDs - Decreases renal perfusion resulting in decreased K delivery to the collecting ducts
7) Succinylcholine - Causes extracellular leakage of K through acetylcholine receptors
Extra - TMP-SMX. Blocks epithelial Na channel in collecting tubule, similar to action of K sparing diuretics. This occurs more commonly in HIV patients who are treated with high doses of TMP, but even normal doses can produce a modest elevation in K.
Thus, patients treated with TMP at high doses require serial monitoring of K to avoid serious complications.
TMP also competitively inhibits renal tubular creatinine secretion and may cause an artifical increase in serum Cr. GFR remains unchanged.
How does Albuterol impact serum K?
Albuterol and insulin both lower serum K by driving K intracellularly. This is temporary but often used to treat hyperK.
In addition, Prednisone has some mineralocorticoid activity and would cause some K loss.
Clinical features of analgesic nephropathy
Clinical presentation
1) Associated with long term use of 1 or multiple analgesics (ASA, ibuprofen) for chronic HAs or other somatic complaints.
2) Usually asymptomatic but can have chronic tubulointerstitial nephritis or hematuria due to papillary necrosis
3) May have renal colic from significant papillary necosis and sloughing
Dx
1) Elevated Cr with UA showing hematuria or sterile pyuria - maybe WBC casts. The hematuria is from analgesic-induced vasoconstriction of medullary blood vessels (vasa recta)
2) Can have mild proteinuria (less than 1.5g per day)
3) CT can show small kidneys with bilateral renal papillary calcifications
Summary: Long term analgesic use with 1 or more analgesics can cause CKD due to tubulointerstitial nephritis and hematuria due to papillary necrosis
Common causes of crystal-induced AKI
1) Acyclovir - kidney rapidly excretes acyclovir into the urine, but the drug has low urine solubility. It easily precipitates in renal tubules, causing intratubular obstruction and direct renal tubular toxicity. This is much more common with IV doses. Less common with oral. Less commonly, IV acyclovir can cause AKI through acute tubular necrosis or acute interstitial nephritis.
2) Sulfonamides
3) MTX
4) Ethylene glycol
5) Protease inhibitors
Clinical presentation and treatment of crystal-induced AKI
Presentation
1) Usually Asx (can be nonspecific like nasuea, flank and abdominal pain)
2) Elevated Cr within 1-7d of starting drug
3) UA can show hematuria, pyuria, and crystals (visible with polarizing microscope)
4) Increased risk with underlying volume depletion, chronic kidney disease
Tx
1) Discontinue drug, volume repletion
2) Concurrent volume repletion while giving drug can prevent kidney injury
Most patients develop it within 24-48h after drug exposure
Acute interstitial nephritis is usually associated with what?
Exposure to medications such as Beta lactams and PPIs.
AIN usually occurs 7-10 days after drug exposure. Patients can develop findings that include skin rash, eosinophilia, eosinophiluria, and pyuria.
Pre-renal azotemia is usually due to what?
Volume depletion with hypoperfusion to the kidneys (or diuretics).
Labs show BUN/Cr over 20 to 1.
Look for signs of volume depletion too - BP issues, orthostasis, etc.
4 mechanisms of peripheral edema and examples for each
Increased capillary hydrostatic pressure
1) HF (LV and Cor Pulmonale)
2) Primary renal sodium retention* (renal disease like nephritis and drugs)
3) Venous obstruction (cirrhosis and venous insufficiency)
Decreased capillary oncotic pressure (hypoalbuminemia)
1) Protein loss (nephrotic syndrome and protein-losing enteropathy
2) Decreased albumin synthesis (cirrhosis and malnutrition)
Increased capillary permeability
1) Burns, trauma and sepsis
2) Allergic reactions
3) ARDS
4) Malignant ascites
Lymphatic obstruction/increased interstitial oncotic pressure
1) Malignant ascites
2) Hypothyroidism
3) LN dissection
What is acute nephritic syndrome? What causes the edema associated with it?
Primary glomerular damage due to causes such as poststrep glomerulonephritis, IgA nephropathy, lupus nephritis, membranoproliferative glomerulonephritis, and rapidly progressive glomerulonephritis
Primary glomerular damage leads to decreased GFR with eventual development of significant volume overload (e.g. pulm edema, distended neck veins, anasarca). Abnormal urinary sediment (RBCs, RBC casts) and variable degrees of proteinuria are present on UA.
Serum Cr may also be elevated. The increased volume also leads to HTN. Significant proteinuria (3 plus) eventually leads to hypoalbuminemia, which further contributes to the edema. Decreased GFR is also the cause of edema in patients with ESRD.
Answer to flash card: Decreased GFR (primary glomerular damage leading to increased capillary hydrostatic pressure). Later on, hypoalbuminemia contributes too.
When is prostate bx indicated?
For suspected prostate cancer in patients with an abnormal prostate exam or persistently elevated levels of PSA above 4.
Hepatorenal syndrome (the overall clinical picture)
Risks - advanced cirrhosis with portal HTN and edema
Precipitating factors
1) Reduced renal perfusion - GI bleed, vomiting, sepsis, excessive diuretic use, Spont Bact Peritonitis
2) Reduced glomerular pressure and GFR - NSAID use (constricts afferent arterioles)
Diagnosis
1) Renal hypoperfusion - FeNa below 1 (or urine Na less than 10)
2) Absence of tubular injury - No RBC, protein, or granular casts in urine
3) No improvement in renal function with fluids
Tx
1) Address precipitating factors (hypovolemia, anemia, infection)
2) Splanchic vasoconstriction (midodrine, octreotide, norepi)
3) Liver transplant
Hepatorenal syndrome - pathogenesis
Patients with severe liver cirrhosis have increased NO generation in the splanchnic circulation secondary to portal HTN. This is thought to cause systemic vasodilation, which reduces peripherap vascular resistance and BP, causing renal hypoperfusion.
Reduced renal perfusion would then activate compensatory pathways (RAAS, sympathetic nervous system, and ADH) that increase water and sodium retention and worsen volume overload.
Any factor that may further reduce glomerular capillary pressure (such as hypotension from GI bleeding) causes an acute decline in glomerular filtration and can precipitate hepatorenal syndrome.
Lab results are similar to prerenal azotemia. Acute renal failure indicated by elevated Cr (above 1.5). Very low urine Na level (typically less than 10). Urine sediment is very bland (no RBCs, casts or protein) reflecting absence of intrinsic renal pathology.
However, patients do not respond to fluids and withdrawal of diuretics. Renal function continues to decline.
How do NSAIDs affect GFR?
Decreases GFR. They constrict afferent arterioles.
Primary renal causes of nephrotic syndrome (5) and their clinical associations
1) Focal segmental glomerulosclerosis - African American and Hispanic. Obesity. HIV. Heroin use. #1 cause in adults.
2) Membranous nephropathy - Adenocarcinoma (breast, lung), NSAIDs. Hep B. SLE. #2 cause of nephropathy in general population.
3) Membranoproliferative glomerulonephritis - Hep B. Hep C. Lipodystrophy.
4) Minimal Change Disease - NSAIDs. Lymphoma. More common in kids.
5) IgA Nephropathy - URI. IgA Nephropathy can present with nephrotic syndrome (10%) but more commonly presents with hematuria following URI (40-50%).
Secondary causes are DM and amyloid (usually associated with MM or chronic inflammatory disease like RA or bronchiectasis).
Screening for bladder cancer
Not recommended, even in those who are at risk for the disease. This is bc of its relatively low incidence and poor PPV of the current screening tests (UA and cytology, bladder tumor antigen, nuclear matrix protein).
What should all patients with suspected BPH receive?
UA (to look for hematuria) and serum Creatinine.
Bladder outlet obstruction should be suspected in any patient with suspected BPH and AKI. Generally, Cr is not elevated by unilateral urinary obstruction (calculus); however it can be significantly elevated in bilateral obstruction. Patients with high Cr should get Renal US to exclude other obstruction causes and assess for hydronephrosis. Placement of catheter in hydro patients can help a lot.
Extrarenal manifestations of ADPKD
1) Intracranial berry aneurysms (5-10%). Although they are common and dangerous when coupled with HTN, routine screening for them is not recommended.
2) Hepatic cysts (most common one)
3) Valvular heart disease - most often MVP and AR
4) Colonic diverticula
5 )Abdominal wall and inguinal hernia
