4C TBL2 (Cardio2 & Renal 2)

Anterior Hemiblock

A block of the Anterior Division of the Left Bundle Branch A slight delay of conduction to the antero-lateral and superior area of the LV causes (late) unopposed depolarization upward and leftward, recognized on EKG as LAD Acute LAD is usually what makes you suspect Anterior hemiblock Finding a Q in I and a wide and/or deep S in III ("Q123") helps to confirm the diagnosis

Light chain cast nephropathy (multiple myeloma, gammopathies)

A type of intrinsic AKI (tubulopathies) Pathophysiology: neoplastic plasma cell producing monoclonal Ig chains= paraproteins; osteoclast activation leading to osteopenia and lytic lesions in bones Presentation: bone pain (often lower back ache due to lytic lesions in the vertebral bodies); constitutional sxs (weight loss, fatigue); recurrent infections (impaired immunity); constipation and muscle weakness (due to hypercalcemia) Labs: Normocytic anemia; AKI/CKD; hypercalcemia, monoclonal proteinemia (the M-spike); proteinuria with a gamma-gap (=total protein minus albumin) of at least 4g/dL) NOTE: urine dipstick may be negative for protein bc most commerical kits only detect albumin, not smaller-weight proteins

Acute tumor lysis syndrome

A type of Crystallopathy Soon after chemotherapy inititation (as soon as 48h!), massive destrcution of malignant cells will lead to the release of uric acid and monosodium urate/MSU (break down products of nucleic acids), LDH, K (Hyperkalemia) MSU crystals precipitate inside the tubular lumen, especially in the most acidic parts- DCT and collecting ducts (NOTE: that pKA of uric acid is 5.4, thus it is soluble if urine pH > 5.5 within physiologic range) Precipitation of uric acid crystals--> obstruction of DCT and CD --> AKI

Renal athero-embolism/cholesterol crystal embolism (CCE)

A type of crystallopathy Emboli of cholesterol crystals arising from the rupture of an atherosclerotic plaque from aortic or other major arteries block smaller arteries (150-200 micrometers in diameter)--> affect kidneys, skin, GI system, eyes, muscles, bones, brain, nerves, internal organs, and limbs Kidneys are located near the abd aorta--> most freq. target organ of CCE Pathology: - Obstruction of arcuate and interlobar arteries by CCs causes cortical and medullary infarcts - Passive (physical) or regulated necrosis of the endothelial cells Diagnosis of AKI caused by CCE difficult--> based on history or precipitating event (catheterization, vascular surgery, angiography) and other organ involvement (skin--> livedo reticularis, "blue-toe syndrome")

Ethylene glycol poisoning

A type of toxin-induced ATN (intrinsic AKI- tubulopathies) Common exogenous toxin- high yield topic in board exams!!!! - Causes ATN by: direct tubular injury via its metabolite glycolic acid; and also tubular obstruction due to percipitation of oxalic acid - Affects mainly PCT - Characteristic high-anion gap metabolic acidosis with high osmolar gap

How do Arrhythmias arise?

A very irritable automaticity focus may suddenly produce either a single beat or may suddenly discharge at a rapid rate - Ex: Ventricular tachycardia The highest "pacemaking" center "fails", and a focus from the next level "escapes" to maintain a heart rhythm - Ex: Drug induced sinus bradycardia is replaced by a junctional (AV nodal) rhythm Blocked impulse transmission anywhere in the conduction system - Ex: Complete A-V block One premature beat initiates re-entry mechanisms - Ex: Atrial tachycardia or other SVTs

Goodpasture syndrome

An intrinsic AKI (glomerulopathies) = Pulmonary-renal syndrome associated with anti-GBM antibodies directed against the NC1 domain of the alpha-3 chain of Type IV collagen (also expressed in alveoli-- hence lung pathology) Clinical presentation: Nephritic syndrome usually associated with hemoptysis, cough and dyspnea (BUT no upper respiratory tract symptoms) Rapid progression to RPGN and AKI--> ESRD/ CKD Labs: - High levels of anti-GBM antibodies in serum - Anemia and iron deficiency due to loss of blood via hemoptysis - Kidney biopsy to diagnose and assess the severity of renal involvement - Immunofluorescence: ribbon-like linear deposits

ECG traces have a ______; this allows the reader to know if the calibration is standard (and the ECG technician to adjust calibration as needed!)

Calibration mark - A 5mm wide by 10mm high calibration box is normal *IF QRS amplitude is high in the precordial leads (due to hypertrophy), then we may use a diff calibration for recording the ECG NOTE: Left ventricular hypertrophy causes an increase in the amplitude or height of the R and S complexes, particularly in the pre-cordial leads - The amplitudes are often reported in mm rather than mV

Left Bundle Branch Block

Causes: - AS - CHF - Cardiomyopathy - HTN ECG findings: - Widening of QRS >0.12s - Deep S, small or no R, V1 - (RSR' left-sided leads, notably V6!) ** LBBB prevents normal septal left to R depolarization

Right Bundle Branch Block

Causes: - Congenital - MI - Myocarditis - HTN - Pulmonary embolus ECG findings: - QRS > .12 seconds - RSR' in V1 *** To assess for BBB, focus on V1!

Ischemia

Causes: - Coronary artery narrowing - Coronary artery spasm ECG findings: - ST segment depression - T wave inversion ** ST segment elevation--> Transmural ischemia or ECG injury ** ST segment depression + T wave inversion--> Subendocardial ischemia with abnormal repolarization

Injury/Infarction or Necrosis

Causes: - Coronary artery occlusion - Myocardial contusion ECG findings: - ST segment elevation (injury) - Loss of R wave or loss of normal "R wave progression"-- In anterior precordial leads (V1-V3): NOT always indicative of infarction** - Q wave - T wave inversion

Hypokalemia

Causes: - Diuretics - DKA - Diarrhea ECG findings: - Flattening of T - U wave as K+ decreases Normal K+: 3.5-5.0 mEq/L

Left Atrial Hypertrophy

Causes: - Mitral stenosis - Mitral regurgitation - Left ventricular hypertrophy ECG findings: - Wide P >0.12 seconds - Notched P wave (looks like McDonalds M) - Biphasic p in V1 "P mitrale"

Right Atrial Hypertrophy

Causes: - Pulmonary HTN - COPD - Pulmonary embolism ECG findings: - Tall P in Lead II >/= 2.4mm

Hyperkalemia

Causes: - Renal insufficiency - ACE inhibitors - Adrenal insufficiency - Hemolysis ECG findings: - Peaked T waves - Widened QRS as K+ increases

Refractory Period

Cells are unable to depolarize during this period Different levels of refractoriness depending on the number of fast Na+ channels recovered from inactive state Absolute: The cells are completely unresponsive Effective: Absolute + a short period of phase 3 resulting in a weak impulse that cannot propagate Relative: Cells can be stimulated but with/at a slower conduction velocity

How is Third Degree (Complete) AV Block diagnosed?

- There is NO relationship between the P waves and QRS - CANNOT establish a pattern of P-R intervals - Atrial rate faster than ventricular rate - QRS morphology can be normal (narrow) or QRS>0.12 depending on heart pathology and source of ventricular pacing

AKI in pts with HTN and CKD

- AKI= form of acute target organ dysfunction in pts with baseline chronic kidney disease (CKD). Any degree of AKI in pts with severe acute BP elevations ("malignant hypertension") and CKD is associated with a greater risk of morbidity and mortality - Malignant HTN causes severe damage to tiny arteries called arterioles- arterioles anywhere in the body can be affected, but it is the eyes, the brain and kidneys that are most commonly worst affected Sxs: Severe, frequent and persistent headache (uncommon with HTN unless BP is very high)- brain involvement sometimes causes HTN encephalopathy with seizures and altered level of consciousness- eyesight may be blurred, and scotomas are noted Damaged retinal arteries and arterioles can be seen on fundoscopy, and the optic disk evidences papilledema Kidney damage can occur rapidly, and it may cause complete severe AKI/ESRD with anuria

Clinical Presentation of Atrioventricular Block

- Asymptomatic - Light-headedness, syncope - Chest pain - Bradycardia - Regularly irregular pulse - Hypotension, hypoperfusion

What are relevant demographics and information that can be helpful in getting information about a pts AKI?

- Fever - Fluid loss: bleeding, diarrhea, vomiting, diuretic use, excessive sweating - Exposure to drugs, toxins - Arthralgia and/or rashes - Cough and hemoptysis - Flank pain - Changes in urine output (either too much, or too little) Physical exams: - Vitals: fever; hypotension or hypertension; tachycardia or bradycardia; irregular pulse; tachypnea or bradypnea; oxygen saturation of Hb <94% - General: lethargic, ill-looking, altered level of consciousness - HEENT - Lungs: use of accessory muscles; crackles - Cardio: S3 gallop of cardiac failure; pericardial rubs - Abdomen: renal artery bruits, palpation of the flanks - Costovertebral angle palpation: pain - Neuro: mental status; hypotonia, abnormal deep tendon reflexes - Skin: obvious scars, pallor; edema

Intra-ventricular Conduction Blocks include

- LBBB (left bundle branch block) - RBBB (right bundle branch block) - LAHB (left anterior hemiblock) - LPHB (left posterior hemiblock)

What are different possible outcomes of AKI?

- Need for dialysis and progression to end-stage kidney diseases (ESKD) after an AKI episode is relatively low (5-20%) - Complete recovery - Incipient chronic kidney disease (CKD) - Progression to ESKD - Even a mild AKI has 90% increased risk of developing CKD

What are the normal intervals from an ECG?

- PR interval should be between 0.12-0.20 sec - QRS complex should be less than 0.10 sec - QT interval should be less than half of one R-R interval

Clinical Presentation of Atrial Flutter

- Palpitations - Fatigue - Poor exercise tolerance - Mild dyspnea - Presyncope - Rapid, mostly regular pulse - Usually a "sick" heart (60%)- same causes as SVT, PACs Mechanism of Atrial Flutter: - A type of SVT caused by re-entry circuit within the RA - Length of re-entry circuit corresponds to size of the RA, producing a fairly predicatble atrial rate of around 300BPM (range 200-400) Ventricular rate is determine by the AV conducction ratio: - Commenst AV ratio is 2:1= ventricular rate of ~150bpm - Higher-degree AV blocks can occur resulting in lower rates of ventricular conduction (3:1 or 4:1 block) due to medications/underlying heart disease Atrial flutter with 1:1 conduction can occur: - Due to sympathetic stimulation or an accessory pathway - Associated with severe hemodynamic instability and progression to ventricular fibrillation How do we know this is atrial flutter? - Flutter waves create a "saw tooth" pattern on ECG; clinically, if "saw tooth" pattern is not clear, try carotid massage and this will slow down ventricular rate and let you see the "saw tooth" - Best visible in leads 2, 3 and AVF - Usually (if new or untreated) there are 2 flutter waves per QRS (2:1 AV block); morphology of QRS is usually normal Causes: 30% have coronary artery disease/ 30% have HTN heart disease/ 30% no underlying heart disease Other causes: - Hypoxia - COPD - PE - Hyperthyroidism, pheochromocytoma - Alcohol consumption; digoxin toxicity Tx: - Control ventricular rate (beta blocker, Ca channel blocker, cardioinversion) - Anti-coagulate - Radiofrequency catheter ablation

Clinical Presentation of Ventricular Tachycardia

- Palpitations - Light-headedness - Syncope - Chest pain - Anxiety - Hypotension, signs of diminished perfusion (altered LOC, pallor) - Tachypnea - Elevated JVP - Cannon a waves Mechanism of Ventricular Tachycardia: Several types based on morphology of QRS: - monomorphic is MOST COMMON - polymorphic - Torsades de Point Re-entry mechanism is MOST COMMON, involves a myocardial injury creating slow and fast pathways - Monomorphic type arises from a single ventricular focus Diagnostic criteria: - Rate +/- 150 - QRS prolonged without morphology of BBB - Fusion beats (merging of sinus beat and ventricular beat- yellow circle) - P-P interval noted (A-V dissociation present) but unrelated to QRS rate (always faster than sinus rate) Causes: - Ischemic heart disease - Dilated cardiomyopathy - Hypertrophic cardiomyopathy - Chagas disease Treatment depends on: - Hemodynamically stable or unstable? - Monomorphic or polymorphic? - LV function? Drugs: - Procainamine - Sotalol - Amiodarone - Lidocaine Synchronized cardioversion

Long QT Syndrome

- Prolonged QT > 450 msec (two large squares) - Due to congenital "channelopathy"; myocardial disease; electrolyte disturbance; drugs Prolonged ventricular repolarization predisposes to malignant ventricular arrhythmias - Pts may present with syncope or cardiac arrest

STEMI appears with

- Q wave - ST elevation (Tomb stone) - T inversion

What are additional important concepts to understand cardiac arrhythmias?

- Refractory period - Re-entry - Overdrive suppression

What are the 3 criteria used by Kidney Disease- Improving Global Outcomes (KDIGO) to diagnose acute deterioration in kidney function seen in AKI (Acute Kidney Injury)?

1. Abrupt (<48h) absolute increase in serum creatinine (sCr) of/ more than 0.3 mg/dL from the baseline; and/or 2. Increase in sCr of at least 50%; and/or 3. Urine output (UO) of <0.5mL/h for >6h

What are the 3 types of AKI?

1. Pre-renal: the main abnormality is decreased blood delivery to the kidney 2. Intrinsic: the abnormality is within the kidney 3. Post-renal: the abnormality is obstruction in the urine flow

FENa is the gold standard for diagnosing prerenal vs. intrinsic AKI with 2 exceptions:

1. Prerenal AKI due to diuretics - Bc they cause naturiesis--> inaccurate FeNa - Best use fractional excretion of urea (FeUrea): <35% in prerenal AKI ** In AKI or CKD all waste products are handled with difficulty by the kidney -- instead of being eliminated as they should, they are retained in unusually high amounts--> hence the raised urea and creatinine in all types of renal failure 2. ATN due to pigment overload (ex. Myoglobinuria, hemoglobinuria) - Bc of vasoconstriction induced by pigment injury--> FeNa may be <1%

Methodical Approach Useful for Identifying Arrhythmias:

1. Rate slow or fast (bradycardia or tachycardia)? 2. R-R interval regular or irregular? 3. Ps present? - Is there a QRS for every P? - More P than QRS--> Heart Block - More QRS than P--> AV dissociation 4. QRS narrow or wide? - QRS narrow: Origin above the ventricles - QRS wide: Ventricular origin 5. Relationship of QRS to previous cardiac cycle 6. Ectopic beats (atrial, ventricular, junctional)? - Premature - Escape

Describe the passage of electric potential through the heart

1. SA node fires 2. Excitation spreads through atrial myocardium 3. AV node fires 4. Excitation spreads down AV bundle 5. Purkinje fibers distribute excitation through ventricular myocardium

Hepatorenal Syndrome

A prerenal AKI - kidneys are intrinsically normal BUT, there is severe liver disease (cirrhosis) with hypoalbuminemia, leading to decreased plasma oncotic pressure, which will cause the H2O to diffuse in the extracellular spaces-- Thus, the pt becomes virtually hypovolemic

Overdrive Suppression

A spontaneously firing cell can suppress all other cells from firing and also suppresses the conductivity of conduction pathway cells SA Node (fires at 100bpm) Atrial foci (60-80bpm) Junctional foci (40-60bpm) Ventricular foci (20-40bpm) *** Overdrive suppression allows the center with the fastest rate to be the dominant pacemaker

Pigment Nephropathy

A type of Crystallopathy May be caused by: - Hb (from hemolysis) or - Myoglobin (rhabdomyolysis- following: heat injury, "crush injury"; strenuous exercise; seizures; tetanus; alcohol or cocaine; severe hypokalemia; Rx - When overwhelming concentrations of pigment are filtered by glomeruli and reabsorbed by renal tubules; pigmented casts may form--> obstruction of the DDCT--> intrarenal vasoconstriction--> ATN - Myoglobinuria= a severe oxidant stress on tubular cells (damage is worse when urine flow slow) Presentation: - Hemolysis: pallor, jaundice, tachycardia, splenomegaly, dark urine - Rhabdomyolysis: muscle pain, brusiing, symptoms of the underlying cause, cola-colored urine Labs: - As opposed ot other causes of ATN, FENa <1% Urinalysis: - Dipstick positive for blood - But sediment NEGATIVE for RBCs= pseudohematuria; urinary Hb or myoglobin; brown granular casts (but absence does not exclude diagnosis) - Increased LDH and haptoglobin in hemolysis - Increased creatinine-phosphokinase (5x upper level of normal) - Hyperkalemia - Hyperphosphatemia - Hypocalcemia

How to determine the Age of Infarction?

Acute: - ST elevation 0 to 3-4 days after Recent/indeterminate: - T wave inversion weeks to months Old: - Q wave can last for years NOTE: Where you find ST elevation and pathological Q waves on the ECG indicates the anatomic area of the problem! - This only holds true for infarction/injury! - Ischemia CANNOT be localized

Microangiopathic nephropathy: Hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP)

An Intrarenal Vascular Disease - HUS & TTP are diff diseases, despite some clinical similarities - TTP: abnormal protease= the von Willebrand factor (vWF)- cleaving metalloprotease ADAMTS13= disintegrin and metalloprotease with a thrombo-spondin type 1 motif, member 13)= reduced activity to <10% - HUS: Normal ADAMTS13 (except in idiopathic HUS, when it is <10%) Etiology: Shiga-like toxin (Stx)- associated: - E. coli (70% in US, mainly serotype O157:H7) - S. dysenteriae type 1 ** Shiga toxin and HUS: toxin damages the capillary lining, platelets clump in the area to stop blood loss and initiate healing, platelets form mesh in capillaries- this damages RBCs and prevents adequate blood flow to affected organs, resulting in organ dysfunction or failure NON-Stx HUS: - Sporadic - Non-enteric bacteria & viruses - Drugs - Malignancies - Transplantation - Pregnancy (pre-eclampsia) - Antiphospholipid syndrome; systemic lupus erythematosus (SLE) - Familial (rare; AD or AR) Pathology: - Micro-angiopathic anemia with schizocytes on peripheral blood - Endothelial cell damage with intravascular and glomerular platelet-rich thrombi Presentation: - Prodromal diarrhea in Stx-HUS - HUS= TRIAD: AKI, microangiopathic hemolytic anemia, thrombocytopenia with purpuric rash - TTP= PENTAD: fever, thrombocytopenia with purpuric rash, microangiopathic hemolytis anemia, neuro impairment, AKI - Neuro disturbances typical for TTP (less in HUS- when usually associated with azotemia) - AKI typical for HUS (less in TTP) - Diagnosis= initially based on clinical presentation- this is an emergency and treatment should not be delayed while waiting for investigations Labs: - Pictures of hemolytic anemia with schizocytes in peripheal blood smear and evidence of hemolysis with a negative anti-globulin test - Unlike DIC, PT and PTT are normal

IgA nephropathy/ Berger disease

An Intrinsic AKI (Glomerulopathies) Most common cause of glomerulonephritis in the US - At any age: mostly in 2nd-3rd decades - A continuum with Hennoch-Schonlein purpura (HSP)- similar pathogenesis Clinical presentation: gross hematuria concomitant with URI or flu-like illness; NO latent period; usually normal BP (if high BP--> poor prognosis) Labs: - Urinalysis: most-isolated glomerular hematuria (dysmorphic RBCs and RBC casts); if proteinuria; it is mild (<1g/day- if proteinuria is more severe, it is associated with poor prognosis and predicts AKI/CKD) - Serum IgA not used for diagnosis- only elevated in 50% in pts - Complement levels are normal (DDx: differentiation from post-infectious glomerulonephritis) - Definitive Dx only by biopsy, but NOT done routinely- only if creatine levels extremely elevated or proteinuria >1g/day. Classic findings- globular mesangial IgA complexes on immune-fluorescence

Toxic-Induced ATN

An Intrinsic AKI (Tubulopathies) Characterisitc focal epithelial necrosis Etiology: Exogenous nephrotoxins: medications, contrast media (contrast-induced nephropathy), synthetic cannabinoids (SPICE, K2), ethylene glycol (oxalate percipitates Ca in tubules--> ATN in ~3 d) Endogenous nephrotoxins: crystal nephropathies (pigment nephropathy caused by myoglobin, Hb, tumor lysis syndrome), Bence-Jones proteins (multiple myeloma), hypercalcemia

Re-Entry

An impulse persistently re-excites atria or ventricles at the end of refractory period Re-entry can occur: - Through an accessory pathway - Through a normal pathway (ie AV node pathways that have different conduction velocities and refractory period) - Through myocardial cells with diff refractory periods Ex: - Atrial extrasystole - Atrial echo - Earlier atrial extrasystole

Posterior Hemiblock

An inferior infarction may impair the blood supply to the Posterior division of the Left Bundle Branch Posterior Hemiblocks cause RAD due to the late, unopposed depolarization forces toward the right Deep or unusually wide S in I and Q in III (known as S1Q3)

Post-infectious Glomerulonephritis

An intrinsic AKI (Glomerulopathies) Clinical presentation: nephritic syndrome= hematuria; edema (periorbital); hypertension; oliguria 1-3 weeks after URI with group A B-hemolytics streptococcus or impetigo/cellulitis with staphylococcus - Nephritogenic antigens include: nephritis-associated plasmin receptor and streptococcal pyogenic exotoxin B - Most cases resolve spontaneoulsy within 1 week, but adults are more likley than children to develop AKI or CKD Labs: - Urinalysis: dysmorphic RBCs and RBC casts; proteinuria <3.5g/24h - Anti-streptolysin antibodies (ASO) and anti-DNAase antibodies elevated; - Low level of complement- CH50 and C3 - Biopsy only needed in pts with atypical presentation (ex. suspected IgA nephropathy; no improvement within 2 weeks; persistently low complement levels beyond 6 weeks): electron-dense deposits of immune complexes in subendothelial and subepithelial spaces

Acute Tubular Necrosis (ATN)

An intrinsic AKI (Tubulopathies) Clinical history is crucial to ascertain the possible etiology of ATN, BUT not helpful in diagnosing ATN itself. Also, knowing the possible etiologies of ATN is importnat bc there is no specific test to prove one etiology or another-- no drug level and no biopsy would indicate that a specific toxin caused ATN Clinical presentation evolves in 3 stages: 1. Inititation= Tubular injury stage (24-36h) 2. Maintenance= Oliguric phase (1-3 weeks)- Decreased UO and eGFR, fluid overload, increased BUN and creatinine (BUN/sCr < 10-15), hyperkalemia, metabolic acidosis 3. Recovery= Polyuric phase (after 3-4 weeks) - Gradual increase in UO with polyuria - There is continued impairment of renal function with electrolyte wasting--> hypokalemia (life-threatening); hypomagnesemia, hypophosphatemia, hypocalcemia 2 Major causes of ATN include: Ischemic and toxin-induced

ANCA-associated glomerulonephritis

An intrinsic AKI (glomerulopathies) Includes: Granulomatosis with polyangitis/Wegener granulomatosis (associated with PR3- ANCA); microscopic polyangitis (MPO-ANCA); Churg-Strauss syndrome (MPO-ANCA); drug-induced ANCA-associated glomerulonephritis (MPO-ANCA) - Rapid progression to RPGN unless start immediately Rx Clinical presentation: Similar to Goodpasture: involves respiratory/pulmonary symptoms and signs in addition to nephritic syndrome Kidney biopsy: necessary for Dx and DDx (vs. Goodpasture)--> minimal immunofluorescence staining; but should not delay Rx.

Henoch-Schonlein purpura

An intrinsic AKI (glomerulopathies) = Leukocytoclastic generalized vasculitis - Predominant in children (rare and more severe in adults) - Male predominance Similar lesions as IgA nephropathy (acute glomerulonephritis picture), but the deposition of IgA immune complexes is widespread to other organs--> multi-system disease affecting: - Skin--> palpable purpura, especially on buttocks and extensor surface of lower limbs - GI tract (mesenteric vasculitis)--> colicky abd pain - Joints (IgA deposits in synovium) --> arthralgia Labs: - Clinical picture is usually classic and suffices for diagnostic, however if the presentation is atypical, a skin biopsy or renal biopsy is indicated - Immunofluorescence- presence of IgA deposits (in mesangium for renal biopsy)

Ischemic Acute Tubular Necrosis (ATN)

An intrinsic AKI (tubulopathies) MOST common ATN Prolonged, untreated prerenal AKI--> patchy loss of tubular epithelial cells with tubular dilatation; flattened tubular cells with loss of brush border and subsequent necrosis and denudation of tubular basement membrane - Most affected= most metabolically-active epithelial cells in the terminal (straight) part of the PCT and thick part of the loop of Henle (medulla) Pathophysiology: i. Renal hypoperfusion due to decreased blood flow to the kidney results initially in prerenal AKI (reduced blood flow to the afferent artery means decreased GFR- thus AKI) ii. If prolonged, the prerenal AKI caused by hypoperfusion leads to ATN due to renal ischemia and even necrosis- the sequence of events is as follows: Prolonged hypoperfusion/ischemia--> release of inflammatory mediators: - Vasoconstriction - Tubular damage --> Obstruction by casts, tubular back-leak, interstitial inflammation - Direct glomerular effect *** ALL these leads to ATN iii. NOTE: "Hypoperfusion" is in fact a stage where the decreased blood flow through the kidney did NOT yet cause real damage to the glomerulus, while "ischemia" and "necrosis" are terms used for stages where there is already reversible damage (ischemia) or irreversible damage (necrosis) to the nephron - Thus simple "hypoperfusion" is only the initial event in development of ischemia and necrosis iv. If ischemia not addressed and is prolonged--> local release of inflammatory mediators--> vasoconstriction and damage to the glomerulus--> decreased eGFR v. Also, there is sig. tubular damage with shedding of tubular epithelial cells- these cells become embedded in the hyaline casts and will cause them to appear brown and granular ("muddy-brown" granular casts). The casts will block the tubular lumen and lead to backflow of urine ultrafiltrate back into the Bowman's capsule, with a corresponding increase in the glomerular hydrostatic pressure, which will further decrease the eGFR vi. Inflammatory elements accumulate in the interstitium, perpetuating the cycle of tubular destruction

Crystallopathies/Crystal nephropathies

Associated with the formation and aggregation of crystals in the tubuli, promoting tissue inflammation and scarring Caused by crystal-forming intrinsic minerals, metabolites, and proteins or extrinsic dietary components and drug metabolites Common causes of drug-induced crystal nephropathies: uric acid, acyclovir; sulfonamies

Most pathologies affecting the kidneys ____ may potentially lead to AKI

BILATERALLY Unilateral kidney disease does NOT cause AKI bc the unaffected kidney is perfectly capable to work on its own- thus, ppl with one kidney- like transplant recipients or donors- have normal UO, sCr, and eGFR BUT, If that single kidney is affected, those pts are at risk of developing AKI

Sometimes premature beats occur regularly such as in:

Bigeminy: one normal + 1 premature Trigeminy: two normal + 1 premature Quadrigeminy: three normal + 1 premature

How do you discriminate between PRE RENAL AKI (simple hypoperfusion) and ATN (ischmeia and necrosis)?

By looking at the time-lapse between the onset of hypoperfusion, by looking at the response to the correction of hypoperfusion, and by looking at urinalysis PRE RENAL AKI - Will be reversed promptly by simply restoring appropriate blood supply to the kidney - In simple hypoperfusion with prerenal picture you have hyaline casts with no cells- nephrons are still ok ATN: - Will have a protracted phase, since the damaged cells need to be replaced - Brown granular casts - these are actually dead cells that get incorporated into their percipitated protein- a sign that the nephrons are damaged

Atrial Fibrillation

Clinical presentation: - May be asymptomatic - Palpitations - Fatigue, poor exercised tolerance - Presyncope, syncope - Weakness, dizziness - CHF symptoms - Irregularly irregular pulse - Usually a "sick" heart Mechanisms: - Understanding is evolving - Need an initiating event - Irritable focus believed to arise from myocardial tissue in pulmonary veins**** - Need a substrate for maintenance - Atrial pathology, such as dilated LA ("AF begets AF") How do we know this is AFib? - Ventricular rate is always irregularly irregular": the R-R intervals change - Rate (if untreated) is 170-190 depending on AV node conduction - An irregular baseline is caused by varying amplitude of fibrillatory waves - QRS normal morphology Causes: - Most common arrhythmia: 2 million in US - Onset is age dependent (4%>60, 8%>80) - Often associated with HTN, Valvular Heart Disease, Heart Failure; 15% without comorbidities Risk of stroke: - 1.5% for age <60y - 30% for age >80y Tx: - Anticoagulants to reduce stroke risk - Rate control: beta blockers, digoxin - Rhythm control: cardioinversion, ablation

Wolff-Parkinson-White Syndrome

Combination of a congenital accessory pathway (Bundle of Kent) AND episodes of tachyarrhythmia - NOT UNCOMMON: prevalence up to 3/1000 - Associated with a small risk of sudden cardiac death - Pts may complain of palpitations, light-headedness, pre-syncope - Pts may be asymptomatic, detected on screening or routine ECGs Mechanism: - "Pre-excitation" occurs: the ventricles activate prematurely due to conduction through the accessory pathway, bypassing the AV node - This is an example of re-entrant tachycardia through the accessory pathway - The accessory pathway may conduct only towards the ventricle (anterograde conduction), only away from the ventricle (retrograde conduction) or in both directions (most common) - Anterograde and retrograde conduction look different on ECG during the tachyarrhythmia ECG characteristics: - Short PR <0.12 sec - Delta wave- slurring slow rise of the initial part of the QRS - Prolonged QRS >0.11sec - ECG will tell you whether the accessory pathway is in the R or L side of the heart: note the positive tall R wave in V1, mimicking RVH- this pt has a left sided pathway

Most common cause of toxic drug-induced ATN=

Contrast media - High urine osmolality despite very low urine [Na] - Why: constriction afferent arteriole--> tubular dysfunction--> massive resorption of Na and H2O - Very rapid rise in creatinine (~24h post-exposure--> peak 3d---> baseline 10d) NOTE: Vancomycin, gentamicin, and amphotericin B may all cause AKI but never after only one dose and usually take 5-10 days to cause tubular damage Risk factors: Patient- related: - Underlying CKD (esp if GFR <30) - Diabetes - Intravascular volume depletion - CHF Procedure-related: - Volume used - Hyper-osmolarity - Intra-arterial Rx

How to calculate Heart Rate from an ECG?

Count # small boxes x 0.04sec= ___ seconds per beat (60seconds/minute)/(___seconds/beat)= HR Exact measure of heart rate: 1. Determine time interval from one heart beat- from R wave to R wave (R-R interval) 2. Time interval divided into 60sec/min= HR (bpm) Quick estimate of heart rate: 300/# big boxes *** Memorize "300,150, 100, 75, 60, 50, 43" IF the rate is slow and the Rhythm is Irregular: 1. Count the number of QRS complexes across a 12 lead trace and multiply by 6 2. IF you only have a rhythm strip, count the number of QRS complexes in 6 seconds (30 big boxes) and multiply this number by 10= bpm

Sometimes premature beats occur in succession and this is called

Coupling

Acute Interstitial Nephritis

Etiology: Drugs (70-75%): - Virtually any drug can cause AIN, but mostly if drugs likely to cause type I (IgE mediated) allergy and those causing Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis, Hemolysis - Common causes of AIN: NSAIDs, beta-lactam antibiotics, sulfa drugs (furosemide, thiazides, antibiotics), quinolones, rifampicin, cimetidine, proton pump inhibitors, allopurinol, phenytoin Autoimmune or systemic disease (10-20%): - SLE, Sjorgen, sarcoidosis, Wegner granulomatosis Non-renal infections (4-10%) - Legionella, strep B, leptospirosis, mycobacteria, E Coli, Candida, adenovirus, EBV Tubulo-interstitial nephritis with uveitis (5-10%) **** Refer to Pathology lectures Diagnostic: - Typically--> Non-specific symptoms and signs of AKI--> must be distinguished from other AKI causes - Distinguishing clinical features of drug-induced AIN= fever, rash, athralgia in a pt with AKI, 3-5 days after exposure Tests: Urine: - WBC and WBC casts - Eosinophiluria: eosinophils and eosinophils casts on Hansel stain- confirms AIN, but not present in all pts - Other conditions with eosinophiluria: UTI (cystitis, pyelonephritis) and prostatis Imaging: U/S Biopsy: GOLD STANDARD: the only definitive method to distinguish AIN from other causes of AKI= renal biopsy HOWEVER, biopsy used only when diagnosis is unclear, or the pt does not improve after removal of possible causes and there are no contraindications

T or F: ALL ST elevation is MI?

FALSE! Examples: Pericarditis - Generalized ST elevation - *Presence of PR depression - Normal T wave amplitude - ST segment/ T wave ratio >0.25 (height) - Absence of "fish-hook" appearance V4 - ECG changes evolve over time Benign Early Repolarization (BER)- Now known as "early repolarization syndrome" and NOT so benign - ST elevation limited to precordial leads - *Absence of PR depression - *Prominent T waves - ST segment/ T wave ratio <0.25 (height)** - *Characteristic "fish-hook" appearance V4 - ECG changes relatively stable over time Other causes: - Sub-arachnoid hemorrhage - Brugada syndrome - Pancreatitis - Large hiatal hernia

The GOLD STANDARD for differential diagnosis of prerenal AKI is NOT the BUN: creatinine ratio but the

FeNa * The BUN: creatinine ratio is LESS specific, and in critical care for example we prefer using FENa NOTE: The BUN: creatinine ratio is still quite important for differentiating the pathophysiology of prerenal and intrinsic AKI, since urea retention in excess of creatinine to a ratio of >20:1 reflects decreased renal blood flow

FeNa values for prerenal vs. intrinsic AKI vs. postrenal AKI

FeNa= % of Na excreted adjusted for urine volume Prerenal: <1% (intact tubuli --> most filtered Na reabsorbed) Intrinsic AKI: >2% (Na wasting) Postrenal AKI: may start with <1% and progress to >2%

How do you determine cardiac rhythm?

For each segment does it look: - Regular? - Have a p? - p for QRS, QRS for p? - QRS wide or narrow? - Ectopic beats

What are different possible locations of Infarction? (on what leads would Q wave & ST changes be present)

Inferior: II, III, aVF + Left axis deviation Anterior: V1-V6 Apical: V5/V6 Lateral: I, aVL, V5, V6 Septal: V1, V2 Posterior: - Reciprocal changes in V1-V2 (mirror image) - Tall R, ST depression, T elevation**

Acute Kidney is broadly defined as an abrupt impairment in

Kidney Functions such as: 1. Hemofiltration - remove waste - electrolyte balance - acid-base balance 2. Blood volume and BP - Renin-angiogtensin-aldosterone - ADH action on the nephrons 3. Calcium metabolism: - Activation of VitD3 (hydroxylation of 25-hydroxy-cholecalciferol to 1,25-dihydroxycholecalciferol) 4. Hematopoiesis: - Erythopoietin synthesis

Left Ventricular Hypertrophy

LV wall is very thick, causing great QRS deflections in the chest leads Causes: - Aortic stenosis - Hypertension - Athletic heart Thickened LV walls result in: - Increased R wave amplitude in the L-sided ECG leads (I, aVL, and V4-6) - Increased S wave depth in the R-sided leads (III, aVR, V1-3) - Prolonged depolarization (increased R wave peak time) - Delayed repolarization (ST and T-wave abnormalities) in the lateral leads Sokolov-Lyon criteria is the most commonly used to diagnose: 1. Deep S in V1, Tall R in V5 (or V6) 2. Depth (in mm) of V1 plus the height of R in V5 >35mm 3. Look for other evidence such as LAD and LAE CAUTION: Criteria are NOT sensitive or specific - Young ppl with thin chest walls often appear to have LVH - Obese pts with LVH may give a false negative Ex: - Markedly increased LV voltages: huge precordial R and S waves that overlap with the adjacent leads (SV2 + RV6 >> 35mm) - LV strain pattern with ST depression and T-wave inversions in I, aVL, and V5-6 - ST elevation in V1-V3 - Left axis deviation

Gentamicin

MOST common cause of drug-induced ATN (an intrinsic AKI- tubulopathies) Filtered across glomerulus, concentrates in PCT--> impaires lysosomal function, protein synthesis and mitochondrial activity--> ATN with focal lesions--> loss of resorptive capacity of PCT--> secondary Fanconi syndrome Dose dependent (after more than 2-3 doses) Onset after 5-10 days (like most drug-induced non-oliguric ATN) OTHER drugs causes toxic ATN: cisplatin, acyclovia, vancomycin and amphotericin B

Supraventricular Tachycardia (SVT)

May be asymptomatic - "Palpitations" (96%) - Dizziness (75%) - SOB (47%) - Chest pain (35%) - Fatigue (23%) - Syncope (20%) Mechanisms: - SVT can be used to refer to any tachydysrhythmia arising from above the level of the Bundle of His - Different types of SVT arise from or are propagated by the atria or the AV node and this typically produces a narrow-complex tachycardia (unless aberrant conduction is present) - Paroxysmal SVT describes an SVT with abrupt onset and offset, characteristically seen with re-entrant tachycardias involving the AV node Ex: A. AV nodal re-entry (AVNRT) ***MOST COMMON B. Atrio-ventricular re-entry (AVRT) How do we know this is SVT? - Rate is ~180-220 - QRS narrow and morphology appears normal - Ventricular rate is regular - P wave is not visible or may occur before, during or after QRS - The rate of the tachycardia is determined by the refractory period of the AV node ** Look closely after the QRS and you will see small positive deflection that is often called a "pseudo R wave" but is actually a P wave! Causes: Same as for PACs Tx: - Slow down conduction in the AV node: If one beat is not conducted the re-entry cycle terminates How can you terminate re-entry cycle? - Carotid massage - Valsalva - Drugs: Adenosine, beta blcokers, digoxin - If the pt is unstable: synchronized cardioversion **** Vagal maneuvers, adenosine and synchronized cardioinversion are interventions in ACLS training! ** Adenosine can successfully convert Supraventricular Tachycardia to Sinus Rhythm

AV nodal re-entry (AVNRT)

Most common mechanism of supraventricular tachycardias - The AV node has conduction fibers with diff. conduction velocities and refractory periods - This allows an impulse to reach into the AV node and turn back using diff. conduction fibers - This phenomenon, properly timed, perpetuates the tachycardia

Describe the clinical presentation of PRE-RENAL AKI

Most pts: Asymptomatic, normal physical examination - Sxs of azotemia: fatigue, nausea, vomiting, oliguria, confusion, shortness of breath - Manifestations of hypovolemic shock/volume depletion: hypotension, orthostatic hypotension, tachycardia, reduced skin turgor, dry mucosae - Manifestations of volume overload: pleural effusion, pericardial effusion, tamponade

What are the different types of AV blocks?

NOTE: For AV blocks there is not a p for QRS, QRS for p & neither is PR normal Types of AV blocks: First-degree incomplete heart block - PR interval= too long (>.20 sec) Second-degree Mobitz Type I: - PR intervals lengthen until QRS "drops" Second-degree Mobitz Type II: - PR interval appears OK, but spontaneous dropped QRS Third-degree Complete Heart block: - Complete dissociation between atrial and ventricular conduction

T or F: NOT all MIs cause ST Elevation?

Non ST Segment Elevation MI (NSTEMI) MI (and ischemia) can occur WITHOUT ST segment elevation This is part of the spectrum of "Acute Coronary Syndrome" which includes: - Unstable angina - NSTEMI - STEMI NSTEMI - Is indicative of LESS myocardial damage - Relegates pts to a diff set of treatments and decision-making protocols

Describe the Pathophysiology of PRE-RENAL AKI

Normal perfusion of kidney to poor perfusion--> Concentrate the urine maximally and avidly reabsorb sodium, in an effect to maintain/ increase intravascular volume and normalize renal perfusion Mechanism: Decreased renal blood supply--> failure of renal vascular autoregulation to maintain renal perfusion --> decreased GFR--> activation of RAAS --> Increased aldosterone release --> increased reabsorption of Na+, H2O--> increased urine osmolality--> secretion of ADH--> increased reabsorption of H2O and urea *** However, creatinine is still secreted in PCT--> sBUN/sCr increases Effects of reduced local renal perfusion of medications: - Decreased perfusion pressure (increased vasodilatory PGs & increased Ang II)--> Nml GFR maintained - Decreased perfusion pressure in presence of NSAIDs (decreased vasodilatory PGs & increased AngII)--> Low GFR - Decreased perfusion pressure in presence of ACE-I or ARB (slight increased vasodilatory PGs & decreased AngII)--> Low GFR NOTE: In normal individuals who are not on any medications- reduced renal perfusion by itself may NOT lead to AKI due to increased vasodilatory PGs that dilate the afferent arteriole and the RAAS activation that constricts the efferent arterilole- BUT in elderly pts and in pts on Rx with NSAIDs and ACE-I/ARBs, the renal perfusion leads to AKI

Premature Ventricular Complex (PVCs)

Often Asymptomatic - "Palpitations" especially if frequent - May be heard as "premature" or "ectopic" beats during cardiac auscultation - May be identified when palpating pulses How do we know these are PVCs? - QRS complex is premature (it occurs b4 the next expected sinus beat) - QRS of the PVC is >0.12 sec - Sinus rhythm is NOT disrupted - The relationship between the previous beat and the PVC (coupling interval) is the same for each morphology of PVC PVCs can be: - Unifocal (same morphology & coupling interval in a given lead) - Multifocal (diff morophologies & coupling intervals in a given lead) These are common and often occur without underlying heart disease: Causes: - Hypoxia and hypercapnia - Low CO (shock) - Drugs (digoxin, sympathomimetics, tricyclics, aminophylline, caffeine) - Substances (cocaine, amphetamines, alcohol, tobacco) - Electrolyte imbalances, particularly magnesium, calcium, and potassium - Myocarditis - Acute ischemia and/or infarction - Catecholamines (exercise, exercise recovery, stress) Tx (not all PVCs must be treated) - First correct underlying cause if possible - Medications: Lidocaine, beta blockers, amiodarone

Premature Atrial Complex (PACs)

Often asymptomatic - "Palpitations" especially if frequent - May be heard as "premature" or "ectopic" beats during cardiac auscultation - May be identified when palpating pulses *** This clinical presentation is similar for PVCs and PACs How do we know these are PACs? - They are preceded by a P wave - P wave is either visible or buried in the T before the premature beat: T is deformed and diff. than previous and subsequent T waves - The QRS is either normal or prolonged (aberrancy) Causes: - Adrenergic (epinephrine) stimulation, either increased sympathetic or reduced parasympathetic effects (stress!) - Stimulants: caffeine, amphetamine, cocaine - Digoxin, ethanol - Hyperthyroidism - Stretch and low O2 (hypoxia) Possible consequences: - Atrial Tachycardia - Atrial Fibrillation Tx: Correct underlying cause if possible (Rarely there is need for medications)

Pathophysiologic vs. Clinical definition of AKI (previously known as acute renal failure/ARF)

Pathophysiologic: Abrupt loss of kidney fx within 48 hr - Retention of urea, creatinine, other waste products - Dysregulation of fluid and electrolyte balance - Impaired AB homeostasis Clinical: Based on creatinine, eGFR, & urine output - abrupt (<48h) increase in creatinine by at least 0.3mg/dL - Increase in serum creatinine of at least 50% - Urine output of <0.5 mL/kg/h for >6h ** Clinical definition flawed bc the loss of kidney function does NOT correspond to degree of decline in estimated GFR (eGFR), and eGFR does NOT reflect tubular function, which is also affected in AKI ALSO - sCr should not be used as standard marker of filtration bc if is NOT only filtered but also secreted by the tubules and this process is affected by age, gender, muscle mass, and muscle metabolism, medication and hydration status sooooo Other endogenous markers are under investigation as candidates to diagnose AKI like.. - Plasma and urinary uromodulin (aka Tamm-Horsfall protein glycoprotein expressed in the TAL and DCT) and cystatin C (Cys C) Cys C is a 13.36kDa non-glycosylated protein, freely filtered through glomerulus, reabsorbed and metabolized in proximal renal tubules - NOT secreted and NOT influenced by sex, race or muscle mass - BUT is affected by age, tobacco, high glucocorticoids levels, thyroid disorders, inflammation, sepsis and malignancy

ST segment/ T wave Height ratio >0.25 is seen in

Pericarditis <0.25 is seen in BER (Benign Early Repolarization) *** BER has characteristic "fish-hook" in V4

Most common cause of AKI is?

Pre-Renal AKI (Acute Kidney Injury): - Decrease in eGFR due to a decrease in renal perfusion pressure, without damage to the renal parenchyma - Maintaining a nml GFR is dependent on adequate renal perfusion: kidneys receive up to 25% of CO--> Failure of general circulation or isolated failure of intrarenal circulation--> profound impact on renal perfusion - REVERSIBLE: no damage to the nephrons; fixing the cause will restore the renal function - IF UNTREATED--> Ischemia and necrosis of the tubule= acute tubular necrossis/ ATN (most common cause of ATN)

Ectopic Beats

Premature Beats (PVCs, PACs, Junctional): An irritable focus spontaneously fires a single stimulus - Atrial - Junctional - Ventricular or Escape Beats: An automaticity focus transiently escapes to emit one beat in absence of the regular beat - Atrial - Junctional - Ventricular

BUN: creatinine ratio to distinguish between prerenal vs. intrinsic AKI vs. post-renal AKI

Prerenal: >20 Intrinsic AKI: <20 (10-15) Post-renal AKI: unreliable

Ventricular Fibrillation (VF)

Presentation: - Life threatening: MOST COMMON arrhythmia associated with cardiac arrest - Loss of consciousness w/o warning - Onset often without warning Prodromal symptoms may include: - Chest pain - Fatigue - Palpitations BP not present, pulse not palpable Perfusion inadequate Mechanisms: Exact mechanism not known Often associated with ischemic heart disease and preceded by: - PVCs - ST changes - R on T phenomenon - Pauses - QT prolongation - Ventricular tachycardia - Supraventricular arrhythmias - Sinus tachycardia Causes: - Myocardial ischemia/infarct - Electrolyte abnormalities - Cardiomyopathy - Long QT, Brugada syndrome - Drugs - Environment (drowning, hypothermia, electrical shock) - PE, cardiac tamponade Tx: - High quality CPR - Rapid defibrillation Drugs: - Vasopressors - Anti-arrhythmics

Analgesic nephropathy

Prolonged and excessive use of analgesics, and especially NSAIDs, causes renal damage through multiple mechanisms: - ATN: direct toxicity to tubuli - AIN: allergic interstitial infiltrate - Membranous GN - Vascular insufficiency: inhibits PG--> constriction of afferent arteriole--> decreased renal perfusion Papillary necrosis due to direct toxicity and sudden vascular insufficiency in pts at risk: - DM - Sickle cell disease - Obstructive nephropathy - Chronic pyelonephritis

Pathological Q waves

Q= Negative deflection before R wave - >40 ms (1 mm wide) - >2 mm deep or - >25% of QRS complex amplitude

What are the 3 ways to determine the mean electrical axis?

Quick & Dirty Approximation: - From the net direction of QRS complexes in Leads I and avF - Lead I (+), aVF (+)---> Normal axis - Lead I (+), aVF (-)---> Left Axis Deviation "Left to Leave" - Lead I (-), aVF (+)---> Right Axis Deviation "Right to Meet" Net Zero Lead Method: - Can only use easily if a lead has a net zero QRS complex - Use limb (I,II,III), and augmented (aVR, aVL, aVF) leads - Find the lead with "net zero" QRS complex - Find the perpendicular lead - The positive or negative deflection of the perpendicular lead is your mean axis Semi-Quantitative Method: - From the net direction of QRS complexes of all six limb leads (but, this takes too long!!)

What are different possible locations of infarcts in regards to the Coronary Circulation?

R dominant- 80% (R coronary artery) L dominant- 5-10% Co-dominant- 10-20% PDA originates from dominant artery, supplies posterior 1/3 of septum Penetrating branches of the dominant artery supply the AV node Right Coronary Artery Lesions Include: Inferior MI: - STE: II, III, aVF - STD: aVL (reciprocal STE) - RCA occlusion distal to RV 58% of MI LAD lesions: Combination of the following: Septal MI: - STE: V1-2 - LAD occlusion Anterior MI: - STE: V3,V4 - LAD occlusion Lateral MI: - STE: V5, V6, I, aVL - LAD occlusion LCX lesions: Posterior MI: - STE: V7-9 - STD: V1-2 (reciprocal STE) - R: S>/= 1: V1-2 - Tall T: V1-2 - RCA and LCX occlusion

Right Ventricular Hypertrophy

RV wall is very thick, so there is much more (positive) depolarization and more vectors) toward the positive V1 electrode - We expect the QRS in lead V1 to be more positive (taller) than usual - Large R wave in V1 - S wave in lead V1 is smaller than R wave in V1 Causes: - COPD - Pulmonary HTN - Atrial septal defect - Pulmonary stenosis - Children <5yo ECG findings: - Tall R in V1 > S in V1 - R in V1 >/= 5mm - plus RAD (Lead I (-), aVF (+)) CAUTION! - In biventricular hypertrophy (both ventricles enlarged) the net electrical forces created by the hypertrophy begin to cancel eachother out - Think: zero sum game in terms of electrical forces - Thus, this condition is difficult to diagnose on ECG

What are the 5 stages of AKI based on severity?

Risk; Injury; Failure; Loss; ESRD (end-stage renal disease)= "RIFLE" Risk: Non- oliguria: abrupt (1-7) days decrease (>25% in GFR or serum creatinine x 1.5 sustained) Oliguria: decreased UO relative to fluid input (UO <0.5mg/kg/h x 6h) Injury: Non-oliguria: Adjust creatinine or GFR decrease >50% serum creatinine x2 Oliguria: UO < 0.5 mg/kg/h x 12h Failure: Non-oliguria: adjust creatinine or GFR decrease >75% serum creatinine x 3 or serum creatinine <4 mg% when acute increase >0.5mg% Oliguria: UO <0.5 mg/kg/h x 12h? Anuria x 12h Loss: Irreverisible AKI or persistent AKI >4 weeks ESRD: ESRD > 3 months ** Risk --> Failure (AKI- earliest time point for provision of RRT- specificity decreases) ----- Caveats for staging: - BOTH creatinine and UO may remain abnormal due to other factors (ex. improper fluid resuscitation) therefore the usefulness the clinical significance and prognosis- determined with caution - Future use of biomakers of renal tubular injury- Cys C- may offer a better alternative for both diagnosis and staging

Papillary Necrosis

Sloughing off of the Renal papillae caused by drugs (NSAIDs) and toxins, or by sudden vascular obstruction with ischemia--> death of cells in papillae and their shedding off in the collecting system of the kidney There is always a background of underlying, pre-existing renal damage- even though sometimes baseline BUN and creatinine seem nml (remember the creatinine only starts rising when a pt has already lost 60-70% renal function) Pts complain of sudden onset flank pain, fever, hematuria-- quite difficult to distinguish from acute pyelonephritis, so you need to look for a history of drug use and prior kidney disease (chronic pyelonephritis, urinary obstruction), sickle cell disease or diabetes mellitus Other criteria differentiating between papillary necrosis vs. acute pyelonephritis Papillary necrosis: - Onset: few hrs - Passed necrotic material in urine - Urine culture negative - Bumpy countour of the structure where the papillae were lost on CT - NO treatment Acute pyelonephritis: - Onset: Few days - Dysuria sxs - Positive urine culture - Diffusely swollen kidney on CT - Antibiotics (anti-gram-negative bacilli) for treatment ****Best initial test= urinalysis: positive for RBC and WBC, as well as fragments of necrotic kidney tissue - Most accurate test= CT scan showing abnormal internal structures with loss of papillae - NO specific therapy- papillae are lost irreversibly

Differentiate between Standard limb leads and Augmented limb leads

Standard Limb Leads: I, II, III Augmented Limb leads: aVR, aVL, aVF *** These standard and augmented limb leads record electrical activity in a frontal plane through the heart Where do the net positive electrical forces go for each limb and augmented lead: I: Left arm II: Right leg III: Left leg aVR: Right arm aVL: Left arm aVF: Left leg ** On normal 12 Lead ECG trace: - aVR, V1, V2 should be negative ANYTHING that interferes with normal conduction will change the appearance of the ECG tracing: - Congenital anomalies - Myocardial hypertrophy - Injury or irritation to the myocardium - Conduction abnormalities (innate and acquired) Six Precordial Leads include: V1, V2, V3, V4, V5, V6 ** These "chest" leads record electrical activity in a transverse plane through the heart REMEMBER! - For any lead, a depolarizing wave moving toward a positive pole gives a positive deflection on the ECG tracing - A depolarizing wave moving toward a negative pole or away from a positive pole gives a negative deflection on the ECG tracing

T or F: NO symptoms of AKI are specific enough to give you the "most likely diagnosis"

TRUE! This is why we need to measure UO and labs!! Urine output (UO): Absolute volume of urine excreted in 24h= most valuble for monitoring renal function if it is too low, or if it varies significantly in a certain direction (increase or decrease) Decreases UO: - Oliguria: UO <0.3 mL/kg/h or <500mL/day - Anuria: UO <50mL/day (some literature 100mL/day) **** AKI is likely if urine output is <0.5 mL/kg/h Investigations: 1. BUN, sCr and eGFR - BEST INITIAL TEST FOR AKI!!!! - An abrupt increase in sCR is an AKI diagnostic criterion per KDIGO - sCr clearance is also used to calculate eGFR ((Urinary creatinine (mg/dL) x Urine Flow (mL/min)/ Serum creatinine (mg/dL)))/ (1. 73m^2 BSA) 2. Serum and urine electrolytes: Na, K, Cl, Ca, Mg - Serum and urinary Na (sNa and uNa) as well as fractioned excretion of Na (FENa) are important in diagnosing AKI of unknown etiology - FENA (%)= (uNa x sCR/ sNa x uCr) x 100 - Serum K tends to accumulate in AKI, causing severe, life-threatening hyperkalemia--> needs to monitor K serum levels and continuous ECG - The other electrolytes may be useful in establishing the AKI etiology 3. Serum and urine osmolarity 4. Urinalysis: protein quantification over 24h, sediment examination 5. Imaging: U/S, CT scan, MRI - 3,4,5 are all Useful in establishing AKI etiology 6. Kidney biopsy: - Useful in establishing AKI etiology and prognosis

Post-renal AKI

This type of AKI may be suspected when there is a history of anuria/oliguria, full bladder sensation, and a suprapubic fullness, which corresponds on abd palpation to a suprapubic mass NOTE that the obstruction must cause bilateral blockage of the urine flow- thus, obstruction of one of the ureters in a pt who has both kidneys may cause hydronephrosis on the obstruction site, but no AKI Causes: - Stones, blood clots, external compression, tumor, retroperitoneal fibrosis - Radiotherapy, chemotherapy with bleomycin or methysergide= clues for postrenal AKI - Prostatic enlargement, blood clots, cancer - Strictures - Obstructed Foley catheter Pathophysiology: - Initially the blockage of the urinary tract will cause a back-flow of ultrafiltrate into the Bowman capsule that will slow down the glomerular filtration and decrease the GFR, hence you see raised creatinine, hence the pt has AKI - Remember that filtration pressure is roughly the diff between hydrostatic pressure in the capillary that pushes the fluid out of the capillary on one hand, and the oncotic pressure in the capillary (which keep the fluid inside) as well as the hydrostatic pressure in Bowmans capsule. - IF there is a back-flow of ultrafiltrate, the hydrostatic pressure will increase in the capsule with a decrease in the overall filtration pressure, and thus filtration will be slowed down or even stopped- initially, the glomerulus is not damaged, thus in the first stages FENa will be 1% or even less In time however, if the blockage is not relieved (ex. by catheterizing the bladder), the glomerulus and the tubuli will be damaged due to the raised pressure of the urine back-flow- the result will be irreversible renal damage, where the post-renal AKI manifests itself as intrinsic AKI, with FENa >2%- this happens for instance in hydronephrosis Therefore, in post-renal AKI initially FENa may be 1% or less, and later, when it causes intrinsic renal damage, FENa will become 2% Thus, FENa is not so useful to diagnose UT obstructions- you need to rely more on your clinical skills for your differential, than just looking at FENa.

Second Degree Heart Block

Types of Second Degree Heart Blocks: Mobitz 1 (AKA Wenckebach block) - Block is in the AV node - May or may not evolve to complete heart block - Can be caused by drugs (ex. Digoxin, Beta Blockers) - Can be caused by fibrosis of the AV node - May need temporary or permanent pacing How to diagnose: - Varying failure of conduction through the AV node occurs - Characterized by an increasing delay of AV nodal conduction until a P wave fails to conduct through the AV node seen as progressive PR interval prolongation with each beat until a P wave is not conducted Mobitz 2: - Indicates block is in the distal conduction system (below the AV node) - Often evolves to complete heart block - Pacemaker therapy is indicated How to diagnose? - PR interval remains constant (NO progressive length) - Periodically a P wave is not conducted (blocked)

In prerenal AKI, what happens to urea?

Urea is drawn back into the blood together with the water - water is absorbed under the action of ADH (this attracts other compounds such as urea and Na) There is also a lot of reabsorption of H2O in the proximal tubules, which leads to the passive reabsorption of urea Later in the distal tubuli, ADH further contributes to the reabsorption of urea Although creatinine excretion is also decreased in prerenal AKI, causing a rise in serum creatinine, this rise is NOT as dramatic as the rise of urea (this explains the BUN: creatinine ratio of >20)

How do the urinalysis, Urine [Na] and Urine osmolality differ in prerenal vs. intrinsic AKI

Urinalysis: - Prerenal: <10 cellular casts/ hpf (often none or hyaline casts: parenchyme intact) - Intrinsic AKI: >10 cellular casts/hpf (type of casts depends on etiology) Urine [Na] - Prerenal AKI: (normal reabsorptive capacity): fluid depletion causes H2O retention--> Na retention--> low U-[Na] < 20 mEq/L - Intrinsic AKI: due to tubular injury: Na NOT reabsorbed--> lost in urine --> increased U-[Na]--> 40-50 mEq/L Urine osmolality: - Prerenal: (tubules not damaged): if dehydration--> increased AD--> H2O reabsorption--> Uosmol >500 (high sg) - Intrinsic AKI: loss of concentrating ability --> Uosmol <450 mOsmol/kg (similar to blood osmol)= 300= isothenuria--> inappropriately high losses of H2O and Na

What would the labs of a pt with PRE-RENAL AKI show?

Urinalysis: increased urine specific gravity (sg) >1.020; hyaline casts, "BLAND" BUN/sCr >20/1 due to the following mechanisms: - Increase in passive of transfer of urea in PCT, following enhanced reabsorption of Na and H2O - Increased urea reabsorption mediated by ADH, which increases the permeability of the inner medullary collecting ducts to H2O and urea, allowing for maximal free H2O retention; - At the same time creatinine continues to be secreted FeNa: % of filtered Na excreted in the urine is <1% - If pt is on a diuretic, FeNa is falsely high (>2%) due to the Na loss, thus it is NOT reliable and should be replaced by fractional excretion of urea= FEUrea (typically <35%) - FENa may also falsely indicate pre-renal AKI (<1%) in ATN caused by pigment damage (myoglobinuria or hemoglobinuria), bc pigment injury causes intense vasoconstriction and thus reduces Na filtration and excretion Urine Na: <20 mEq/dL *** NOTE: Prompt improvement of renal function after fluid resuscitation in a pt with AKI--- suggests a PRE RENAL cause*****

Describe the pathogenesis of PRE-RENAL AKI

a. Decreased intravascualr volume ("true" intravascular volume depletion) - Hypovolemia (dehydration, hemorrhage) - Hypo-albuminemia - "Third spacing" (ascitis) - Diuretics b. Reduced cardiac output: - Cardiogenic shock - CHF - Tamponade - Cirrhosis (hepato-renal syndrome) c. Changes in vascular resistance- systemic vasodilation: - Sepsis - Anaphylaxis - Anti-HTN Rx (ex. ACE inhibitors, ARBs) d. Local renal hypoperfusion: - Renal artery stenosis, embolism, thrombosis (especially bilateral) - NSAID's - ACE-inhibitors, ARBs

The etiologies of INTRINSIC AKI can be grouped according to the site of pathology as follows:

a. Glomerulopathies: acute glomerulonephritis; crystallopathies - Both a cause and risk factor for AKI - Any type of glomerulopathy may lead to AKI- BUT most are usually chronic - Pediatric PSGN, IgA nephropathy, TBMN, Alport's, minimal change NS unlikely to develop into AKI/CKD - Most severe form, often with acute progression: crescentic GN-- RPGN b. Tubulopathies: acute tubular necrosis (ATN) i. Acute Tubular necrosis/ ATN ii. Crystallopathies - Pigment nephropathy - Uric acid nephropathy - Renal cholesterol embolism c. Interstitium: acute allergic interstitial nephritis (AIN) d. Micro-angiopathies: HUS/TTP; renal artery emboli e. Analgesic nephropathy

Extra-renal vascular diseases include

i. Bilateral Renal artery stenosis (RAS) - Causes: atherosclerosis; fibromuscular dysplasia - Manifesting by resistant HTN secondary to continuous stimulation of RAAS - Dx: sxs and signs of multiorgan ischmeia, including CNS involvment (headaches, TIAs, stroke, aneurysms); mesenteric ischmeia (with abd pain after eating); extremity claudication) - ONCE added an ACE-I to the tx of HTN caused by RAS--> AKI - Bc in bilateral RAS GFR is maintained by PG-induced vasodilation of afferent arteriole and the RAAS- induced vasoconstriction of efferent arteriole--> if RAAS inhibited by ACE-I --> glomerular filtration pressure decreases--> GFR and filtration fraction decrease, while at the same time sCr increases - If a pt is also on a diuretic, this needs to be stopped, bc in the setting of fluid depletion there is an increased dependence on RAAS to maintain GFR - Radiology: U/S small kidneys, CT/MR angiography (in FMD characteristic "string-of-beads") ii. Renal artery thrombosis/ Renal infarction/ cardioembolic disease - AKI may be causes by large thrombi that obstruct both RAS--> wedge-shaped necrosis of the renal parenchyma - Kidneys are predisposed bc of their increased perfusion rate and limited RA collaterals - Risk factors: HTN, obesity, atrial fibrillation - Presentation: acute onset flank pain, CVA tenderness, frank hematuria - Characteristic increase in LDH due to necrosis

Hypertrophy of a chamber of the heart implies an

increase in the thickness of the chamber wall - The increase in the muscular thickness of the wall of a hypertrophic chamber, as well as dilation of a chamber of the heart may be diagnosed on ECG - Increase in the muscle wall results in a higher vector as seen in the leads oriented towards those chambers

In intrinsic AKI, there is NO secretion of ADH & water reabsorption is deficient due to damage to the

nephron - Thus, reabsorption of urea is NOT going to be as super-efficient as in prerenal AKI-- this is why, while urea does rise, creatinine rises more dramatically than urea and the BUN: creatinine ratio is around 10-15 (<20)

Pacemaker current (If) drives the

pacemaker cell from maximum diastolic potential to threshold potential Cardiac cells will depolarize if they: - reach threshold potential - are sitmulated by another cell that suppresses their automaticity HR is influenced by: - Maximum diastolic potential - Threshold potential - Pacemaker current (If)- determined by the kinetics of individual pacemaker cells 5 Action Potential of the myocardium correlated with the ECG: - SAN - Atrium - AVN - Purkinje - Ventricle - ECG Lead I