aral tayo

Erratum: inspiration DECREASES intrathoracic pressure

Why do the HOCM and MVP murmurs follow the opposite of the "classic" VHD murmurs (e.g., MR, MS)? A: Because classic VHD murmurs increase with volume (more turbulent flow across a small valve), while: - HOCM depends on degree of outflow tract obstruction - Timing of MVP depends on relative LV filling time (larger LV = more time before prolapsing) Example: 🔸️Increases in LV volume > more turbulent flow across AV > louder AS murmur 🔸️Increases in LV volume > more LV distension > wider LV outflow tract > less LVOT turbulence > softer HOCM murmur 🔸️Increases in LV volume > more time to fill the LV before the mitral valve prolapses into the LA > delayed systolic click, shorter MVP murnur

DYNAMIC AUSCULTATION - certain maneuvers can affect the intensities of murmurs coming from the R heart, the L heart, or both. - effects usually depend on the change in volume of the affected sides of the heart 🔹️Respiration - affects lung size > affects amount of blood in pulmonary circuit - increases volume of one side of the heart, decreases the other 🔹️Alterations in SVR - largely affect preload and/or afterload; exert the same effect on both sides of the heart - Increase heart volumes: squatting, PLR - Decrease heart volumes: abrupt standing, Valsalva maneuver (strain) 🔸️Hand grip maneuver - used to differentiate between MR and AS (both are systolic murmurs)

IRON STUDIES 🔸Serum iron (50-150 mcg/dL) - initially maintained by mobilization of iron stores (ferritin) 🔸Total iron-binding capacity (TIBC) (300-360 mcg/dL) - indirect measure of saturated transferrin - the more saturated transferrin molecules, are, the less additional iron they can bind 🔸% Transferrin saturation (25-50%) - calculated from TIBC (%TS = (Serum iron/TIBC) * 100) - amount of circulating transferrin bound to iron 🔸Serum ferritin (M: 100 mcg/L; F: 30 mcg/L) - most convenient marker of iron stores - first to fall; most easily distinguishes IDA from AI - <15 mcg/L: absent iron stores 🔹️Bone marrow iron stain - gold standard for diagnosis of IDA, but more difficult to perform

IRON METABOLISM - Iron is an important but toxic molecule - Iron cycle is an elaborate mechanism ensuring proper utilization and sequestration of iron - Most of iron goes to RBCs for O2 transport IMPORTANT MOLECULES 🔹Transferrin - the iron transport protein, found in circulation 🔹Ferritin - the iron storage protein, found in iron-utilizing cells (unoccupied form: apoferritin) 🔸Ferroportin - the iron export channel 🔺️Hepcidin - the primary regulator of iron metabolism*, upregulated by inflammation (esp. infection via IL-6) *Hepcidin acts by inhibiting ferroportin. 1️⃣ Iron is absorbed in the duodenum and proximal GIT. 2️⃣ Iron exits the gut cell via ferroportin. 3️⃣ Iron binds to transferrin and travels in the bloodstream. 4️⃣ Transferrin-iron complex binds to receptors and is endocytosed. 5️⃣ Iron is separated and utilized in cells (e.g., as part of Hgb) 6️⃣ Excess iron binds with apoferritin, forming ferritin. 7️⃣ Transferrin reenters the circulation.

APPROACH TO ANEMIA - CBC and PBS with RC are important for determining the etiology of anemia. - Anemia is divided into 3 broad categories: 1) production disorders, 2) maturation disorders, and 3) hemolytic disorders. 1️⃣ PRODUCTION DISORDERS (HYPOPROLIFERATIVE ANEMIAS) - can result from: 🔸Marrow damage 🔸Substrate deficiency (iron) 🔸Stimulus deficiency (EPO deficiency, inflammation, endocrine) - Characteristic picture: normocytic, normochromic anemia, RPI < 2.5% Lab tests: 🔹Iron studies 🔹Renal and thyroid FTs 🔹Possible marrow biopsy/aspirate Iron deficiency - low iron, high TIBC, low transferrin saturation, low ferritin Inflammation - low iron, norm/low TIBC, low transferrin saturation, norm/high ferritin 2️⃣ MATURATION DISORDERS - can result from: 🔸Cytoplasmic defects (SEVERE iron deficiency, inflammation, thalassemias, MDS) 🔸Nuclear defects (Vit B12 or FA deficiency, drug induced, MDS) - Characteristic picture: micro/macrocytic anemia, RPI < 2.5% Lab tests: 🔹Iron studies 🔹Cobalamin or folate assays, methylmaloante, endoscopy etc. if macrocytic Iron deficiency - low iron, high TIBC, low transferrin saturation, low ferritin Inflammation - low iron, norm/low TIBC, low transferrin saturation, norm/high ferritin Thalassemias, MDS - norm/high Iron, norm/high transferrin saturation Cobalamin/Folate deficiency - may present with neuropsychiatric symptoms, glossitis, gastritis 3️⃣ HEMOLYTIC DISORDERS - can result from: 🔸Blood loss 🔸Infection (malaria, HUS) 🔸Toxic (nitrates, hyperbaric O2, cisplatin, dapsone) 🔸Inherited hemoglobin/cytoskeleton disorders (HS, HE, PKD, etc.) 🔸Immunologic diseases (WAIHA, PNH, cold agglutinin disease) - Characteristic picture: RPI > 2.5% Lab tests: 🔹Urinalysis 🔹TB/DB/IB 🔹may need more specialized tests if blood loss is ruled out (i.e., immunologic testing)

ANEMIA: INITIAL LABORATORY TESTING (2/2) RETICULOCYTE COUNT (RC) - represented as percentage of all red cells; normal value = 1% - the apparent reticulocyte count still needs 1-2 corrections: 1️⃣ FOR ANEMIA ("Corrected RC") 🔹In anemia, the number of mature RBCs decreases, but the number of reticulocytes remains the same. 🔹️Apparent percentage made up of reticulocytes becomes ERRONEOUSLY HIGH. To correct, use ratio and proportion: Corrected RC = RC * (Actual Hgb or Hct/Normal Hgb or Hct) 2️⃣ FOR POLYCHROMASIA ("Reticulocyte production index") - ignore if no polychromasia seen. Use the Corrected RC as the RPI instead. 🔹Peripheral reticulocytes last ~1 day in circulation before becoming mature RBCs. 🔹However, in states with premature release, the precursors linger in the circulation for multiple days instead, ERRONEOUSLY INCREASING the RC again. 🔹e.g., if reticulocytes are relased 1 day earlier, the total amount of circulating reticulocytes is DOUBLE the amount actually produced today -> overestimated To correct, divide by correction factor: RPI = Corrected RC / (correction factor*) *correction factor: number of days reticulocytes linger in circulation; varies from 1 to 3 based on anemia severity. Usual value = 2. —————————————- INTERPRETING THE RPI RPI < 2.5%: suspect maturation or proliferation defect RPI >= 2.5%: suspect hemolysis

ANEMIA: INITIAL LABORATORY TESTING (1/2) COMPLETE BLOOD COUNT (CBC) 🔸Microcytosis: MCV <80 (cytoplasmic maturation defect) 🔸Macrocytosis: MCV >100 (nuclear maturation defect) 🔸Hypochromia: low MCHC PERIPHERAL BLOOD SMEAR (PBS) 🔸Poikilocytosis: variations in cell shape (maturation defects) 🔸Anisocytosis: variations in cell size 🔸Polychromasia: presence of larger, more grayish-blue RBCs ("shift cells;" EPO-mediated premature reticulocyte release)

ANEMIA - defined as Hgb < 120 g/L in females and Hgb < 130 g/L in males ACUTE ANEMIA - usually due to either of these two: 🔸Blood loss - in acute blood loss, anemia is not primary concern but hypovolemia - Signs of vascular instability appear at 10-15% loss of total blood volume - Orthostatic hypotension, tachycardia: -30% TBV - Hypovolemic shock: -40% TBV 🔸Hemolysis - Intravascular: can manifest with acute back pain, tea-colored urine, AKI - Extravascular: majority CHRONIC ANEMIA - initially counteracted by increase in 2,3-BPG (right shift in O2 dissociation curve) until loss is around 20-30 g/L - Pallor: Hgb <80-100 g/L - Majority of symptoms (weakness, fatigue, etc.): Hgb <70-80 g/L (severe anemia)

Erythropoietin (EPO) - primary regulatory hormone for RBC production - secreted by peritubular cells in the kidney - stimulus for production: hypoxia - response: increased release of reticulocytes (sometimes released prematurely = polychromasia) - takes days to weeks to exert peak effects

Empiric treatment of HAP and VAP (HPIM 21st ed.)

IDSA 2016 GUIDELINES ON MANAGEMENT OF HAP AND VAP INITIATING/TAILORING TREATMENT 🔹Initiate based on clinical criteria 🔹Tailor based on semiquantitative cultures (ETA GS/CS) when available 🔹Procalcitonin is NOT a guide for INITIATING antibiotics! CHOOSING AN INITIAL ANTIBIOTIC REGIMEN 🔸Include staphylococcal and gram-negative (including Pseudomonas) coverage in ALL regimens regardless of MDR risk 🔸If (+) risk factors for MDR pathogens (refer to above table): - Use 2 antipseudomonals of different classes - Add vancomycin/linezolid as needed for MRSA coverage - Antipseudomonal monotherapy is reserved for patients without MDR risk who are being treated in ICUs where ≤10% of gram-negative isolates are resistant to the agent being considered for monotherapy (AKA not PGH). LENGTH OF THERAPY 🔹A 7-day course of IV antibiotics is recommended for both HAP and VAP 🔹De-escalation to a narrower-spectrum antibiotic regimen is encouraged as needed 🔹Procalcitonin CAN be used as a guide for DISCONTINUING antibiotics 🔹Discontinuation of therapy based on the Clinical Pulmonary Infection Score (CPIS) is not recommended. INHALED ANTIBIOTICS - reserved for Gram-negative VAP patients with cultures susceptible ONLY to aminoglycosides or polymyxins - given on top of systemic antibiotics

Hospital-acquired pneumonia (HAP) - pneumonia occurring >=48h after admission, excluding any incubating illness at the time of admission Ventilator-associated pneumonia (VAP) - pneumonia occurring >=48h after intubation - NHSN 2022: if intubated prior to inpatient admission, ventilator day count begins with the admission date TO THE FIRST inpatient location - NHSN 2022: If a break in mechanical ventilation occurs for at least one full day, ventilator day count RESTARTS upon reintubation

Risk factors for MDR pathogens (IDSA 2016 guidelines on HAP and VAP)

"When is an RR of 30s-40s acceptable?" - Always decide based on trends and on the whole set of vitals, not on isolated values. Case 1: intubated patient presents with RR of 32. On chart review, you noted that they presented at the ER with RR 42, A> sepsis, started on empiric antibiotics, intubated and placed on NE, with noted gradual improvement in T + BP + RR -> you don't need to do anything right now! Case 2: intubated patient presents with RR 34. On chart review, you noted that his RR in the ward is usually 18-22, visibly dyspneic -> intervene! try increasing LPM, switching devices, nebulizing with salb/epi, or intubating if persistently dyspneic and desaturated.

Quick rule of thumb for ventilation adjustments: Dyspneic - adjust flow (NC/FM/HFNC) or Vt (BIPAP/MV) first Desaturating - adjust FiO2 first