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597 Cards in this Set
- Front
- Back
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Quinidine
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Antiarrhythmic
- Class IA--dec Na current and ROR moderately - inc APD---prolong ERP ----high Na channel block ----moderate K channel block ----Low M2 block ----low a&B AR block |
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Lidocaine
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Antiarrhythmic--ACUTE VENTRICULAR ARRHYTHMIAS
- Class IB---dec I_Na and ROR modestly - Dec APD - SEIZURES |
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Procainamide
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Antiarrhythmic---USED ACUTELY
- Class IA--dec Na current and ROR moderately - inc APD---prolong ERP - NAPA metabolite is K channel inhibitor - hepatic metabolism and renal excretion TORSADE |
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Flecainide
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Antiarrhythmic
- Class IC--dec I_Na and ROR Strongly - No change in APD |
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Propafenone
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Antiarrhythmic
- Class IC--dec I_Na and ROR Strongly - No change in APD |
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Propanolol
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Antiarrhythmic--non specific BB
- Class II--B_AR blocker - Dec exciatability and conduction velocity in AV node - nightmares and sedation |
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Metoprolol
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Antiarrhythmic--B1
- Class II--B_AR blocker - Dec exciatability and conduction velocity in AV node |
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Esmolol
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Antiarrhythmic--B1
- Class II--B_AR blocker - Dec exciatability and conduction velocity in AV node |
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Atenolol
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Antiarrhythmic--B1
- Class II--B_AR blocker - Dec exciatability and conduction velocity in AV node |
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Adenosine
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Antiarrhythmic
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Digoxin
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Antiarrhythmic
- Na-K exchange pump inhibitor - M2 agonist---activates vagal input - shortens refractory periords...inc excitability of accessory pathway fibers - monitor plasma levels -Avoid in patients with AVRT (WPW)-->A.Fib - Cognitive and vision effects |
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Class I Antiarrhythmic Drugs
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Fast Na Channel Blockers
- dec Na current...dec rate of rise phase 0 - dec excitability of non-nodal tissues |
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Disopyramide
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Antiarrhythmic
- Class IA--dec Na current and ROR moderately - inc APD---prolong ERP |
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Carvedilol
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Antiarrhythmic--nonspecific BB and a1 blocker
- Class II--B_AR blocker - Dec exciatability and conduction velocity in AV node |
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Labetalol
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Antiarrhythmic--nonspecific BB and a1 blocker
- Class II--B_AR blocker - Dec exciatability and conduction velocity in AV node |
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Amiodarone
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Antiarrhythmic----rarely causes Torsade
- high Iodine content...hypo (or hyper)thyroidism - delayed onset as it accumulates ***Pulminary fibrosis can be fatal, blue photosensitive skin - Class III--K+ channel blocker - inc refractory period ----low Na channel block ----moderate K channel block ----Low CCB ----moderate a&B AR block |
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Sotalol
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Antiarrhythmic
- Class III--K+ channel blocker - Inc refractory period -PRODUCES LONG QT-->TORSADE ----High K channel block ----high B AR block |
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Dronedarone
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Antiarrhythmic
- Class III--K+ channel blocker - Inc Refractory Period - Non-iodinated Amiodarone derivative...less side effects - GOOD FOR A. Fib |
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Ibutilide
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Antiarrhythmic (IV)
- Class III--K+ channel blocker -PRODUCES LONG QT-->TORSADE |
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Dofetilide
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Antiarrhythmic (IV)
- Class III--K+ channel blocker -PRODUCES LONG QT-->TORSADE |
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Class II Antiarrhythmics
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Beta Blockers
Slow conduction velocity and dec excitability AV node |
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Class III Antiarrhythmics
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K+ Channel Blockers
Increase Refractory period May cause long QT (Sotalol, Ibutilide, Dofetilide) |
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Class IV Antiarrhythmics
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L-type Calcium Channel Blockers
Block slow, non-inactivating Ica Mainly effect SA and AV nodal cells ---slow conduction velocity and inc refractoriness |
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Verapamil
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Antiarrhythmic--LTCC blocker
non-dihydropyridine...mostly effects cardiac ccs ---slow conduction velocity and inc refractoriness - avoid in WPW, AVRT-->A. Fib |
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Diltiazem
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Antiarrhythmic--LTCC blocker
non-dihydropyridine...mostly effects cardiac ccs ---slow conduction velocity and inc refractoriness - avoid in WPW, AVRT-->A. Fib |
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Adenosine & Digitalis
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Unclassified Antiarrhythmics
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Why does sotalol cause long QT?
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Binds effectively to resting channels
Promotes long QT and torsade at slow HR ***Inc HR w/pacing or Isoproterenol to stop torsade |
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When do most K+ Channel blockers bind effectively the channel?
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During activity...so high HR...
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MAP = ?
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(1/3)SBP+(2/3)DBP = Mean Arterial Pressure
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Isolated Systolic Hypertension
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SBP > 140 w/ DBP < 90
- old ppl w/stiff vessels |
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BP = ?
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BP = CO * TPR
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CO = ?
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CO = HR * SV
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Renin converts what?
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Angiotensinogen --> Angiotensin I
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Angiotensin converting enzyme converts what and where?
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ANG I --> ANG II
Lungs and renal endothelium ALSO inactivates Bradykinin |
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Bradykinin
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Potent vasodilator...inactivated by ACE
ACE inhibitors can cause increased bradykinin see angioedema |
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Mechanisms of Primary Hypertension
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- unable to handle Na and H2O properly
- overactive/stimulation of SYMP system - Ca handling abnormalities in smooth muscle - Defective RAAS |
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Mechanisms of Systolic Hypertension in the elderly
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- dec large artery compliance
- dec baroreceptor activity - inc SYMP stim - dec B-AR in blood vessels - dec RAAS - dec Creatinine clearance - volume expansion |
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Hyperinsulinemia and Hypertension
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- Inc renal NA retention
- Inc vascular muscle hypertrophy - Augments Ca - Stimulates SYMP |
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End organ effects of hypertension
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- hemorrhage, stroke
- retinopathy - peripheral vascular disease - Renal failure - LV hypertrophy, CHD, CHF |
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Hypertensive retinopathy
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see cotton wool spots
papilloedema flame haemorrhage hard exudates |
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Major end points of Hypertension
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- MI (50%)
- Stroke (30%) - Renal disease (30%) |
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Malignant Hypertension
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- severe inc in BP---especially DBP
- rentinal hemorrhages, papilledema - renal failure - LV failure and angina |
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BP Goals
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- all patients less than 140/90mmHg
- maybe 150 for elderly |
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Methods for lowering blood pressure
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- life style changes
- medication - renal nerve ablation |
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lifestyle changes for lowering BP
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- weight loss ---5-20mmHg/10lbs
- dec dietary Na - exercise - dec alcohol and tobacco |
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First Line Anti-hypertensives
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- ACE inhibitors
- Angiotensin Receptor Blockers - BB - CCBs - Diuretics |
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Diuretics (thiazides) side effects
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- gout
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Beta blockers side effects
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- Asthma or A-V block
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CCB side effects
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A-V block
Severe LV dysfunction HF |
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ACE inhibitor side effects
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Angioneurotic edema
Hyperkalaemia Bilateral renal artery stenosis **BAD for pregnancy |
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Angiotensin receptor blocker side effects
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Hyperkalaemia
Bilateral renal artery stenosis **BAD for pregnancy |
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Mineralocorticoid receptor antagonists
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acute or severe renal failure
hyperkalaemia |
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What is the rule of TENS
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each additional drug should drop BP by 10mmHg
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Renal Denervation
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- radiofrequency ablation of sympathetic afferent and efferent activity
- See sustained 30 mmHg reduction at 3 yrs post procedure |
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Causes of Secondary Hypertension
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- Chronic kidney disease
- Renovascular Disease - Adrenal Disease - Pheochromocytoma - Obstructive Sleep apnea |
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Chronic Kidney Disease mechanism for HTN
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- Na retention
- Kidney injury--RAAS, SYMP stim, dec NO signaling - see hyperparathyroidism and increased [Ca]i - Erythropoietin treatment gives higher hemoglobin - aortic stiffness |
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Renal artery stenosis causes--renovascular disease
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decreased flow triggering RAAS and efferent ANGII mediated vasoconstriction
- reduce GFR and load via decreasing ANGII vasoconstriction |
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Adenoma or adrenal hyperplasia mechanism of HTN
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adrenals overproduce aldosterone--inc volume--inc BP
see increased Na reuptake..and K loss...block with spironolactone or surgically remove |
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Mineralocorticoid excess and hypertension
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Aldosterone acts on renal mineralocorticoid receptor causing Na retention and K excretion
with excess cortisone there is conversion to cortisol and mineralocorticoid receptor activity |
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Licorice Ingestion and mineralocorticoid excess
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Glyayrrhetinic acid promotes cortisol production
see increased Na retention and K excretion |
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Congenital Adrenal Hyperplasia (CAH)
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21 hydroxylase deficiency---Na wasting
11 hydroxylase deficiency--- htn, hypokal, see elevated 11 deoxycorticosterone 17 hydroxylase deficiency (rare)--- htn, hypokal, amenorrhea...boys are pseudohermaphrodites |
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Glucocorticoid Remediable Hypertension
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- autosomal dominant low renin system
- hyperaldosteronism ALDO secretion is controlled by ACTH NOT ANG II See complete suppression of aldo by exogenous glucocorticoids |
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Secondary HTN:
High Aldo High Renin |
- Renovascular disease
- Hypovolemia---LV failure - Rare renin secreting tumor |
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Secondary HTN:
High Aldo Low Renin |
Adrenal adenoma--hyperplasia or cancer
Familial - GRA |
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Secondary HTN:
Low aldo Low renin |
Apparent mineralocorticoid
- excess syndrome - cushings syndrome Liddle's Syndrome CAH 11 and 17 hydroxylase difficiency |
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Pheochromocytoma
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Neuroendocrine secreting tumor
- medulla of the adrenal gland...chromaffin cell origin - Hypertension, headache, sweating, palpitations - See plasma Catecholamines super high w/high metanephrines and VMA |
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How to treat Pheochromocytoma
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- alpha block for BP
- Beta block for tachyarrhythmia (after alpha block) - Alpha methyl-p tyr inhibits catecholamine synthesis |
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Obstructive Sleep apnea
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intermittent asphyxia, elevated BP, fragmented sleep
- predisposition to cardiovascular morbidity - daytime hypersomnolence - Treat w/ positive pressure device and weight loss |
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Drugs that cause HTN
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cocaine
steroids NSAIDS alcohol estrogen |
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Hydralazine
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Direct vasodilator---arterial
no known mechanism |
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Minoxidil
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Direct Vasodilator---arterial
Katp channel opener |
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Venodilation cardiovascular effects
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dec preload
postural dec in BP dec LV filling pressure in cardiac work dec pulmonary BP |
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Arteriodilation cardiovascular effects
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Dec afterload
non-postural dec BP High LV filling pressure inc Cardiac work and HR Inc salt/H2O retention |
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Hydralazine
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reflex inc CO, HR, Na/H20 retention
combined w/diuretic for HTN Liver acetylation-->inactive Good for eclampsia Lupus like syndrome antioxidant in hydralazine isosorbide dinitrate for CHF |
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Minoxidil
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Katp channel opener KCO
reflex inc CO, HR, Na/H20 retention combined w/diuretic for HTN more potent loop diuretic needed liver activation hypertrichosis |
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Diazoxide
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Katp channel opener
- treat hyperinsulinemia, hypoglycemia, sulfonylurea OD Will decrease insulin release via hyperpolarization |
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Adenosine
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Indirect KCO
acts on adenosine A2 receptor arteriovasodilator fast t1/2 act on cardiac A1 to open Katp during preconditioning Bradycardia...exacerbate asthma through A1 |
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Sulfonylureas
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Katp channel inhibitors-->inc Beta cell membrane potential-->insulin release
oral glucose lowering agent |
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Katp channels in ischemia/hypoxia
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hypoxia-->dec ATP/inc ADP-->Katp open-->dec APD and contractility-->dec O2 demand
Will cause vasc smooth muscle relaxation-->inc blood flow Protective |
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Katp and the Beta cell
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High gluc-->high ATP-->close Katp-->inc Vm and release insulin
Membrane depolarization activates LTCC-->secretion |
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Ischemic Preconditioning Effects
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Coronary occlusion causes regional wall motion changes
If short occlusion see slow recovery over 2 days--stunning Long occlusion--see small infarct if preconditioned |
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Acute and Delayed Phase Ischemic preconditioning
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acute--up to 3 hrs, open Katp---close mito PTP
delayed--adter 24 hrs last through 48 hrs---RISK kinases increase transcription of HSPs and superoxide dismutase...protective proteins |
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Methods for pre/postconditioning
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- PTP inhibitors
- Adenosine infusions to ease in reperfusion - cyclic limb occlusion-->protective factors |
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Sympatholytic Agents
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deplete NE storage within vesicles
--RESERPINE inhibit symp outflow from CNS --methyldopa, clonidine, monoxidine inhibit NE synthesis --metyrosine |
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Reserpine
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Irreversibly Blockes VMAT
- slowly deplete vesicular monoamines Adverse: inc depression, potentiate depressants alcohol, exacerbate parkinsonism, seizure |
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Clonidine
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Central a2 agonist--dec symp outflow (baroreceptor intact still)
Used for opiate withdrawl..anesthetic adjunct, GH releaser Bad--drowsiness, dry mouth (xerostomia), withdrawal can cause excess SYMP stim--exacerbate htn, ischemia |
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Methyldopa
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Central a2 agonist--dec symp CNS outflow
Good in pregnancy Bad--drowsiness, dry mouth (xerostomia), withdrawal can cause excess SYMP stim--exacerbate htn, ischemia |
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Moxonidine
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Imidazoline Receptor Blockers
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Metyrosine
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Tyrosine Hydroxylase inhibitor-competitive
used to manage Catecholamine secreting tumors |
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Verapamil
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Ca Channel Blocker
Phenylalkylamine Frequency Dependent---Cardiac - Strong vasodilation and strong dec in contractility - Strong dec HR and Strong dec Conduction velocity |
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Diltiazem
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Ca Channel Blocker
Benzothiazepine - more effective for Cardiac relaxer...freq dependent - medium vasodilation and dec in contractility - strong dec HR and dec Conduction velocity |
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Nifedipine
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Ca Channel Blocker
- Dihydropyridine - more effective for vascular smooth muscle relaxation - Strong vasodilation and little dec in contractility - little dec HR and no dec Conduction velocity |
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Amlodipine
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Ca Channel Blocker
- Dihydropyridine - more effective for vascular smooth muscle relaxation |
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Open vs. inactivated Ca channel
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Open state of LTCC is frequency dependent
---Verapamil and diltiazem stabilize Inactivated state is voltage dependent ---Dihydropyridines stabilize |
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L type Ca Channel modes
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Mode 0 --- closed, stabilized by CCBs
Mode 1 --- brief open state Mode 2 --- PKA stabilized long open state |
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L type Ca Channel Block Causes:
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- Dec HR
- Dec automaticity (SA node) - Dec conduction velocity - Dec contractility |
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Adverse effects of dihydropyridines
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- hypotension
- flushing - headache - inc symp activity - swollen ankles ---altered capillary hemodynamics NOT volume expansion |
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Verapamil and Diltiazem adverse effects
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- LV dysfunction
- AV block - DON'T COMBO w/ BB - GI constipation |
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Ca Channel Blocker Metabolism
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- liver by CYP34A
---careful w/ grapefruit juice, protease inhibitors, erythromycin, and statins |
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Renin Release is stimulated by
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- dec CO, dec BP/blood volume, dec systemic vasc resistence--->dec pre-glomerular BP, dec NaCl, inc NE
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Renin does what?
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Converts Angiotensinogen to ANG I
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Role of ACE2
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counters the adverse cardiac and atherogenic effects of excess ANGII---creates vasodilatory metabolites ANG 1-7
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ANG II acting on AT1 Receptors causes what?
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- altered cardiac structure: Hypertrophy/remodel
----inc protooncogenes, inc GFs, inc ECM proteins ----inc afterload and inc vascular wall tension - altered renal function: SLOW PRESSOR ----Inc Na reabsorption, inc aldo - altered peripheral resistance: RAPID PRESSOR ----direct vasoconstriction, inc SYMP |
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RAAS and Bradykinin and Prostaglandin
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- Converted to inactive metabolite by ACE does not catalyze Arachidonic Acid to Prostaglandin
- bradykinin is a potent vasodilator |
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How is arachidonic acid released from phospholipids
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B2 AR stimulation via PLC
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ACE inhibitors cause what side effects
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Angioedema of the arytenoids and tongue
- dry cough |
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Enalapril is converted to?
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Enalaprilat---ace inhibitor
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Fosinopril is converted to?
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Fosinoprilat---ace inhibitor
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Captopril effects on RA, Aldo, and ANG II
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- inc PRA
- dec PA - dec ANG II |
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Pathologic effects of aldosterone
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- hypertension
- fibrinoid necrosis and inflammation of the renal and coronary arteries |
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Physiologic effects of aldosterone
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- Na reabsorption
- K secretion |
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Aldosterone Antagonists
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Spironolactone
Eplerenone |
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ANG Receptor Subtype Effects:
AT1 |
- inc phospholipases
- dec adenylyl cyclase - inc tyrosine kinase ***ARBs are AT1 selective overall vasoconstrict and aldo release |
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ANG Receptor Subtype Effects:
AT2 |
- inc tyrosine phosphatases
overall vasodilation, antiproliferation, differentiation |
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ACE inhibitors RAAS profile
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- inc PRA
- inc P ANG I - dec P ANG II - dec P Aldo - inc Bradykinin and PGs---cough & angioedema |
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ARBs RAAS profile
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- inc PRA
- inc P ANG I - inc P ANG II - dec P Aldo - no change in Bradykinin and PGs |
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Renin inhibitor RAAS profile
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- dec PRA
- dec P ANG I - dec P ANG II - dec P Aldo - no change Bradykinin and PGs |
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Common RAAS inhibitor benefits
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- antihypertensive
- combination with diuretic potentiates - regress LV hypertrophy - good for diabetics |
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Common RAAS inhibitor adverse effects
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- hypotensive, dizzy, hypovulemic
- HYPERKALEMIA - renal failure and RENAL ARTERY STENOSIS - TERATOGENIC |
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how do RAAS inhibitors cause Renal Artery Stenosis
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RAAS inhibition-->efferent arteriole dilation-->dec GF Pressure-->inc renal failure
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Atrial &/or ventricular distention releases what?
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ANP causes dec Na reabsorption
BNP is a biomarker for Myocardial injury |
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What do natriuretic peptides do?
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ANP and BNP cause:
- dec peripheral vascular resistance...dec BP - increase Na excretion See inc GFR, dec arterial tone, lusitropic and vagal cardiac effects |
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Nesiritide
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recombinant human BNP
- improves shortness of breath but that's it... |
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Atherosclerosis is
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hardening of the arteries
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Coronary artery disease can cause what end points
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- chronic stable angina
- Acute coronary syndromes - sudden death - CHF |
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Where does atherosclerosis occur within the lumen and what is the key event in pathogenesis
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- occurs at areas of altered flow
- focal accumulation of lipid and cells beneath endothelium is key event |
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Earliest visible sign of atherosclerosis
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fatty streak
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A fibrous plaque may impede blood flow and cause what:
heart, brain, foot, aorta |
MI, Cerebral infarct, Gangrene, abd aortic aneurysm
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Endothelial cells originate from where
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bone marrow-->circulating endothelial progenitor cells
endothelial cells live 100-1000 days |
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Endothelial derived factors for vascular tone
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- NO
- Prostaglandins -----prostacyclin -----Thromboxane - endothelial hyperpolarizing factor - ANG I C-type natriuretic peptide |
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Endothelial derived hemostasis factors
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- NO
- Tissue plasminogen activator - heparins - thrombomodulin - prostaglandins - PAI-1 - Tissue factor - Von Willibrand's factor |
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What is BART used for?
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BART- Brachial artery reactivity test
- normal ~12% increase...old only 5% assess health of endothelium non-invasively with ultrasound after brachial artery occlusion...should see vasodilation |
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Effect of statins on flow mediated vasodilation
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see increased vasodilation with decreased cholesterol
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Effect of cigarette smoking on flow mediated vasodilation
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see immediate drop in vasoactivity that returns after 90min
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Causes of abnormal endothelial activity
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- hypercholesterolemia
- hypertension - diabetes - age - smoking |
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What improves endothelial function
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- statins
- ace inhibitors - diabetic control - stop smoking - exercise - L-arginine - antioxidants |
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Formation of the foam cell
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vascular injury--> inc adhesion molecules
see subendothelial lipid droplets monocytes enter become macrophages and eat lipid-->FOAM CELL |
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Pathogenesis of Foam cell
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endothelial injury--> lipoproteins in subendothelial space-->chem modifications to lipoproteins-->recruit monocytes-->macrophage conversion-->LDL uptake-->FOAM CELLS
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Foam cells to Fibrous plaque
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- secrete cytokines, PDGF, Tissue factor--->cause smooth muscle cells to migrate into intima and produce extracellular matrix-->fibrous plaque
over time get collagen, capillaries, cholesterol crystals |
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Foam cells and smooth muscle cells degenerate to create what
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Necrotic core of debris
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Key marker of endothelium dysfunction
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decreased NO
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Why do plaques like branch points
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areas of low shear stress
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Where does atherosclerosis start
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large and medium arteries
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As plaque accumulates within the vessel wall what happens to lumen diameter?
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see compensatory expansion followed by occlusion from plaque
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What is wrong with vessel remodeling in diabetics?
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instead of vessel expansion with plaque, diabetics get vessel narrowing which leads to quicker occlusion
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Describe a stable plaque
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hard, fibrous, small lipid core, lack inflammatory cells...cooler temp
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Describe a vulnerable plaque
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soft plaque with a large lipid core, thin fibrous cap with hot inflammatory cells
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Acute MI is caused by what plaque
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soft vulnerable plaque rupture...leak thrombogenic material-->thrombus
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Stable angina is caused by
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narrowing of vessel lumen with hard stable plaque
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Common plaque rupture site
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shoulder region
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Complications of plaque
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- rupture and acute MI
- aneurysm from muscle cell atrophy - fragmentation and embolism - Angina claudication---from progressive narrowing |
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Atherosclerosis risk factors
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- men, old, family hx, genetics
- hyperlipidemia, htn, smoking, diabetes, diet |
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What is metabolic syndrome?
|
- truncal obesity---apple shaped women
- elevated blood sugar - hypertriglyceridemia - low HDl - HTN |
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Etiology of aortic stenosis
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- congenital (bicuspid valve not tri)
- Rheumatic Disease - Senile calcific AS |
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Rheumatic disease AS
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see scarring and fusing of the commisures
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Bicuspid valve AS
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only 2 leaflets wear and tear see calcification
- congenital <60 yr old patient |
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Senile Calcific
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See calcification over time
>60 yr old patient |
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AS pathogenesis
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- inflammatory process leading to calcification
- more common in men and hypercholesterolemia |
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William's Syndrome
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- dysmorphic face
- mental retardation and abnormal teeth - supravalvular aortic stenosis |
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AS pathogenesis
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- increased pressure gradient across valve
- see concentric hypertrophy of LV |
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Effects of LV hypertrophy
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- increased LV stiffness
- inc LV EDP - inc O2 demand---syncope and angina |
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Aortic stenosis leads to 3 main things
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- HF
- Angina - Syncope---can't inc CO |
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Physical findings of Aortic stenosis
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- murmur
- sound - carotid - apex |
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S2 occurs when?
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when ventricular pressure drops below aortic pressure
--aortic valve closes |
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S1 occurs when?
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Ventricular Pressure>aortic valve pressure---mitral valve shuts
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With aortic stenosis does LVP=Aortic Pressure?
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No---LVP must be greater---pressure gradient
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Describe aortic stenosis murmur
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Crescendo then decrescendo...flow murmur
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Ejection click is?
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early systolic sound suggests bicuspid aortic valve
occurs before the crescendo |
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Carotid pulsation as a clue to aortic stenosis
|
- should be rapid rise followed by linear drop
- abnormal see slower rise and a smaller pulse ---parvus et tardus |
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S4 diastolic abnormality
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early pre-S1 apical impulse
- may feel at apex |
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Labs for aortic stenosis
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- chest x ray---LV prominence
- EKG---LVH - echo---see severity and etiology |
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Doppler shift with echo is for what
|
flow assessment through aortic valve...more narrow stenosis gives higher velocity
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Pressure velocity (gradient) =
|
Gradient is 4 times the velocity across the valve^2
Gradient = 100...velocity = 5m/s |
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Continuity equation for valve area calculation
|
flow across aorta = flow across outflow tract
V*A_aorta = V*A_outflow get size of hole for flow |
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If non-invasive tests are equivocal for AS do what?
|
Catherization to detect CAD
- always for ppl>50 |
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|
Antibiotic prophylaxis for cardiac problems ONLY:
|
- give before dental procedure
---prosthetic valve ---prior endocarditis ---specific congenital heart disease |
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Heart failure, Angina, Syncope + critical stenosis (gradient >50mmHg) do what
|
Replace the valve
- mechanical valve ---ball in cage, bileaflet, tilting disk - tissue valve--porcine, bovine, homograft |
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mechanical valve advantage and disadvantage
|
long lasting but need anticoagulation/warfarin
- can get clots or bleeding (due to warfarin) |
|
|
tissue valve advantage and disadvantage
|
degenerates but no need for anticoagulation
- operations every 10 yrs or so...better for older people |
|
|
Aortic bypass valve
|
tube from ventricle directly to abdominal aorta
|
|
|
bioprosthetic compressed stents
|
minimally invasive
|
|
|
Fibrillin 1 deficiency
|
Marfan's disease-->aortic bicuspid valve
|
|
|
Aortic regurgitation
|
abnormal leaflets:
- congenital, rheumatic, endocarditis abnormal of roots: aortic dissection, Marfan's syndrome, syphilis, annuloaortic ectasia |
|
|
Aortic regurgitation
|
inability for leaflets to coapt---rapid backflow to ventricle...
---can see low diastolic pressure with high systolic pressure ---classically see wide pulse pressure |
|
|
wide pulse pressure in Aortic Regurgitation contributes to
|
volume overload and LV dilation---see eccentric hypertrophy
|
|
|
Compensated AR to decompensated AR
|
--late systolic HF---see reduced EF and increase EDP
thus the LV dilates and CHF |
|
|
AS = pressure overload =>
AR = volume overload => |
hypertrophy...systolic issue
LV dilation...diastolic issue |
|
|
Wide pulse pressure is big clue to?
|
Aortic regurgitation
|
|
|
Physical findings of Aortic regurgitation
|
- wide pulse pressure
- cardiomegaly - murmur---start 2nd heart sound and decreases during diastole |
|
|
Describe AR murmur
|
- murmur---start 2nd heart sound and decreases during diastole--
- high pitched early diastolic murmur at R or L sternal border |
|
|
Flow of aortic regurgitation
|
- see blood coming back from aorta into the L. ventricle
|
|
|
Acute aortic regurgitation caused by
|
- dissection
- endocarditis--can see stiffness or perforations |
|
|
Chronic vs. Acute AR
|
- chronic see inc diastolic pressure but compensated via dilation and inc capacitance
- acute---no time for dilation---super high LV diastolic pressure and massive pulmonary edema |
|
|
Signs of acute aortic regurgitation
|
---no cardiomegaly
---no wide pulse pressure ...short diastolic murmur NOT long diastolic |
|
|
Mitral valve stenosis is caused by what?
|
--RHEUMATIC HEART DISEASE
- see fusion of the cusps, fibrosis and calcified leaflets |
|
|
Hockey stick on echo
|
Classic for mitral valve stensis
|
|
|
Mitral valve opens twice why?
|
- flow opens then eddy currents start closing then atrium contracts opening the valve....ventricular systole leads to closure
|
|
|
What pressures go up with mitral stenosis
|
Left atrial pressure---incr pulmonary pressure---HF
large atrium and atrial fibrillation |
|
|
Clincal manifestations of mitral valve stenosis
|
- palpitations and a fib
- pulmonary hypertension-- R. Sided HF ----see edema, GI issues, liver congestion, ascites |
|
|
Opening snap---sudden tensing of the leaflets
Mid to late Diastolic low rumbling murmur Loud S1 |
Mitral valve stenosis murmur
- roll person to the lateral decubitus position |
|
|
use the bell to hear what 3 things:
|
low freq S3
low freq S4 Rumble of Mitral stenosis - roll person to the lateral decubitus position |
|
|
EKG mitral valve stenosis signs
|
- P wave enlargement due to LA hypertrophy
- RV hypertrophy as well |
|
|
Chest x ray for mitral valve stenosis
|
see straightening of L heart border
|
|
|
Treat Mitral valve stenosis
|
- slow heart rate
- ablate a fib if needed - anti-coagulate to stop atrial appendage clot formation - mitral commisurotomy or valve replacement |
|
|
mitral valve regurgitation via injury to what anatomic structures
|
annulus calcification
valve- myxomatous degeneration, rheumatic disease endocarditis chordae--rupture or endocarditis papillary muscles- ischemia or infarct base/LV wall-cavity dilation |
|
|
Mitral regurgitation means:
|
VOLUME OVERLOAD
elevated LA volume and pressure--LA dilatation less output to aorta and volume related LV stress--LV dilatation |
|
|
Assess EF to see if valvular or cardiomyopathy induced mitral regurgitation
|
- low EF bad pump
- high Ef good pump...volume overload and valvular |
|
|
Acute mitral regurgitation vs. chronic mitral regurgitation
|
---chronic is slow dilation LV and LA and increased atrial compliance
---acute there is no dilation of LV and LA see pulmonary edema |
|
|
Mitral regurgitation signs on physical exam
|
holosystolic murmur
S3 Hyperdynamic apex with palpable thrill |
|
|
Ventricular pressure is always higher than aortic pressure in mitral regurgitation thus murmur will:
|
start at S1 and go past S2
then with lots of LA blood we see S3 during ventricular filling |
|
|
Management of mitral valve regurgitation
|
- dec afterload---vasodilators nitroprusside
- diuretic for pulmonary edema and HF surgery |
|
|
mitral valve prolapse
|
- part of leaflet does not get pulled down fully
- prolapse into atrium during systole parachuting valve w/long chordae tendonae |
|
|
Mitral Valve prolapse pathology
|
- enlarged valve leaflets
- replace collagen and elastin with myxomatous tissue in spongiosa layer |
|
|
Mitral Prolapse on physical exam/ascultation
|
mid-to-late systolic click and late systolic murmur
- timing of murmur changes with maneuvers --standing causes the click to be closer to S1 --squat causes click and murmur to be later in systole |
|
|
Chordae tendonae rupture in Mitral prolapse causes
|
acute mitral valve regurgitation---severe
- may see a flailed leaflet far up in LA - need surgery |
|
|
Vasodilator and Antiplatelet molecules
|
NO
Prostacyclin |
|
|
Antithrombogenic molecule
|
tPA-tissue plasminogen activator
|
|
|
Antimitogenic molecule
|
TGFB
|
|
|
Vasoconstrictor and Platelet Aggregation molecules
|
Thromboxane
Endothelin-1 |
|
|
Mitogenic Molecule
|
PDGF-platelet derived growth factor
|
|
|
Thrombogenic molecule
|
PA-I: Plasminogen activator inhibitor
|
|
|
ACh induced EDRF- endothelium derived relaxing factor
|
Vessel relaxation upon stimulation with ACh is derived from endothelium-->NO
|
|
|
Molecules that stimulate EDRF release and smooth muscle relaxation
|
ACh
Histamine BK Shear stress ADP--from aggregating platelets 5-HT--from aggregating platelets Thrombin Arachidonic Acid-->PGI2 |
|
|
NO synthesis
|
ACh or shear stress--> Inc Ca+calmodulin or kinase/phosphatase activity-->eNOS activity
Arginine + O2 via eNOS--->citrulline +NO |
|
|
NO relaxation mechanism
|
NO binds to Fe of Guanylate cyclase:
GTP-->cGMP-->relaxation |
|
|
L-NMMA (N-monomethyl-L-arginine)
|
NOS inhibitor
- methylated products of arginine |
|
|
Tilarginine
|
NOS inhibitor
- methylated products of arginine |
|
|
ADMA (Asymmetrical dimethylarginine)
|
NOS inhibitor
- methylated products of arginine - elevated ADMA predictive of CV mortality |
|
|
NO in host defense?
|
Host cell sense LPS-->TNF-a-->activates macrophages via NF-K B-->activate iNOS (inducible NOS)
NO kills bacteria |
|
|
Describe eNOS localization and activation
|
- endothelial and some neurons
- membrane associate in caveolae - constituitively expressed but upregulated by shear stress and estrogen - Ca+calmodulin activates eNOS by coupling catalytic modules |
|
|
NO cell function as concentration increases
|
- activate guanylate cyclase
- antioxidant for ROS - Activate/inactivate Heme proteins - Induce thiols/stress proteins - Apoptosis and DNA damage-->cell death |
|
|
inorganic nitrates are source of what
|
nitrites which are active compounds
|
|
|
Amyl nitrite
|
Nitrovasodilator
organic nitrite---active NO donor |
|
|
Glyceryl Trinitrate
|
Nitrovasodilator- Short t1/2
Potent venous dilation, coronary dilation, biliary and esophageal smooth muscle (not arterioles) Enzymatic NO release in select cells Adverse--tolerance limited PO/Lipid soluble |
|
|
Isosorbide dinitrate
|
Nitrovasodilator--med t1/2
Good w/hydralazine for HF Potent venous dilation, coronary dilation, biliary and esophageal smooth muscle (not arterioles) Enzymatic NO release in select cells Adverse--tolerance limited PO/Lipid soluble |
|
|
isosorbide mononitrate
|
Nitrovasodilator--long t1/2
Potent venous dilation, coronary dilation, biliary and esophageal smooth muscle (not arterioles) Enzymatic NO release in select cells Adverse--tolerance limited PO/Lipid soluble |
|
|
Nitroprusside
|
Nitrovasodilator--
Relaxes Coronary arteries and Arterioles/resistance vessels NO donor by non-enzymatic process Adverse: Toxic thiocyanate accumulation IV salt |
|
|
Nicorandil
|
Nitrovasodilator
NO donor |
|
|
Describe NO Cycle
|
dietary NO3-->NO2 by GI bacteria
NO2 enters circulation during hypoxia or acidosis binds deoxyHb to form NO L-Arg+O2-->NO via eNOS enters circulation converted to NO2 or NO3 by oxyHb or oxidase |
|
|
Why use organic nitrates and adverse effects
|
- rapid symptomatic relief
- exercise tolerance for angina pectoris - acute HF decreases pulmonary congestion - NO BENEFIT for progression or mortality in CAD - Adverse: headaches, postural hypotension, TOLERANCE |
|
|
Organic nitrate tolerance occurs how?
|
Bioactivation of glyceryl trinitrate (GTN) by mito aldehyde dehydrogenase (ALDH2) reductase activity
antioxidant combo: hydralazine or folate or ascorbate ameliorates the Nitrate tolerance |
|
|
G-->A polymorphism in ALDH2 causes
|
alcohol intolerance and flushing in Asians
|
|
|
Venodilation causes
|
dec preload
dec LV diastolic pressure dec wall tension/O2 demand inc O2 supply |
|
|
Coronary artery dilation causes
|
inc perfusion-->inc O2 supply
coronary resistance vessels are unaffected by organic nitrates |
|
|
Reduced TPR (small effect) causes what?
|
dec afterload --- dec O2 demand
reflex tachycardia --- inc O2 demand BAD |
|
|
Describe coronary steal
|
if one were to arteriolar dilate cornary arterioles the occluded vessel would get less perfusions since other vessels would open more
|
|
|
Erectile response is mediated how autonomically
|
Parasympathetic relaxation of vascular and non vascular smooth muscle
Mediated by NO release |
|
|
Sildenafil mechanism
|
PDE5 inhibitor
amplifies erectile response to arousal by blocking the inactivation of cGMP by phosphodiesterase 5 |
|
|
Vardenafil
|
PDE5 inhibitor
|
|
|
Tadalafil
|
PDE5 inhibitor
|
|
|
PDE 5 inhibitors do what to nitrovasodilators
|
Increase/potentiate nitrovasodilators uncontrollably
|
|
|
Lipids at birth vs 6 months
|
TC: 70---135
LDL: 30---60 HDL: 34---55 TG: 40---50 |
|
|
ideal cholesterol
|
120
average american adult has 200 |
|
|
Describe a lipoprotein particle
|
- Triglyceride and cholesterol ester core
- Phospholipids, apolipoproteins and free cholesterol shell |
|
|
ApoB- containing lipoproteins
|
- atherogenic (non HDL)
- LDL - IDL - VLDL/VLDL remnants - Chylomicron remnants - Lp(a) |
|
|
HDL contains what apo protein
|
ApoAI
- antiartherogenic |
|
|
Total cholesterol breakdown
|
LDL--65%
HDL--25% VLDL---10% |
|
|
How to estimate/calculate cholesterol
|
LDL = TC-TG/5-HDL
or LDL = TC-TG/6-HDL |
|
|
Cholesterol Transport
|
intestinal-->liver-->VLDL-->IDL-->LDL
LDL binds to LDL-R on hepatocyte and recycles cholesterol LDL convers to FA or cholesterol in muscle, heart, adipose tissue via LDL-R LDL move subendothelial and atherosclerosis occurs |
|
|
LDL-R life cycle
|
LDL-R made in ER sent to golgi and plasma membrane
Binds LDL, internalizes in clathrin coated vesicle/endosome - LDL sent to lysosome -LDL-R recycled to plasma membrane |
|
|
Role of PCSK9 and the LDL-R
|
host cell PCSK9 targets LDL-R to the lysosome for degradation
- more plasma LDL...less LDL-R recycled |
|
|
Familial Hypercholesterolemia
|
- LDL-R deficiency
----heterozygote 1/500---2 fold inc in LDL, MI < 60 ----homozygote 1/1mil----6 fold LDL inc, MI before 20 |
|
|
Genes causing familial hypercholesterolemia
|
- LDL-R---hepatocyte receptor binds ApoB on LDL
- ApoB---Ligand on LDL binding to LDL-R - PCSK9---degrades LDL-Rs--autosomal dominant - LDLRAP1---helps internalize clathrin vesicles |
|
|
Xanthomas are what and found when?
|
- cholesterol tumors on tendons
- found in familial hypercholesterolemia homozygotes |
|
|
Findings in Familial Hypercholesterolemia
|
- xanthomas
- xanthelasmas - corneal arcus/ring around iris |
|
|
Secondary Hypocholesterolemia caused by:
|
hypothyroidism
nephrotic syndrome obstructive liver disease diabetes mellitus Drugs: ---progestin ---corticosteroids ---anabolic steroids ---cyclosporine ---diuretics |
|
|
Familial combined hyperlipidemia
|
- elevated LDL/VLDL cholesterol and/or triglycerides
- dec HDL - overproduction of apo B-100 - 1/100 ppl - inc coronary heart disease |
|
|
ApoE isoforms and hyperlipidemia
|
- Type 3 hyperlipidemia
- homozygote Apo-E2 - total cholesterol reduced including LDL..VLDL inc - need a second defect as well...hypothyroidism, obese, etc |
|
|
Triglyceride metabolism
|
ingest TG--->chylomicrons circulate make free fatty acids or chylomicron remnants-->taken up by liver and packaged into VLDL
|
|
|
Insulin resistance can increase TG levels because
|
TG released from lipolysis of adipocytes --> inc ffa and vldl
- see smaller and denser HDL and LDL(more atherogenic) |
|
|
Why are smaller more dense LDL particles more atherogenic?
|
less affinity for LDL-R--more time in plasma
more easily oxidized and enter subendothelial area |
|
|
Triglyceride profile
|
Ideal < 100 mg/dL
Normal <150 mg/dL Borderline high 150–199 mg/dL High 200–499 mg/dL Very high 500 mg/dL |
|
|
Very high triglycerides can cause what cutaneous signs
|
eruptive cutaneous xanthomas filled w/foam cells
lipemic plasma |
|
|
How to lower Triglycerides
|
weight loss
mediterranean diet marine derived PUFA less carbs less trans fat |
|
|
Relationship between coronary Heart disease and HDL
|
Inc HDL---see less CHD
|
|
|
Factors that lower HDL
|
- sedentary behavior
- obese - smokers - BBs - steroids - progestins |
|
|
Process of HDL anti-atherosclerotic effects
|
- reverse cholesterol transport
|
|
|
Describe reverse cholesterol transport
|
free cholesterol is removed by macrophages and returned to liver and excreted as bile
ABCA1 mediates cholesterol uptake by HDL from macrophages LCAT- lectine/cholesterol acetyltransferase SR-B1 scavenger HDL receptor on hepatocytes |
|
|
LCAT deficiency results in what eye issue
|
corneal opacification
|
|
|
Myocardial Ischemia definition
|
inadequate O2 supply to heart muscle to meet demands
|
|
|
Myocardial infarction definition
|
irreversible necrosis of myocardium from prolonged ischemia
|
|
|
Factors that contribute to O2 demand
|
- HR
- Contractility - Wall tension--pressure and volume |
|
|
O2 supply to myocardium via
|
Coronary blood supply
|
|
|
Describe the ischemic cascade
|
over 20 secs
anaerobic metabolism-->relaxation/diastolic abnormalities-->contraction/systolic abnormalities-->ECG ST changes-->angina |
|
|
Describe Chronic Stable Angina Pectoris
|
- visceral deep discomfort
- pain at sternum - stress induced - Stop stress stop pain in <10-15 min |
|
|
Typical angina symptom complaints
|
- pressure, indigestion, aching, squeezing
|
|
|
Fixed atherosclerotic lesion typically causes
|
effort related angina pectoris...lack of O2 relative to needs during exercise
|
|
|
Coronary Heart Disease Risk Factors
|
- hypercolesterolemia
- hypertension - smoking - diabetes - age - Family History |
|
|
Describe Prinzmetal's Angina
|
- spontaneous rest pain
---Coronary artery spasm - Treat with Nitrates or CCBs - ST segment elevation - not exercise induced |
|
|
3 types of acute coronary syndrome
|
- STEMI- ST segment elevated MI
- NSTEMI- Non-ST segment elevated MI - Unstable Angina |
|
|
Typical signs of Acute Coronary Syndrome
|
- crushing chest pain
- Levine sign - Diaphoresis |
|
|
What acute coronary syndrome does not kill myocardium
|
Unstable Angina
|
|
|
Describe White Thrombus
|
- plaque rupture releases collagen causing platelet aggregation
- partial occlusion-->NSTEMI or Unstable angina |
|
|
Describe Red Thrombus
|
- plaque rupture releases tissue factor causing RBC and Fibrin accumulation
- complete occlusion-->STEMI |
|
|
What does ST segment depression indicate
|
Subendocardial ischemia---transient ischemia
|
|
|
What does ST segment elevation indicate
|
large transmural ischemia or infarction
|
|
|
What does the Q wave indicate
|
prior MI
- transmural infarction causes loss of QRS force in necrotic region FOREVER |
|
|
Frontal plane leads
|
avR
avL 1 2 3 |
|
|
Inferior anterior leads
|
3 avF 2
|
|
|
Inferior infarct think occlusion in what vessel?
|
RCA
|
|
|
Key diagnostic test for MI
|
elevated cardiac enzymes
- CK-MB--starts 3 hr normal in 3 days - cTnl---Troponin--rise in 3 hrs detectable 7-10 days |
|
|
Exercise Stress test
|
look for ST segment depression in ischemic zone leads
|
|
|
High Risk Signs of Stress Test
|
- early onset chest pain--HR<90
- late recovery from pain-->7min - Marked ST depression >2mm - Multiple leads - Hypotension |
|
|
Perfusion studies are needed when
|
ECG stress test is inconclusive for pain
- Give patient Thallium 201 or sestamibi radioisotope - Viable cells take up isotope - Transient cold spot---ischemic tissue - Fixed cold spot---dead infarct |
|
|
If patient can't exercise how can you do a stress test?
|
Use Dobutamine B1 stimulator===inc BP and HR
Use Regadenoson===Adenosine Receptor Agonist--arteriolar dilation |
|
|
Value of the echocardiogram
|
assess wall motion abnormalities
|
|
|
Coronary arteriography value
|
Identify presence and extent of anatomic coronary artery disease
place stent or send for CABG |
|
|
CAD treatment options
|
Revascularization: PCI (angioplasty +stent)
Meds: Nitrates, BB, CCBs |
|
|
Common CABG vessels
|
internal mammary artery
saphenous vein |
|
|
Survival advantage for CABG when
|
Left main disease
Multiple vessel disease w/ dec LV function |
|
|
Line of therapy for angina
|
1) NITRATES
2) Beta Blockers 3) CCBs |
|
|
Nitrates cause dilation of what vessels
|
- coronary artery
- peripheral artery - peripheral veins |
|
|
Venous dilation from nitrates does what
|
pool blood in legs and dec preload/volume to heart
|
|
|
Physiologic cardiac effects of nitrates
|
- inc HR (Baroreceptor reflex)
- inc contractility (baroreceptor reflex) - dec pressure and dec volume ***these directly alter O2 demand - inc subendocardial flow - inc vasodilatation ***these alter O2 supply |
|
|
Nitrate side effects
|
headache and hypotension
|
|
|
If patient has severe drop in BP on nitrate what do you do?
|
Raise their legs
|
|
|
Effect of Beta Blockers on O2 demand
|
- dec HR
- dec contractility - dec wall tension---pressure and volume ***all decrease O2 demands |
|
|
Nitrate + BB causes drop in what
|
HR
Contractility Pressure of walls Volume |
|
|
Why do we use BBs?
|
symptomatic relief and mortality reduction
|
|
|
Beta blocker side effects
|
fatigue
HF Excess bradycardia worsen diabetic control bronchoconstriction |
|
|
When use Ca Channel Blockers
|
**If other drugs fail
- Prinzmetal's angina - cause coronary dilation |
|
|
Ranolazine
|
Inhibits late Na current
Treat chronic angina |
|
|
Most crucial med in CAD
|
Aspirin
|
|
|
Mortality associated with MI
|
- early is arrhythmia
- late is pump failure |
|
|
what is the wavefront of necrosis w/MI
|
- large area of ischemic tissue but viable at 40 min with minimal necrotic tissue
- more necrosis at 3 hr with full necrosis at 24hrs |
|
|
Options to open the artery after plaque rupture
|
- PCI
- Fibrinolytics |
|
|
When are Fibrinolytics indicated
|
- can't get to cath lab fast (>>90 min)
- STEMI ONLY |
|
|
Fibrinolytic agents include
|
- t-PA
- r-PA - SK |
|
|
Antiplatelet agents
|
aspirin
clopidogrel prsugrel glycoprotein IIb/IIIa inhibitors |
|
|
Antithrombotics agents
|
- unfractionated heparin
- low molecular weight heparin - Bivalirudin - Fondaparinux |
|
|
Do we use NSAIDs (except ASA)
|
Not after STEMI
- inc risk of death, hypertension, HF, and myocardial rupture |
|
|
Preventable risk factors for CAD
|
- smoking
- hypertension - hypercholesterolemia |
|
|
what is hemostasis
|
the process that stops blood flow after vascular injury
|
|
|
Main elements of hemostasis
|
blood vessels--constrict and activate platelets
platelets---adhere and aggregate plasma proteins---fibrin clot |
|
|
Platelet actions
|
ciculation
endothelial surveillance adhesion activation secretion aggregation clot retraction |
|
|
Glycoprotein Ib/IX/V binds what and causes what
|
von Willebrand's factor bound to type III collage
causes platelets to adhere to endothelium & activate |
|
|
Glycoprotein Ia/IIa are what type of proteins and bind what
|
platelet integrins
bind type III collagen |
|
|
Glycoprotein IIb/IIIa are what type of proteins and bind what
|
platelet integrins
bind to fibrinogen |
|
|
How do activated platelets aggregate
|
bind to opposite ends of fibrinogen with activated IIb/IIIa integrins
|
|
|
What are the coagulation factors
|
Fibrinogen
Thrombin V VII VIII IX X XI XII XIII |
|
|
What are the thombolytics
|
Plasmin
Tissue plasminogen activator PAI-1 a2-antiplasmin |
|
|
What are the clotting control proteins
|
Antithrombin
Protein C and S Tissue Factor Pathway Inhibitor |
|
|
Endothelial proteins include
|
P-selectin
Thrombomodulin |
|
|
Endothelial sugars
|
Heparins
Syndecan-1 |
|
|
Subendothelial proteins
|
Tissue factor
Type III collagen |
|
|
Endothelial secretions
|
vW factor
Prostacyclin NO tPA Factor VIII |
|
|
Primary hemostasis is the
|
platelet plug
|
|
|
Secondary hemostasis is the
|
fibrin clot
|
|
|
How does endothelial damage cause platelet aggregation?
|
exposes substrates collage III vWF thrombin, ADP
removes endothelial platelet inhibitors: NO and PCI2(prostacyclin) |
|
|
Where/When is tissue factor expressed
|
in all cells constituatively except endothelium
induced in endothelium via inflammatory cytokines |
|
|
Tissue Factor binds to Factor VII leading to what
|
the generation of thrombin
|
|
|
Role of thrombin
|
platelet activator
activates TAFI-thrombin activatable fibrinolysis inhibitor ---inhibiting the fibrinolysis and protecting the clot activates endothelial cells for t-PA and PGI2 release |
|
|
Platelet inhibiting molecules
|
PGI2-prostacyclin
NO Antithrombic effect |
|
|
Role of von Willebrand's Factor
|
- endothelial cells secrete multimers
- ADAMTS13 chops into smaller multimers - binds to Collagen III and then to GPIb,IX, V on platelets activating them |
|
|
ADAMTS13 does what
|
chops up large vW factor into smaller multimers
|
|
|
Activation of platelets causes what?
|
- dense granules release- ADP, ATP, Ca2+, histamine, serotonin and epi
- alpha granule secretion-heparin binding protein fibronectin adhesion protein, PDGF - Thromboxane A2 secretion - Interleukin-1-beta secretion -express surface adhesion molecules |
|
|
Activation, Secretion and Aggregation by platelets is coupled to what awesome cation
|
Ca++
|
|
|
How many pumps is the heart?
|
2 pumps
R. heart and L. heart |
|
|
R. Ventricle takes what kind of blood and sends it where
|
deoxy systemic blood from R. Atrium up the pulmonary artery to lungs
|
|
|
Does the RV have the same Stroke volume as LV
|
Yes...but less work because the pulmonary artery has lower pressure/resistance to flow
|
|
|
Pulmonary hypertension and lung disease can cause what RV changes
|
hypertrophy and shape alteration
--can enlarge enough to compress LV |
|
|
RV vs. LV differences
|
- RV thinner 3-4mm wall
- RV has lower EF but larger volume giving same SV - atypical parastalitic contraction patter - share the septum thus RV--LV interact |
|
|
La Place's Law
|
Wall Tension = Pressure*Radius/(2*wall thickness)
- RV is thin walled handles P inc worse |
|
|
Acute RV failure
|
- pulmonary embolism
- Sepsis syndrome via inflammation - acute lung injury - mechanical ventilation - MI |
|
|
Blood supply to RV via...damage is a complication of what MIs
|
RCA
inferior MIs |
|
|
RV MI is stunned
|
temporary loss of contractile function
hypotension increased JVP |
|
|
If RV has infarct how doe the RV still deliver good SV
|
Increase the Preload
--need to be careful of hypotension in cases of RV MI----avoid systemic vasodilators |
|
|
RV systolic performance is related to what
|
Volume
BUT...RV can't tolerate infinite amount of fluid |
|
|
Pulmonary Embolism causes what
|
Marked inc in Pressure----thus marked inc in RV wall tension
- Treat with anticoagulations |
|
|
Goals of Care for acute RV failure
|
- optimize volume--starling curve
- reduce RV afterload - enhance RV contractility - treat underlying cause (ischemia or PE) |
|
|
If person has high CVP with systemic edema do what?
|
Diuretics
(be cautious after inferior MI...need volume) |
|
|
RV compensation
|
- hypertrophy---to reduce wall tension
- dilation---increase volume |
|
|
Decompensated RV displays
|
- dyspnea
- edema ***occurs after marked pulmonary HTN ***dilation to point of LV compression |
|
|
Symptoms of RV failure
|
- dyspnea
- fatigue - lethargy---low CO bc low delivery of blood to LV - exertional syncope---with arteriole dilation can't inc CO - anorexia---back flow of - abdominal swelling--ascites later sign - edema---volume overload...reduced CO mech |
|
|
Physical exam signs of RV failure
|
- loud P2
- RV heave - TR murmur---tricuspid regurg murmur holosystolic *****dilation or pressure - Hepatomegaly--volume overload - Inc JVP---volume overload |
|
|
What is Cor Pulmonale
|
RV dysfunction in the setting of chronic lung disease
- COPD, interstitial Lung disease, pulm fibrosis |
|
|
How does hypoxia effect pulmonary vasculature
|
- lung adapted to disease due to bacteria pneumonia .... shunt blood away from disease
---pulmonary atriolar vasoconstriction ***RV doesn't like this Treat with O2, diuretics |
|
|
How does LV failure cause RV failure?
|
Inc LV pressure leads to inc LA and pulmonary hypertension-->inc afterload on RV
|
|
|
Treat tricuspid regurgitation with
|
valve repair or replacement
|
|
|
Why is pulmonary hypertension so bad
|
modest elevations in pulm HTN trigger significant reduction in stroke volume for the RV
---wall tension issue making RV pressure sensitive |
|
|
Chronic lung disease from smoking leading to cor pulmonale, treat with
|
O2
|
|
|
Patient with ascites and edema and elevated JVP are
|
fluid overload with systemic venous congestion
give diuretics |
|
|
If decreased RV contractility not being compensated well treat with
|
- dobutamine
- milonerone |
|
|
Pericardial diseases--what 4
|
- pericarditis
- pericardial effusion - pericardial tamponade - constrictive pericarditis |
|
|
2 layers of the pericardium
|
- inner serosal- visceral pericardium
- outer fibrous layer- parietal pericardium |
|
|
Purpose of the pericardium
|
- fixes heart within the mediastinum--limit motion
- prevent extreme dilation - act as barrier to infection spread |
|
|
Forms of infectious pericarditis
|
- idiopathic/viral most common (echovirus or CoxB)
- TB - Pyogenic bacteria |
|
|
what is serofibrinous pericarditis
|
- plasma proteins like fibrinogen
- rough and shaggy - 'bread and butter' appearance ---can see fibrous strands |
|
|
Clinical features of acute pericarditis
|
- hear pericardial friction rub
----creaking leather with 3 components - pleuritic chest pain--may radiate to back ***relieved by sitting up - fever - EKG changes |
|
|
3 components of the pericardial rub
|
- atrial systole component
- ventricular systole component - ventricular relaxation componet |
|
|
EKG signs of pericarditis
|
- see diffuse/multi-lead ST segment elevation
***(like STEMI and Prinzmental's Angina) - PR segment depression |
|
|
Echo signs of pericarditis
|
- normal or a little extra fluid
|
|
|
Treatment of Pericarditis
|
- bed rest
- NSAID for pain relief - avoid anti-coagulants ***do PPD to assess for TB |
|
|
Purulent Pericarditis is caused by
|
- trauma or surgery or TB or cancer (bloody)
- staph aureus, pneumococcus, G- rods Treat with catheter drainage and antibiotics |
|
|
Forms of non-infectious pericarditis
|
- post MI
- Uremia - Neoplasia--lung, lymphoma, breast cancer - Radiation induced - connective tissue disease- lupus, RA - drug induced- Procainamide, hydralazine |
|
|
Dressler's Syndrome
|
later/wks after MI
transient pericarditis |
|
|
Blood in pericardium think of
|
cancer
|
|
|
Transudate vs. Exudate
|
- transudate--clear fluid low protein, non-inflammatory
-exudate- inc vasc permeability, protein, bloody, pus |
|
|
Causes of transudate
|
- CHF
- Cirrhosis - Nephrotic syndrome - hypothyroidism |
|
|
If you see hemopericardium after stabbing person has
|
blood in pericardium
|
|
|
Chylopericardium is what
|
free chyle in pericardium due to cancer inflammation or lymphatic injury
|
|
|
Symptoms of someone with effusion
|
usually asymptomatic
|
|
|
Clinical signs of pericardial effusion
|
- dec heart sounds
- can't feel apical beat - Ewart's sign/dullness over posterior lung |
|
|
Diagnose via
|
- chest x ray see big water bottle heart
- echo to see fluid/space ---treat via nothing or drainage |
|
|
What is cardiac tamponade
|
hemodynamic abnormalities from pericardial effusion/fluid under pressure
|
|
|
Fluid in the pericardial space causes what
|
can raise pericardial pressure up to the diastolic pressure of atria, RV, then finally LV
***See equilization of all filling pressures in tamponade |
|
|
What happens to CO during cardiac tamponade
|
once all diastolic pressures are equilized the CO drops
|
|
|
What is most important component of the rise of pericardial pressure
|
the rate of fluid accumulation
|
|
|
Most common cause of cardiac tamponade
|
Cancer
or Hemorrhage from trauma, rupture, A. dissection rarely in the cath lab |
|
|
Classic signs of cardiac tamponade
|
Beck's triad:
- hypotension - inc venous pressure---JVP - diminished Heart sounds |
|
|
With inspiration what happens to blood flow to the heart
|
increased blood flow to the R. heart
BUT lungs expand and take this So LV SV decreases only slightly |
|
|
With cardiac tamponade what do you see with BP upon inspiration
|
Pulsus paradoxus---drop of BP by 10mmHg during inspiration...might feel pulse go away
might be due to septal shift after RV filling |
|
|
What causes the 2 jugular vein pulses
|
a: atrial contraction
x descent: atrial relaxation v: passive filling of the atrium during systole y descent: rapid filling of the ventricle after tricuspid opens |
|
|
With cardiac tamponade what JVP changes do you see
|
blunted y descent
|
|
|
What do you see on EKG with tamponade/effusion
|
- see altered amplitude of QRS
- electrical alternates |
|
|
How to treat tamponade
|
Draw fluid out of pericardial space
--pericardiocentesis --pericardial window ---pericardiotomy |
|
|
What is chronic pericarditis
|
see thick concstrictive pericarditis
- caused by radiation induced scarring, cardiac surgery or prior pericarditis |
|
|
Clues to constrictive pericarditis
|
- pericardial knock
- prominent y descent in JVP - Kussmaul's sign |
|
|
what do you see on chest x ray for constrictive pericarditis
|
calcified rim around the heart
- MRI to measure pericardial thickness |
|
|
Hemodynamic changes with constrictive pericarditis
|
--heart squeezes/systolic contraction fine
- restricted relaxation in diastole ***see fast dip and plateau in diastolic pressure |
|
|
What causes the pericardial knock
|
the stopping/resistance due to constrictive pericardium
---when diastole can't relax further..sudden stop |
|
|
How to treat constrictive pericarditis
|
Operate and dissect off the pericardium
|
|
|
2 critical functions of platelets
|
- form platelet aggregates to stop bleeding
- provide surfaces to activate plasma coagulation |
|
|
Coagulation cascade is
|
a sequence of reactions to produce thrombin
- clotting factors (proenzymes) activated by proteolytic cleavage - activated factors activate further factors |
|
|
Describe the extrinsic pathway for coag cascade
|
Tissue factor converts VII-->VIIa converts X-->Xa converts II-->IIa converts fibrinogen to fibrin
|
|
|
Describe the intrinsic pathway for coag cascade
|
XII-->XIIa converts XI-->XIa converts IX-->IXa w/Factor VIII converts X-->Xa converts II-->IIa converts fibrinogen to fibrin
|
|
|
Deficiency of which factor does not cause bleeding
|
Factor XII
|
|
|
Factor VIII deficiency causes what?
|
classic hemopholia (Hemophilia A)
|
|
|
Factor IX deficiency causes what?
|
Hemophilia B
|
|
|
Factor XI deficiency causes what
|
mild bleeding tendency
|
|
|
Which clotting factors are Vitamin K dependent?
|
II, VII, IX, X
- these acides chelate Ca against the neg charged platelet phospholipids |
|
|
Initiation step of coagulation cascade
|
Macrophage or fibroblast derived Tissue Factor interacts with VIIa to convert X-->Xa converts II-->IIa activates Va, VIIIa, XIa ACTIVATED PLATELETS
TF-VIIa converts IX-->IXa |
|
|
Amplification step of coagulation cascade
|
VIIIa-IXa from activated platelet converts X-->Xa w/Va converts II-->IIa amplifies Va, VIIIa, XIIa, TAFI, and FIBRIN
|
|
|
Propagation step of coagulation cascade
|
more platelets activated by IIa-->thrombin burst
|
|
|
Factor VII and TF relationship
|
Factor VIIa is more active when bound to tissue factor---even more active if bound to activated platelet surface
|
|
|
Role of phospholipid scrambling in coagulation
|
Movement of negatively charged PLs to surface promoting the binding of Ca and Vit K
|
|
|
Which coagulation pathway is dominant normally?
|
Extrinsic pathway
|
|
|
What molecule is a key controller of thrombin activity?
|
Antithrombin--inhibits thrombin activity
--deficiency causes increase thrombosis |
|
|
Which drug is mediated by antithrombin?
|
Heparin
|
|
|
What does Antithrombin inhibit?
|
IIa, Xa strongly
XIIa, XIa and IX weakly |
|
|
How is plasminogen activated?
|
By tissue Plasminogen Activator
|
|
|
What inhibits plasminogen?
|
antiplasmin
|
|
|
What inhibits tissue Plasminogen Activator?
|
plasminogen activator inhibitor
|
|
|
What are the key proteins in anticoagulation and fibrinolytic mechanisms?
|
- Protein C and S which inhibit VIIIa and Va
- Tissue Factor Pathway Inhibitor which inhibits Xa and VIIa |
|
|
What is the role of thrombomodulin?
|
surface protein on normal endothelial cells that bind thrombin---converts thrombin from pro- to anti- coagulant
|
|
|
What does thrombin activate?
|
V
VIII XI XIII Platelets Fibrinogen TAFI |
|
|
Thrombin bound to thrombomodulin activates?
|
Protein C
Protein S inactivates PAI-1 (plasminogen activator inhibitor) |
|
|
Steps in the life of a hemostatic plug
|
Formation
Consolidation Fibrinolysis Repair |
|
|
Describe plug formation
|
Initial attachment and recruitment of platelets, activation of plasma coagulation, and formation of the platelet – fibrin plug
|
|
|
Describe plug consolidation
|
retraction of the hemostatic plug by active shortening of platelet contractile filaments.
|
|
|
Describe fibrinolysis
|
Plasmin, a protease formed from the proenzyme plasminogen, cleaves fibrin and fibrinogen to smaller fragments
|
|
|
Describe the endothelial repair phase of hemostasis
|
Endothelial cells grow in to fill deficit from the edges
|
|
|
How does the resting endothelial cell prevent thrombosis?
|
- express thrombomodulin on surface to turn any thrombin from pro-->anti coagulant
- Secretes tissue plasminogen activator - exposes heparin to act as cofactor for antithrombin-->inactivating free thrombin |
|
|
When do negative phospholipids appear on endothelium?
|
endothelial injury
|
|
|
Common platelet conditions effecting hemostasis
|
thrombocytopenia
thrombocytopathy--poor function |
|
|
Prothrombin Time (PT) Test
|
Assesses function of the extrinsic pathway
- add TF, phospholipid, and Ca++ to plasma - should convert VII-->VIIa and lead to Fibrin ***used to monitor Warfarin Therapy ***gets longer when coag inhibited or low factors |
|
|
Activated Partial Thromboplastin Time (APTT)
|
Assesses function of the intrinsic pathway
- add activator and phospholipid to plasma - use Ca for activation --activator converts XII-->XIIa ***should be 30s...aPTTr >1.3 abnormal |
|
|
INR for warfarin monitoring
|
International normalized ration
--use measured prothrombin time, and the mean normal prothrombin time and the international sensitivity index ***above 1.3 abnormal |
|
|
Labs for platelet assessment
|
- platelet count
- bleeding time--stop bleeding skin incision - platelet aggregation--spectroscopy - thromboelastogram |
|
|
Describe Thromboelastogram
|
- wire with pin in plasma solution...apply clotting factors and assess strength of clot
**hemophilia see slow thrombin generation **thrombocytopenia not a robust pull **fibrinolysis see clot dissolution **hypercoagulation see rapid overcoagulation |
|
|
von Willebrand's Disease
|
- causes mucosal bleeding
- endothelium secretes low amounts of vWf ---freq nosebleeds, heavy menses, bruising ---prolonged dental bleeding, surgery bleeding - 1/100 people very common |
|
|
Effects of low vWf
|
- abnormal platelet adhesion
- reduced levels of factor VIII ---vWf is a carrier protein for VIII in blood |
|
|
vWf synthesis
|
preproVWF is translated...remove 22aas forms provWF monomer
proVWF monomers dimerize cterm to cterm in ER dimer building blocks joined nterm to nterm in Golgi |
|
|
what are petechiae
|
very small hemorrhages...
|
|
|
what is purpura?
|
intermediate sized purple blotches not raised
|
|
|
what are ecchymoses?
|
larger areas of intradermal hemorhage, bruise
|
|
|
Why does bleed time increase with von Willebrand's disease?
|
only a small number of platelets are tethered and activated
- wet mucosa washes off more platelets so it's sensitive |
|
|
How to diagnose vWd?
|
- history of bleeding
- assay for vWf antigen - Factor VIII binding/activity assay |
|
|
How to treat vWd
|
- avoid unnecessary bleeding
- DDAVP increases vWf secretion - treat severe bleeding w/vWf |
|
|
Effects of low platelets in platelet disorders
|
- bleeding immediately after injury...skin, mucosa, CNS
- looks like vWf |
|
|
Low platelets are well tolerated until how low?
|
normal is 150K to 400K
bleeding when <10-20K |
|
|
Thrombocytopenia is caused by
|
decreased platelet production
increased platelet destruction |
|
|
Decreased platelet production is common after what
|
- stem cell injury--aplastic anemia, chemo, radiation
- metastatic tumor-->marrow replacement - ineffective thrombopoiesis--folate or B12 deficient |
|
|
Increased platelet destruction is caused by what
|
autoimmune: idiopathic, lupus, lymphoid malignancy, infection/HIV
Disseminated Intravascular Coagulation (DIC) Bypass for cardiac surgery alloimmune in neonates drugs: quinine/quinidine, heparin |
|
|
How does heparin induce thrombocytopenia
|
- Antibodies form against Heparin-platelet factor 4 complex
- these antibodies are platelet activating-->arterial or venous thrombosis |
|
|
Types of platelet dysfunction
|
- extrinsic: NSAIDs, renal failure
- intrinsic: rarely inherited, hematopoietic stem cell disorders |
|
|
Acute leukemia treatment causes
|
myelotoxicity---stop making blood cells for a few weeks
- give RBC transfusion and platelet transfusion |
|
|
What is the critical platelet level?
|
5K/mcL
|
|
|
Coagulation Factor Disorders
|
- Deficiency in Factor VIII (hemophilia A)--x linked
- Deficiency in Factor IX (hemophilia B) - Deficiency in Factor XI less severe bleeding |
|
|
What is hemophilia arthropathy
|
recurrent joint bleeding-->synovial hypertrophy and cartilage erosion
|
|
|
How to treat hemophilia A (factor VIII def)
|
give Factor VIII...expensive
|
|
|
Hemophilia A
|
X linked
dec Factor VIII:C nl VWF activities hematomas, hemarthoses Rx: replace VIII:C |
|
|
von Willebrand's Disease
|
Autosomal - Chr 12
dec Factor VIII:C dec VWF activities cutaneous & mucous membrane bleeding Rx: replace VWF |
|
|
What are some acquired coagulation factor disorders causing decreased platelet production
|
- Vit K deficiency...or II, VII, IX, X
--give Vit K or plasma therapy - liver disease |
|
|
Temperature dependence of vWF induced Ca signaling
|
- @30 deg C vWF path is gone in 50% of ppl and reduced in 75%
|
|
|
Effect of pH on Factors Xa/Va
|
increases as pH increases
|
|
|
Causes of disseminated intravascular coagulation
|
- sepsis, trauma, Cancer, OB complications, Vascular issues, snake venom, amphetamines, allergic rxn, transfusion rxn
|
|
|
What is DIC
|
systemic uncompensated activation of hemostatic mechanisms-->thrombosis and thrombocytopenia see schistocytes
|
|
|
How to treat DIC
|
- treat underlying disease...shock, sepsis, etc
- replace factors/platelets if needed |
|
|
What is anti-VIII:C
|
most common alloantibody
- see abnormal mixing studies--dec VIII:C |
|
|
Thrombophilia
|
excessive blood clotting
- Anti-thrombin III deficiency- - See lots of DVTs - die of massive PE young - see leg edema from R. HF due to pulm hypertension - Protein C or S def |
|
|
Interaction of oral contraceptive
|
Interaction between Factor V Leiden and clotting risks like smoking, pregnancy or immobilization
|
|
|
What are the HMG-CoA Reductase Inhibitors
|
- Statins
- lovastatin - pravastatin - atorvastatin--lipitor ***key dec in LDL-C w/ good Dec TG and inc HDL |
|
|
Bile-acid binding resin
|
- cholestyramine
- Colestipol - Colesevelam ***good LDL-C dec |
|
|
Cholesterol Absorption Inhibitors
|
Ezetimibe
***minimal LDL-C dec |
|
|
Nicotinic Acid (= Niacin = Vit B3)
|
Cholesterol lowering agent
***key inc in HDL 35% |
|
|
Fibrates
|
Gemfibrozil, Fenofibrate
*key is dec in TG 50% |
|
|
How do dietary lipids enter the body
|
as Chylomicrons
|
|
|
Features of Familial hypertriglyceridemia
|
dec Lipoprotein lipase
inc VLDL secretion |
|
|
Familial Combined Hyperlipidemia
|
inc VLDL secretion--inc VLDL and inc LDL
|
|
|
Remnant Removal Disease
|
Inc VLDL secretion
dec ApoE2 |
|
|
How do statins work?
|
inhibit HMG-CoA reductase-->inc LDL-R expression-->dec plasma LDL
**also improve endothelial fcn, plaque stabilization, dec Ox Stress, dec C reactive protein |
|
|
Sivastatin, Pravastatin, Lovastatin
|
1st generation statins
|
|
|
Atorvastatin, Rosuvastatin
|
2nd generation statins
|
|
|
adverse effects of statins
|
- hepatitis--monitor transaminases
- muscle pain - new onset diabetes - Teratogenic - Polyneuropathy - CYP450 drug interactions as it reduces CYP450 ------diminish warfarin protein binding |
|
|
How do statins and bile acid binding resins work well together?
|
- statins dec cholesterol production w/inc LDL uptake
-bile acid binding resin dec recycling of bile acids from intestine |
|
|
Bile acid binding resins do what
|
prevent enterocyte reuptake of bile through the Asbt
cause hepatic cholesterol shift to utilization for bile |
|
|
Farnesoid x receptor does what
|
decreases FGF15
|
|
|
FGF15 does what
|
acts on FGF4R to inc Cyp7a1 and increase bile acid production
|
|
|
adverse effects of bile acid binding resins
|
GI distress
adsorb vitamins and drugs like statins inc plasma TGs in hyperTG ppl |
|
|
How does ezetimibe work?
|
inhibits NPC1L1 and cholesterol endocytosis
- effective in sitosterolemia from excess plant sterol - glucuronidated ezetimibe undergoes enterohepatic cycling---excreted in feces |
|
|
How does nicotinic acid (niacin) work?
|
inactivates nicotinamide
inc HDL, Dec TG, inc LDL size and dec density |
|
|
Adverse effects of Niacin
|
prostaglandin flush, gi distress, hepatotoxic
hyperglycemia |
|
|
How do Fibrates work?
|
inc lipoprotein lipase
dec ApoC-III-->inc lipolysis inc FFA oxidation and dec TG synthesis inc ApoAI and ABCA1 expression-->inc HDL |
|
|
How do PCSK9 targeted monoclonal Antibodies work
|
- decrease ability of PCSK9 to target LDLR for internalization and lysosomal degradation
--More LDLR= lower plasma LDL |
|
|
Does Rheumatic fever kill the young or old?
|
young
|
|
|
how does acute rheumatic fever always start?
|
Acute pharyngitis
|
|
|
what bug for rheumatic fever?
|
Group A B-hemolytic streptococcus
|
|
|
What caused the drop off of deaths associated with Rheumatic fever?
|
Penicillin
* real reason we get penicillin after throat swab is RF |
|
|
Why is there a latent period after the acute pharyngitis of Rheumatic Fever?
|
- M protein in the coat of Gr. A streptococcus is antigenic and latent period is the development of immune response to M protein
|
|
|
What is M protein cross reactive with?
|
cardiac myosin
|
|
|
Define Rheumatic fever
|
Inflammatory reaction
follows Gr. A streptococcal pharyngitis involves: heart, joint, and CNS |
|
|
What is the Jones Criteria
|
(need 2) major: Carditis, Polyarthritis
or 1 major and 2 minor + recent streptococcal inf |
|
|
Suspicion of acute rheumatic fever because of
|
- recent streptococcus infection
- murmur - joint pain - fever - high sedimentation rate |
|
|
Describe pan-carditis with Rheumatic Fever
|
- pericarditis--hear friction rub
- valvular thickening and inflammation - myocardium--multi-nucleated GIANT CELLS |
|
|
What are non cardiac signs of Rheumatic Fever
|
- Subcutaneous nodules on tendons...similar to those seen in RA
- Erythema Marginatum - CNS--sydenham's chorea/dance-like motion - migratory poly-arthritis (L Knee to R ankle etc) - high anti-streptolysin O |
|
|
How do you treat Rheumatic Fever?
|
- Kill any residual streptococcus
- treat with anti-inflammatory ----Aspirin (watch out for Reye's Syndrome) ----Steroids (esp if carditis is involved) - give supportive care - doesn't prevent recurrence or late sequele |
|
|
Prevention of Primary and Secondary RF
|
- primary give full course antibiotic for strep
- secondary give daily oral penicillin or monthly benzathine***consider exposure risk |
|
|
Late sequelae of RF
|
- Mitral stenosis--fish mouth deformity
- fusion---hockey shaped deformity - Mitral > aortic > r. sided valves ***decades after initial event |
|
|
What do you have to have to get endocarditis?
|
- bacteremia
- virulent organism - susceptible host--valve issues |
|
|
Most endocarditis virulent bugs?
|
Stapylococcus aureus
Streptococcus viridans |
|
|
How can you be susceptible to endocarditis
|
- congenital heart disease ( bicuspid aortic valve)
- abnormal valve architecture--mitral valve prolapse - prosthetic heart valves - IV drug users--R. Sided Valves - non-bacterial thrombotic endocarditis |
|
|
Valvular vegetation consists of what
|
fibrin strands with bacterial colonies
- need 4-6 wks of IV bacteriacidal antibiotics - see on echocardiography |
|
|
Diagnosis of Endocarditis
|
- clinical suspicion
- new regurgitant murmur - blood culture - echo - peripheral manifestations: splinter hemorrhages, Osler nodes on painful and purple on pads of fingers, subconjuctival hemorrhages, Roth spots on retina, |
|
|
If you suspect endocarditis but don't see it on trans-thoracic echo what do you do?
|
get a trans-esophageal echocardiogram
|
|
|
Myocardial abscess after endocarditis
|
- can see hole in valve
- conduction block - new pericardial friction rub---rupture of abscess into pericardial space ***Need Surgery |
|
|
What are mycotic aneurysm?
|
mushroom shaped aneurysms can be anywhere in body
|
|
|
What can endocarditis cause in the kidneys?
|
glomerulonephritis--deposition of immune complex
|
|
|
Treatment of endocarditis
|
- 4-6 wks of bactericidal antibiotics
- supportive care - surgery if there is a failure of medical therapy ---abscess, recurrent bacteremia, CHF from valve erosion, 10mm mobile left side vegetation |
|
|
Prevention of endocarditis
|
- identify susceptible hosts (w/valvulopathy)
- if undergoing procedure like denistry may benefit from prophylaxis antibiotics |
|
|
Cardiac shunt
what are the most common shunts? |
- pattern of blood flow in the heart that deviates from the normal circuit
- atrial septal defects (ASD) - ventricular septal defects (VSD) - patent ductus arteriosi (PDA) |
|
|
Fick's Principle with congenital heart disease
|
input and output concentrations of a substance to rate of consumption allowing calculation of flow rates
|
|
|
Atrial Septal Defects
|
- secundum---persistent foramen ovale
- Primum---basal area including mitral and tricuspid valve leaflets - Sinus venosus defects...poor communication with wall of SVC or IVC and Atrial septum - coronary sinus defects...dilated RV no reason |
|
|
What is shock?
|
The state in which profound and widespread reduction in the effective delivery of O2 and other nutrients to tissues leads to first reversible and then if prolonged to irreversible cell injury
|
|
|
Forms of shock?
|
- cardiogenic shock
- extracardiac - hypovolemic - distributive---sepsis |
|
|
Forms of cardiogenic shock
|
- myopathic---acute MI, dilated cardiomyopathy
- Mechanical---mitral regurg, VSD, Ventricular aneurysm |
|
|
Forms of extracardiac shock
|
- pericardial tamponade
- Massive PE |
|
|
How to diagnose shock?
|
- BP < 90mmHg
- also need: ---poor perfusion-CNS, Renal low urine output, cold/cyanic skin |
|
|
Unfractionated Heparin
|
Anti-coagulant---pregnancy safe
inhibits factor Xa - requires antithrombin cofactor - monitor aPTT |
|
|
Low molecular weight heparin
Enoxaparin |
Anti-coagulant- pregnancy safe
inhibits factor Xa - requires antithrombin cofactor - side effects: bleed, thrombocytopenia |
|
|
Rivaroxiban
|
Anti-coagulant
inhibits factor Xa - use stroke, systemic, non-valve a fib, DVT, PE - does not require antithrombin - Avoid w/CYP 3A4 inhibitors |
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Apixaban
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Anti-coagulant
inhibits factor Xa - dec stroke, sys embolism in non valv a fib - Avoid w/CYP3A4 inhibitors |
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Warfarin
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Anti-coagulant- Vit K antagonist
-binds to Vit K epoxide reductase, no Vit K regeneration -VKOR polymorphisms influence dosing - Antithrombic effect lasts 4-5 days - prosthetic valves, DVT/PE |
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Bivalirudin
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Anti-coagulant
inhibits thrombin---binds to free and clot thrombin - don't need anti-thrombin - inhibits cleavage of fibrinogen to fibrin, and platelet activation - Acute coronary syndrome, PCI, heparin sensitive patients |
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Dabigatran
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Anti-coagulant
direct inhibitor of thrombin, IIa--both free and clot - interacts w/Rifampin to dec effect if dabigatran |
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Antithrombin (synthesized in liver) inhibits
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activated coagulation factors in the intrinsic and common pathways: thrombin, Xa, IXa, XIa, and XIIa
Antithrombin rapidly inhibits thrombin only in the presence of heparin |
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Anticoagulants do what?
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Interfere with platelet aggregation
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Side effects of heparin
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Thrombocytopenia
prolonged bleeding --give Argatroban to counter effects |
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What drug counteracts the effects of heparin
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Argatroban
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Side effects of Warfarin
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- bleeding
---can adjust dose if minor ---Vit K or Fresh frozen Plasma infusion if bad - skin necrosis - BAD FOR PREGNANCY |
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Side effects of Bilavirudin
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- bleeding
- Acute coronary thrombosis |
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Fibrinolytic agents
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- t-PA--5 min t1/2---use for strokes
- r-PA- plasminogen activator--longer t1/2 - SK - streptokinase |
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What do fibrinolytics do?
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- degrade fibrin and fibrinogen to soluble products
- clot busters |
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Streptokinase
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- activates plasmin by binding to plasminogen
- generalized lytic state - loading dose to overcome plasma Antibodies against the bacterial protein - adverse: fever, allergic rxn, anaphylaxis, headache |
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Tissue Plasminogen Activator
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- plasminogen activator--strong when fibrin present
- serine protease |
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Uses of Fibrinlytic Drugs
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- Venous Thromboembolism
- STEMI - Interventional Radiology - Stroke |
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Adverse effects of Fibrinolytics
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- bleeding--cranial, puncture sites
- no surgery within 10 days - GI bleeds ---stop drug and give whole blood if bad |
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Treatment of white vs red thrombus
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white: antiplatelet agents
red: anticoagulants and fibrinolytics |
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Salicylates
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Asprin
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Phosphodiesterase inhibitors
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Dipyridamole
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Thienopyridine
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Clopidogrel
Prasugrel |
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Cyclo-pentyl-triazolo-pyrimidine
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Ticagrelor
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Glycoprotein IIb/IIIa inhibitors
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Abciximab
Eptibfibatide Tirofiban |
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How does Aspirin work?
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- Cox1&2 inhibitor
- leads to decreased thromboxane A2 - dec vasoconstriction and platelet aggregation - good for stable angina or STEMI, CABG, stents - weak antiplatelet drug |
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Aspirin side effects
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- allergy/sensitivity
- GI intolerance - GI bleed - resistance |
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Dipyridamole
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- inhibits platelet cAMP phosphodiesterase
- inc cAMP inhibits Thromboxane A2 formation - inhibits platelet activation |
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Clopidogrel
Prasugrel Ticagrelor How do they work? |
- inhibit ADP-induced platelt activation
- block P2Y12 receptor and activation of the GPIIb/IIIa complex |
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Why do patients respond different to clopidogrel and prasugrel?
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- different activity of metabolism by CYP2C19 and other CYP450 oxidases in the liver
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Is ticagrelor biotransformed and inactivated
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No...has 7-8 hr half like
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How do antiplatelet drugs work?
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- prevent platelet activation and aggregation
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When to use clopidogrel?
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Reduced MI, stroke, vascular death in patients with recent MI, CVA, peripheral vascular disease
ALWAYS with STENTS |
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Side effects of clopidogrel
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bleeding
rash GI upset |
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Benefits and adverse effects of Prasugrel
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- less ischemic events than clopidogrel
- less stent thrombosis - not better for medically managed patients - not good for patients with TIA/stroke |
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How do GPIIb/IIIa antagonists work?
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- block the final common pathway of platelet aggregation after activation
- antibody---abciximab - tirofiban and eptifibatide synthetics |
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GP IIb/IIIa receptor blocker side effects
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- bleedeing
- thrombocytopenia - monitor platelet count - CNS hemorrhage |
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What are GP IIb/IIIa inhibitors best for?
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- NSTEMI patients getting PCI
- given with heparin |
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Sotalol blocks what current?
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I_kr---rapid hERG channel
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Ibutilide blocks what current
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I_kr---rapid hERG channel
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Amiodarone blocks what K current
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I_ks---slow K current
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What causes the phase 1 dip in the cardiac AP?
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- inactivation of Na channels
- opening of Kto - also have LTCC opening but not at steady state with K |
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What causes the plateau in phase 2 of cardiac AP
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Na current + Ca current = K current
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Define Effective Refractory Period
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- even if AP were generated the inward current would be too low and rise too slow to excite neighboring cells
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What is relative refractory period
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threshold for AP generation is elevated
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How to interrupt arrhythmia, what strategies?
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increase threshold by dec Na or Ca current
extend refractory period by decreasing delayed K current |
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Describe funny current activation
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I_f is active at hyperpolarized Vm
- give EPI inc cAMP will shift If activation to more positive potential - PKA will increase LTCC sensitivity |
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What is Brugada's Syndrome
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- Defect in Na channel-->VT
- SCN5a mutation - SE Asia |
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Wide complex tachycardia
--monomorphic causes --polymorphic causes |
- monomorphic is around a fixed scar
- polymorphic is due to channelopathy?? burgada or long QT |
