CVD & Obesity Flashcards
Exam III
BP equation
CO x PVR
CO equation
HR x SV
SV components
Preload
Contractility
Afterload (arterial vessel diameter)
PVR components
Blood viscosity
Afterload (arterial vessel diameter)
Preload components
Fluid volume
Venous vessel diameter
Humoral regulation
Vasodilators
BNP & ANP
NO
Prostacyclin
Endothelins
Vasoconstrictors
Epi & norepi
ADH
Angiotensin II
HTN
Persistent elevation in systolic OR diastolic blood pressure due to an increase in cardiac output, peripheral resistance, or both.
Hyaline Sclerosis
Hardening and stiffening of arterioles due to accumulation of hyaline (glass like) proteins
Hypertension of aging
Leading cause of death in the US
heart disease
Atherosclerosis
Hardening due to accumulation of plaque/lipids in the arteries
Primary HTN and the pressure-natriuresis curve
Shifts curve to the right
Meaning: a higher pressure is required to excrete salt compared to a person with normal blood pressure (they retain salt)
Contributors to HTN
Obesity;
SNS, RAAS, and natriuretic hormone dysfunction;
Inflammation
—>
Vasoconstriction and renal salt/fluid retention
Adipocytes characteristics and effects
Store triglycerides as one drop
Hyperplasia and hypertrophy in obesity
Increase angiotensinogen synthesis
Secrete leptin (with leptin resistance)
Inhibit adiponectin
Increase inflammatory mediators
Increase FFAs
Adipokines
Hormones produced by adipocytes
Autocrine, paracrine, and endocrine functions:
Control of food intake and energy expenditure
Lipid storage
Insulin sensitivity
Immune and inflammatory response
Coagulation, fibrinolysis, angiogene
Fertility vascular homeostasis
BP regulation
Bone metabolism
Adipokines increased in obesity
Angiotensinogen
Angiotensin type 1 and 2 receptors
Renin
ACE
Leptin
Adipokine decreased in obesity
Adiponectin
Leptin
Responsible for satiety
Stimulates energy expenditure
Upregulates the SNS in the brain (sympathoactivation)
Insulin sensitizer for skeletal muscle and liver
Plays a modulating role in reproduction, angiogenesis, immune response, BP control, and osteogenesis
Pro-inflammatory
Obesity associated w leptin resistance
Orexigenic neurons
Increase appetite
Decrease metabolism
Anorexigenic neurons
Suppress appetite
Increase metabolism
Adiponectin
Increases insulin sensitivity
Antiatherogenic
Anti-inflammatory
Increases NO release
HTN Dx
Based on averages of two blood pressures on two separate occasions
US vs European HTN tx
US/AHA:
>130/80 definition
ACE-I, CCB, and Diuretics are first line tx; BB are second line
Europe/ESH:
>140/90 definition
BB included as first-line therapy
Chronic HTN manifestations
Mostly asymptomatic until end organ damage has occurred to the arteries/arterioles of eyes, kidney, heart, & brain
Gradual loss of visual acuity
CKD
Cardiomyopathy, HF
Dementia
HTN crisis
Acute development of severe hypertension (>180 and/or >120) that causes acute end organ complications
Retinal hemorrhages (visualized by ophthalmoscopic exam), papilledema, blindness
AKI
ACS
CVA
Treat by gradual reduction in BP over 24-36 hours
Atherosclerosis definition
The hardening (sclerosis) of the arteries by atheromatous (low density lipoprotein = LDL) plaque
Atherosclerosis causes
Endothelial cell injury from
1. uncontrolled HTN
2. smoking
3. hyperlipidemia
Inflammatory response leading to atherosclerosis
Subendothelial accumulation of LDL cholesterol activates the inflammatory response
This oxidizes the LDL
The oxidized LDL activates adhesion molecules for monocytes (further increasing inflammation)
Monocyte differentiates into ingesting macrophage
The macrophage penetrates the endothelium, where it engulfs and oxidizes LDL cholesterol
Foam cells create a fatty streak
The fatty streak forms an atherosclerotic plaque
Smooth muscle covers the plaque
Stable atherosclerosis
Has a small lipid core and thick, calcified cap
Unlikely to rupture, but size will OCCLUDE the blood vessel
Typical cause of stable angina
Unstable atherosclerosis
Has a large lipid core and thin, friable cap
Ruptures easily, allowing contents to leak and cause a blood clotting response –> thrombus formation
Can cause acute arterial occlusion and acute coronary syndrome
Lipoprotein components
Triglycerides
Cholesterol
Phospholipids
Apolipoprotein
HDL
Good cholesterol
Anti-atherogenic
Desired level > 60
LDL and VLDL
Bad cholesterol
Pro-atherogenic
LDL desired level <100
LDL-lipoprotein A
Apolipoprotein
Very bad cholesterol
Proatherogenic, increases the adherence of LDL to vessel walls
Dyslipidemia
Hypercholesterolemia
General cholesterol levels do not address the relative risk for a patient developing atherosclerotic disease
Triglyceride levels
Desired <150
*Fasting
Total cholesterol level
Desired <200
Atherosclerosis risk stratified cholesterol guidelines
More clinically relevant
Risks drive treatment with LDL targets
Risks: very high LDL, diabetes mellitus, and existing atherosclerotic disease
Primary prevention of atherosclerotic cardiovascular disease (ASCVD)
No hx of MI or CVA
**Treat if:
LDL is very high
DM
10 year risk is >%75
DM and atherosclerosis
An accelerator to atherosclerosis, regardless of cholesterol levels
Secondary prevention of ASCVD
Clinical atherosclerotic disease
Goal: reduce cholesterol levels to LDL <70 or by 50%
Atherosclerosis complications
Cerebrovascular disease
Peripheral arterial disease
Coronary artery disease
L main carotid artery
Short and truncated
Divides almost immediately into the left circumflex and the left anterior descending coronary arteries
RCA
Provides arterial blood to the RV and inferior heart
White adipose tissue (WAT) characteristics
Visceral and subcutaneous
Physiologic functions:
Coagulation
Immunity
Appetite regulation
Glucose and lipid metabolism
Reproduction
Angiogenesis
Fibrinolysis
Body weight homeostasis
Vascular tone control
Visceral WAT normally hypertrophies, resulting in:
Insulin resistance (diabetes),
inflammation (DM, cancer, atherosclerosis),
Altered lipids (NAFLD/NASH, atherosclerosis),
Renin and angiotensin increase (HTN)
Subject to hormones (esp estrogen)
Metabolically active
Lipotoxicity
Tissue exceeds supporting vascular supply, leading to cell necrosis and increased inflammation
Beige adipose tissue (bAT)
“Brown in white”
Develops within WAT following:
Chronic exposure to cold (but reverts back to WAT with warm adaptation)
Exercise
Exposure to synthetic ligan of peroxisome proliferator-activated receptor-y (PPARy; “Pee-par-gamma”) or thiazolinediones (TZD)
Increased bAT is a promising target for obesity tx
Bone marrow adipose tissue (MAT):
Found mostly in long bones
Metabolically active
Releases adipokines
Excess is associated with osteoporosis (takes up space of the bone)
Last fat to be used for energy (Starvation states; chronic negative energy balance)
Obesogens
Chemicals in our environment that stimulate the development of fat/obesity
Epigenetic influences
Disrupt hormone signals
Cross the placenta and are in breastmilk
Passed down through generations
Hypothalamus role in food intake
Regulates food intake and energy metabolism through orexigenic and anorexigenic neurons
Controls reward, pleasure, memory, and addictive behavior
Medical conditions predisposing to obesity
Cushing syndrome
PCOS
GH deficiency
Hypothyroidism
Anorexia of aging related factors
○ Reduced energy needs
○ Waning hunger
○ Diminished sense of taste and smell
○ Decreased production of saliva
○ Altered GI satiety mechanisms
○ Co-morbidities
○ Medications
○ Decreased orexigenic and increased anorexigenic signals
○ Delayed gastric emptying
○ Decreased small intestine motility
○ Sensory impairments
○ Medical/psychiatric disorders
○Social isolation, abuse, neglect
Causes of cardiac ischemia (myocardial oxygen deficit)
- Increased demands
□ Exercise
□ Valvular disease (esp. aortic narrowing)
® Heart must generate higher pressure to move blood through stenotic valves
□ Hemodynamic abnormalities
® Increased preload
® Increased PVR - Insufficient supply
□ Plaque or thrombus
□ Anemia
□ Hypoxemia
□ Hypotension
Stable angina
Stable atherosclerosis and cap
CP is predictable; induced by exercise and relieved by rest/nitrates
Demand ischemia
No necrosis
NOT an ACS
Negative troponin
ECG changes with stable angina, unstable angina, and NSTEMI
transient ST segment depression and T wave inversion
Acute coronary syndromes
Transient ischemia – Unstable angina
Sustained ischemia – MI (N-STEMI or STEMI)
Involve cardiac infarction (manifestation of tissue necrosis)
Almost always characterized by thrombus formation
Ischemia cellular pathophysiology
Intracellular myocyte ion dysregulation:
□ Na+ and Ca++ accumulate inside the cell → myocyte swelling and cell wall damage
□ Dysregulated ions → electrophysiologic abnormalities (especially reentry circuits) → dysrhythmias (ventricular fibrillation)
Neurotransmitter and hormonal responses:
□ Catecholamines (norepinephrine and epinephrine) increase free fatty acids (FFA)
® FFA have detergent effect on myocyte membrane → cell wall damage (break down phospholipids)
□ Norepinephrine and angiotensin II → vasoconstriction → decreased coronary blood flow
Unstable angina
Unpredictable CP occurring at rest and increasing in frequency (usually resolves, but can progress to NSTEMI)
Myocardial injury
+ HIGH SENSITIVITY troponin (HS3 cTnl)
NSTEMI
MI and its associated acute CP
Subendocardial ischemia and necrosis
+ troponin
MI chest pain
Unpredictable, sudden, severe, crushing
Radiates to jaw, neck, shoulder, L arm
Usually associated with anxiety, N/V, indigestion
may also have anginal equivalents
STEMI ECG changes
ST segment elevation
Resolves in time and patient develops pathological Q wave
STEMI
Transmural ischemia and necrosis (throughout the myocardial wall)
+ troponin
Reperfusion injuries
increases cell injury through:
- Reactive oxygen species:
◊ Incomplete oxygen utilization by damaged mitochondria → reactive oxygen species (ROS) → damage to cell walls - Inflammation:
◊ Inflammatory response produces cytokines → damage to cell walls - Sarcoplasmic reticulum (normally regulates Ca++availability for contraction and relaxation) dysfunction:
◊ Sarcomere => the contractile unit of the myocyte
◊ IRI impairs the SR’s ability to recycle calcium (Ca2+ is continuously available)
–Causing continual contraction (“Stunned” myocardium) and Cell wall damage
Auscultation with ACS
S3 – suggestive of LV dysfunction
New onset MR – suggestive of papillary muscle dysfunction
New onset inspiratory crackles – suggestive of pulmonary congestion/LV dysfunction
Troponin labs
To diagnose injury/necrosis
Results need to be contextualized with the patient since other conditions may cause false positives
Normal values:
□ cTnI: 0 - 0.04 ng/mL
□ hs-cTnI:
♀ < 16 ng/L
♂ < 34 ng/L
Natriuretic peptide (BNP)
dx HF
ACS workup
Presentation
H&P
Serial 12 leads
Labs (+ Serum markers)
Echo
Cardiac cath & coronary angiogram (time to table 90 min)
HF definition
a clinical syndrome caused by a structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion
HF risk factors
○ Increasing age
○ Pregnancy
○ Valvular heart disease
Esp. aortic stenosis
○ Myopathies – dilated (restrictive and hypertrophy)
○ Infections
Forward and backward effects
Forward effects: Decreased cardiac output and stroke volume causes inadequate arterial tissue perfusion
□ Brain: AMS
□ Circulatory system: weak, thready pulses; tachycardia; hypotension
□ GI tract: nausea, anorexia, abd discomfort
□ Kidneys: decreased UOP, increased BUN/Cr, CKD
□ Skeletal muscle: weakness, chronic fatigue, exercise intolerance
□ Skin: cool, mottled, cyanotic
Backward effects: Decreased cardiac output and stroke volume causes left ventricular volume overload which is transmitted “backwards” to the pulmonary circulation (congestion) and eventually the venous circulation (edema)
□ Respiratory s/sx: tachypnea, hypoxemia, air hunger
□ Venous congestion: JVD, hepatomegaly
EF calculation
EF= SV/EDV ×100
Example with normal values:
EF= (70 mLs)/(100 mLs ) ×100=70%
HFrEF anatomical chx and manifestations
EF </= 40%
Myocardial walls thin and weak
Chamber dilates
End diastolic volume and pressure is high → ↓ SV
Myocytes exchanged for scar tissue and fibroblasts, surrounded by collagen
Cardiomegaly
S3 heart sound
HFrEF co-morbidities & pathophys
Hypertension + atherosclerosis → coronary heart disease → acute coronary syndrome → myocardial injury/infarction → myocytes replaced with scar tissue (not contractile)
RAA and SNS contribute to abnormalities
HFpEF anatomical chx and manifestations
EF >/= 50%
Myocardial hypertrophy and stiffness (non-compliant)
Remodeling and thickening
More densely packed collagen and fibroblasts around myocytes (fibrotic muscle)
Chamber volume small → ↓ SV
Tachycardia shortens diastolic filling time and exacerbates symptoms
S4 heart sounds
HFpEF co-morbidities & pathophys
Aging + HTN + DM + aging + obesity + renal dysfunction
→ activation of inflammatory and fibrotic mechanisms
→ hypertrophy and LV remodeling
→ myocardial dysfunction
→ fibrosis, extracellular collagen excess
HIGH PRESSURE
LOW VOLUME
DM effects on cardiomyocytes
ROS
Glucose toxicity
– Chronically elevated glucose levels increase AGEs and have a profibrotic change on the heart
—Primarily has a dominant effect on diastolic dysfunction
Advanced glycation end productions (AGES)
– Myocardium has receptors for advanced glycation end productions (RAGES)
– Increases ROS, oxidative stress, and inflammation
– Glycation: glucose attachment to Hgb
S3 heart sound
Gallop
Passive atrial filling of an overfilled ventricle in early diastole yields an S3 heart sound (gallop)
The ventricle should be empty because of the previous stroke volume; however, it is overfull due to HF, so as atrial blood enters, it produces the S3 sound
S4 heart sounds
Atrial contraction into non-compliant ventricles leads to an S4 heart sound
Blood at very end of diastole is from atrial contraction/kick
Natriuretic peptide labs
B-type natriuretic peptides (BNP) and n-terminal pro B-type natriuretic peptide (NT-BNP)
Cells in the cardiac ventricles release NP in response to distension
Elevated values correlate to increased end diastolic volume
NPs trigger sodium triuretic (diuresis), which is an adaptive response (removes blood volume)
AHA HF Stages
A: @ risk but NO structural disease or sx
B: Structural disease but NO sx
C: Structural disease WITH sx (prior or current)
D: Refractory HF requiring specialized interventions
NYHA functional classifications
I: No limitations or sx
II: Slight limitations and sx with ordinary activity
III: Marked limitations and sx with less than ordinary activity
IV: Sx at rest or inability to perform any physical activity
Universal definition of HF classification by EF
HFrEF <40%
HFmrEF (mildly reduced) 41-49%
HFpEF >50%
HFimpEF (improved) 10 point increase from BL (<40%) and a second measurement >40%
RV HF
Pulmonary vessels constrict in response to disease
Increased PVR and afterload on RV
Problems with gas exchange (hypoxemia)
High output HF
Heart is normal (sufficient blood volume and contractility), yet cannot meet the oxygen needs of the body
Excessive tissue oxygen demands –> tissue hypoxia –> catecholamines –> increased HR and SV –> increased CO
The hyperdynamic heart cannot keep up with the O2 demands –> tissue hypoperfusion –> ischemia/injury/ necrosis + metabolic (lactic) acidosis
HF in sepsis
Causes a release of histamines and leukotrienes
—Cause gross vasodilation of blood vessels
◊ SVR decreases (arterial resistance), thus reducing afterload
— Bacteria (esp. gram -) release toxins that prevent cells from uptaking O2
Increased CO, but heart cannot keep up with demands
