Cardio last exam... pray for me and my people

What statistic does hypertension affect poeple in the united states. what is teh result of untreated hypertension

it affecrs ½ of people over 18 and 2/3 of people above 65

• it is the leading cause of chronic kidney disease, heart attack, and stroke. does not discriminate agains ancenstry, reaces and genders

Describe the trends based on the hypertenison chart

konw what causes each

What is the root of the hyepertension issue: essential hypertension/ genrereal population/raas)

essential hypertension (90-95%) of cases

• no primary/ identifiable cause

General populaiont

• typically begins with hypervolimea (increased sodium and water retention

  • this shifts the pressure naturesis curve= higher arteiriol pressure is needed to maintain sodium blanace

• Enhanced raas pathway activity

What is the ma equation

Co x svr

Waht is essential hypertension adnd how is it diagnoesd/ what causes it

• Diagnosi by exclusion

• vascular changes contribute to yperstensive states = hypertrophy oer time

• it is related to heredity, age, race, socioeconomic status, sexual orientaion, sex, and gender

• some patients with essential hupertension are more easily influenced by stress than normotensive ones

How does the raas pathway impact trends i essential hyertension. what changes

What are te 3 hormonal systems affecting blood pressure and what hormeones are invovled

1. sympathetic nervous system

   1. norepinephrine

2. hyperothalimic pituitary axis (HPA)

   1. Cortisol

3. Rening angiotensin aldosterone system

   1. Angiotensin II and aldosterion

Do general mechanism of hypetension extend to everyone?What does it depend on and what impacts it. how does this impact phenotyping each patient

high strss = higer sympathetic responses

Chronic strss = associated with blutned cortosol/ disruptid HPAaxis activity

symathetic outflow is a diriver of RAAS

• sometimes sympathetics are so high that RAAS is supressed

phenotyping each patient wil lbe the best way to manage bp using druigs

What are some of the statistic s in margionalized communityes. What people are more vulneraeabl e

1. Race, ethnicity, socioeconomic status, and lgbtq idenity = asoicated with hypertension

   1. Trans men have 4x the risk compared to cis women  of MI

   2. Trans women havee 2x compared to cis men of MI

   3. Bisexual women and gay men have 1.2x the risk of having hypertensio 

   4. Black adults are 2.2 times more likely to have hypertension vs their white pears

   5. 55% of white adults achive bp control while onl y 48% of black and 47% of hispanic and 44% of asian adults did

What are som eof the social determinants of helath

1. Socioeconomic status

2. Gender 

3. Sexual orientation

4. Racialization and ethnicity

What is the minority stress model and draw it out . what are the different layers. life stressors, factors, risk)

Understand this diagram. stress and fear neaural circutry. what does it mean?

Describe the trends inneural control of sympathetic parasympathetics. higher centers, hypothalamus, nts, vagal, sympathtic, rvlm, dvn, na and the heart and blood vessles

Describe the humoral mechanisms in stress. what is the diagram

1. There is a chronic stressor

2. The amygdala signals the hyothalamus

3. CRH (corticotropic releasing hormone) is released by the hypothalamus

4. CRH activates ACTH release (adrenocorticotropic hormone) from the ant pituitary

5. ACTH signals to adrenal cortex to produce and release cortisol

What are some of the organs cortosol affects in the body and how

1. liver

   1. increased neuogluonsis

   2. inccreased glycogen storange

   3. potenation of glucagone and epinephrine effects

2. brain

   1. strss reactivity regulation

   2. control of sleep-wake, appetie and memeory

3. pancreas

   1. decreased inslulin secretion

4. muscle

   1. reduced glucose transport via glut4 internalization

5. fat

   1. increased lypolysis and ffa release

   2. reduced glut4 transport

6. bones

   1. increased bone reabosrption

7. immune response

   1. antiinfamitory and immunosuppressie actions

8. heart

   1. incrreased sodium reabsorption and pottasium secretion

9. kidneys

Understanding the diagram: What are some of ehe affects on cortosol in the vasculature- cells, vseesels, and patietns

1. Cells: proliferation, migration, ecm production, oxidative stress, inflammation

2. Vessels: vascular remodeling, vascular fibrosis, vasoconstriction, altherosclorosis 

3. Patients  : vascular aging, hypertension, stroke, myocardial infarcion

Waht is the effect of chronic stress on MAP

Increased cortisol = increased sympathetic output  = increased hr, sv, and arteriolar tone = map increases

Waht is the effect of elevated BP on the body

Hypertorpy in peripheral arteirols

• increased resisntance regardless of SNS input

Cardiac hypertrophy

• excsssive fillign pressures

• reduced co2

REsetting of the baroreflex

• increaed toelrance for higer range of BP

What are some of the interveitions to use in hypertensio n

1. Map = co x svr 

   1. Treating essential hypertension you must adress the main drivers of arterial pressure

      1. Decrease Vasoconstricction

         1. Decrease in vascular sympathetic or RAAS input

      2. Decrease cardiac output

         1. Decrease blood volume and caridac sympathetic input

1. ACD reginemnd 

   1. At1 blockade/ ace inhinhibitors

   2. Calcium channel blocek rs

   3. Diuretics

How effective are treatment methods for hypertension

1. You can reduce systolic bp to less than 130 and diastolic to less than 80 

   1. Decreases stroke risk, decrease chronic kidney disease risk, decreases cardiac death 

      1. If left untreated 50% will develo heart faieure 

      2. 25% develop renal faileure

      3. 25% develop cerebral complications 

Describe the mechanisms for CA2+ channel blockers

Desccribe the mechanisms for alpha-antagonist on hypertesion (cycole)

Describe the mechanisms for beta blockers on hypertension (cycle)

What are some of the trends in the data for hypertension in marginalized communities

1. Lesbian and bisexual women are shown to display more cortisol than heterosexual women 

2. Gay and bisexual mena re shown to display less cortisol then heterosexual men 

What are some other ways to manage bp and how

1. Exercise: mormalizes bp through enhanced parasympathetic tone and baroreflex normality 

2. Access to counseling, cognitive behavioral thray 

3. Effective primar medical care- getting diagnosed without bias and worry

Public health interventions: describe the casual continuum (negative)

Describe the individual level interveition theory: healht velivf model

How much exercise is resccomended a day for an individual

18-65 eyeasr should participate in  moderate activity for atl 30 minutes fo 5 days a week

What are trends in exerfise in the untied states

1. As of 2020 24.4% of us meet the 2018 acsm a guidelines 

2. Hispanic men and non hispanic black women were at least likely to meet these guidelines

3. Queer americans reprot higher rates of fear of physical activity due to concerns of discrimination

How can exercise be benificial to ones health and what mechanisms are used

1. It icreases o2 demand by 15-25 percent

2. Increase delervery driven by 

   1. Incrased co

   2. Redistribution of BF

   3. Inactive organs - working skeletal muscle

Waht are some of the integratvie response of map duing aerobic exercise

1. Map = co x tpr 

   1. Tpr decreaeses during full body aerobic exercises, what sustains the increase in ma 

      1. Increases in co (cognitive output)

how do negative feed back loops impact bloodpressure during exercise: what is under the negative feedback loop section

What are the autonmic adaptations of exercises

1. Altered central (brain) integration/ controller (feedforward and feedback)

2. Set point and operating point shifts 

   1. Decreasing blood pressure and chronic straining 

3. Accuracy of feed forward (expected) controller 

   1. Icnreased model accuracy

      1. Improved hr response 

Feedforward (Central Command)

• When: Before & at onset of exercise

• Trigger: Brain → motor cortex

• Mechanism: ↑ sympathetic activity, ↓ parasympathetic

• Effect on BP: Rapid ↑ systolic BP (via ↑ HR & CO)

• Purpose: Anticipates exercise demands

🔄 Feedback (Peripheral Reflexes)

• When: During exercise

• Trigger: Working muscles & blood vessels

• Mechanisms:

  • Muscle metaboreflex (metabolites: H⁺, CO₂, lactate)

  • Mechanoreceptors (muscle stretch)

  • Baroreceptor resetting

• Effect on BP: Maintains / fine-tunes BP, prevents hypotension

• Purpose: Matches BP to actual exercise intensity

Key idea:

How is bloodflow redistributed during exercise

1. At rest bloood flow to skeletal muscles is 15-20 percent. During exercise its 80-85% (simulatenous with an increase in sympathetic tone seen during exercises)

What are some of the acute autonomic adaptations to exercise aerobic

What is and whate drive functional sympaholsis. What are the molecules that allow for vasodialation

1. Sympathetic transduction is not linear 

2. Signaling molecules such as ATP, ADO, H+, K+, and NO resulting in skeletal muscle vasodielation

3. Vasoconstrictiong signals from the sns are blunted = vasodialtion of arteriols feeding skeletal muscles (fine tooned) supply = demand

also leads into a long term decrease in systematic blood pressure and diastoli

c pressure

What is msna and What is the effect of MSNA following exercise training (muscle symatheitc nerve activity)

• associated with CVD risk and elevated in cv-related disorders

• independant predictor of poor prognosis and mortality

• if meeting exercise guildlines reduces mortalkit = modulaiton of msna tracks with exercise

wha tis it

• A measure of sympathetic nervous system outflow to skeletal muscle blood vessels

What it does:

• Causes vasoconstriction in skeletal muscle arterioles

• Helps regulate blood pressure and vascular resistance

Effect of Exercise Training on MSNA:

• ↓ Resting MSNA

• ↓ Sympathetic vasoconstrictor tone

• Improved autonomic balance (↓ sympathetic, ↑ parasympathetic influence)

Mechanisms:

• Improved arterial baroreflex sensitivity

• Reduced central sympathetic outflow

• Improved vascular function and endothelial health

• Reduced reliance on the muscle metaboreflex at a given workload

Functional Outcomes:

• ↓ Resting blood pressure

• ↓ Peripheral resistance

• More efficient BP regulation during exercise

• Especially beneficial in hypertension, aging, and heart failure

One-liner to remember:
👉 Exercise training quiets the sympathetic nervous system at rest.

Why do hepef pattens appear to to be

hfpef = the lv of the heart becomes stiff and cant relax properly to fill with blood

it pumps mrore than 50 percent = blood back up

= not enough blood for functional sympatholisis

What are some of the changes follwing chronic lv adaptations to long term aerobic exercise

1. ollowing aerobic exercise, the LF exeprinces greater edv and mass 

2. Increased preload and cardiac load during exercise initiate eccentric hypertrophy 

   1. Decreased resting co 

   2. Increased working co 

3. At rest and submaximal exercise, HR decreases 

   1. Downregulation of beta andregenic receptors

What is the difference between pysiologic and pathologic hypertrophy

• Physiological hypertrophy (like an athlete's heart) is a beneficial, adaptive heart enlargement from normal stress (exercise, pregnancy), resulting in normal/enhanced function, normal structure (no fibrosis), and reversible changes. Pathological hypertrophy (from hypertension, disease) is a maladaptive response, causing thickened walls, chamber shrinkage, impaired pumping (leading to heart failure), fibrosis, inflammation, and cell death, often irreversible. The key difference is function: Physiological = enhanced; Pathological = failing

Physiological hypertrophy = exxentric hypertrophy but the chamber space increases in proportion to increased musculature

pathological stimuli

concentri (hfpef)- hpertrophy = reduces lv space

eccentric hypertrophy = prolapse of left ventrical (hfref)

What happens during maximal exercise

the heart’s oxygen consumption increases by 10 fold to increse damand

1. The athletic heart describes thea daptationi to this increased demand

   1. Cardiac hypertrophy without proliferation of cardiomyocites

   2. Camber size is unaffected

   3. Increased mitochondrial energy production

2. Pathological hypertrophy is serve remodeling that devolves into hf and dysfunction

What are some of the chronic LV adaptations to aerobic exrecise, venous return to the heart increases? What alters the frank starling mechanism

1. The frank starling effect

   1. Skeletal muscle pump 

   2. Respiratory pump 

   3. Venoconstriction

2. This resuutls in volume overload which increases relative wall thickens (relative to chambers ize)

How does hypertension-induced pathological hypertrophy differ from adaptive (physiological) cardiac hypertrophy?

Hypertension-Induced Pathological Hypertrophy

• Cause: Chronic ↑ afterload (long-standing HTN)

• Duration: Chronic increase in cardiac demand

• Geometry: Concentric hypertrophy → may progress to dilated cardiomyopathy

• Cellular changes:

  • Myocyte thickening with fibrosis

  • Altered gene expression

• Reversibility: Not fully reversible

• Outcome: Impaired relaxation, ↓ compliance, risk of HF

---

Adaptive (Physiological) Hypertrophy

• Cause: Temporary or intermittent ↑ cardiac demand (e.g., exercise)

• Duration: Short-term / training-related

• Geometry: Proportional chamber & wall growth

• Cellular changes:

  • Minimal/no fibrosis

  • Normal cellular architecture

• Reversibility: Fully reversible

• Outcome: Maintained or improved cardiac function

How do chronic pathological vs physiological cardiac hypertrophy differ at the gene-regulation level?

---

Pathological Hypertrophy (e.g., HTN, Aortic Banding)

• Trigger: Chronic pressure overload

• Gene regulation: Reactivation of fetal gene program

  • ↑ ANP (atrial natriuretic peptide)

  • ↑ BNP (B-type natriuretic peptide)

  • ↑ β-myosin heavy chain (β-MHC) (fetal isoform)

• Metabolism:

  • ↓ fatty acid oxidation (FAO)

  • ↑ glucose metabolism

• Cellular outcome:

  • Fibrosis

  • Reduced efficiency and contractile dysfunction

• Key evidence:

  • Aortic banding induces this fetal gene activation

---

Physiological Hypertrophy (Exercise Training)

• Trigger: Intermittent, adaptive ↑ cardiac demand

• Gene regulation: No fetal gene reactivation

  • ANP/BNP not pathologically elevated

  • No ↑ β-MHC

• Metabolism:

  • ↑ fatty acid oxidation (FAO)

• Cellular outcome:

  • Normal structure

  • Preserved or enhanced function

• Key evidence:

  • Swimming alone or swimming + aortic banding prevents fetal gene activation

---

Bottom line:
👉 Pathological hypertrophy reverts to a fetal gene + glucose-dependent state
👉 Physiological hypertrophy maintains adult gene expression + FAO dominance

What are some chronic mitochondiral adaptations to exercise

1. Mitochondrial biogenic adaptation following exercises decreased in disease sates

2. Likely follow similar adatations as seen in skeletal muscle 

   1. Upregulation of citrate synthase 

   2. Increased cardolin levels

   3. Etc complex activity (limited by nDNA and mtDNA)

   4. mtDNA copy number (respond to deconditioning)

3. Keay regulator in cardiac and SKMSC - peroxisome-activated receptors gama coactivator 1 alpha (pgc1-alha)

   1. Try to understand knock dowon models

      

1. What are teh long term adaptations to exercise

1. Aerobic training: increased heart diameter

2. Increased flow mediated dilation

3. Improves sympatholica bility

4. Co increases = bloodflow increases = redistrbutes to skeletal muscles = increased shearing forces = enos activation = enhanced no production = begf = arterioal growth = enlargement 

1. What are some of the interactions of hemodynamic stimuli during exercise

1. Increased flow induce EC proliferation

2. Increased pp and distensitibilty arteries result in cynical cercumfrential strain

3. Decreased intracellular ca2+ despite increased influx

4. Increased slow release from the sr

5. Exercise activates kv channels

6. Ec reorganize perpendicular to force vectors = matrix and gf modulation

1. What are some of the chronic vascular adaptations

1. Increased hr and sbp iniduce circumfrential strain on the aorta parealleed with peak flow

2. Strain activates endothelium independent vasodiletory pathways 

   1. Enos

   2. Edhf

3. Chronically elevated BP: ROS+ adheaasion molecules >> enos 

What are the general chornic CV adapatatoins fo rthe following locations: endothelial function, autonomic balance, vascular remodeling, and cardiac preconditioning

How many people ar eliing with heart faleure in the us today

1. Over 6million with a 46% increase

What are the symptoms of heart failerue

1. Heart is unable to supply adequate blood flow to peripheral tissues/ organs or is unable to do so only at elevated fillign pressures 

2. Most commonly includes the left ventricle

3. Mild heart failure initially resents as reduced exercise capacity and the development of shortness of breath (exteritional dyspnea

   1. Sever forms patients present dysnpea at rest 

   2. Patitents will likey have a significant pulmoary or systemic edima ina more sever form 

What are the intrinsic causes of heart faileure: note there ar 6

Intrinsic causes

1. Coronary artery disease (CAD) * is the most common

   1. Reduces blood flow/O2 to the heart

2. Myocardial infarction *very common 

   1. Incrased demands lead to functional changes

3. Valvular disease and congetial defects

4. Cardiomyothopies (intrinsic disease of the myocardium)

   1. Bacterial, viral, alcohol induced unknon origin (idiopathic)

1. Intrinsic causes continued

   1. Ineffecve or noniffective myocardis

      1. Inflammation of the myocardium

   2. Chronic arrhythmias 

      

What are teh different types of cariomyoatheis

1. Dialated cardiomyopath

   1. Results in valvar dilation

2. Hypertrophic cardiomyophphy

   1. Reductuction in in chamber space in the left ventricle

What are the extrinsic causes of heart failure (hit there are 4)

1. Sustained elevations in afterload (uncontroled in hypertension)

2. Increased stroke volume

   1. Volume load (too much pree load) = arterioul venous shunts

3. Increased body demands

   1. High output failure 

      1. Thyrotoxiosis - an excess of thyroid hormone in the body 

      2. Pregnancy ‘

What is the differene between HFpEF and HFrEF

1. HFrEF (when the heart) (systolic faliure)

2. s main pumping chanmber. becomes weak and cant squeese hard enough to sufficently pump sufficient blood tho the body (less than 40%)

   1. Result from impaired ability of the heart muscle to contract = reduced sv and co

   2. Caused by changes in cellular signal transduction mechanism s and excitation-contraction coupling that impair ionotrypy

      1. Causes a downward shift in frank starling curve

         

3. HFpef (diastolic falirue) (heart failure with preserve ejection fraciton, condition where the heart bcomes too stiff and cant ill properly but ejection fraction is still mroe than 50%

   1. casuses reudced sv and co

4. Caused by either:

    Decreased ventricular compliance

    Most commonly ventricular hypertrophy

    Impaired relaxation (decreased lusitropy)

    Other causes:

    Hypertrophic cardiomyopathy

    Normal age-related changes to cardiac structure

    Type 2 Diabetes

What is the effect of hfref on the frank straling curve and preload

increase in preload to make way for the lack in blood = activates frank starlign to make up for loss of ionotorphy

• no compensary increase = decline in sv would be creater for a loss of ionotrophy

• the heart will not be able to pump efficenlty and be exhusted if this persist since the sarcomeres will be pulled to its max leigth

the lv dialates = more sarcomeres in serices = more compliace = more filling without increases in pressu re

draw the frank starling curve for hfref

Draw out the frnak starling curve for HFpef. how does that impact sv

• dpending upon the relative change in sv and edsv the ejection fraction might not chnange = ejection fraction is only useful as an indicator of systolic falieure

elevated diastolic pressures = pulminary edima (increased afterload)

peerhiperal edima and abodminal sceites with r ventricular flaure

Draw out the frank starling curve for both systolic and diastolic failure

What is congenstion and what are the signs of congesion (hint there are 5)

definitions: chronic condition where the heart muscle weakens and can't pump enough blood to meet the body's needs, causing blood and fluid to back up (congestion) in the lungs

signs:

1. Dyspnea (exertional → resting):
   Shortness of breath caused by fluid congestion in the lungs; it first appears during physical activity and, as congestion worsens, occurs even at rest.

2. Orthopnea:
   Shortness of breath when lying flat due to increased venous return and pulmonary congestion; relieved by sitting up or using multiple pillows.

3. Cough:
   Often a dry or frothy cough caused by pulmonary congestion and fluid accumulation irritating the airways.

4. Peripheral edema (pitting edema):
   Swelling of the lower extremities due to venous congestion and fluid retention; pressing on the swollen area leaves a temporary indentation.

5. Paroxysmal nocturnal dyspnea (PND):
   Sudden episodes of severe shortness of breath at night caused by redistribution of fluid to the lungs during sleep, forcing the person to wake up gasping for air.

What are some of the comensary mechnanisms in heart faileure

Goal: icnreas MAP

• symathetic activity is increased

  • barroreflex reseting

• increased fluid retention

  • increased RAAs activation

  • increaed ADH release

• increaed catechlamine release

• arterial and venous vaso constriction

What are ways to treat hf and what are the appraches and goals 3 and 4

3 primary goals of treatment:

1. Treat symptoms of edema & dyspnea

2. Improve CV function & exercise capacity

3. Reduce mortality

 4 approaches to treatment

1. Reduce venous pressure – reduce blood volume & vasodilate

2. Reduce afterload - vasodilate

3. Increase ventricular inotropy – inotropic agents

4. Use beta-blockers…? – reduce mortality

 Unsure of the mechanisms of how this is effective

5. Angiotensin receptor-neprilysin inhibitor (ARNI)

Waht are sglt2 inhibitors

• What they are:
  Medications originally developed for diabetes that block the sodium–glucose cotransporter-2 (SGLT2) in the kidneys, increasing glucose and sodium excretion in the urine.

• Use in HF:
  Reduce hospitalization and mortality in heart failure (both HFrEF and HFpEF), even in patients without diabetes, by decreasing fluid congestion, lowering preload/afterload, and improving cardiac and renal outcomes.

Examples include dapagliflozin and empagliflozin.

What are some of the fucntions of mitochondria and what are functional,intermediate, and dysfuctional

1. Functional

   1. Atp production

   2. Growth and adaptation: biosynthesis, protein modification, mitochondrial nuclear communication

   3. thermogenisis

2. Intermediate

   1. Ca2+ transport: metabolic stimulation, stress response, ca2+ homeostasis

   2. ROS: oxidative stress, redox regulation, cell signaling 

3. Dysfunctional

   1. Inflammation: mtDNA or peptides ROS

   2. Cell death: mptp opening, cytochrome c relase, Energy deprivation

What are the fule and give ofs of mitchondria

1. Calories (fuel)

2. Gives off: thermal energy, molecular energ (atp) oxidants

3. The ehart consumes ~ 5600 l of oxygen and 6k of atp daily

What are th 13 oxidative phosphrilation subunits

1. 7 comple 1

2. 1 complex 3

3. 3 complex 4

4. 2 complex 5

1. 22 translate

2. 2 rrnas

how many copies of the mitochondrial DNA are in a single mitochondrion

a. 5 -10 copies

What is mitochondrial heteroplamsy

1. When a single cell contains a mixture of different mitochondrial DNA types usually in combinations with wild types 

2. 60 % of individuals in the population carry 

How are mitchondrial heteroplasmic varients inherited

1. Maternally (they are accuired) (male variants are rejected)

What genes encode oxidative hsphorilation

1. Nuclear and mitchondrial genes

do mitocondrial genetic varients play a role in cardiovascular idsese: what are some of the genetics of mitochondrial disae

1. 281 different mitochondrial games either nuclear are imlicated

2. 47% are varients of unknown significance

3. Heterognety within familes carryign the same pathologic variant 

   1. 33% of neonatal/pediactric disease onset

   2. 75% of adult disesse onset 

   3. Accumulation of pathologic mitochondrial DNA varient

• Mitochondrial heteroplasmy → energetic failure + oxidative stress

• Heart is especially vulnerable due to high ATP demand

• Disease appears once mutant mtDNA crosses a functional threshold

• Drives cardiomyopathy, heart failure, and progression with aging

One-liner to remember:
👉 Mitochondrial heteroplasmy compromises cardiac energy supply, pushing the heart toward failure when mutant mtDNA reaches a critical level.

Define mitochondrial heteroplasmy and its relationship to cardiovascular disease and aging.

• Mitochondrial Heteroplasmy is the state where a single cell contains a mixture of different mitochondrial DNA (mtDNA) types, including pathogenic variants alongside wild-type mtDNA

• The number of heteroplasmic variants increases with age in the heart (atrial appendage and left ventricle), suggesting implications for age-related CVD

• They have a higher risk than people who formerly smoked or never smoked at all age groups

1. Do mitochondrial genetic variants in teh general populatiosn associate with cardiovascular disease 

Mitochondrio haplogroups associate with cardiovascular diseases. Mitochondrial heteroplasmy → energetic failure + oxidative stress

• Heart is especially vulnerable due to high ATP demand

• Disease appears once mutant mtDNA crosses a functional threshold

• Drives cardiomyopathy, heart failure, and progression with aging

One-liner to remember:
👉 Mitochondrial heteroplasmy compromises cardiac energy supply, pushing the heart toward failure when mutant mtDNA reaches a critical level.

What are the specific

how are pluirpotent cells introduced

1. They do not reuqire the use of embryos

2. They are derived from donated skin/ blood ccells from a patient

3. Indefinelty self renewing 

4. Ability to become any cell type

5. Patients own genetic background

How does mitochondrial genetic variation in blood relate to that in the heart

1. Only 13% of heteroplasmic varients were shared between all tissues 

2. 50% were shared in the left ventricle and atrial appendage 

3. As you age there are more variants in the atrial appendage, left ventricle but less in the blood 

Are mitocondrial disease associated with cardiomyopathy

yes

what hapens when heteroplasmic varients accumulate in the body

they are assoicated with mitochondrial disease onset

What is the difference between heteroplasmic varients in the heart compared to the blood

1. Only 13% of heteroplasmic varients were shared between all tissues 

2. 50% were shared in the left ventricle and atrial appendage 

3. As you age there are more variants in the atrial appendage, left ventricle but less in the blood 

Describe the personalized medicine approach for studying mitochondrial genetic variants using iPSCs.

Reprogramming: Peripheral blood cells from a patient are reprogrammed into Induced Pluripotent Stem Cells (iPSCs). 2. Differentiation/Editing: The iPSCs (representing the patient's genetic background) are directed to differentiate into cardiomyocytes. Gene editing techniques may be applied to correct pathogenic nuclear DNA variants. 3. Phenotyping: These cells undergo deep molecular and functional phenotyping (e.g., contractility, OXPHOS activity) and are used for in vitro screening of drugs/drug combinations.

What is the influence of mitchondiral heteroplasmy in mitochondiral diseases and onset and aging

What is the differneeceb etwen cardiomyopathy and heat failuer

• Cardiomyopathy is a disease of the heart muscle that causes structural or functional abnormalities (e.g., dilated, hypertrophic, restrictive).

• Heart failure is a clinical syndrome where the heart cannot pump enough blood to meet the body’s needs, often resulting from cardiomyopathy or other heart diseases.

• Cardiomyopathy (CMP)

  1. Abnormal cardiac structure and function due to a specific etiologuy

  2. May be asymptomatic for a period of time before progressing to hf

  3. Specific strategies may be employed to attenuate the risks and clinical sequale of the underlying cardiomyopathy 

• Clinical diagnosis *heart faleure)

  1. Inablituy to maintain cardiac output to  meet perfusion and oxygenation requirement by tissues while maintaining normal filling pressure

  2. Standand therapies such as diuretics and guideline-directe medical therapy (GDMT) are applied- hgih lelved heart faieure assingemnts include heart fialure with reduced ejection fraction and preserved ejeciton fraction

How do we diagnose hf. congestion vs low perfusion (note the same approach is used for hfpef and hfref)

This approach classifies heart failure patients based on volume status (congestion) and cardiac output (perfusion) using bedside clinical findings.

The Two Axes

• Congestion: “Wet” (fluid overloaded) vs “Dry” (no congestion)

• Perfusion: “Warm” (adequate perfusion) vs “Cold” (poor perfusion)

Four Hemodynamic Profiles

1. Warm & Dry

   • Adequate perfusion, no congestion

   • Compensated HF (goal state)

2. Warm & Wet (most common)

   • Adequate perfusion with congestion

   • Symptoms: dyspnea, edema, crackles

   • Treat with diuretics ± vasodilators

3. Cold & Dry

   • Poor perfusion without congestion

   • Symptoms: fatigue, cool extremities, hypotension

   • Treat with fluids or inotropes

4. Cold & Wet (worst prognosis)

   • Poor perfusion and congestion

   • Symptoms: shock, severe dyspnea, edema

   • Treat with diuretics, inotropes, ± vasopressors

Why It’s Used

• Provides a rapid bedside assessment

• Guides treatment decisions

• Predicts prognosis

🧠 Quick memory aid:
*Wet = congestion; Cold = low output; Warm & Dry = winning combo.

What are teh ssteps to a jvp assesment

how would you clasify congesiton clinicaly using elevate pcwp and elevated rap

Pulmonary congestion (Left-sided congestion)

• Elevated PCWP (pulmonary capillary wedge pressure)

• Reflects increased left atrial pressure

• Clinical signs/symptoms:
  Dyspnea, orthopnea, paroxysmal nocturnal dyspnea, pulmonary crackles, cough

2. Systemic congestion (Right-sided congestion)

• Elevated RAP (right atrial pressure)

• Reflects increased systemic venous pressure

• Clinical signs/symptoms:
  Peripheral (pitting) edema, jugular venous distension (JVD), hepatomegaly, ascites

3. Biventricular congestion

• Elevated PCWP and elevated RAP

• Combined pulmonary and systemic congestion

• Clinical signs/symptoms:
  Dyspnea plus edema, JVD, ascites

🧠 Key takeaway:

• PCWP ↑ = lung (left-sided) congestion

• RAP ↑ = body (right-sided) congestion

Describe the valsava squre menuver in diagnosis. whata re teh steps. waht is the square

what is thesqare

•A ”positive square” has been shown in several studies to have excellent correlation with elevated PCWP (≥ 18 mmHg) (rho correlations 0.75-0.90)

•

• During normal Valsalva, BP falls then recovers

• In heart failure with high filling pressures, BP does not fall and instead stays elevated, producing a “square wave” arterial pressure tracing

•Applies to both HFpEF and HFrEF

What is the use of swan-gantz catherders

What it measures

• Right atrial pressure (RAP) → preload/systemic congestion

• Right ventricular pressure

• Pulmonary artery pressure (PAP)

• Pulmonary capillary wedge pressure (PCWP) → left atrial pressure / pulmonary congestion

• Cardiac output (thermodilution)

• Mixed venous oxygen saturation (SvO₂)

Clinical uses

• Diagnose and classify heart failure hemodynamic profiles

• Differentiate cardiogenic vs noncardiogenic shock

• Assess volume status and perfusion

• Evaluate pulmonary hypertension

• Guide therapy in severe or refractory HF

Relation to right heart catheterization

• Right heart catheterization is the procedure

• Swan–Ganz catheter is the tool used to perform it

• The catheter is advanced through the right atrium → right ventricle → pulmonary artery, allowing measurement of pressures along the way

what are the cardiac output calculations (fick and thermomodulation and what is its use

• Cardiac Output (CO):
  CO = Heart Rate × Stroke Volume

• Thermodilution (Swan–Ganz):
  CO is calculated by injecting cold saline into the right atrium and measuring the temperature change in the pulmonary artery; a smaller temperature change = higher CO, larger change = lower CO.

• Fick Equation:
  CO = O₂ consumption ÷ (arterial O₂ − venous O₂)
  Uses the difference between arterial and mixed venous oxygen content to calculate CO.

Key:

• Thermodilution → invasive, catheter-based

• Fick → based on oxygen delivery and consumption

if possible analize this case study. do they hae hf

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What are the teraputic methods for hfpef

• Diuretics:
  Mainstay for symptom relief by reducing volume overload and congestion

• SGLT2 inhibitors (dapagliflozin, empagliflozin):
  Reduce HF hospitalizations and mortality; benefit patients with or without diabetes

• Blood pressure control:
  Use ACE inhibitors, ARBs, or ARNI to reduce afterload and LV stiffness

• Mineralocorticoid receptor antagonists (MRAs):
  May reduce hospitalizations and improve symptoms in selected patients

• Rate and rhythm control (especially AF):
  Beta-blockers or nondihydropyridine CCBs to improve diastolic filling time

• Treat comorbidities:
  Manage hypertension, obesity, diabetes, sleep apnea, CAD

• Lifestyle interventions:
  Exercise training, sodium restriction, weight management

what are some of the theraputic methos for hfref

• ACE inhibitors / ARBs / ARNI (sacubitril/valsartan):
  Reduce mortality, hospitalization, and afterload

• Beta-blockers (e.g., carvedilol, metoprolol succinate):
  Improve survival, reduce arrhythmias, and improve remodeling

• Mineralocorticoid receptor antagonists (spironolactone, eplerenone):
  Reduce mortality and hospitalizations

• SGLT2 inhibitors (dapagliflozin, empagliflozin):
  Reduce hospitalizations and mortality, even in non-diabetic patients

• Diuretics:
  Symptomatic relief of congestion and edema

• Device therapy:

  • ICD: Prevent sudden cardiac death

  • CRT: For patients with wide QRS and LV dyssynchrony

• Lifestyle interventions:
  Sodium restriction, fluid management, exercise, weight control

• Advanced therapies:
  Heart transplant or LVAD in refractory HFrEF

What is the universial definition and classifcaiton of hf chart and undeerstand it. what is at risk, prehf, hf ,advanced. waht is its stages, what is its definition, how do you classify

What is the fuction of GABA on stress funcrioning and exrcises

it is an inhibitory neuro transmitter that reduces stress siganling by blockign the pvn in the hypothalmus = CRTH is not released from the. hypothalamus = stress hormones not produced

= helps calm the nervous system =

Does swimming induce gene activation changes? why or why not

the aerobic and anarobic properites of experices cancel eachother out = you seeno gene activation patters of fao or glucose metabolism

what is the use of PGC1 -alpha

used in the mitochondria = increase of FFA acid use and beta oxidation = more ATP use

What is the difference between mitochondrial energy use for pathologic adaptations and physiologic adaptaion

patholodic remodeling

• biogenisis, FAO

physilogic

• adaptive hypertrophy

• presered functioning

  • increased biogenesis, FAO