The Cardiovascular System

Dr Suzannah Phillips

Summary

Overview of structure and function

Common disorders of the CVS

– Cardiac Markers

– Clinical application of cardiac markers

Structure and Function

The cardiovasular system

Consists of the heart and blood vessels.

Function

– Transport mechanism:

oxygen

nutrients - glucose, electrolytes

antibodies / white blood cells to sites of infection

hormones

waste products of metabolism

heat

The Cardiac cycle

BP 120/80

The Circulatory System

The Capillary Bed

Arterial Structure

Venous Structure

Cardiovascular disorders

1. Cardiovascular disease

2. Coronary heart disease

3. Heart Failure

4. Hypertension

1. Cardiovascular Disease (CVD)

Atherosclerosis which effects arteries in the heart, brain and peripheral tissues.

Atherosclerosis – deposition of lipid and matrix protein in the

arterial wall (medium to large arteries)

– narrowing of the vessel lumen

– reduced blood supply

– Heart – causes coronary heart disease

– Brain – causes stroke

Atherosclerotic plaques

Steps by which smooth muscle cells (SMC) colonize the atherosclerotic plaque.

Hofnagel O , Robenek H Cardiovasc Res 2009;81:242-243

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Risk factors for CVD

Age Gender Race Family History Smoking Cholesterol Hypertension Obesity Diabetes Mellitus Low physical activity

Biochemical – Homocysteine

2. Coronary Heart Disease (CHD)

Failure of the coronary circulation to meet the demands of the heart (increased

demand/decreased supply)

Caused by:

– cardiovascular disease (coronary arterial disease, CAD)

– Vasospasm, anaemia, arrhythmias

Lack of oxygen - Ischaemia

Also called ischaemic heart disease (IHD)

Myocardial Infarction (MI)

End result of CHD

Prolonged ischaemia – cell death (necrosis)

May also get collagen scarring

Most commonly a result of CAD

CAD

Atherosclerosis in coronary arteries causing inadequate oxygen supply to the heart.

This leads to

1. Stable angina

2. Acute coronary syndrome (ACS)

Stable angina

– partial occlusion of cardiac artery

– unable to supply oxygen if increased demand (excerise, stress)

Acute coronary syndrome

Due to plaque rupture.

Causing:

1. Unstable angina

2. Myocardial infacrtion

Diagnosis of ACS and MI

1. ECG changes

2. Biochemical Cardiac Markers of CVD

Cardiac enzymes Myoglobin Troponins

Cardiac enzymes

1. ALT (alanine aminotransferase) liver, skeletal and cardiac muscle, kidney.

Cytoplasm of cells

Increased in plasma following circulatory failure, MI.

X10 URL

2. AST (aspartate aminotransferase) liver, skeletal and cardiac muscle, kidney.

Cytoplasm of cells

Increased in plasma following circulatory failure, MI.

X10 URL

Cardiac enzymes 3. LDH (Lactate dehydrogenase)

Wide tissue distribution.

Five isoforms LDH1 – LDH5. LDH1 – significant in MI

Measure total LDH

X10 URL

4. CK (Creatine Kinase) Skeletal and cardiac muscle, brain.

Dimer of two subunits M or B.

3 isoforms: MM (skeletal and cardiac), MB (35% of cardiac activity, 5% skeletal), BB (brain)

Measure CK and CK-MB (both raised in muscle damage)

Myoglobin

Present in all muscle

Haem protein – oxygen transport.

Found in cytoplasm

Troponins (Tn)

Three proteins: Troponin T – binds to tropomyosin Troponin I – inhibitor of ATPase Troponin C – binds calcium

Troponin T and I used as markers for cardiac damage (cardiac specific isoforms).

Troponin I more specific, skeletal troponin T isoforms cross react in cardiac Troponin T assay.

High sensitive assays (hsTnT / hsTnI) – lower detection limits

Detection time depends on:

Size Cellular location Plasma clearance

myoglobin

Cardiac marker

Starts to rise (hrs)

Time to peak value (hrs)

Duration of rise (days)

myoglobin 2-4 8-10 1

AST 6-8 24-48 3-4

LDH 12-24 48-72 7-12

CK-MB 2-6 18 1-2

Troponin 4-6 12-24 7-10 / 3-10

Cardiac Marker Detection in Serum

Use in the diagnosis of MI

1950 1960 1970 1980 1990 2000

AST in

AMI

Optimized

CK Assay

CK-MB

Monoclonal

Antibody cTnI in

AMI

Electrophoresis

for CK and LDH

LDH in

AMI

CK in

AMI

POC

Testing

CK-MB

Mass

Assay cTnI for Risk

Stratification

First

CK-MB

Assays

RIA for

Myoglobin

cTnT

in AMI

WHO definition of MI

Other causes of a raised troponin

Trauma Congestive heart failure–acute and chronic Hypertension Hypotension, often with arrhythmias Renal failure Critically ill patients, esp with diabetes Hypothyroidism Myocarditis Pulmonary embolism Sepsis Burns, esp if TBSA > 30% Amyloidosis Acute neurological disease, including CVA Rhabdomyolysis with cardiac injury Vital Exhaustion Polymyositis

3. Heart failure (HF / CHF)

Failure of heart output to meet demand.

Symptoms:

– SOB, fatigue, oedema

Causes:

– Cardiomyopathy

– Inflammation

– Valvular heart disease

– Ischaemic heart disease

Diagnosis of HF

Echocardiogram – gold standard

Markers of Heart Failure:

Brain natriuretic peptide (BNP)

BNP

• Natriuretic peptide secreted primarily from ventricules as a prohormone (proBNP).

• Immunoassays available for BNP and NT-proBNP

BNP

Increased in

– cardiac failure

– ventricular hypertrophy

Useful ‘rule-out’ test – echo referral

Negative result excludes heart failure.

Prognostic indicator in heart failure

4. Hypertension

BP >140/90 mmHg Risk factor CVD – CHD or stroke Essential hypertension – unknown cause Endocrine hypertension - Conn’s, Cushings,

phaeochromocytoma.

Biochemical markers: ― No specific biochemical markers for hypertension ― Diagnosing endocrine causes ― Management/monitoring treatment

― renal function ― electrolytes

The Respiratory System

Dr Suzannah Phillips

Summary

Overview of structure and function

Common disorders

Basic Structure

Function:

1. Gas exchange: CO2 exchanged for O2 (ventilation)

2. Acid-base regulation

Regulation of respiration: • Respiratory centre in medulla – controls rate and depth of breathing.

• Driven by CO2 concentration (PCO2). Maintained within tight limits.

Arterial blood gases (ABG)

Blood gases: PCO2 and PO2 – gas exchange

Acid base: pH, PCO2, HCO3 – acid base balance

Monitoring lung function

PCO2 levels:

Determined by ventilation in the aveolar

Areas of good ventilation in the lung are able to compensate for any aveoli with poor ventilation by hyperventilation

PO2 levels:

Determined by Ventilation in the aveolar Concentration of O2 in the inspired air Perfusion of the lung

Hypercapnia ↑PCO2 Hypocapnia ↓PCO2

Disorders of Respiration

Hypoxaemia – ↓O2 in the blood

TYPE 1

• adequate ventilation • defective oxygenation • hypoxaemia

TYPE 2 • inadequate ventilation • hypercapnia and hypoxaemia

Hyperventilation • hypocapnia

PO2 PCO2

Type 1 ↓ N

Type 2 ↓ ↑

Hyperventilation N ↓

Common Causes

Type 1:

– Pneumonia, PE, COPD, ARDS

Type 2:

– COPD, exhaustion, opiates

Hyperventilation

– Anxiety, salicylate, hypoxaemia

Chronic Obstructive Pulmonary Disease • emphysema • bronchitis

Other respiratory disorders:

1. Cystic fibrosis

Part of the UK Newborn Screening programme

Immuno-Reactive Trypsin (IRT)

2. A1AT deficiency

No inhibition of neutrophil elastase - emphysema

A1AT

3. Carbon monoxide poisoning

CO has higher affinity for Hb than O2 - hypoaemia

Carboxyhaemoglobin (COHb)

Learning points!

Basic understanding of CVD and know common risk factors

Understand CHD and its consequences e.g. ACS Know the role of cardiac markers in CHD and

their limitations Know the role of cardiac markers in HF Understand the basic physiology of the lung Understand the role of ABG in monitoring lung

function. Know the common causes of respiratory

dysfunction