SCOFYL

GROSS ANATOMY
Cledera, Thurl Hugh C.

Borders of the Heart

Valve Areas

Chambers of the Heart

Cardiac Vasculature

Cardiac Innervation

Conducting System of the Heart

Cardiac Pain

Radiographic Anatomy of the Heart

HEART SOUNDS
Choa, Jay Ebethe

Heart sounds
Noises generated by beating heart

Turbulence created when the valves snap shut

Heart sounds

Primary heart sounds

Normal heart sounds

Associated with heart valves closing, causing changes in

blood flow

Primary heart sounds

S1 lub of lub-dub M1 and T1 Sudden block of reverse blood flow due to closure of the atrioventricular valves at the beginning of ventricular contraction, or systole

Primary heart sounds

S2 dub of lub-dub A2 and P2 Sudden block of reversing blood flow due to closure of the semilunar valves at the end of ventricular systole and the beginning of ventricular diastole Splitting normally occurs during inspiration

Extra heart sounds

S3 Protodiastolic gallop, ventricular gallop lub-dub-ta Beginning of diastole after S2 and is lower in pitch than S1 or S2 Benign in youth, some trained athletes, and sometimes in pregnancy Best heard with the bell side of the stethoscope

Extra heart sounds

S4 Presystolic gallop or atrial gallop Produced by the sound of blood being forced into a stiff or hypertrophic ventricle ta-lub-dub Sign of a pathologic state, usually a failing or hypertrophic left ventricle, as in systemic hypertension, severe valvular aortic stenosis, and hypertrophic cardiomyopathy

Extra heart sounds

S4 Best heard at the cardiac apex with the patient in the left lateral decubitus position and holding his breath Atrial contraction must be present for production of an S4 Absent in atrial fibrillation and in other rhythms in which atrial contraction does not precede ventricular contraction

Murmurs
Produced as a result of turbulent flow of blood strong

enough to produce audible noise Usually heard as whooshing sounds

Murmurs

Murmurs

Systolic heart murmurs

Heart murmurs heard during systole

Can be classified by when the murmur begins and ends,

between S1 and S2 Many involve stenosis of the semilunar valves or regurgitation of the atrioventricular valves

Systolic heart murmurs in MI

Late systolic

Papillary muscle dysfunction

Mild mitral regurgitation

Starlings hypothesis
Chianpain, Carl Joshua M.

Starlings hypothesis
The fluid movement due to filtration across the wall of a

capillary is dependent on the balance between the hydrostatic pressure gradient and the oncotic pressure gradient across the capillary.

Starlings Equation
Qf = k[(Pc + i) - (Pi + p)]
Where: Qf= fluid movement Pc= capillary hydrostatic pressure Pi= interstitial fluid hydrostatic pressure p= plasma oncotic pressure i= interstitial oncotic pressure k= filtration constant for the capillary membrane

Example
Qf = k[(Pc + i) - (Pi + p)]

http://en.wikipedia.org/wiki/Starling_equation

PATHOPHYSIOLOGY
Chua, Nicole Allyson A.

Inhalation of cigarette smoke Aromatic products formed from tobacco combustion Inhibition of tetrahydrobiopterin

Nicotine absorption Systemic release of catecholamines Binding to alpha-1 adrenergic receptors on vascular smooth muscle

Carbon monoxide absorption Formation of carboxyHgb Reduction of O2carrying capacity of RBC Compensatory erythrocytosis

Nitric oxide absorption Initiation of free radical reactions NO catalyzes oxidation of LDL

Decreased production of nitric oxide synthase

Production of H2O2

Smooth muscle contraction and consequent vasoconstriction

Increased viscosity of blood

Diminished nitric oxide production

Impaired blood flow to capillaries

Oxidative vascular endothelial injury

Non-Modifiable Risk Factors Age > 40 y/o (58 y/o) Gender (Male)

Modifiable Risk Factors (+) history of cigarette smoking (+) HPN (for 5 years) (+) hyperlipidemia, hypercholesterolemia

Damage to endothelial lining of blood vessels

Inflammatory processes occur

Production of chemoattractant cytokines

Recruitment of leukocytes to endothelial surface

Firm adhesion mediated by ICAM-1 and VCAM-1 (protein adhesion molecules in endothelium)

Diminished endothelial nitric oxide production

Firm adhesion mediated by ICAM-1 and VCAM-1 (protein adhesion molecules in endothelium) Rapid increase in expression of ICAM-1 and VCAM-1 Activation of endothelial cells More leukocyte adhesion Transmigration of monocytes/ macrophages into arterial intima More extensive arterial injury Endothelial denudation

Endothelial denudation Exposure of collagen of subendothelial matrix Platelet adhesion and aggregation Aggregated platelets secrete platelet-derived growth factor (PDGF) Transmigration of smooth muscle cells from the tunica media into the intima Proliferation and elaboration of a rich and complex extracellular matrix

Secretion of matrix metalloproteinase

Formation of fibrous cap

Recruitment of leukocytes to endothelial surface Macrophages engulf oxidized LDL Formation of foam cells More cytokine release Secretion of matrix metalloproteinase Promotion of cell death Cell death (apoptosis) occurs in the established lesion

Deposition into the intima (fatty streak)

Formation of lipid-rich necrotic core

Formation of fibrous cap

Proteoglycans of extracellular matrix bind to circulating lipoproteins Prolonged residence of lipoproteins in the intima Increased susceptibility to oxidative modification and glycation Sustained inflammatory response Progression of atheromatous lesion

Progression of atheromatous lesion Scar tissue formation Calcification

Formation of lipid-rich necrotic core

Formation of fibrous atheromatous plaque

Endothelial Cell Injury

Migration of Inflammatory Cells

Accumulation of Lipids and Proliferation of SMCs

Plaque Structure

Formation of fibrous atheromatous plaque

Increase in size of atheromatous lesion Encroach on the lumen of artery Blood vessel occlusion Slowing and turbulence of blood flow

Sustained inflammation
Plaque instability, ulceration and rupture

Plaque instability, ulceration and rupture Exposure of collagen of subendothelial matrix Tissue factor expression initiates extrinsic coagulation pathway

Platelet aggregation Local generation of thrombin and deposition of fibrin

Thrombus formation

Occlusion of small arteries (e.g. coronary arteries)

Occlusion of small arteries (e.g. coronary arteries) Reduced blood flow to the heart Disparity in myocardial oxygen supply and demand Myocardial tissue necrosis Damage to heart muscle (+) Troponin T, borderline CKMB (3 mcg/L)

(+) chest pain, radiating to left arm

Gradual replacement of myocardial cells to scar tissue

Scar tissues in the areas of the myocardium lack ability to contract and initiate or conduct action potentials (+) hypokinetic anteroseptal wall on 2D-ECHO

Scar tissues in the areas of the myocardium lack ability to contract and initiate or conduct action potentials

Limited distensibility of ventricular wall

Low compliance

Left ventricle relaxes more slowly Rapid filling of ventricle occurs (+) S3 heart sound over apex of the heart

Damage to heart muscle Reduced ability of actin and myosin to form cross-bridges Reduced myocardial contractility Increased end-systolic volume (ESV) Reduced stroke volume

Low ejection fraction (40%)

Loss of cardiac reserve

Reduced cardiac output Sympathetic stimulation as compensation

(+) easy fatigability

Sympathetic stimulation as compensation Release of catecholamines Stimulation of the beta-1 receptors of the myocardium (+) tachycardia (PR=102 bpm)

Decreased renal perfusion

Stimulation of alpha-1 receptors of vascular smooth muscle Vascular smooth muscle contraction Peripheral vasoconstriction

Increased cardiac output

Increased systemic vascular resistance (+) elevated BP (140/90)

Decreased renal perfusion Renin secretion Conversion of angiotensin I to angiotensin II Stimulate posterior pituitary gland to release anti-diuretic hormone (ADH/ vasopressin) Peripheral vasoconstriction Increased systemic vascular resistance (+) elevated BP (140/90) Increased afterload

Stimulate adrenal cortex to release aldosterone Tubular resorption of Na+ and H2O

Increased intravascular fluid

Increased preload Increased cardiac workload

Increased cardiac workload

Overloading

(+) dilated left ventricle on 2D-ECHO (+) cardiomegaly on chest x-ray (+) wide and deep Q waves in V1-V4 (+) tall R waves in V5-V6 (+) PMI at 6th ICS

Heart muscle exhaustion

Reduced myocardial contractility

Improvement on myocardial contractility to some extent

LEFT-SIDED HEART FAILURE Increased end-systolic volume (ESV) Pulmonary edema/ congestion (+) accentuated pulmonary vascular markings on chest x-ray (+) wheezes and crackles at bases of both lungs (+) shortness of breath (+) orthopnea (+) paroxysmal nocturnal dyspnea

Backflow to left atrium then to pulmonary circulation

Accumulation of fluid in lung tissue

ELECTROCARDIOGRAPHY
Ciocon, Stephen Lowell

Electrocardiography
Interpretation of the electrical activity of the heart over a

period of time, as detected by electrodes attached to the surface of the skin and recorded by a device external to the body The recording produced by this noninvasive procedure is termed an electrocardiogram

 ECG is used to measure the rate and regularity of

heartbeats, as well as the size and position of the chambers, the presence of any damage to the heart, and the effects of drugs or devices used to regulate the heart

 The ECG device detects and amplifies the tiny electrical

changes on the skin that are caused when the heart muscle depolarizes during each heartbeat This is detected as tiny rises and falls in the voltage between two electrodes placed either side of the heart which is displayed as a wavy line either on a screen or on paper

Leads and Electrodes

Ten electrodes are used for a 12-lead ECG.

Limb electrodes

Chest electrodes/Precordial leads

 Usually, more than two electrodes are used, and they can

be combined into a number of pairs (For example: left arm (LA), right arm (RA) and left leg (LL) electrodes form the three pairs LA+RA, LA+LL, and RA+LL). The output from each pair is known as a lead.

 word lead may refer to the tracing of

the voltage difference between two of the electrodes and is what is actually produced by the ECG recorder Lead I is the voltage between the (positive) left arm (LA) electrode and right arm (RA) electrode: Lead II is the voltage between the (positive) left leg (LL) electrode and the right arm (RA) electrode: Lead III is the voltage between the (positive) left leg (LL) electrode and the left arm (LA) electrode:

Hexaxial reference system

Generation of ECG tracing

EVENT Atrial depolarization Septal depolarization Apical Depolarization Ventricular Freewall Depolarization Posterobasal depolarization Ventricular Repolarization

DIRECTION ILP HRA ILA ILP SRA SRA

Left Ventricular Hypertrophy

Left ventricular hypertrophy (LVH) is a hallmark of chronic

pressure or volume overload of the left ventricle and is associated with a markedly elevated risk of cardiovascular morbidity and mortality. LVH may be characterized by increased wall thickness (concentric LVH), increased chamber volume (eccentric LVH) or both

 When the myocardium is hypertrophied, there is a

larger mass of myocardium for electrical activation to pass through and thus the amplitude of the QRS complex (ventricular depolarization) is increased. Likewise, when the myocardium as abnormally thickened and electrical activity takes longer to traverse throughout the whole heart, thus the duration of the QRS complex may be widened.

 LVH results in increased R wave amplitude in the left-

sided ECG leads (I, aVL and V4-6) and increased S wave depth in the right-sided leads (III, aVR, V1-3). The thickened LV wall leads to prolonged depolarisation (increased R wave peak time) and delayed repolarisation (ST and T-wave abnormalities) in the lateral leads.

ECG criteria for LVH

The Sokolow-Lyon index: S in V1 + R in V5 or V6 (whichever is larger) 35 mm ( 7 large squares) R in aVL 11 mm The Cornell voltage criteria: S in V3 + R in aVL > 28 mm (men) S in V3 + R in aVL > 20 mm (women)

 Romhilt-Estes LVH Point Score System: If score = 4, then LVH present with 30-54% sensitivity. If score > 5, then LVH is present with 83-97% specificity. Amplitude of largest R or S in limb leads >20 mm (3) Amplitude of S in V1 or V2 > 30 mm (3) Amplitude of R in V5 or V6 > 30 mm (3) ST and T wave changes opposite QRS without digoxin (3) ST and T wave changes opposite QRS with digoxin (1) Left Atrial Enlargement (3)

Left Axis Deviation (2)

QRS duration > 90 milliseconds (1) Intrinsicoid deflection in V5 or V6 > 50 millisecond (1)

 Other voltage-based criteria for LVH include: Lead I: R wave > 14 mm Lead aVR: S wave > 15 mm Lead aVL: R wave > 12 mm Lead aVF: R wave > 21 mm Lead V5: R wave > 26 mm Lead V6: R wave > 20 m

LIPID METABOLISM
Chong, Jose Marion Jan B.

TAG Biosynthesis

Figure 1. TAG biosynthesis

TAG Biosynthesis
Next steps: Phosphatidic acid phosphatase to produce 1,2-diacylglycerol Acyl transferase to produce TAG

Cholesterol Biosynthesis

Figure 2. Cholesterol biosynthesis I

Cholesterol Biosynthesis

Figure 3. Cholesterol biosynthesis II

Cholesterol Biosynthesis

Figure 4. Cholesterol biosynthesis III

Cholesterol Biosynthesis

Figure 5. Cholesterol biosynthesis IV

Cholesterol Degradation
Cholesterol and other steroids cannot be degraded into

smaller molecules. The most important mechanism for this is the synthesis of bile acids in the liver.

Lipoprotein Metabolism
Four major lipoprotein classes: High density lipoprotein Very low density lipoprotein Low density lipoprotein Chylomicrons

Lipoprotein Metabolism
Table 1. Major apolipoproteins

Chylomicrons
Produced in the intestinal mucosal cells and secreted into

the lacteals of the lymphatic system Main sites of metabolism: adipose tissues and skeletal muscles. Contains: apoprotein B48, and receive apoprotein E and apoprotein C-II (from HDL)

Very Low Density Lipoproteins

Produced in the liver and major carrier of endogenously

synthesized TAG Contains apo B-100 and receives apo C-II and apo E from HDL

Low Density Lipoproteins

Cholesterol rich lipoproteins containing apo B100

Transports cholesterol from the liver to peripheral tissues

High Density Lipoproteins

Synthesized in the liver

Main transporter of cholesterol from the peripheral tissues

to the liver Circulating reservoirs of apo C-II, apo E and apo A-I Contains cholesterol ester transfer protein (CETP)

Clinical Applications
Hyperlipidemia

atherosclerosis Oxidized LDL monocyte foam cells growth factors and cytokines Atherosclerotic plaques platelet adhesion and aggregation activated platelets secrete cytokines thrombus formation occlusion of affected blood vessels

LIPID PROFILE
Cielo, Angela V.

1. DIFFERENTIATE AND CLASSIFY THE GENERAL CLASSES OF HYPERLIPEDEMIA

Type

Plasma Lipid
Chole TAG LDL Chylo (beta)
Inc

Lipoprotein
VLDL (pre-beta)
Inc

Principal Lipoprotein Abnormality Increased

Chylomicrons

Type I (Familial
LPP Lipase Deficiency)

Type II-A (Familial

Hypercholesterolemi a)

Inc

Inc

B-lipoprotein

Type II-B Mixed

Defect (Familial Combined Hyperlipidemia)

Inc

Inc

Inc

Inc

B-lipoprotein and pre-B

Type III (Familial

Dysbetalipoproteine mia)

Inc

Inc

Inc

Broad pre-beta band

Type IV (Familial
Hypertriglycedemia)

Inc

Inc

Pre-beta

Type V

N or Inc

Inc

Inc

Inc

Chylomicrons and prebeta

Patients Lipid Profile

RESULT NORMAL VALUES

Total Cholesterol = 6.8

mmol/L Triglyceride = 3.5 mmol/L LDL = 4.93 mmol/L HDL = 0.27 mmo/L

3.64-5.2 mmol/L <1.69 mmol/L 2.6 3.34 mmol/L >1.56 mmol/L

Type

Plasma Lipid Chole TAG LDL Chylo (beta)

Inc

Lipoprotein VLDL (pre-beta)

Inc

Principal Lipoprotein Abnormality Increased

Chylomicrons

Type I (Familial
LPP Lipase Deficiency)

Type II-A (Familial

Hypercholesterolemi a)

Inc

Inc

B-lipoprotein

Type II-B Mixed

Defect (Familial Combined Hyperlipidemia)

Inc Inc Inc Inc

Inc Inc Inc

Blipoprotein and pre-B

Broad pre-beta band

Type III (Familial

Dysbetalipoproteine mia)

Type IV (Familial
Hypertriglycedemia)

Inc

Inc

Pre-beta

Type V

N or

Inc

Inc

Inc

Chylomicrons and pre-

4. Explain why LDL is referred to as the bad cholesterol and HDL the good cholesterol

High Density Lipoprotein / Alpha Lipoprotein (HDL)

Smallest but most dense lipoprotein

Produced by the liver and intestine

Transports excess cholesterol from the tissues and return

it to the liver Cardioprotective Apolipoproteins: Apo A-I, Apo A-II, Apo C

Low Density Lipoprotein/Beta Lipoprotein (LDL)

Synthesized in the liver

Major end product resulting from the catabolism of VLDL

Transports cholesterol to the peripheral tissues Most cholesterol-rich of the lipoproteins and most

atherogenic Primary target of cholesterol lowering therapy better marker for CHD risk Apolipoproteins: Apo B-100 and Apo-E

6. EXPLAIN THE DIAGNOSTIC VALUES OF CKMB AND TROPONIN T IN THE CASE OF CORONARY HEART DISEASE

Cardiac Markers
Myoglobin

Aspartate Transaminase (AST)

Lactate Dehydrogenase (LDH) Creatine Kinase (CK-MB) Test Troponin Test

CK-MB
Elevated CK-MB is considered the most specific indicator

of myocardial gamage, particularly AMI Begins to rise within 4 8 hrs Peaks at 12 24 hrs Normalizes within 24 72 hours

Patients result
RESULT NORMAL VALUE

CK-MB = 3ng/dL

0 3 ng/ DL

INTERPRETATION: BORDERLINE HIGH

TROPONIN
Complex of three proteins that bind to the thin filaments of

cardiac muscles Regulators of actin an myosin Types: TnC, TnI anf TnT
TnI and TnT: cardiac markers TnC: binds calcium ions that regulate muscle contraction

Troponin T (TnT)/Tropomyosin-binding subunit

Specific for eart muscle; valueable tool in the diagnosis of

AMI Useful in monitoring the effectiveness of thrombolytic therapy in AMI patients Early and late AMI; elevated also in renal diseases and muscular dystrophy More sensitive for detection of unstable angina (angina at rest) Rises within 3-4 hrs Peak level at 10-24 hrs Return in 7 days

Troponin I (TnI)/Inhibitory subunit or Actinbinding unit

Only found in the myocardium

Highly specific for AMI NOT elevated in renal failure

patients and no detectable amout in skeletal muscles 13x more abundant in the myocardium than CK-MB Very sensitive indicator of even minor amount of cardiac necrosis Rises 3 6 hrs Peaks in 12 18 hours Normalizes in 5 10 days

Patients Result

Troponin T =

POSITIVE

HISTOLOGY
Chua, Nicolette Eunice T.

MICROSCOPIC FEATURES & DIFFERENCES BETWEEN VARIOUS SIZES OF ARTERIES AND VEINS

Circulatory System
consists of these three layers:
Blood Vessels Tunica interna Tunica intermedia Tunica externa Tunica intima Tunica media Tunica adventitia Heart Endocardium Myocardium Epicardium

Blood Vessels
Tunica Adventitia Outer fibrous coat Fibro-areolar connective tissue blood vessels (vasa vasorum) Tunica Media concentric layers smooth muscle fibers elastin

 Tunica Intima endothelium (flattened; simple squamous) in blood vessels basement membrane corrugated subendothelial connective tissue* internal elastic layer (lamina)*

Arterial System
Elastic arteries Major distribution vessels Aorta, brachiocephalic trunk, common carotid & subclavian arteries Lumen > wall

 Tunica Intima Single layer of flattened endothelial cells w/ subendothelial layer No internal elastic lamina Tunica Media Elastic & smooth muscle fibers Tunica Adventitia Small w/ vasa vasorum

 Medium Sized (Muscular) arteries Main distributing branch Radial, femoral, coronary & cerebral arteries Wall > Lumen

 Tunica Intima Endothelial cells, Corrugated Thicker subendothelial layer Prominent internal elastic lamina Tunica Media Smooth muscles Vasa vasorum External elastic lamina Tunica Adventitia Collagen Vasa vasorum

 Arteriole Prime controller of BP Terminal branches Wall > lumen

Venous System
Low pressures

Carries blood back to the heart

Backflow prevented by valves Lumen > Wall Well developed tunica adventitia

 Venules Intima: no elastic fibers, thin Media: 1-2 layers of smooth muscle cells Adventitia: collagen, thick & well developed Small veins Intima: endothelium & subendothelium, vasa vasorum Media: smooth muscle with elastic tissue Adventitia: thick

 Medium sized veins Intima: thin endothelium, no subendothelium, with Valves in extremities, vasa vasorum Media: small bundles of smooth muscle Adventitia: thickest, collagen fibers

 Large veins Intima: narrow lining endothelium with abundant lamina Media: Poorly developed tunica media; Abundant CT Adventitia: Longitudinal layers of smooth muscles

Comparison
Artery Thickest coat Tunica Media Vein Tunica Adventitia

Thickness of wall
Tunica intima Rigidity Internal elastic lamina Valves Wall:Lumen thickness Vasa vasorum Lumen

Thicker
Corrugated Rigid Prominent None Wall > lumen except large arteries Tunica media Smaller

Thinner
Uncorrguated, fibrous Less rigid Medium sized veins Lumen > wall Tunica intima Bigger

EVOLUTION OF ATHEROSCLEROSIS AND HOW IT AFFECTS THE BLOOD VESSEL WALL

 The most common cause of MI is thrombus formation that

blocks a coronary artery. Atherosclerotic lesions partially block blood vessels, resulting in turbulent blood flow, and the surfaces of the lesions are rough. These changes increase the probability of thrombus formation.

Atheroma formation
Damaged endothelium Cholesterol accumulates Monocyte/macrophage attempt to digest cholesterol and

become foam cells Foam cells degenerate and release contents forming atheroma Calcium salts and fibrous tissue accumulate within the atheroma and hard plaque forms. Artery wall elasticity is reduced and lumen narrows= increase in BP Endothelium ruptures exposing collagen Platelets aggregate to form platelet plug Blood clots and forms fibrin mesh which traps blood cells

 Features of atherosclerosis: The tunica intima is severely thickened There is fragmentation & partial duplication of the internal elastic lamina There is smooth muscle infiltration of the intima (from the media), i.e. red staining of the intima. There is significant luminal narrowing.

HEART

DIFFERENTIATE ORDINARY CARDIAC MUSCLE FROM PURKINJE FIBER

Specialized cardiac muscle fibers: Purkinje fiber

Shorter & wider in diameter

2 or more nuclei
Fewer myofibrils Appear lighter (microscopically) Less branching & intercalated discs

Lacks T-tubules
Abundant glycogen rich sarcoplasm Higher conduction velocity

SARCOMERE, CONDUCTING SYSTEM & PURKINJE SYSTEM

Conducting system
SA node of Keith and Flack

AV node of Tawara
AV bundle of His

AMI
sudden loss of blood

supply to myocytes with resultant ischemic necrosis area of infarct (top arrow) that is paler than the relatively viable area (right arrowhead).

 necrosis is followed by

infiltration of neutrophils seen at about 12-24 hours after onset of infarction. area of infarction with edema and heavily infiltrated by neutrophils (top arrow). sharply demarcated from relatively preserved myocardium (bottom arrowhead).

 damaged

myocytes (arrowheads) with dissolution of cellular bodies in areas of neutrophilic infiltrate (arrow).

MACROPHAGE
Cledera, Darlene Mae E.

Macrophage
A major cell population in most of the tissues in the body, and their numbers increase further in inflammation, wounding and malignancy

Formation of Macrophage

Formation of Macrophage
All blood cells are formed in the bone marrow from by a

process called haematopoiesis Haematopoietic Stem cells give raise to myeloid progenitors which can further differentiate into several blood cell types, among them monocytes Monocytes are the blood precursors of macrophages The term macrophage refers to a blood monocyte that has accessed a tissue through a process known as extravasation*

Monocyte
Largest of the WBCs

Kidney/Horseshoe shaped nucleus

Frosted Glass Cytoplasm 2 to 10% of leucocytes in peripheral blood Spend an average of 3-4 days in circulation before

emigrating into the: (1) Tissues-macrophages ; or (2) Spleen (Cords of Bilroth/Red Pulp)- as a reservoir

Formation of Macrophage

Mononuclear Phagocyte System (Monocyte-Macrophage System)

A single functional unit consisting of circulating

monocytes, the bone marrow precursors and tissue macrophages. Included are the:
Kupffer cells of the liver

Microglia of CNS
Langerhans cells of skin Alveolar macrophages in lung Antigen-Presenting cells of the lymphoid organs

Osteoclasts of bone

Alveolar Macrophage
Primary resident phagocytes in alveolar space

One alveolar macrophage in each alveolus

Exhibit a lobulated nucleus surrounded

by vacuolatedcytoplasm containing abundant mitochondria and secondary lysosomes

Function of Macrophage in Respiratory Tract

1. Serve to remove apoptotic cells and damaged tissue debris in the lung 2. First line of phagocytic defense against foreign agents that reach that gas exchanging units of the lung
Have potent phagocytic microbicidal and secretory functions

Play pivotal role in initiating the inflammatory and immune

responses in the lung

Ingestion of Particles
PHAGOCYTOSIS ATP-dependent process that involves rearrangement of actin cytoskeleton elements in the cytoplasm and formation of pseudopods Complex process in which a number of cell signaling pathways are activated leading to alterations of various cellular functional states including:
Gene transciption Protein secretion Oxygen and nitrogen intermediated generation Cell survival Programmed death

Ingestion of Particles
PHAGOCYTOSIS....

Initial step: Chemotaxis movement towards particles or

microbes by
Chemoattractants:
Products from microbes themselves Collagen and elastin fragments Chemokines generated by inflammatory cells Surfactant proteins produced by epithelial cells

Ingestion of Particles
PHAGOCYTOSIS....

Binding with the particle or microbe occurs, facilitated by

receptors expressed on the surface of alveolar macrophages

Receptors:
Mannose receptors recognizes terminal mannose residues on fungal

polysaccharides and mycobacterial glycolipids Type A scavenger receptors recognizes:

LPS of Gram-Negative bacteria Lipoteichoic acids of Gram-positive bacteria Sulfatides of Mycobacteria

Ingestion of Particles
ENDOCYTOSIS A receptor-mediated process Not ATP-dependent and does not require actin involvement Occurs in calthrin-coated pits in macrophage membrane

Destruction of Ingested Particles

Once internalized by either process, foreign particles

reside in cytoplasmic vacuoles termed phagosomes Phagosomes are fused with other organelles such as lysosomes (contains digestive proteases, antimicrobial peptides, lysolipids, reactive oxygen and nitrogen species) resulting in degradation of the pathogens

Destruction of Ingested Particles

Intracelllular fate of pathogens that have entered the cell

are different depending on the receptor type

Ex. Phagocytosis through Fc receptors triggers oxidative burst and

reactive oxyfen intermediates

Other immune defense mechanisms such as

development of cell-mediated Immunity and local activation helps in the eradication of microbes

Function of Macrophage in Respiratory Tract

3. Responsible for clearance of dust particles and small loads of pathogenic organism deposited in the terminal airways in normal respiration -most common particles are carbon -after phagocytosing the particles, most macrophages pass into airways , trapped in mucus, and coughed up as sputum

Defense Against Pathogens

RECRUITMENT OF PMNs When pathogens are too virulent or too large to be contained by the macrophage Capable of generating chemoattractants for PMNs such as
Chemotactic peptides (IL-8, MIP-2 and other CXC chemokines) Complement fragments (C3a and C5a) Arachidonic acid metabolites (Leukotriene B4)

Defense Against Pathogens

PROINFLAMMATORY MEDIATORS

Cytokines (TNF-alpha, IFN-gamma, IL-1beta, OL-12)

Exert autocrine and paracrine functions to stimulate other cells in the local environment Facilitate recruitment of mononuclear leukocytes thereby expanding the macrophage populationg

CC Chemokines

Growth Factors Lipid Mediators

Defense Against Pathogens

ANTI-INFLAMMATORY Ex. IL-4, IL-10 Role in regulation of the pulmonary host defense response Role subsequent resolution of local inflammatory reactions

Heart Failure Cells

Hemosiderin-containing alveolar macrophages

Not restricted to those with Congestive Heart Failure

Found in any lung

where congestion or haemorrhage occurs

Congestive Heart Failure

Left-sided heart failure is more common which

primarily affects the left ventricle

Left atrial and pulmonary venous pressure increase

resulting in pulmonary congestions Capillaries in the alveolar septa fill with blood and small ruptures allow erythrocytes to escape Alveolar macrophages carry out lysis of leaked RBC converting iron from heme into numerous brown granules of hemosiderin

CLINICAL EPIDEMIOLOGY
Chua, Jared

Research Questions
Diagnosis of coronary artery disease Is using ECG a better exam for the diagnosis of coronary heart disease in susceptible patients (patients with risk factors for CAD) rather than using the Echocardiogram?
P(population)- susceptible patients I (intervention)- ECG C( Control or comparison)-Echocardiogram O-(outcome)- Diagnosis of Coronary heart disease

Research Questions
Treatment of Coronary artery disease In the treatment of CAD among people affected, are cholesterol modifying medications more effective compared to beta blockers ?
P- people with CAD I- Cholesterol modifying medications C- beta blockers O-treatment of CAD