CP I Midterm

Ribs

1-7○

Costal cartilage articulates directly with sternum

Vertebrocostal○

True ribs•

8-12○

Costal cartilages do not attach directly with sternum

Vertebrochondral○

Ribs 8-10 articulate with the costal cartilage above them forming the costal margin

○

False ribs•

11 & 12○

Floating/free ribs•

3-9

Contain a head region that attaches to the vertebral body and a tubercle that articulates with the TVP of the vertebrae

Typical○

1 & 2, 10-12

Atypical○

Osteology•

Fx generally occur at the weakest area just anterior to the angle of the rib

○

Dislocation occurs when costal cartilage is displaced from sternum

○

Seperation is dislocation of the costocondral joint

○

Misc.•

Intercostal SpaceNamed by the rib above it•

Intercostal Vein○

Intercostal Artery○

Intercostal Nerve○

Vascular bundle runs in each groove and contains in order from superior to inferior:

•

Collateral bundle is a mirror image of intercostal bundle ("NAV")

○

Bundle splits and the intercostal bundle runs below the superior rib and the collateral bundle runs above the inferior rib

•

Thoracocentesis must be performed in the exact center of the intercostal space to avoid damaging either bundle

•

Thoracic VertebraOnly T2-T9 contain demifacets (superior & inferior)

•

T1 contains a superior costal facet AND a typical inferior demifacet

•

T10-T12 contain bilateral costal facets•

`Presents as excessive thoracic kyphosis

○

"Dowager's Hump"○

Inflation of a balloon within the vertebral body followed by filling cavity with bone cement

□

Kyphoplasty

Direct injection of bone cement into vertebral body (without balloon inflation)

□

Vertebroplasty

Treatment○

Vertebral Fx due to osteoporosis•

Sternal AngleAngle of Louis•Between manubrium and sternum•Aortic arch begins and ends behind angle•Trachea bifurcates into L/R bronchi•Landmark for heart sounds•

DiaphragmChief muscle of inspiration•Innervated by the phrenic nerve (C3-C5; motor) and intercostal nerves (sensory)•

Vena cava foramen (T8)○

Esophageal hiatus (T10)○

Aortic hiatus (T12)○

3 openings•

Thoracic Bones & Joints

Anatomy

Lymphatic Drainage

Found along thoracic artery○

Sternal/parasternal nodes (internal thoracic)

•

Intercostal nodes•

Diaphragm○

Phrenic nodes•

Thoracic Cavity

Contains lungs and pleurae

Two lateral compartments (pleural/pulmonary)○

Contains all other thoracic structures

Level of T4/T5 to superior thoracic aperture

Can present as "sail sign" in child, looks like enlarged cardia shadow

►

Thymus◊

Arch of aorta◊

Trachea etc.◊

Left recurrent laryngeal nerve (branch of vagus n., loops under the aorta)

◊

Contains:

Superior mediastinum□

Anterior

Pericardium►

Heart►

Contains◊

Middle

Posterior

Inferior mediastinum□

Further divided into:

One central compartment (mediastinum)○

Has three compartments•

Pleura

Adhered to thoracic wall, mediastinum and diaphragm

○

Costal

Mediastinal

Diaphragmatic

Cervical

4 parts:○

Parietal pleura•

Adherent to lung○

Visceral pleura•

Clinical CorrelatesLacerations 2-3 cm above the medial clavical may penetrate the pulmonary cavity, causing pneumothorax

•

Inflammation of pleura○

Upon auscultation, pleural rub is heard○

Can result in pain and adhesions○

Pleuritis•

Pericardiocentesis is performed where the pericardium is in contact with the thoracic wall on the left side near the 5th rib

○

Thoracocentesis is performed on the left side around the 9th rib

○

Pleural recesses•

Mesothelioma"asbestos cancer"•Patients present with pleural effusion, dyspnea and chest pain

•

Neoplastic cancer growing within the pleural space

•

Thoracic Cavity & Lungs

Anatomy

Pericardium

Outer fibrous covering○

Parietal layer next to fibrous covering

Visceral layer next to heart

Double-walled serous layer○

Double layered sac:•

Pericardiocophrenic artery and vein○

Azygous vein○

Blood supply•

Vagus n.○

Vasomotor

Sympathetic trunks○

Sensory/pain

Phrenic○

Innervation•

Serous Pericardium-Visceral Layer

Transverse space between the artrial and venous mesocardia

○

Behind aorta & pulmonary trunk but in front of superior vena cava

○

Transverse sinus•

Space behind the entire heart (posterior)

○

Oblique sinus•

Heart OrganizationPulmonary trunk is anterior•Aorta is posterior•Mitral valve is left ventricle (L w/ L)•Tricuspid is right ventricle•Semilunar valves separate ventricles from arteries

•

Mitral & tricuspid separate atria from ventricles

•

Anterior = top; posterior = bottom. P = pulmonary, A = Aorta, M = mitral, T = tricuspid.

Projection of Pericardium & Heart on Body Wall

2nd rib - 5th intercostal space○

2cm to left and right of sternum○

Pericardium•

3rd rib - 5th rib○

Heart•

Just to left of xiphoid process

Angle needle in posterosuperior direction

Upper left of xiphochondral junction○

Pericardiocentesis•

Superficial Heart

Anatomy

Surfaces of the Heart

Anterior○

Little of RA & RV (pressed during CPR)

○

Sternocostal•

Inferior○

L & RV○

Diaphragmatic•

LV & LA

Left○

RA

Right○

Pulmonary•

Top of the heart○

L & RA, great vessels○

Base•

Bottom left (tip of left ventricle○

Apex•

Depression on the surface of the RA

○

SA node resides here○

Sulcus terminalis•

Seperation of atria & ventricles○

Coronary sulcus•

Anterior and posterior grooves indicating the interventricular septum

○

Interventricular sulci•

Shallow vertical groove seperating RA and superior vena cava

○

Sulcus terminalis•

Coronary Arteries/Veins

Sinoatrial nodal branch○

Conus branch○

Right marginal branch○

Atrioventricular nodal branch○

Atrial branch○

Posterior interventricular branch○

Branches of the right coronary artery•

Left anterior descending (LAD)○

Circumflex○

Branches of the left coronary artery•

Coronary sinus○

Anterior cardiac veins○

Main cardiac veins•

Anatomy

Primitive Circulation/Atrial FormationUmbilical vein carries oxygenated blood to the fetus•Umbilical artery carries deoxygenated blood away from the fetus

•

Heart tube folds, creating ventricles anterioinferiorly•

Develop from ant/posterior walls□

Divide atria and ventricles□

Endocardial cushions

1st atrial septum (septum primum) grows down from the top of the heart towards the cushion

○

Top portion of the septum primum is obliterated○

Forms one-way valve allowing blood to pass from right to left atrium

90% of atrial septal defects are closure problems in the foramen ovale

Septum secundum grows down and never becomes complete, leaving an oval opening (foramen ovale)

○

Superior/inferior vena cava

Coronary sinus (valve of Thebesius)

Openings in the right atrium○

Remnant of the fused foramen ovale

Fossa ovalis, located on the right, interatrial septum○

Atrium partitioning•

Ventricular Partitioning

Stops short creating interventricular foramen

○

Closed by migratory neural crest cells to form membranous I.V. septum

○

Muscular interventricular septumgrows from apex of heart up towards atria

•

90% VSD's are found in the membranous portion

○

Ventricular septal defects are often seen w/ Fetal Alcohol Syndrome

•

Papillary Muscles

Anterior attaches to anterior and posterior cusp○

Posterior attaches to posterior and septal cusp○

Septal attaches to septal and anterior cusp○

Three in the right ventricle (attach to tricuspid valve)•

Attached through chordae tendineae•Both papillary muscles in the left ventricle (anterior & posterior) attach to both cusps of the mitral valve (anterior & posterior)

•

Left Ventricle2-3x thicker than the right ventricle•Covered by trabeculae carnae•Aortic sinuses house the openings to the right & left coronary arteries respectively

•

Semilunar Valves

Central nodule○

Curved border moving away from nodule

Lunula○

Each cusp has a:•

Conduction System

Right VentricleAlso covered with trabeculae carneae•

Contains part of right conducting bundle○

Partially gives rise to the anterior papillary muscle○

Septomarginal trabeculae•

Heart Interior

Anatomy

Conduction SystemSA node is located at the junction of the SVC and the RA, above the terminal crest

•

Transfers AP from atria to ventricles○

AV node depolarizes the Bundle of His•

Wolff-Parkinson-White

See a delta wave on EKG

Bypasses th AV node if conduction through AV node/Bundle of His isn't operating properly

○

Bundle of Kent•

Delta wave visible in QRS

Cardiac PlexusSA node is innervated by the right half of the cardiac plexus•AV node is innervated by the left half•

Anatomy

Contents of Posterior MediastinumThoracic aorta and branches•Esophagus & nerve plexus•Azygous venous system•Splanchnic nerves•Thoracic duct•Sympathetic trunks•

AortaDescending begins at sternal angle (T4/T5)•Left of vertebral column•

Bronchial AA.○

Esophageal AA.○

Posterior intercostal AA.○

Branches•

EsophagusHas a reverse S course•Slight curve to the left high, right middle & left again in the lower thorax

•

Posterior to trachea, which is posterior to thyroid, carotids & laryngeal NN.

Cervical○

Posterior to aorta which is also slightly to the left, along with the thoracic duct

Azygos vein is anterior and slightly right of the esophagus

Thoracic○

Esophagus is to the left of the midline

Abdominal○

Relations•

Branches off the aorta○

Blood supply•

Recurrent laryngeal○

Cervical sympathetics○

Vagus N.○

Innervation•

Vagus Nerve

Enters thorax between brachiocephalic trunk & vein along the right side of the trachea

○

Right recurrent laryngeal passes under the right subclavian

○

Passes posterior to root of the right lung spreading into posterior pulmonary plexus

○

Right Vagus N.•

Enters thorax between left common carotid & left subclavian AA.

○

Left recurrent laryngeal passes under the aortic arch & ligamentum arteriosum

○

Passes posterior to root of left lung and joins posterior pulmonary plexus

○

Left Vagus N.•

Posterior pulmonary plexus○

Esophageal plexus○

Cardiac plexus○

Forms:•

Forms anterior gastric plexus

Anterior Vagal trunk○

Forms posterior gastric plexus

Posterior Vagal trunk○

Trunks•

Azygous SystemDrains posterior Thorax and abdominal walls•

Splanchnic Nerves

All three pierce crus of the diaphragm

○

T5-T9

Greater splanchnic N.○

T10-T11

Lesser splanchnic N.○

T12

Ends in renal plexus

Lowest splanchnic N.○

3 Thoracic splanchnic nerves:•

Thoracic DuctLies between aorta & azygous vein•

Connects to left subclavian & left brachiocephalic veins○

Moves to the left of the midline at T4•

Union of left & right lumbar trunks○

Arises at T12•

Everything except right side of head & neck, & right arm (Right lymphatic duct)

○

Drains:•

Dilation of distal (caudal) thoracic duct○

L1-L2○

Cisterna chyli•

Posterior to esophagous in the thorax•

Posterior Mediastinum

Anatomy

CT at T7

EsophagusA.AortaB.Azygous veinC.Hemiazygous veinD.IVCE.

E

Anatomy

RBCs are approx. 8 µm in diameter•

% of RBCs in plasma○

Hematocrit•

Smears vs. SectionsSmears contain better cell detail•The relationship between cells in only visible on a section

•

RBC MaturityNew RBCs are a bit larger and don't quite have the biconcave disc shape

•

>1.5%○

A large % of young RBCs (reticulocyte count) indicates recent hemorrhage or hemolysis and possibly pathological condition

•

Spectrin-AnkryinSystem on the RBC membrane that gives it it's biconcave shape

•

Glycophorin on the outside is very hydrophilic and prevents RBCs from sticking to each other

•

Spherocytosis is a lack of Spec-Ank system

•

Centrifuged BloodPlasma is the liquid portion, not having clotted

•

Serum is the liquid portion of the blood if the blood HAS clotted

•

Buffy coat contains the WBCs and platelets•

WBCsAll are larger than RBCs•

Basophils

Eosinophils

Also called polymorphonuclear leukocytes

□

Neutrophils

Granulocytes○

Lymphocytes

Monocytes

Agranulocytes○

Typically divided into two groups:•

Granulocytes

Pursue and kill bacteria○

Collagenase

Lactoferrin

Lysozyme

Contain specific granules:○

Mostly hang onto vessel walls until stress hormones rise

○

Can also give their lives by shooting out their DNA creating bacterial "nets"

○

Live for about 3 days○

Neutrophils•

Kill worms○

Contain basic granules ("love acid" stain)○

Identified by saucer shaped granules○

Eosinohils•

Contain acidic granules ("love base" stain)○

Histamine

Heparin

Specific granules are ○

Basophils flow in the blood, mast cells are found in the tissue

○

Basophils• NEUTROPHIL

Basic Blood

Histology

EOSINOPHILBASOPHIL

NEUTROPHIL

EOSINOPHIL

BASOPHIL

Agranulogytes

Mostly B and T cells○

Contain one large nucleus○

Lymphocytes•

Precursors to tissue phagocytes and dendritic cells

○

Nuclei are large but kidney shaped○

Monocytes•

Histology

MONOCYTE (similar kidney shaped nuclei on EM) LYMPHOCYTE

Platelets (Thrombocytes)Lack a nucleus•Much smaller than RBCs•Granulomere is the area inside the platelet cell, surrounded by the clear hyalomere zone

•

Platelets release their granules (clotting factors) rapidly using this system (platelet release reaction)

○

There is also a system of canals beneath the hyalomere called the open canalicular system

•

Platelets live for about 10 days•

PLATELET (arrows indicate hyalomere)

Histology

Endocardium

Innermost component

Single layer of squamous endothelial cells

Endothelium○

Thin layer of loose connective tissue

Subendothelial connective tissue○

Contains some vessels & nerves

Purkinje fibers are paler than other myocytes

□

Purkinje fibers (conduction fibers)

Subendocardium○

Contains three components•

Endocardium thickness differs between the atria (thick, needs more support due to less myocardium) and ventricles (thinner)

•

Endocardium at the top with mostly myocardium (M) at the bottom. PF = purkinje fibers; CT= connective tissue (subendothelial CT at top).

Heart Tunics

Inside○

Endocardium•

Middle○

Red○

Myocardium•

Outside○

Epicardium•

Cardiac Cell StructureContain 1 T-tubule and one terminal cisterna of SR to form diad

•

40% of the cytoplasm contains mitochondria•

Heart

Histology

Epicardium (Visceral pericardium)

Epithelium lining the walls & contents of the closed cavities of the body (in this case, the heart)

Mesothelium○

Connective tissue with nerves & vessels

○

Hallmark identifier for epicardium

Adipose tissue○

Contains:•

EPICARDIUM

Cardiac Skeleton

Keeps valves patent○

Attachments for leaflets and cusps of valves

○

Attachment for myocardium○

Electrical "insulator" seperating atrial and ventricular conduction

○

Roles:•

4 rings that surround valve openings

Annuli fibrosae○

2 triangular masses connected to the annuli fibrosae

Trigona fibrosae○

Dense fibrous plate that forms parts of interatrial and interventricular septa

Septum membranaceum○

Parts:•

Annuli fibrosae (circles); Trigonal fibrosae (triangles); Septum membranaceum (SM & dotted line)

Valve Histology

Connect cusp free edge of AV valve to papillary muscle○

Has a dense connective tissue core with a thin endocardium covering○

Chordae tendineae•

Myocardial bundle○

Papillary muscle•

Folds of endocardium○

Lined by endothelium○

Semilunar valve•

Histology

Wall Structure

Ciliated pseudostratified columnar○

Goblet cells○

Respiratory Epithelium•

Loose CT○

Seromucous glands○

Elastic fibers○

Bone/cartilage○

Smooth muscle○

Lamina propria•

Collagen & elastic fibers○

Adventitia is the outermost connective tissue covering any organ

○

Adventitia•

Respiratory Epithelium

Ciliated columnar1.

Secrete hydrophilic glycoproteins (mucin, extrecellularly become mucus)

Goblet cells2.

Other columnar-shaped cells

Base has afferent nerve endings

Brush cells3.

Small round stem cells

Give rise to ciliated columnar, goblet, & brush cells

Basal cells4.

Numerous granules of peptide hormones & catecholamines

Secretions (granules) exert paracrine effect on other cells

□

DNES cells (diffuse neuroendocrine system)

Small granule cells5.

5 Cell types•

Brush and granule cells are often not identifiable•

Immotile ciliary syndrome○

Infertility in men, chronic respiratory infection in both sexes

○

Cilia & flagella are immobile○

Primary Ciliary Dyskinesia•

Metaplasia changes cells to stratified squamous

○

Decrease movement of mucus○

Smoker's respiratory epithelium•

G=Goblet; B=Basal; BM=Basement Membrane; C=Ciliated Columnar

Lamina Propria

Some cells are serous & others mucous

○

Found from nasal cavity to bronchi○

Seromucous glands1.

Increase towards alveoli○

Elastic fibers2.

Prevents respiratory tube collapse○

Skeletal CT3.

Regulates luminal diameter○

Smooth muscle4.

Cartilage & smooth muscle is lost as you decend while elastic fibers increase

•

Recurrent Laryngeal Nerve

Posterior to the ligamentum arteriosum

○

It then ascends to innervate the larynx (motor) for vocalization

○

The left recurrent originates from the left vagus nerve at the aortic arch and loops under the it

•

Damage or tumoral involvement

○

Lung cancer○

Aneurysm of aortic arch○

Due to the innervation of the larynx, if something is affecting (compressing) the nerve, patient will present with hoarseness, cough etc.

•

Respiratory System

Histology

Trachea

Hyaline cartilage○

Fibroelastic ligament

Smaller diameter increases the velocity of expired air

Narrows during cough reflex□

Tracealis muscle

Posterior ends bridged by:○

Diagnostic feature is 16-20 C-shaped rings•

Respiratory epithelium○

Seromucous glands○

Blood vessels○

Chondrocytes

Hyaline cartilage○

Identification•

Trachea

BronchiMain differentiation is presence of alveoli•Still has cartilage & smooth muscle•Each succesive branches of bronchi have less cartilage (islands of cartilage)

•

Anatomical, structural & surgical unit of the lungs

○

A surgeon can resect a segment w/o seriously damaging the surrounding lung

○

Bronchial pulmonary segment•

BALTBronchus associated lymphoid tissue•

BronchiolesDiffer from bronchi in the absence of cartilage and glands•

NO GOBLET CELLS!○

Contains ciliated cuboidal○

Secrete Clara cells secretory protein (CCSP) and lung surfactant

Detoxify harmful substances

Clara cells○

Terminal bronchioles•

Shunt air to areas w/ good blood supply○

Smooth muscle can change the airway resistance•

Parasympathetic fibers are from Vagus N. (CN X) and stimulate bronchial constriction (GVE)

○

Sympathetic fibers cause dilation (GVE)○

GVA fibers carry pain, airway irritants & cough reflex○

Innervation•

Dead SpaceConducting airways are dead space

•

No gas exchange occurs•~150ml of air (a breath is usually 400ml)

•

Respiratory Portion

Followed by alveolar ducts & sacs

○

Alveoli start to popup in the respiratory bronchioles

•

Main differentiation of respiratory bronchioles (from terminal bronchioles) is the presence of alveoli

•

Histology

Alveolar Gas Exchange

Volume of air reaching the alveoli

○

~4L○

Ventilation•

From right ventricle○

~5L blood/min○

Perfusion•

Diffusion of each gas (O2 & CO2) is independent of one another

•

Alveolar Ducts & SacsAlveolar sacs are clusters of alveoli•

Structural support is provided by elastic & reticular fibers

○

Smooth muscle is no longer present•

AlveoliAlveoli are seperated by interalveolar septa that consist of two simple squamous epithelial layers w/ an interstitium (capillaries embedded in elastic tissue) between them

•

Squamous alveolar epithelium

Type I○

Surfactant secreting cells

Surfactant creates surface tension, preventing alveolar collapse

Type II○

Alveolar macrophages that consume RBCs found in lumen due to congestive heart failure

□

Heart failure cells

Alveolar macrophages (dust cells)○

Cell types:•

Surface area corresponds to the number of alveoli•

Blood-Air BarrierRefers to the sructures that O2 & CO2 must cross during gas exchange•

Cytoplasm of squamous epithelial cells○

Fused basal lamina of Type I alveolar cells & capillary endothelial cells○

Cytoplasm of capillary endothelial cells○

Includes:•

~0.6 microns thick•As distance increases diffusion rate decreases•

O2 gas exchange will be effected pathologically much sooner than any problem with CO2 is seen○

CO2 requires almost no time in a pulmonary capillary for adequate exchange○

O2 requires 0.25 seconds for adequate exchange○

If the lungs aren't in peak condition, the patient will fatigue (stress test)

Normally, it takes a RBC ~0.75 seconds to move through a pulmonary capillary, however during exercise and RBC is pushed through in 0.25 seconds

○

Diffusion coefficient of CO2 is 20x that of O2•

DLO2

Diffusion capacity for oxygen of the lung

•

Measure using carbon monoxide (CO)

•

DLO2 = 1.23 x DLCO•

Histology

The biggest drop in BP occurs between the arterioles & capillaries

•

TunicsAKA layers•

Prevents clot formation by releasing prostacyclin (vasodilator & inhibits platelet aggregation)

Endothelium○

Consists of type-IV collagen

Basal lamina○

Subendothelial layer○

Intima•

Most pronounced layer○

Predominantly smooth muscle○

Thickest in arteries○

Media•

Outermost layer of collagen & elastin fibers○

"vessels of vessels" that supply the cells to far from the lumen to be reached by diffusion

□

Epect more vaso vasorum in veins due to lower O2 content

□

Vaso vasorum

Contains vessels and nerves○

Thickest in veins○

Adventitia•

Vircow's TriadFactors leading to thrombosis•Injury1.Turbulent2.Hypercoaguability3.

Elastic ArteriesAorta & its primary branches•Stretches during systole, contracts during diastole•

Smooth muscle & reticular fibers (collagen II)○

Media•

Elastic & collagen I fibers○

Vasa vasorum ("a" for aftery)○

Adventitia•

Elastic Artery. I=intima; M=media; A=adventitia. Notice large A.

Muscular ArteriesDistributing arteries•Most named arteries in the body•

Prominent internal elastic lamina○

Intima•

Still prominent media, but not so overrun with elastic fibers (more SM)

•

Vascular Histology

Histology

Muscular Artery. Prominent internal elastic lamina (iEL).

Small ArteriesMedia more developed than arterioles•Lumen is larger than arteriole•

ArteriolesNuclei bulge into lumen•1-5 layers of smooth muscle•

Arteriole

Capillaries~1 RBC thick•

Chief structural component

Simple squamous epithelial cells

Endothelial1.

Pericytes2.

Two cell types:•

Smooth, nonporous

Zona occludens□

Cells are tightly attached

Found in all types of muscle, brain & nerves

Continous○

Contains some pores

Kidney, intestines etc□

Found where rapid exchange between tissues & blood is required

Fenestrated○

Gaps between endothelial cells

Abundant fenestrations

Found in liver & hematopoietic organs

Sinusoidal (discontinuous)○

Types of capillaries•

Large Veins

Histology

Large VeinsSuperior & inferior vena cava & pulmonary veins•

Extensions of intima protruding into the lumen

Contain valves ○

Intima•

Sparse elastin○

Media•

Best developed in large veins○

Adventitia•

Veins will be flatter than arteries•

Small/Medium Veins

No internal elastic lamina○

Intima•

LOOK FOR COMPANION ARTERY!•

Vein. Arrows point to valves.

Venules

Very thin w/ few smooth muscle cells

○

Media•

Thickest tunic○

Adventitia•

Lymphatic VesselsLook like venules•May have valves•CLEAR, NO RBCs!•

Histology

Structure75% α-helical•

Each globin chain contains 8 α-helicies○

Hemoglobin contains 4 globin chains (tetramer)•

There is communication between chains (cooperative binding)

•

Binds oxygen stronger○

Fetal hemoglobin contains 2 α chains and 2 γ chains•

Adult hemoglobin contains 2 α chains and 2 βchains

•

Heme Group

Planar and hydrophobic

Porphyrin ring○

4/hemoglobin

Binds oxygen

One Fe2+ per chain○

Composed of:•

Heme group is found between the E and F α helical domains in each globin chain

•

Adjacent histidines reduce the affinity of Fe for CO

•

Allosteric ControlRegulates O2 affinity•

O2 is more readily released from hemoglobin○

Shifts the O2 dissociation curve to the right○

Associated with high demand for O2 such as in exercising muscle○

H+ (low pH), CO2 , and 2,3-bisphosphoglycerate reduce the affinity for oxygen •

Hemoglobin

Biochemistry

Action Potential (AP) ReviewMembrane potential crosses threshold1.Na+ open, Na+ enters cell2.Rapid depolarization3.Na+ gates close4.K+ gates open, K+ leaves cell5.Cell repolarizes6.

Cardiac AP Must be self generating•

All or none○

Must propagate from myocyte to myocyte•

Heart is contracting

Initiated by depolarization of ventricular myocytes

Systole○

Heart is relaxed

Follows myoctye repolarization

Diastole○

Phases of cardiac AP•

SA node○

Atria○

AV node○

Purkinje system○

Ventricles○

Sequence•

Atria, ventricles and purkinje system

Resting potential4.Rapid depolarization0.Initial, incomplete repolarization1.Plateau2.Repolarization3.

5 phases

Fast○

SA and AV nodes

Automatically depolarizes during rest phase

Slow○

Types of cardiac APs•

AP Points of InterestUsually, concentration gradients are maintained, even after several APs

•

EX: most ion changes are the result of a salt, which is a positive ion attached to an equal and opposite negative ion

○

Changing the plasma concentration of ions usually doesn't change the net charge either because the change is usually accompanied by a equal and opposite change in the other ion species

•

The more beats/min, the shorter the duration of depolarization (Phase 1/2)

•

Fast Action PotentialCaused by changes in permeability (conductance) of K+ , Na+ , and Ca+ +

•

These changes are the result of voltage dependent gates

•

Fast○

High K+ , low Na+ and Ca+ + permeability○

Phase 4•

High Na+ permeability○

Na+ flows in○

Phase 0•

Decreasing Na+ permeability, increasing K+ permeability

○

K+ flows out○

Phase 1•

High Ca+ + permeability, low K+ permeability○

Ca+ + gates open, K+ gates close○

Ca+ + flows in, offsetting repolarization by K+○

Phase 2•

Phase 3•

Cardiac Action Potential

Physiology

High K+ permeability (causative change), low Na+ and Ca+ + permeability

○

Timed K+ gates open, K+ flows out, repolarizing cell

○

Different gates are in different areas of the heart

Depolarization in Phase 0 caused the Ca+

+ gates to open, the opening of the K+

gates closes them

Duration of K+ gate timer determines length of AP/contraction force

○

Phase 3•

Resting potential○

High K+ , low Na+ and Ca+ + permeability○

Phase 4•K+ and Ca+ + have an inverse relationship

Slow APNo fast Na+ gates so depolarization proceeds slowly

•

Resting potential is closer to -60mV (vs. -80mV in fast)

•

The amplitude of the depolarization is smaller

•

Slow AP tissues will spontaneously depolarize slowly during Phase 4 to reach threshold without outside influence

•

Conduction Velocity of APThe greater the AP amplitude, the faster the depolarization in Phase 0, and the larger the cell diameter,the faster the conduction velocity

•

Slow vs. Fast TissueFast type contractlie myocytes are larger diameter and have high amplitude and rapid onset AP's

•

Fast type non-contractile myoctyes (purkinje fibers) have very large diameter with rapid upstroke

•

Slow tissues have a small diameter with low amplitude AP's and slow depolarization

•

Physiology

Body Fluid

3.5L is plasma○

Average individual contains 42L of fluid

•Blood Cell Production

In the liver and spleen in the fetus○

Distal long bones and axial skeleton in the child & adolescent

○

Axial skeleton in the adult○

RBCs originate:•

Starts production of hemoglobin○

Progresses to erythroblast, reticulocyte (lose nucleus) and finally erythrocyte

○

Genesis of RBCs begins w/ the proerythrocyte•Erythrocyte ProductionEach RBC contains millions of molecules of hemoglobin

•

Hypoxia causes cells to form HIF (hypoxia-inducible factor)

○

HIF stimulates kidneys to produce EPO (erythropoietin)

○

EPO stimulates bone marrow production of RBCs

○

Stimulis for erythrocyte production:

•

Oxygen Loading

T configuration (tight) is when no O2 is bound○

Allows more O2 to bind

Converts to R configuration (relaxed) when O2 binds○

Interaction among hemoglobin chains•

Oxygen carrying capacity (SO2 )○

For saturation, multiply SO2 by sat. %

1.34ml O2 x Hb (X gm/dL) = SO2○

1 gram of Hb can transport 1.34ml O2 (100% SO2 )•

AnemiaA decreased concentration of Hb in the blood•Hematocrit is linearly related to Hb concentration and is used as an index

•

Hemorrhagic○

Hemolytic○

Non-functional marrow

Aplastic○

Fe deficiency○

B12 deficiency

Pernicious○

Common types:•

RBCs in Solutions

RBC size increases○

Hypotonic•

Stays same○

Isotonic•

RBC shrinks○

Hypertonic•

V0C0 = V1C1○

V = volume; C = concentration of solution○

Volume change can be predicted :•

PolycythemiaExcessively high RBC concentration/Hct•

Decreased O2 in the blood which increases the levels of EPO

○

Genetic aberration (polycythemic vera)○

Causes:•Energy ConsumptionGlycolysis•Maintains electrochemical & ionic gradient

•

Maintains membrane flexibility & integrity

•

Reduction of methemoglobin (Fe3+) to hemoglobin (Fe2+)

○

Reduced glutathione protects RBC against oxidative injury to Hb and membrane

○

Resist oxidative damage through:•

Erythrocyte Physiology

Physiology

O2 Dissociation CurvesFetal Hb is left shifted•Addition of CO shifts curve to left•

Higher temps in exercising tissues

○

Increased temperature shifts the curve to the right

•

2,3-bisphosphoglycerate shifts curve to the right

•

O2 Transport in Blood97% is attached to Hb; 3% dissolved•Dissolved % is proportional to the PO2•

Gm Hb/dL blood x 1.34 ml O2 /gm Hb○

Hemoglobin's ability to carry O2 (SO2 )•

Solubility of Respiratory GasesPaO2 = 100mmHg in normal individual•PaCO2 = 40mmHg in normal person•

Partial pressure of the gas○

Solubility of the gas ○

Temperature○

Volume of gas dissolved is dependent on:•

PO2 = PB x FO2○

PB = barometric pressure, at sea level = 760mmHg

○

FO2 is the decimal fraction of O2 in the gas mixture

○

Determining O2 's partial pressure:•

Can be used for any gas•For humidified gas subtract 47mmHg from PB•

Carbon MonoxideBinds tighter than O2 to Hb•CO is colorless, tasteless & odorless•CO does not stimulate ventilation (unlike CO2 )•Produces a cherry-red color in the pt (versus CO2

which produces a blue color)•

CO2 Interactions

Formed as CO2 binds with amino acids of protein

○

Reaction occurs without enzymes○

Carbamino compounds•

HCO3 - in plasma is converted to CO2 in the RBC

○

CO2 diffuses through RBC membrane and into the alveoli at the lungs

○

Unloading CO2 at the lungs (bicarbonate formation):

•

10% dissolved CO2○

30% carbamino compounds○

60% bicarbonate○

Source of CO2 evolved in the lungs:•

Blood w/ decreased O2 can carry CO2

better○

Shifts curve up○

Increases CO2 carrying efficiency○

Haldane Effect•

Haldane & Bohr Effect InteractionOxygenated blood reaches metabolicly active tissues

•

The Bohr effect (low pH etc.) shifts the O2

dissociation curve to the left•

O2 is released•Release of O2 increases the CO2 carrying capacity of the blood (Haldane effect)

•

The CO2 dissociation curve is shifted up•The effectiveness of CO2 transport is increased

•

CO2 is carried away•

Blood-Gas Transport

Physiology

Steps in HemostasisHemostasis are the steps taken by the body to limit blood loss

•

Vascular spasm1.Formation of platelet plug (sometimes only need 1 & 2)

2.

Formation of blood clot3.Repair of damage4.

Four steps:•

PlateletsPlatelets are actually cell fragments•Physiological range is 150,000-300,000/um3•Production of platelets is controlled by thrombopoietin•

Protein hormone (like EPO)○

Produced by liver & kidney○

Increases differentiation of stem cells & maturation rate

Found on platelets, megakaryocytes & hematopoietic cells

○

Thrombopoietin (TPO)•

Continually secreted○

Internalize & destroy TPO

Platelets bind TPO (MPL receptor)○

Very little amt of free TPO to act on megakaryocytes

Little platelet production

A high number of platelets means a large amt of TPO is bound

○

Large platelet production

Low number of platelets has opposite effect○

Control of TPO secretion•

Platelet Contents

Cell contraction○

Actin & myosin•

ATP & ADP○

Mitochondria•

Ca++ storage○

Remnants of ER•

COX1•Fibrin stabilizing factor •

Repair○

Platelet derived growth factor•

Serotonin•

When activated, become sticky, adhering to other platelets

Glycoproteins○

On cell membrane:• Step 1. Vascular Spasm

Direct response to injury○

No neurons○

Reflexes involved (minimally)○

Myogenic•

Step 2. Formation of Platelet PlugCollagen is exposed upon vessel damage•

Plasma protein

Bind between collagen & platelet receptor

VonWillebrand factor1.

Binding of platelet receptor (integrin) directly to collagen

2.

Platelets bind to collagen in two step process•

Platelet swells & extends podocytes○

Activation of platelet•

Platelets bind to each other and vessel wall

Make platelets sticky○

Thromoxane A2 & ADP○

Contraction releases granules from platelet•

Step 3. Blood Coagulation

Formation of prothrombin factor1.

Prothrombin is converted to thrombin

Activation of thrombin2.

Thrombin converts fibrinogen to fibrin monomer

Fibrin stabilizing factor (from platelets) causes monomers to polymerize

Creation of fibrin from fibrinogen3.

Three steps:•

Excess fluid is removed from within clot

○

Requires Ca++

Actin & myosin in platelets contract, pulling clot together

○

Clot retraction•

Step 4. Repair of DamagePlatelet-derived growth factor (secreted by platelets) stimulates fibroblast growth

•

Fibroblasts differentiate into smooth muscle etc. to close hole•

Hemostasis

Physiology

Clot RemovalThrombin converts Protein C into Activated Protein C

•

tPA inhibitor can no longer inhibit plasminogen activator

○

Plasminogen activator is released by damged tissue

○

Activated Protein C inactivates tPA inhibitor

•

Made by liver

Floating in plasma

Plasminogen○

Plasminogen is converted into plasmin•

Plasmin lysis fibrin within the clot•

Preventing Clotting

Prevents platelet rupture

Blood vessels have a smooth surface○

Glycocalyx repels platelets

Thrombomodulin changes thrombin activity

Membrane proteins○

Blood vessels•

Binds thrombin & prevents it from working

Fibrin○

Causes vasodilation

Limits platelet aggregation

Prostacyclin (PGI2)○

Works as anticoagulent when bound to thrombin

Antithrombin III○

Derived from mast cells

Increases antithrombin efficacy

Heparin○

Chemicals•

Impaired Hemostasis

<25,000 platelets○

Produces spontaneous bleeding○

Stem cell damage

Leukemia

TPO or mpl gene mutation

Causes:○

Thrombocytopenia•

Vitamin K deficiency•

Genetic absence of clotting factor

Hemophilia○

Congenital absence of vWF

VonWillebrand's disease○

Alteration of platelet receptor of collagen molecule

○

Genetic•Inappropriate ClottingRough surfaces on blood vessels•

Thrombosis○

Blood stasis (slow moving)•

Clots are small/asymptomatic○

Uncontrolled bleeding ensues

Clotting proteins are eventually exhausted○

Disseminated intravascular coagulation (DIC)•

Physiology

AutomaticitySome cardiac tissues will gradually depolarize during phase 4

•

SA node○

AV node○

Purkinje fibers○

Tissues include:•

Begin opening during phase 3○

Continue to open during phase 4○

Cause membrane potential to gradually depolarize

○

Slow depolarization in phase 4 is due to special Na+ channels

•

Normal pacemaker○

Sinus rhythm○

SA node usually depolarizes first•

AP's originating anywhere else besides the SA node (ectopic pacemaker)

○

In absence of ventricular depolarization, Purkinje fibers take over (overdrive suppresion)

○

Ectopic focus•

Action Potentials

Intercalated disks & gap junctions○

APs spread throughout heart as if it was one, giant cell

•

When AP's spread throughout the tissue, they eventually meet

○

Once they meet, they cannot proceed further as the tissue in front of them is in a refractory period

○

When AP's never meet

AP "chases it's tail" around and around the heart

Fatal

Reentry○

Termination of AP's•

Parasympathetic further slows, sympathetic speeds up

○

When AP travels from SA node through the atria, it reaches the AV node where conductance is drastically slowed down

•

Autonomic Influences

Positive chronotropic effect○

Beta 1 receptors○

Norepi○

Increases Ca++ permeability○

Sympathetic stimulation increases the depolarization rate

•

Negative chronotropic effect○

Muscarinic receptors○

Ach○

Increased K+ permeability○

Parasympathetic stimulation decreases depolarization rate

•

Electromechanical CouplingAP travels along surface of myocytes•AP penetrates cells via T-tubules•Ca++ enters the cell from the surface and T-tubules during AP plateau

•

Different from skeletal muscle○

The elevated intracellular Ca++ trigers more Ca++ release from the SR

•

Ca++ binds to troponin & contraction proceeds

•

Top is contractive force, bottom is tension force.

Force of Contraction

Frank-Starling law of the heart○

The more actin/myosin fibers are stretched, the stronger the force of contraction

○

Preload is defined as the tension on the ventricular or atrial walls as contraction begins

○

PRELOAD•

Cardiac Electromechanical Coupling

Physiology

Sympathetic Stimulation

Norepi & cardiac glycosides (Digoxin) have same effect by inhibiting Na+/K+ pump

Increases intracellular Ca++○

Causes a greater force of contraction (along w/increased speed)

•

Shortens phase 2 (systole)○

Also increases rate of Ca++ reuptake•

Parasympathetic has only a weak effect on contractile myocytes

•

K+/Ca++ Changes

Causes hyperpolarization○

Low K+ leads to membrane depolarization because loss of ability to pump Na+ out

Needs K+ for ion exchange

Influences Na+/K+ pump○

Hypokalemia•

Partial membrane depolarization○

Reduced amplitue of the AP

Causes a slowed AP & alters phase 3○

Hyperkalemia•

Causes decreased contractility○

Hypocalcemia•

Increased contractility○

Hypercalcemia•

EKG

AP spreading through atria○

P wave•

AP spreading through the ventricles○

QRS•

Repolarization of the ventricles○

T wave•

Atrial repolarization is hidden in the QRS complex•

The last cell to depolarize is the first to repolarize○

Repolarization in the ventricles occurs mirror-like•

Physiology

EKG CharacteristicsMeasures electrical POTENTIAL, not contraction•

Different from intercellular potential, which was measures by sticking electrodes WITHIN the cell

○

EKGs are measured from the outside○

Therefore, opposite○

At rest, the extracellular potential in the heart is +90mV

•

During phase 2, the extracellular potential is -15mV•

Part of the cardiac tissue is at a different potential than the rest of the heart

○

No change when atria and ventricles are different potential because they are electrically isolated

AND current can flow between those regions○

A change in the EKG is only seen when •

Cardiac Depolarization Path

Depolarizes atria○

P wave○

SA node•

Delays signal ○

PR interval○

AV node•

Bundle of His•Purkinje fibers•

Generally from right to left○

Apex to base○

Prolonged QRS could indicate ventricular damage

QRS complex○

Ventricles depolarize•

QT interval○

Action potential phase 2 delays repolarization

•

T wave○

From left to right and base to apex○

Last cell to depolarize is first to repolarize (due to K+ channels)

○

Ventricles repolarize•

Atrial repolarization is buried in the QRS complex

•

EKG Leads

RA - Right arm

LA - left arm

LL - left leg

Placement○

Connects LA to RA

Looks right to left through heart

Lead 1○

Connects RA to LL

Looks from upper right to lower left

Lead 2○

LA to LL

Upper left to lower left

Lead 3○

Standard limb leads•

Lead 1, 2 & 3 form Einthoven's triangle•

Between RA and combo of LA & LL

Lower left to upper right

aVR○

Between LA and combo of RA & LL

Lower right to upper left

aVL○

Between LL and combo of RA & LA

Looks directly down

aVF○

Augmented leads•

STANDARD LEADS

AUGMENTED LEADS

Basic EKG

Physiology

Cardiac Output (CO)

TPR (total peripheral resistance)○

CO = Q (or flow)○

Assume venous pressure equals 0

BP is just mean arterial pressure

BP = change in BP (mean arterial pressure - venous pressure)○

CO = BP/TPR•

SV (stroke volume)○

HR (heart rate)○

EDV (end diastolic volume)

ESV (end systolic volume)

SV = EDV - ESV○

EF = SV/EDV x 100%

Ejection fraction is the percentage of blood pumped out with each beat

○

CO also equals SV x HR•

Cardiac Function

Chronotropy

Change the HR1.

Inotropy

Change the force of contraction

2.

2 ways to alter cardiac function:

•

Sympathetics go to the SA & AV nodes

○

Secrete norepi which acts on Beta-1 receptors

○

Sympathetic regulation•

Vagus N. goes to both SA & AV nodes

○

Secrete Ach which acts on muscarinic receptors

○

Parasympathetic regulation•

Vasomotor Center

Sense changes in systemic arterial BP○

Mean firing rate is proportional to BP ○

Acts on vasomotor center in the medulla○

High pressure baroreceptors are located in the carotid sinus & the aortic arch

•

Chemoreceptors that are stimulated to increase ventilation simultaneously increase the HR

•

Low pressure baroreceptors increase HR•

Inotropy

Frank-Starling Law of the heart

Intrinsic 1.

Mediated by autonomic system

Extrinsic2.

Contractility (inotropy) is controlled by two mechanisms:

•

Cardiac Output

Physiology

Velocity

Therefore, the velocity is the least○

The greatest summed cross sectional area is in the capillaries•

In a closed tube, the diameter and velocity are inversely proportional if flow remains constant○

When diameter decreases, pressure decreases and velocity increases

Pressure drops over clot and velocity increases□

Seen with artherosclerosis

Diameter and hydrostatic pressure are directly proportional○

Velocity vs. Pressure•

Flow (Q)

R = 8Ln/r4π○

P1 = inpt pressure○

P2 = output pressure○

r = radius○

n = velocity○

L = length○

Poiseuille's Law○

R = resistance○

Q = (P1-P2)r4π/8Ln

Rearranged:○

Q = P1-P2/R•

Could substitute CO, TPR etc.•Radius is the most important factor influencing resistance

•

Excess RBCs

Increased blood viscosity

○

Polycythemia•

ResistanceMost resistance resides in the arterioles which represent the most important component in altering resistance through changes in vessel diameter

•

Increasing vessel length increases diameter•Adding vessels in parallel (pregnancy) decreases the resistance

•

Laminar flow reduces resistance•

Due to high velocity○

Vessel irregularities○

Stenosis○

Potentiates artheriosclerosis○

Turbulent flow increases resistance•

ComplianceHow easily the vessels or heart can be stretched•Expansion in the heart & arteries stores energy•

Pulse PressureDifference between systolic & diastolic pressure

•

Flow & Resistance

Physiology

Peripheral Circulatory ControlMeant to control flow, not BP•

Reduces pressure□

Increased pressure causes vasoconstriction (myogenic reflex)

Increased sheer stress causes vasodilation

Mechanical force on the vessel wall change tone○

Metabolic products○

Local control of flow is mediated by altering the resistance/ vessel radius by:•

Increase in BP stretches walls of arterioles○

Stretch causes smooth muscle contraction○

Purpose is to maintain tissue flow, not alter TPR (although there would be a small increase)

Vasoconstriction increases R to the tissue○

Net effect is that if central BP changes, tissue flow remains the same○

Myogenic reflex•

Downstream resistance decreases due to increased metabolism, flow increases○

NO is secreted causing vasodilation

This upstream change compliments downstream changes

Upstream this causes a drag on endothelial walls○

Sheer stress•

CO2, H+, K+, or O2 reduction causes vasodilation○

Reduction in resistance increases flow○

Metabolic regulation•

Reactive Hyperemia

Causes an extreme vasodilation due to accumulation of vasodilator substances

○

Vascular inflow to an area is interrupted or obstructed

•

When flow is returned, the area is flooded with a great than normal flow (hyperemia) possibly causing damage

•

Special CirculationsHeart ignores sympathetic stimulation of the vasculature of the heart and only responds to local control

•

Brain also ignores sympathetic stimulation•

Directs blood to areas that have O2○

Pulmonary circulation lacks sympathetic stimulation but instead vasoconstricts to alveolar hypoxia

•

Local Control

Physiology

AfterloadPressure or forcethe heart must develop to produce ejection

•

BP = CO x TPR•Increasing TPR increases afterload•

Vessels

Baroreceptor firing decreases○

HR increases

Contractility increases

Vessels increase TPR

BP increases

Norepi stimulates Beta-1 receptors□

In contractile tissue (heart):

Releases of norepi stimulates alpha receptors

□

In vasculature:

Sympathetic activity increases○

As BP decreases:•

Increases contractility and SV□

Increases preload

Vasomotor center causes vein constriction○

Venous•

Can cause either constriction or dilation○

Beta-2 receptors

Dilation○

Alpha receptors

Constriction○

Adrenal glands•

Low Pressure BaroreceptorsLocated in low pressure areas such as the atria & pulmonary vasculature

•

Increased atrial volume causing increased HR

○

Vasodilation & fluid excretion in response to increased BP

○

Reflexes:•

Can act as "brakes" when BP may become to high

•

Measuring CO

Beilman○

Thermal dilution method•

Dye dilution•

Uses O2○

Fick method•

High flow will dilute to greater extent than low

•

Central Control

Physiology

Normal Pressure• Pressure in the pulmonary arteries pushes

the blood towards the capillaries

○ Pressure in the pulmonary capillaries (7mmHg)

• Wedge pressure

• Pressure in pulmonary veins is ~1-6mmHg

Gravity and the Lungs

○ Blood pressure in the capillaries at the bottom of the lungs is higher than that at the top

• The blood at the top of the lungs pushes down on the blood below

Capillaries at the top Closed/collapsed at rest

○ Zone 1

Closed during diastole, open during systole

○ Zone 2

Capillaries are always open○ Zone 3

• Zones in the lung

Resistance

Stretching of Vascular walls Increased radius reduces

resistance

□ Increase in flow causes a decrease in resistance that limits the increase in BP

□ Pulmonary circulation must be maintained at low pressure

BP = Q x R

1. Passive

If O2 alveolar concentration falls, vessels in that area increase their resistance by constricting (hypoxic vasoconstriction)

2. Response to O2

• Pulmonary resistance is altered using two mechanisms:

Bronchial Artery• Originates from left side of the heart• Delivers oxygenated blood to the lungs

Blood leaves the left heart and returns to the left heart w/o passing throung pulmonary circulation

○ Right to left shunt

Similar to above but starts in right ventricle and doesn't pass through systemic capillary bed

○ Left to right shunt

• Part of bronchial artery results in a right to left shunt

• Right to left shunt from bronchial artery is when the venous end empties into the pulmonary venous circulation

Fluid Movement• Net filtration pressure is positive and

fluid continuously leaves the capillaries

○ Surfactant○ Lymphatic drainage○ Interstitial oncotic pressure○ Negative interstitial hydrostatic

pressure

• Alveoli don't fill w/ fluid because

Pulmonary Edema• When interstitial hydrostatic pressure

is to great and fluid enters the alveoli

○ Capillary inflammation○ Pulmonary hypertension○ CHF○ Alveolar hypoxia

• Caused by:

Gas Pressures

○ 79% Nitrogen○ 21% Oxygen

• Dry air contains:

○ 47mmHg ○ So when calculating partial pressures

(760mmHg total at sea level) must subtract 47mmHg before calculation

• Nasal passages saturate air w/ water

Pulmonary Blood Flow

Physiology

Right Ventricular Function

○ Causes increased systemic pressure

○ Seen as elevated JVP of edema (ascites)

• RV failure causes backup of fluid into systemic circulation

Left Ventricular Function

RV pumps harder to increase flow through lungs

Pulmonary vasculature dilates to decrease resistance and keep pressures in check

○ Exercise

• Normally, right heart and lungs adapt to changes induced by the systemic circulation and left ventricle

Increased leakage of fluid out of pulmonary circulation and into interstitium

CHF Heart failure cells

○ If LV fails to pump all blood received from pulmonary circulation, blood backs up into the lungs

• LV failure

Physiology

β-Lactams

Narrow is effective only against one (or one group of) species

○

Extended has an intermediate range of activity

○

Broad has a spectrum against a wide range of bugs

○

Spectrum•

Inhibits cell wall synthesis by binding to Penicillin binding proteins (PBPs)

○

MOA•

β-lactamase degradation○

PBP alteration (MRSA, pen-resistant S pneumoniae (PRSP))

○

Decreased penetration○

MOR•

Except against Enterococcus○

Time-dependent○

Bacteriocidal•

Used in combo with β-lactams to overcome resistance due to degradation

○

Clavulanate○

Sulbactam○

Tazobactam○

Amox/clav

Amp/Sulb

Pip/Sulb

Ticar/Clav

Combos include:○

β-lactamase inhibitors (anti-β-lactamases)

•

Important for patients with renal failure

○

Some preparations of IV penicillins contain a large amount of sodium

•

Combined with imipenem to prevent degradation of imipenem by dehydropeptidase (dehydropeptidase inhibitor)

○

Cilastatin•

Glycopeptides & Others

Binds firmly to D-alanine-D-alanine portion of cell wall precursors

Inhibits addition of peptidoglycan units to growing polymer chain

MOA○

Some Enterococcus sp. show resistance (VRE)

Bacteriocidal (except Enterococcus)○

Terminal D-ala replaced with D-lactate

MOR○

Not absorbed via the gut

Good for treating C. difficile orally because it will not be absorbed and thus stay in the gut and kill C. difficile

Given IV (except for C. difficile)○

Flushing, rash etc. on face and torso□

Red-Man syndrome

Adverse effects○

Vancomycin•

D-ala-D-ala (like Vanco) but also depolarizes cell membrane

Concentration dependent

MOA○

Metallic taste

Foamy urine

Abnormal fetal development, do NOT take while pregnant

□

BLACK-BOX warning

Adverse effects○

Telavancin•

Cyclic lipopeptide○

Causes rapid depolarization of cell membrane


MOA○

IV only○

Death, serious complications

DO NOT use to treat pneumona○

Reserved for serious infx caused by resistant bacteria

○

Myopathy and CPK elevation

Adverse effects○

Daptomycin•

Inhibits incorporation of AAs and nucleotides into cell wall

○

Bacteriostatic○

Causes nephrotoxicity when used systemically (topically only)

○

Bacitracin•

Cell Wall Synthesis Inhibitors

Pharmacology

β-LACTAMS

CLASS FAMILY PRE/ SUFFIX

NAME(S) SPECIAL/DOC

Penicillins Natural penicillins

-cillin Penicillin G, Penicillin VK

Syphillis, Neisseria meningitidis, pen-susceptible S. pneumoniae

Penicillins Penicillinase-resistant penicillins

-cillin Nafcillin, Dicloxacillin, Oxacillin, Methicillin

Anti-Staphylococcal (MSSA), especially skin & soft tissue; can cause renal failure (methicillin & nafcillin)

Penicillins Aminopenicillin -cillin Ampicillin, Amoxicillin

Greater action against gram (-) aerobes; Enterococcal infections

Penicillins Anti-Pseudomonal penicillins

-cillin Ticarcillin, Piperacillin

Pseudomonas aeruginosa, Bacteroides, Clostridium (not difficile)

Cephalosporins 1st Gen. Cef- Cefazolin, Cephalexin, Cefadroxil

Best against gram (+) aerobes; do not penetrate the CNS; surgical prophylaxis

Cephalosporins 2nd Gen. Cef- Cefuroxime, Cefoxitin, Cefotetan, Cefprozil

Better than 1st Gen. against gram (-) aerobes; some anaerobes

Cephalosporins 3rd Gen. Cef- Cefdinir,Cefixime, Cefotaxime, Ceftazidime, Ceftibuten, Ceftizoxime, Ceftriaxone

Greater against gram (-) aerobes; SOME are best for gram (+) aerobes including PRSP (Ceftriaxone & cefotaxime); P. aeruginosa(ceftazidime); can cross BBB

Cephalosporins 4th Gen. Cef- Cefepime Extended spectrum gram (+) & (-); P. aeruginosa & Enterobacter sp.; cross BBB

Carbapenems -enem Imipenem/cilastin, Ertapenem, Meropenem

Most broad spectrum of activity of all antimicrobials; hospital-aquired infx, polymicrobial infx & empiric therapy; NOT covered include MRSA, VRE, coag (-) staph., C. difficile, S maltophilia, Nocardia;cross BBB; Imipenem can cause seizures

Monobactams Aztreonam Gram (-), including P. aeruginosa;Penicillin-allergic patients who need gram (-) coverage; cross BBB

Pharmacology

GLYCOPEPTIDES & OTHER

CLASS NAME(S) SPECIAL/DOC

Glycopeptides

Vancomycin MRSA, gram (+) bacteria (especially those with allergies to β-lactams

Glycopeptides

Telavancin/Vibativ® MRSA, gram (+)

Other Daptomycin Gram (+), MRSA, VRE, Enterococcus faecalis

Other Bacitracin Gram (+) & (-); Used topically

Pharmacology

Selection of Antimicrobial Drugs

Tetracycline produces tooth discoloration and enamel hypoplasia

Pregnancy○

Older people have lower clearance rates

Can't give tetracycline to kids under 8 (teeth)

Age○

Host factors•

Antimicrobial activity•

Chloramphenicol

Tetracyclines

TMP-SMZ

Drugs that do penetrate include:

□

CNS

Bone

Prostrate

Ocular tissue

Sites not easily penetrated by drugs○

Pharmacokinetic properties•

Adverse effects•Cost•

Tetracyclines

Inhibit bacterial protein synthesis by binding to 30S subunit

○

Bacteriostatic○

MOA•

Efflux of tetracycline○

Decreased permeability○

Enzymatic inactivation○

MOR•

Good tissue penetration○

Minimal CSF penetration○

Distribution•

Photosensitivity○

Discoloration of teeth in children○

Adverse effects•

GlycylcyclinesTigecycline is only drug•

Binds 30S subunit (5x higher than other tetracyclines)

Similar to other tetracyclines○

MOA•

Macrolides/KetolidesInhibit protein synthesis by binding to 50S subunit•

Time-dependent○

Bacteriostatic•

S. pneumoniae○

Mef gene encodes for efflux pump

Active efflux○

Erm gene alters binding site

Altered target sites○

MOR•

Minimal CSF penetration○

Distribution•

GI effects○

Elongation of QT interval○

Adverse effects (Macrolides)•

Dizziness, headache

CNS○

Severe liver injury

Hepatotoxicity○

Blurred vision○

Worsening symptoms

Contraindicted for patients w/myasthenia gravis○

Elongation of QT interval○

Adverse effects (Ketolides)•

Aminoglycosides

Binds to 30S subunit

Inhibition of protein synthesis○


Bacteriocidal○

MOA•

Decreased penetration○

Aminoglycoside-modifying enzymes

○

Alteration in binding site○

MOR•

Vertigo, hearing loss etc.

Ototoxicity○

Acute tubular necrosis

Nephrotoxicity○

Neuromuscular blockade○

Hypersensitivity reactions○

Adverse effects•

Streptogramins Chloramphenicol

Protein Synthesis Inhibitors

Pharmacology

CLASS NAME(S) PRE/SUFFIX

SPECIAL/DOC

Tetracyclines Demeclocycline, Doxycycline, Minocycline, Tetracycline

-cycline Community-aquired pneumonia (doxycycline); Rickettsial Infx (RMSF); Chlamydia; Anthrax; Lyme disease (DOC for Borrelia burgdorferi)

Glycylcyclines Tigecycline NA Gram (+) & (-) aerobes, MRSA & VRE; Doesn't cover P. aeruginosa; Both types of pneumonia; intraabdominal infections

Macrolides/ Ketolides

Azithromycin, Clarithromycin, Erythromycin, Telithromycin (Ketolide)

-thromycin Gram (+) & (-) aerobes; Intracellular organs (STDs); Mycobacterium; Telithromycin covers all macrolides PLUS multi-drug resistant Streptococcus pneumoniae

Aminoglycosides Amikacin, Gentamicin, Neomycin, Streptomycin, Tobramycin

-mycin/ -micin

Gram (+) & (-) aerobes, not streptomycin; Mycobacteria (tuberculosis)

Streptogramins Quinopristin/ Dalfopristin (Synercid®)

NA VRE, MRSA, MSSA or Streptococcus pyogenes; not active against E. faecalis

Oxazolidinones Linezolid NA MRSA, VRE & E. faecalis;

Clindamycin Clindamycin NA Gram (+) & (-) Anaerobes outside of the CNS

Chloramphenicol Chloramphenicol NA Gram (+) & (-) aerobes & anaerobes; spirochetes; Rickettsia; chlamydia,

Streptogramins

Combo agent that acts on 50S subunit

○

Protein synthesis inhibitor○

Bacteriostatic○

MOA•

Alterations in binding sites○

Enzymatic inactivation○

MOR•

Clindamycin

Binds 50S subunit○

Bacteriostatic○

MOA•

Erm gene


Mef gene encodes for effllux pump

Active efflux○

MOR•

GI○

C. difficile colitis○

Adverse effects•

Chloramphenicol

Binds to 50S subunit○

MOA•

Penetrates CNS•Limited usee due to adverse effects•

Bone marrow suppression

Anemia, leukopenia etc.

Aplastic anemia (fatal)

Hemolytic anemia

Hematologic○

High serum concentrations□

Newborns have a decreased ability to conjugate drug

Gray baby syndrome○

Optic neuritis

Headache, depression & confusion

CNS○

Adverse effects•

OxazolidinonesOnly Linezolid•

Binds 50S subunit○

Bacteriostatic○

Time-dependent○

MOA•

Moderate CSF penetration•

Pharmacology

Flouroquinolones

Inhibit topoisomerases○

Concentration-dependent○

Bacteriocidal○

MOA•


Altered cell wall permeability○

Active efflux○

MOR•

GI○

Headache, hallucinations, insomnia

CNS○

Extended QT interval

Cardiac○

Articular damage○

Tendonitis○

Adverse effects•

Metronidazole

Inhibits DNA synthesis○

Given as a prodrug○

Concentration-dependent bacteriocidal○

MOA•

GI○

CNS○

Avoid during pregnancy○

Adverse effects•

SulfonamidesMetabolic inhibitor•

Inhibits dihydrofolate reductase (DHFR)○

MOA•

Individually are bacteriostatic, together are bacteriocidal

○

TMP-SMX•

Point mutations in DHFR○

MOR•

GI○

Hematologic○

Skin disorders○

Adverse effects•Anti-pseudomonal Antibiotics

Ticarcillin○

Piperacillin○

Penicillins•

Carbapenems•Aztreonam•Cipro•

Ceftazidime○

Cefepime○

Cephalosporins•

Gentamicin○

Tobramycin○

Amikacin○

Aminoglycosides•

Anti-MSSA Antibiotics

Nafcillin/Oxacillin○

Dicloxacillin○

Amox/Clavulanate○

Ticar/Clav○

Pip/Tazo○

Penicillins•

Imi, dori, erta, mero○

Carbapenems•

Anti-MRSA Antibiotics

DOC for hospital aquired MRSA○

Vanco•

Teicoplanin•Dapto•Linezolid•TMP-SMX•Clindamycin•Tigecycline•

Agents for C. difficile

Vanco○

Teicoplanin○

Telavancin○

Glycopeptides•

DOC for C. diff colitis○

Metronidazole•

Doripenem○

Ertapenem○

Imipenem○

Meropenem○

Carbapenems•DOCs

Syphilis○

Neisseria meningitidis○

Penicillin•

Lyme disease○

Borrelia burgdorferi○

Tetracycline•

Legionella pneumophila○

Macrolides & Flouroquinolones•

MRSA hospital aquired○

Vanco•

Pseudomembranous colitis due to C. difficile

○

Metronidazole•

Pneumocystis jiroveciipneumonia

○

TMP-SMX•

Nucleic Acid Synthesis & Metabolic Inhibitors

Pharmacology

CLASS FAMILY NAME(S) PRE/SUFFIX

SPECIAL/DOC

Flouroquinolones 1st Gen. Nalidixic acid NA Gram (+) & (-); atypicals; DOC for Legionella pneumophilia; RTIs; UTIs; STDs

Flouroquinolones 2nd Gen.

Ciprofloxacin, Norfloxacin, Ofloxacin

-xacin "

Flouroquinolones 3rd Gen. Levofloxacin -xacin "

Flouroquinolones 4th Gen. Moxifloxacin, Gatifloxacin

-xacin "

Metronidazole NA Metronidazole NA Protozoa; anaerobes (including CNS); DOC for pseudomembranous colitis due to C. difficile

Sulfonamides NA Trimethoprim/ Sulfamethoxazole (TMP-SMX)

NA RTIs; DOC for Pneumocystis jiroveciipneumonia; traveler's diarrhea (Salmonella & Shigella)

Pharmacology

Lung Development

Positioning of lung primordium and primary lung bud formation

Early○

Mechanism of bronchial branching and cytodifferentiation

Late○

Early and late phases•Early Phase

Linked to an increase in retinoic acid produced by adjacent splanchnic mesoderm

○

Location determined by TBX4•

Originates from the foregut○

Stems from endoderm○

Outgrowth of foregut grows into the surrounding mesoderm

○

Development begins in week 4 w/ formation of laryngeotracheal diverticulum

•

Tracheoesophageal FistulaMost common malformation•Abnormal connection between trachea & esophagus

•

Caused by improper formation of tracheoesophageal septum

•

Development of the BronchiLeft & right bronchial buds form around week 5

•

Trachea & bronchi are endoderm, everything else is mesoderm

•

Stages in Lung Development

Formation of laryngeotracheal diverticulum & all major bronchopulmonary segments

○

Embryonic (weeks 4-7)•

Major formation of duct systems○

No respiratory components○

Glandular stage (weeks 8-16)•

Formation of respiratory bronchioles & terminal sacs (primitive alveoli)

○

Begin of POSSIBLE viability○

Premature birth before this stage is deadly○

Canalicular stage (weeks 17-26)•

Primarily through septation of existing alveoli

Up to 90% of alveoli form after birth○

Postnatal•

Cell Types

Form part of blood-air barrier○

Type I pneumocyte•

Secretory cells○

Produce surfactant○

Type II•

Terminal sacs (alveoli) develop from respiratory bronchioles

•

Respiratory Distress SyndromeOccurs primarily in immature lungs•Labored breathing•Deficiency/absence of surfactant•Congenital Neonatal Emphysema

Over distention w/ air of one or more lobes of the lung•Caused by collapsed bronchi•Bronchial cartilage doesn't develop• Pulmonary Agenesis

Complete absence of lungs, bronchi & vasculature

•

Bronchial buds don't develop•

Respiratory System

Embryology

Pulmonary HypoplasiaPoorly developed bronchial tree•

This provides lung distention & is necessary for normal development

○

During normal development, amniotic fluid enters the lungs through fetal breathing

•

Pulmonary hypoplasia is a result of lack of distention of lungs & increased amniotic fluid pressure from the OUTSIDE IN (versus correct pressure from within the lungs)

•

Potter syndrome•

PolyhydramniosFetus also swallows amniotic fluid•Polyhydramnios develops if fetus is unable to swallow

•

Associated w/ CNS abnormalities & esophogeal atresia

•

Partitioning of the Body Cavity

Forms between heart and lungs○

Grows lateral to medial○

Phrenic nerve (C3-5) grows with formation○

Pleuropericardial membrane•

Seperates lungs and abdominal cavity○

Sheets of somatic mesoderm from dorsolateral wall○

Pleuroperitoneal membrane•

Seperates heart and abdominal cavity○

Septum transversum•

Septum transversum forms central tendon○

Pleuroperitoneal membranes○

Sources of the diaphragm•

Congenital Diaphragmatic HerniasHerniation of abdominal contents into the pleural cavity

•

Embryology

Follow OLDCARTSMP3○

Most common clinical component/symptom is pain

• Five Finger Method

Art of taking a good history is everything○

History•

Physical•EKG•X-Ray•Lab•

PhysicalCheck jugular venous pressure (JVP)

•

PMI (point of maximal impact)

○

Apex of heart found lower left (5th intercostal)

○

Precordial palpation•

Not to useful○

Percusion•

Heart sounds•Grading system of murmurs•

Inspection○

Palpation○

Percussion○

Auscultation○

Perform the proper sequence:•

History

Non-specific○

Fatigue, dyspnea, chest pain, palpations, syncope•

Hypertensive

Ischemic

Infection

Congenital

Valves

Underlying etiology will usually be one of the following:

○

Which chamber is involved

Which valve

Listen while patient leans forward to hear friction between visceral and parital pericardium

□

Pericardium

MI?

Anatomical abnormalities○

Arrythmia

CHF

Physiological disturbance○

How strenuous is the physical activity necessary to elicit symptoms

No physical limitations□

Class I

Slight limitation□

Ordinary activity causes symptoms□

Class II

Marked limitation□

Less than ordinary activity elicits symptoms

□

Asymptomatic at rest□

Class III

Symptomatic at rest□

Class IV

Functional disability○

Always consider:•

Scale for Risk of Heart Disease Development

People who have risk factors, but at this time do not have any impairment

A.

People with structural changes but no symptoms yet

B.

Patient with current symptoms of disease

C.

Advanced diseaseD.

4 stages:•

Murmurs Grading SystemBarely audible1.Soft2.Loud, without thrill3.Loud with thrill4.Loud with minimal contact of stethescope & thrill

5.

Loud, can be heard w/o stethoscope, thrill

6.

Thrills can be felt•

Normal Heart

Internal Med

Jugular Venous Pressure

1st heart sound○

Mitral, tricuspid closure○

S1•

2nd heart sound○

Aortic, pulmonic closure○

S2•

S1 - S2○

Systole•

Beginning of S2○

Diastole•

Atrical contraction○

Tricuspid valve is open○

Obsruction between RA & RV

Increased pressure in RV

Pulmonary hypertension

Atria contracts against a closed valve

□

Complete heart block□

"Cannon A waves"□

A-V dissociation

Giant A waves seen:○

A wave•

Backward push by the closure of the tricuspid valve

○

C wave•

Passive atrial filling○

Atria is relaxed○

Steep X descent indicates constrictive pericarditis

○

Tricuspid valve is still closed○

X wave•

Atria is filling as pressure increases○

Tricuspid valve is still closed○

V wave•

Open tricuspid valve○

Rapid RV filling○

Y Slope•

Measuring JVPPlace patient in supine position to allow veins to engorge, then raise patient to 30-45⁰

•

Add 5cm (due to RA 5cm below sternal notch)

○

Normal is 0-9cm○

Measure from sternal notch up to level of waveform in jugular vein

•

SVC obstruction

HF

Constrictive pericarditits

Also:○

Most common cause of elevated JVP is elevated RV diastolic pressure

•

Positive indicatesproblems○

Hepatojugular reflex (HJR)•

Kussmauls Sign

Seen in R heart failure○

Venous column rises during inspiration, rather than falls

•

Heart Sounds

Apex of heart○

Mitral•

4th left intercostal space (ICS)○

Tricuspid•

2nd right ICS○

Aortic valve•

2nd left ICS○

Pulmonary valve•

Internal Med

Shades of Gray

Air○

Fat○

Water○

Bone ○

Metal○

Dark to light•Most chest views are inspiration

Best visualized with an expiration chest view○

Rib Fx can lead to pneumothorax•

Cardiac SizeShould be 50% of less of entire chest diameter•

Cardiac Landmarks. 1.SVC 2.RA 3.Aortic arch 4.Main pulmonary artery 5.Left atrial appendage 6.Left ventricle

Etiologies of Alveolar Disease

Hemorrhagic○

Pneumonia○

Edema○

Aspiration○

Acute•

Lots○

Chronic•

Infiltrate visible○

Cough 5 days

Fever 102

Elevated WBC

Symptoms○

Round Pneumonia•

Infiltrate○

Cough 5 weeks

Fever 99

WBC ok

Symptoms○

An good history is the difference in diagnosis between cancer and pneumonia

○

Bronchogenic carcinoma•

X-Ray Signs of Interstitial DiseaseGround glass pattern•Nodular patterns•

Interstitial edema○

Kerley B's•

Interstitial fibrosis○

Honeycombing•

Interstitial edema○

Viral or mycoplasma pneumonia○

Pneumocystis carinae pneumonia○

Acute etiologies•

Lots○

Chronic etiologies•

Kerley B's visible above diaphragm. Interstitial edema.

Chest X-Ray Interpretation

Radiology

CP I Midterm

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Transcript of CP I Midterm