-essential to life

-brief loss of function= death

-impaired function= damage to other organs

-affected by a variety of primary and secondary disorders

-substrate delivery

-waste disposal

-endocrine signaling

-immune response

-thermoregulation

-hemorrhage

-myocarditis

-congenital malformations

-parasitic infection of heart and vessels

-burns, vomiting, diarrhea

-liver disease

-kidney disease

-GI tract disease

-heart rate

-heart sounds

-blood pressure

-capillary refill time

-mucous membrane color

-respiratory rate/effort

-body position

-edema

-Echocardiography

-Electrocardiography

-Radiography

-pump: heart

-fluid: plasma

-suspended particles: RBCs

-dissolved substances: Na+, Glucose, O2

-Tubing: vasculature

-LV

-Because the LV goes to the heart and lungs

-water

-ions and small molecules

-proteins

-formed elements

-Plasma (with anticoagulent)

-Cells

-Serum

-arterial circulation

-capillaries

-venous circulation

-fibers branch

-connect at intercalated disks: allows it to be electrically and mechanically linked

-self-excitable

-to electronically and mechanically link cardiac muscle cells

-functional syncytium: acts like same cell

-coordinated heart motion

-3rd most abundant protein in cardiac muscle

-30,000 AAs

-links Z line and M line

-gives muscle stifness, acts as a spring

1. AP in cardiac contractile cell

2. Travels down T-tubules

3. Entry of smal amount of Ca2+ from ECF

4. Release of large amnt of Ca2+ from SR

5. Inc Cytosolic Ca2+

6. Troponin-tropomyosin cplx in thin filaments pulled aside

7. Cross-bridge cycling between thick and thin filaments

8. Thin filaments slide inward between hick filaments

9. Contraction

-L-type Ca2+ channel (dihydropyridine receptor)

-SR Ca2+ release channel (ryanodine receptor)

-Location: plasma membrane

-Function: voltage activated, alows Ca2+ into cytoplasm

-Location: SR membrane

-Function: releases Ca2+ from SR for contraction (CICR)

-SR Ca2+-ATPase (SERCA)

-Na+-Ca2+ exchanger (NCX)

-Plasma membrane Ca2+ pump

-Location: SR membrane

-Function: pumps Ca2+ back into SR

**2nd largest user of ATP in cardiac muscle

-Location: plasma membrane

-Function: transports Ca2+ out of cell and Na+ in

-Phospholoamban

-Calsequestrin

-

-inhibits SERCA

-reversed by phosphorylation by PKA or CaMKII blocks ih, causing faster relaxation

-Ca2+ binding protein in SR

-helps SR contain in a large amnt of Ca2+ (18-50 Ca2+ ion per molecule)

-disease

-titin and dilated cardiomyopathy

-makes up the wall of hollow organs and tubes

-either/or

Where is vascular SMC found?

Is it tonic or phasic?

Single or multi-unit?

Myogenic?

-makes up the majority of vessel walls (except in capillaries)

-tonic

-single-unit

-myogenic

-cells are electrically linked by gap junctions

-tissue contracts as a single unit (most other smooth muscle, including vascular)

-contraction is initiated by nerves

**all multi-unit smooth muscle is neurogenic

-contraction is initiated by the muscle itself

***all single-unit smooth muscle is myogenic

=> contraction can still be modulated by NS influences

-long

-spindle-saped

-arranged in sheets

-not striated

-Ca2+ mainly from outside the cell (not SR)

-Ca2+-calmodulin dependent process

-changes in myosin (not actin) initiate cross-bridge cycling

-signaling pathways (NO, prostacyclin/ PGI2)

-stretch (muscle will relax to maintain constant tension)

-SR

-dephosphorylated (MLCP)

-SkM: somatic

-CM: autonomic

-SM: autonomic

-SkM: neurogenic

-CM: myogenic (pacemake potentials)

-SM: neurogenic or myogenic

-SkM: yes

-CM: yes

-SM: tropomyosin  only

-Sk: SR

-CM: ECF and SR

-Sm: ECF

-Sk: troponin

-CM: troponin

-Sm: myosin light chain kinase

-striated

-heart

-electrical

-mechanically

-nonstriated

-GI tract, repro tract, bladder, eye, skin, and blood vessels

-BP

-blood flow

-do not

-innervation only modifies heart rate (inc or dec)

-a denervated heart will continue to beat

0: depolarization

1: rapid (partial) repolarization

2: Plateau

3: Repolarization

4: resting membrane potential

0: Depolarization

1: Rapid/partial repolarization

2: Plateau

3: Repolarization

4: Resting membrane potential

-NA+, Ca2+, K+ current

-non-selective cation (+) current

-Na+: depolarizes

-K+: repolarizes

-Ca2+: depolarizes

-voltage-gated

-fast

-anesthetic effect on nerves

-Antiarryhthmic effect on cardiac cells

-Tetrodotoxin

-voltage-gated

-slow

Phase 4: Pacemaker current, dec K+ current

Phase 0: L-type Ca2+ channels open

Phase 1,2: not present in SA node AP

Phase 3: Ca2+ channels close; K+ channels open

-Right= SA node

-Left= AV node

-ACh

-decreases it

-breath holding, dipping face in cold water, coughing, tensing abdominal muscles

*mammalian diving reflex

Phase 4: no major currents active

Phase 0: Fast Na+ channels open

Phase 1: Fast Na+ channels close

Phase 2: L-type Ca2+ channels open

Phase 3: L-type Ca2+ channels close; K+ channels open

-cell is repolarizing

-some Na+ and Ca2+ channels can be activated

-SA node fails (sinus arrest)

-APs from SA node not normally conducted by the AV node

-"AV node block"

-Slow

-To deliberately delay ventricular depolarization to allow ventricles time to fill before contracting

-limits number of APs from the SA node which are conducted to the ventricles

-prevents atrial flutter/ fibrillation from becoming centricular fibrillation

-prevents AP from being conducted back into atria from ventricles

-Sympathetic: inc

-Parasympathetic: dec

-Sympathetic: dec

-Parasympathetic: inc

-myofibers specialized for rapid electrical conduction

-few myofibrils, little contraction

-6

-150

-longer

-several

-pacemaker

-L-type Ca2+ channels

-funny current

-slow

-delay

PRESSURE

-Open P_upstream>P_downstream

-Close P_downstream>P_upstream

1. Inflow

2. Isovolumetric Contraction

3. Ejection

4. Isovolumetric Relaxation

-almost simultaneous

-Volumes are the same

-P in Right are lower

-vibrations from valve closure

-S1 (1st heart sound): closure of itral and tricupsid valves

-S2: closure of aortic and pulmonary valves

-S3: near end of ventricular filling, caused by inc tension in chordae tendinae

-S4: associated with atrial contraction

May be heard in normal horses

-L: smaller surface to volume ratio= high pressure development

-R: larger surface to volume ratio= low presssure development

-Volume of blood ejected by the ventricle with each beat

EDV-ESV

-percent of the blood ejected with each beat

SV/EDVx 100

-amount (mL) of volume put out per minute

SV x HR

-the reduction in the diameter of the left ventricle (LVD) that occurs during contraction

(LVD_diastole-LVD_systole)/(LVD_diastolex100

-Normal value: 35-40%

-proportional

-venous return

-inc

-inc

inc

-inotropic agents

-act by increased Calcium ion levels

-valve defect in which the valve does not close properly, blood leaks through

=>aka insufficiency, regurgitation

-Tricuspid Incompetence: blood flows from RV->RA

-Mitral Incompetence: LV->LA

-Ventricular septal defect (VSD): LV->RV

-Pulmonic Stenosis: RV->Pulmonary Artery

-Aortic Stenosis: LV->Aorta

-Pateent ductus arteriosus (PDA): Aorta-> Pulmonary artery

-Tricuspid Stenosis: RA->RV

-Mitral Stenosis: LA->LV

-Pulmonic Insufficiency: Pulmonary artery-> RV

-Aortic insufficiency: Aorta-> LV

-Patent ductus Arteriosus: PDA

What are the causes of Mitral/Triscuspid Regurgitation? (3)

What does it frequently cause?

-congenital, degenerative, infection

-frequently causes heart disease in dogs

-Mitral valve does not close fully, blood leaks back into LA

-inc work of the LV=> inc LA P

-eventually leads to left heart failure

-less common than MR, often found along with it

-inc RA P => inc RV work

-eventually leads to right heart failure

-valve does not close properly, causing regurgitation

-puts increased workload on heart, may progress to heart failure

-thickening and shortening of valve leaflets due to degeneration of CT

-thickened, stretched, or ruptured chordae tendinae

-inflammation of the endocardial layer caused by bacterial infection

-various causative organisms (infections)

-occurs on valves with damaged endothelium

damage=> exposure of sub-endothelial collaged=>platelet adherence and clot formation=> bacteria become embedded in the clot=> infection=> progressive destruction of valve

-aortic valve (left)

-pulmonary valve (right)

-the branching of vessels

Describe the change in the following from Aorta--> terminal arterioles:

a) individual vessel diameter

b) individual vessel area

c) number of vessels

d) total vessel area

a) individual vessel diameter dec

b) individual vessel area dec

c) umber of vessels inc

d) total vessel area inc

Describe the change in the following from Venules--> Vena cava:

a) individual vessel diameter

b) individual vessel area

c) number of vessels

d) total vessel area

a) individual vessel diameter inc

b) individual vessel area inc

c) number of vessels dec

d) total vessel area dec

-constant

-varied

-varied

From least to greatest, order the following in terms of aggregate cross-sectional area:

aorta, small arteries, arteioles, capillaries, vena cava

From least to greatest, order the following in terms of aggregate flow:

aorta, small arteries, arterioles, capillaries, vena cava

From least to greatest, order the following concerning mean linear velocity:

aorta, small arteries, arterioles, capillaries, vena cava

-slowest

-must allow time for gas exchange

-vascular endothelial cells (EC)

-vascular smooth muscle cells (SMC)

-fibroblasts, pericytes, leukocytes,nerve endings, vasa vasorum, connective tissue (adventitia)

-thin, flat cells in a single layer that lines all blood vessels

-Function: interface for gas exchange

-YES, exposed to flowing blood, thus shear stress

-cause them to orient to flow axis

-interface for exchange

-release vasoactive cpds (NO, prostoglanduns, edothelin, etc) to influence blood flow

-produce and respond to growth factors (VGEF) to cause new vessel growth

-interact with circulating BCs in inflammation

-regulates blood clotting

-normal endothelium inhibits clot formation (anti-thrombatic)

-DAMAGED OR ABSENT endothelium is pro-thrombotic

-all vessels larger than capillaries

-NOT directly exposed to any forces (b/c NOT directly exposed to blood)

Collagen fibers contribute stretch/tensile strength

conversely

Elastic fibers contribute stretch/tensile strength

Collagen=tensile strength

Elastic fibers= stretch

Between Arteries, Arterioles, Capillaries, and Veins order them from least to greatest concerning the following:

a) Endothelium thickness

b) Elastic fibers

c) Smooth muscle

d) Collagen fibers

a) All equal

b) arterioles and capillaries have none< veins< arteries

c) capillaries have none< veins< arterioles< arteries

d) capillaries have none < arterioles< arteries< veins

1) Intima: endothelial cells, smooth muscle cells, elastic fibers

2) Media: smooth muscle cells & elastic fiber

3) Adventitia: CT, mainly collagen

Describe the pressre, vascular wall, and flow rate of elastic arteries.

Any exceptions?

-Pressure: high due to pressure flow of oxygenated blood (except pulmonary artery)

-Thick wall

-High flow rate

-Pressure: high due to high-pressure flow of oxygenated blood

-High flow rate

-low pressure

-slow flow rate

-thin walls

-YES

-allowed by their ability for passive expansion

-how much change in volume occurs with a given change in pressure

-Veins, thinner walls

-dec

-inc

-opposite

-fastest

-slowest

-interface for exchange between blood and tissue

-regulate hemostasis

-contraction of underlyine SMC

-smallest arterioles

-capillaries

-smallest venules

-smallest branches of arteries, control entry of blood to capillary

-blood flow regulated by diamter ("resistance vessels")

-Metabolic control

-myogenic control

-circulating hormones

-neural control

-endothelium-derived substances

__________ + __________ = Autoregulation

Where is this relevant?

-Metabolic control+ Myogenic control= Autoregulation

-precapillary sphincters and arterioles

-dec O2

-inc CO2

-inc lactic/carbonic acid

-inc K (Na/K-ATPase can't restore gradient fast enough)

-inc osmolarity (inc metabolite levels

-Adenosine( breakdown of ATP)

-dec P= vasodilation to dec R

-inc P= vasoconstriction to inc R

-sympathetic

-can

-are not

            =>Adrenergic receptorsG-protein coupled

                        A1 :causes constriction, NE > EPI; IP3/Ca2+

                        B2 : EPI (adrenal gland); cAMP, causes relaxation (fight or flight/ adrenal medulla)

 => Cholinergic receptors:

                        Acetylcholine induces vasodilation; nitric oxide dependent

                        ***Quick rule: 1 – excitatory; 2 – inhibitory

                        -Endothelium-derived substances

-4-9 um in diameter

-single layer of endothelial cells

-Types: continuous, fenestrated, sinusoidal

-NOT CONSTANT

-opened and closed by precapillary sphincters periodically

-adipose tissue, muscle, placenta, lungs, CNS

-most common of the three types

-solute molecules move from hihger concentration to lower concentration WITHOUT COSTING E

-Simple diffusion: occurs unassisted

-Facilitated diffusion: carrier proteins

-concentration gradient: directly

-surface area: directly

-lipid solubility: directly

-molecular weight of the solute: inversely

-diffusion distance: inversely

-occur in response to inc metabolic demand

-Acute: opening of additional capillaries shortens diffusion distance

-Chronic: capillry proliferation (angiogenesis) shortens diffusion distance

-O2

-CO2

-FAs

-Hormones

-Drugs

-they both diffuse across capillary wall along concentrations gradients

-O2 high in capillary

-CO2 hich in tissue

OPPOSITE IN PULMONARY CIRCULATION

-continuous capillary

-have tight junctions, carriers, and aquaporins to constitute Blood-Brain Barrier

-AAs: osme are neurotransmitters

-Small molecules: like glucose

-Hormones

-Cytokines

-Proteins

-Some drugs

-inhaled anesthetics, hydrophobic, easily cross BBB

-ex: Sevoflurane, isoflurane, enflurane

-potency related to hydrophobicity

Definiciont: Fenestrated capillaries

Why are they fenestrated? Where are they found?

-capillaries with small holes (fenestrae) that are less than 0.1 um in diameter

-allows for rapid difussion of solutes and water (inc diffusion area)

-found in SI, exocrine./endocrine glands, kidney

Definition: Discontinuous/Sinusoidal Capillaries

Where are they found?

-leakiest capillaires with gaps large enough to allow proteins and whole cells to cross

-found in liver, spleen, and bone marrow

PROTEINS CAN CROSS

-Plasma proteins: synth in liver (albumin)

-Clotting factors: synth in liver

-Drugs and toxins: met in liver, many circulate bound to plasma proteins

CELLS CAN CROSS

-Blood cells: synth in bone marrow (erythrocytes, leukocytes, platelets, circulating stem cells)

-low

-thin

-capillaries

-veins

-hydrostatic pressure

-oncotic pressure (colloid osmotic pressure)

-Pre: arterioles, precap sphincters

-Post: venous resistance

-inc due to low compliance

-Pc dec along the length of the capillary

-this force favors movement of water OUT of capillaries, thus causing filtration

=>Lower in venular end

Definition: Colloid Pressure

Why does this occur?

-osmotic pressure due to protein

-occurs because most capillaries are not permeable to protein

FALSE; constant along capillary length

-favors fluid flux into capillary

-hydrostatic P

-osmotic P

-filtered out

-reabsorbed into

>>

-reabsorption along capillary

>

filtration along entire capillary

-PRIMARILY: removes fluid not reabsorbed by capillaries

-prevents fluid accumulation in interstitium

-returns protein lost from blood

-a "second circulation" no central pump

-slow, regular contractions (pulse= approx5/min)

-pressure reaches aprox 25 mmHg during contraction

-inc capillary hydrostatic pressure (P_c)

dec capillary colloid osmotic pressure (π_c)

-dec lymphatic drainage

-inc capillary permeability

-inc P_venous (blood "backs up" in capillaries 

-heart failure

-overly tight dressings

-inc P_c increases filtration

-RV doesn't empty effectively

-blood backs up in vena cava

-peripheral capillaries have increased pressure

What causes left-sided heart failure? What does it cause? How does it change peripharal capillary pressure?

-LV doesn't empty effectively

-blood backs up in pulmonary vein

-lung capillaries have increased pressure

Cause: decreased protein synthesis (liver disease, malnutrition)

Cause: increased protein loss (enteropathy, kidney disease)

-Effect: dec π_c increases filtration

Causes: congenital malformation, obstruction, or surgical resection of lymphatic vessels

Effects: dec removal of interstitial fluid by lymphatic system allows accumulation in tissues

Causes: histamine release in inflammation, allergic reation (insect bits, plants, drugs/chemicals)

Effect: inc filtration of fluid and protein, produces localized edema (hives, blisters)

-inc filtration increases P_if which reduces net filtration pressure by dec the hydrostatic pressure gradient

-inc P_i stimulates lymph flow

interstitial protein carried away in lymph, replaced with water, reduces π_i favoring reabsorption

=>these mechanisms less effective in lymphedema

-out

-changes

-kidney

-intestine

-fluid

-protein

-central pump

-pumping

-peripheral

-pulmonary

-Na+

-citrate

-K+

-EDTA

-Heparin

Definition: Serum

-how does this affect how we draw blood?

-fluid remaining after clot formation

-draw blood without anticoagulant

-Albumin, Fibrinogen, clotting factors, some globulins

-needed to maintain osmotic pressure and clotting function

-edema, bleeding

-due to lack of plasma proteins made in the liver (needed to maintain osmotic pressure and clotting function)

-Nuc: enucleate

-Shape: circular, biconcave

-Lifespan in circulation: dog 100-130, cat 70-80, horse 140-150, ruminants 125-150

-red cell number

-red cell size

-plasma volume

Erythrocyte: hematocrite (packed cell volume), hemoglobulin, erythrocyte count

-Calculated: mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration

-anemia, especially in kidney failure

-blood doping

-10%: intravascular hemolysis

-90%: destroyed by phagocytic cells in bone marrow, liver, spleen

-Iron is removed from heme and conserved

-bilirubin

-liver

-bile

-gut bacteria

-feces

-urine

-Liver damage: bilirubin not removed from circulation efficiently

-Bile duct blockage: bilirubin not secreted to gut

-Clinical signs: yellow color in tissues (icterus/jaundice)

-larger

-nucleated

-tissue inflammation: endothelial cell activation

-leukocytes attach to vessel wall, crawl through spaces beteen cells, move through tissue to site of inflammation

-megakaryocytes

-mature in circulation

-enucleate

-short lifespan: 8-12 days

-platelets send out pseudopods, become spikey

-contractile proteins contract

-granules move towards center of platelet, fuse with open canalicular system, release contents

-YES, in these species, the granules fuse with the platelet's plasma membrane

-ADP, serotonin, TxA2, PAF

-these substances promote adhesion and activation of more platelets

1. Injury and Adhesion: vascular injury exposes underlying proteins that platelet receptors bind to

2. Activation: platelets become activated

3. Recruitment (subs prdcd by act platelets promote further platelet act) and Aggregation (platelets adhere to each other)

4. Stabilization: fibrin synthd to stabilize plug

-serum

-plasma

-cells

-erythrocytes

-enucleate (in mammals)

-O2 transport

-leukocytes

-do

-largest

-participate in inflammation and response to infection

-Neutrophils

-Eosinphils

-Basophils

-Monocytes

-Lymphocytes

Definition: Dense granules

Examples?

-storage site for biochemical mediators

-Ex: adenine, nucleotides (ADP,ATP), serotonin, Ca2+

Definition: α-granules

Examples?

-storage site for proteins

-Ex: cloting proteins (fibrinogen, vWF, Factor V), albumin, growth factors (PDGF, TGFbeta, VEGF)

-vasoconstriction

-increased tissue pressure

-platelet plug formation

-clot formation

-by thrombocytopenia

-Petechiae: tiny hemorrhagic spots

-platelets

-enucleate

-hemostasis

-plugs larger leaks

-YES

-generation of thrombin

-conversion of fibrinogen to fibrin

-intrinsic pathway

-extrinsic pathway: major pathway

-common pathway

-activated by Factor III/tissue thromboplastin, expressed on nonvascular cells

-inflammation can cause monocytes and endothelial cells to express FIII/TT (contributes to disseminated intravascular coagulation/ DIC in sepsis)

Defintion: Fibrinolysis

-What performs this?

-the breakdown of fibrin

-performed by plasmin

-anticoagulent effect

-upregulatedrrrrrrrrrrrrr

-normally clotting is inactive or localized

-endothelial cells release anticoagulant factors, thus negatively charged endothelium repels negatively charged quiescent platelets

-Prostaglandin I2 (PGI2, prostacyclin): inhibits platelet activation

-Nitric oxide (NO): inhibits platelet adhesion and aggregation

-Thrombomodulin: binds thrombin

-Antithrombin III: inhibits factor X, thrombin

-Tissue factor pathway inhibitor: TFPI

Definition: Thrombocytopenia

-name a few instances in which this is found

-low blood platelet count

-liver disease, cancer chemotherapy, infectious disease, immune disorders

-Ehrlichiosis (Ehrlichia platys or E. canis)

-Rocky Mountain Spotted Fever (Rickettsia rickettsii)

-Nonsteroidal anti-inflammatory drugs (NSAIDs)

-NSAIDs inhibit cyclooxygenase (COX)

-COX-1: constitutive; found in most tissues, prostaglandins (GI, renal), TXA2 (platelets)

-COX-2: inducible; inflamatory cells, inflammatory prostaglandins, pain perception

-relieve pain/inflammation without affecting constitutive COX activity

-unexpected MI and stroke in humans thus withdrawals by FDA

FALSE; COX selectivity varies with species

human DOES NOT EQUAL veterinary

=>required cofactor for several clotting factors

-K1: phylloquinone

-K2:menaquinone

-K3: menadione

-aka phylloquinone

-obtained in foods, green leafy forages

-major source for monogastric animals