OMSI- CRS II

lung US procedure

• linear best for pleural line

• curvilear or phased array for other aspects

• probe marker to pt head (should show 2 ribs)

• 13 cm deep

when would point of care lung us be used

• chronic heart failure

• pneumoia

• pneumonia

• restrictive dieases

reflective artifact us

interface of a smooth surface and air, such as the pleural line

A-line us

a reverberation reflection of the pleural line on lung us.

• indicates the probe is deep enough

submental scan

• geniohyoid- attaches to both mandable and hyoid bone

thyroid region scan- jugular region

thyroid region scan- anterior

• platysma muscle (py)

• sternocleidomastoid muscle (scm)

• sternohyoid muscle (sh)

• sternothyroid (sth)

• thyroid (thy)

• esophagus (eo)

• common carotid artery (CA)

• internal jugular veins (IJV)

• omohyoid muscle (om)

vertebral artery us

interscalene brachial plexus

supraclavicular brachial plexus us

cardiac muscle cells features

• high levels of mitocondira for constant ATP recycling

• many energy sources, typically fatty acids (60%) and carbohydrates/lactate (35%). Rest are amino acids and ketones

• 98% of cardiac ATP is generated through aerobic metabolism. Although in low oxygen it can do glycolysis only (will run out in around a minute)

cardiac fuel stores

• low glycogen storage. Has insulin response GLUT4 transporters to get glucose from blood sugar

• stores triacylglycerols, but still only limited amounts in NORMAL conditions. Excess is pathological

• has the highest levels of lipoprotein lipase

• creatine

lipoprotein lipase (LPL)

is needed to cleave fatty acids in chylomicrons to make them usable

• chylomicron surface lipoprotein APO C-II will interact with cell surface LPL

• triggers cleavage, fatty acids can enter cell at this point while glycerol goes back into circulation

• in cardiac muscles, LPL activity is inversely related to insulin levels

hormone sensitive lipase (HSL)

Within adipose tissue, stimulated by epinephrine and inactivated by insulin.

• regulated mobilization of free fatty acids in the blood that can be used by cardiac muscle

what happens in hypoxic conditions

• electron transport chain is stopped

• buildups of electron carriers stops TCA cycle

• entirely dependent of anaerobic glycolysis

• local acidity increases to regernate NADH

reperfusion after cardiac hypoxia

reintroducing oxygen after hypoxic conditions. can cause an increase of reactive oxygen species, but cells can avoid this

• during hypoxia, hypoxia-inducable transcription factors are stabilized. increased levels of CD39 and CD73 on cell surface

• inflamatory cells migrate to cardiac muscle, releases ATP and ADP into blood

• these proteins will convert ATP/ADP in the blood to adenosine

• adenosine will bind to A1AR surface cardiac cell receptors => cardio protection for ischemic-reporfusion.

ATP cytoplasmic maintinance

• cardiac myocytes have a lot of cytosolic ATP

• This makes it hard for ATP/ADP antiporter to shuttle ATP out of mitocondrial matrix

• phosphocreatine shuttle fixes this

phosphocreatine shuttle

• in mitocondira inter-membrane space, ATP’s phosphate is transfered to creatine through creatine kinase 1

• creatine can leave outer membrane as creatine-P

• in cytosol, CKg will immidiately transfer any ATP phosphates to creatine to generate ADP and creatine-P

• CKc maintains equilibrium between all 4

• CKa generates ATP from cytosolic creatine-P, active during muscle contraction

metabolic reporgramming in a failing heart

cardiac metabolism is reverted back to something similar to the fetal heart

• increased glycolysis untilization and decreased expression of beta oxidation genes. this is due to failing hearts being oxygen deprived

• these genes are coexpressed with regenerative potential

• using mainly glycolysis will reduce oxidative stress on heart

fetal heart

• relies on maternal glucose for energy

• after birth, glycolysis genes are down-regulated while genes for fatty acid b oxidarion is upregulated

• glucose metabolism is crucial to maintain proliferative potential

cardiac metabolism in type 2 diabetes

leading cause of death in type 2 diabetes is cardiovascular complications. Due to altered metabolism

• T2D increases both glucose and fatty acids in blood, cells response to insulin dulls

• heart cells use more fatty acid utilization, and twice as much fat accumulates in cardiomyocytes. (could cause limited proliferation)

• glycolysis decreases

• long chain fatty acyl coA allosterically inhibits hexokinase (ezyme that initially phosphorylates glucose let in through glut4)

cardiac metabolism in obesity

increases risk of coronary artery disease and heart failure

• similar mechanism to T2D

• obesity increases fatty acids in the blood and hepatocytes. Higher in women, women are at a higher risk

cardiometabolic disease

the result of long term changes in metabolism caused by obesity or insulin resistance

• insulin resistant state will increase inflammation and oxidative stress. can lead to metabolic syndrome, prediabetes, and non-alcoholic fatty liver disease

• this can progress into cardiometabolic disease

A1c

glycation is the non-enzymatic addition of sugars to proteins and lipids

• hemoglobin A1c is glycated hemoglobin

• alters normal activity of proteins and lipids

• levels correspond to chronic high blood glucose, major risk factor

• contributes to atherosclerosis development

advanged glycation end products

aka AGE

• AGE can interact with receptors called RAGE. found on endothelial cells, smooth muscle, platelets

• binding will lead to endothelial injury, and changes in platelets or smooth muscle

• AGE can crosslink structural proteins and result in reduced elasticity

cardiolipin

a diphosphosphatidylglycerol lipid that constitutes 20% of lipids in inner mitocontrial membrane and only in there

• has 4 long chain alkyl groups

• complex I, II, IV and V bind to cardiolipin. nessicary for funtion.

• can create a unique structure in membrane that traps protons. helps to maintain proton gradient and function as a buffer

barth syndrome

rare X-linked, loss of function of taffazzin enzyme

• causes dilated cardiomyopathy, skeletal myopathy, neutropenia, and short stature. usually incompatable with life

• tafazzin is an acytltransferase needed to form cardiolipin

oxidative stress in the heart

causes a ton of issues

• can be produced in vascular cells through upregulated NADPH oxidase (NADPH => NADP+)

• inactivation of endothelium derived nitric oxide, causes reactive nitrogen species

cardiac disease biomarkers

cell lysis can release proteins that diffuse into blood. presence is affected by:

• bigger ones diffuse slower

• half life of the protein. cardiac myoglobin can be used, but has a very short half life (about a day)

• specificity of the protein in tissues. For cardiac, cardiac troponins (cTnT and cTnI) are pertinent positive.

asprin and heart attack/stroke

• can be used in people with a history of heart attack or stroke to prevent it

• prevents clotting by inhibiting COX1 and COX2 on platelets. Ultimately, this inhibits thromboxane A2

• also produces lipoxin that has anti-inflamatory capabilities

nasal cavity epithelium

very similar to other respiratory epithelia, has specialized olfactory epithelia

• sensory cells, bipolar neurons with sensory cillia. will interpret signals and transduction to brain

• also has supporting cells for structural and nutritional support

• basal cells (stem cells) can differentiate into both cell types

cells in the trachea and bronchi

• cilliated cells- move mucus/debris/pathogens from passages. attach to basement membrane

• goblet cells- produce mucus

• basal cells- clustered around basement membrane

• brush cells- chemosensation and absorbtion, microvili increase surface area

• neuroendocrine cells- secrete hormones

pulmonary ionocytes

speciealized cells that start to appear in bronchi

• regulate ion balance of cells

• promotes osmosis for water to leave cells and keep mucus layer hydrated

• less than 1% of cells

• high levels of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), which conducts Cl across apical membranes.

cells in the bronchioles

• ciliated cells, goblet cells, and basal cells become less numerous

• brush cells- air quality sensors

• neuroendocrine cells

• pulmonary ionocytes

• club cells- secreate surface-avtive agent (similar to surfactants)

cells in respiratory bronchiles

aka branch off branchioles

• fewer cilliated cells

• club cells

cells in alveoli

• type 1

• type 2

• dust cells- alveolar macrophages

• intramural cells: capillary endothelial, fibroblasts, smooth muscle (sometimes), ionocytes

goblet cells on light mirocgraph

large amount of lipids in muscus means they will stain very light or not at all.

• non-cilliated

• connect with basal lamina and apical site

• more numerous during chronic irritation

• mucus is composed of glycoproteins MUC5AC and MUC5B

club cells

secrete surface active agents that acts as a surfactant, prevents airway collapse

• non cilliated, but can differentiate into cilliated cells to protect epithelium

• can also differentiate into alveolar cells (alveolar bronchiolization)

• found in terminal bronchioles

how does cyclic fibrosis affect pulmonary ionocytes

• normal ionocyte has CFTR (Cl- leave cell) and ENaC (allows sodium to get inside cell).

• CFTR plays a regulatory role for ENaC to balance

• in cystic fibrosis, CFTR doesn’t work. Cloride cannot leave cell, ENac does not let sodium into cell.

• water does not flow into ECM, mucus get’s thick

what drives airway smooth muscle contraction

• MLCK (myosin light chain kinase) promotes contraction- promoted by calcium and calmodulin

• MLCP (myosin light chain phosphatase) promotes relatation- activated by PKA that inhibits the IP3 pathway (release of calcium)

• sympathetic (B2-AR) and parasympathetic (M3 receptor)

alveolar type 1 cells

• simple squamous allows for gas exchange

• communicated with type 2 alveolar cells, senses more surfactant need by stretch mechanosensors

• communicates through paracrine factors like ATP

alveolar type 2 cells

• plump, polygonal shape

• progenitor cells for type 1 cells

• produce surfactant, stored in lamellar bodies (vesicals). looks stringy

true sufactant proteins

• 4 types: A and D are hydrophilic and B and C are hydrophobic

• composed of lipoproteins, phospholipids, colesterol

• SP-A modulates surfactant turnover

• hydrophobic proteins have structural roles

• SP-B allows lamellar bodies to form

SP-A and surfactant homeostasis

• SP-A feedback regulator

• surfactant synthesis

• fusion of lamellar bodies with plasma membrane

purinergic receptors

on alveolar type 2 cells

• activated by nucleotides/nucleosides

• includes P1, P2Y, P2X

surfactant production in alveolar type 2 cells

• P2Y2 receptors are activated by nucelotides secreted by type 1 cells

• This GPCR activates Gq, activates PKC through phospholipase C

• PKC stimulates exocytosis of lamellar bodies

respiratory system components

• ventilation mechanism- ribs. diaphragm, intrensic muscles

• conducting portion- transports air but to gas exchange

• respiratory region- where gas exchange occures

respiratory epithelia

• cilliated

• columnar

• pseudostratified

conducting airways characteristics

gets progressively thinner as it get’s deeper in lung

• respiratory epithelia

• glands in lamina propria

• smooth muscle

• elastic fibers

• cartilage

nasal cavity

3 regions

• vestibular- opening of nasal cavity

• respiratory- main body of nasal cavity

• olfactory- at the top of nasal cavity

vestibular area of nose

• lined with stratified squamous epithelium

• typical skin- keratinized and hair follicalse

• slowly transition to respiratory epithelia

respiratory area of nose

• respiratory epithelium with thick basement membrane

• nasal chonanae (grooves in cavity)

• layer of CT below basement membrane is called lamina propria- mixed glands, plexus of thin veins, merges with periosteum of underlying bone

olfactory area of nose

olfactory epithelia

• pseudostratified columnar with cillia, no goblet cells

• 3 cell types: olfactory, sustentacular cells (supporting cells), basal cells

• below basement membrane is lamina propria, glands with serous secretions

pharynx divisons

• nasopharnx- posterior to nasal cavity, air passageway

• oropharynx- behind oral cavity, has the palatine tonsils. food and air passage. superior boundary is uvula

• laryngopharynx- behind epiglottis, above esophagus. seperate food to esophagus and air to trachea

eustation tube

• connect middle ear to nasopharynx

• opens during swallowing/yawning

• equalizes pressure

• in children, this tube is more horizontal than in adults. raises risk of ear infections

uvula

most posterior extension of soft palet, separates nasopharynx and oropharynx

• numberous mucus glands

• cross-striated muscle

• nonkeritinized, statified squamous epitheium

oropharynx

• lined by not keratinized statified epithelia

• Pantene tonsils (superior) and lingual tonsils (inferior)

• submucosa has glands, and the muscles of pharyngeal wall

laryngopharynx

starts at epiglottis, both trachea and esophagus

• epithelium can varies. treacheal aspect is respiratory epithelium and esophageal is statified squamous, non-keritinized epithelum

larynx

• epiglottis

• false vocal fold- aka vestibular fold, includes mucus glands in the lamina propria

• true vocal fold- aka vocal fold, actual skeletal muscle in lamina propria and affect voice generation.

• both folds have epithelium is stratified squamous, nonkeritinized

epiglottis

• lid of larynx

• elastic cartilage backbone

• anterior surface is lined by digestive-like epitheial that transitions to respiratory as it wraps around

trachea wall

• contains respiratory epithelia with goblet cells.

• composed of 16-20 overlapping rings

broncus to bronchioles

• bronchioles do not have cartilage in them

• much more branching into terminal bronchi- have low columnar or cuboidal epithelia with no goblet cells

• is considered a respiratory bronchiole when alveoli start to appear. no cillia

respiratory region of lung contains

• respiratory bronchioles

• alveolar ducts- 2 or 3 elongated branches off respiratory bronchiole

• atrium- mildly expanded area between sacs and ducts

• alveolar sacs- 2 to 3 branch off atrium

• alveolus- a single pouch

alveolar pores

small openings between adjacent alveoli, helps to equilize pressure to avoid a collapsed lung.

• one alveoli cannot crush another

• although can be a path for infection

smooth muscle in alveolus

• at the the “knobs”

• found with increased elastic and collagen fibers

bronchial veins

join with the pulmonary veins returning oxygenated blood to heart, very short.

• arteries and veins run with bronchial tree. can be differentiated from pulmonary veins because they will be in the parenchyma

intercalated discs

• longitidinal site- cell sides, communication (gap junctions) and adhesions (desmosomes)

• transverse site- cell ends, firmer adhesions (desmosomes and fascia adherens) and force transmission.

plakophilic-2 (PKP2) mutations

a linker molecules for intermediate filaments to desmosomes in cardiomyocytes and skin. mutations can:

• weaken desmosomes adhesions

• cardiomyocytes detach (will die)

• associated with arrhythmogenic right ventricular cardiomyopathy (ARVC) because of impaired conduction

• exacerbated by exercise, when athletes suddenly collapse

• histological changes are seen- irregular nuclei and cell arrangement

cardiomyocyte dyad

composed of T-tubule membrane (L-type Ca channels) and junctional SR (ryanodine receptor 2) seperate by a narrow state.

• L-type channel lets calcium enter

• will activate ryanodine 2 to make SR release more calcium

cardiac excitation coupling

• L type Ca channels open and allow calcium into cell

• ryanodine 2 receptor is activated, more calcium is relased in SR called a “calcium spark”

• triggers cross bridge

• afterwards calcium is sequestered back into SR by type 2 SR Ca/ATPase (SERCA2), inhibited by phospholamban

regulation of RyR2 receptors

• PKA phosphorylates receptor, stimulating it

• low calcium stimulates by binding to high affinity site, while high cytosolic Ca inhibits by binding to low affinity site. Helps end contractions.

• on lumen side is a calcium sensor

• calsequestrin inhibits RyR2

calsequestrin

binds to calcium in SR lumen to act as a ion buffer. Helps SR store a lot of calcium in SR.

• 2 isoforms: 1 is in skeletal muscle, 2 in cardiac

• interacts with junctin/triadin to regulate RyR. When lumen SR is high, CSQ is busy binding calcium. when lumen calcium is low, CSQ is free to interact with junctin/triadin to inhibit RyR2

phospholamban

phosphorylated by sympathetic pathway to promote relaxation

• dephosphorylated: stimulated, in turn inhibits SERCA2

• phosphorylated: inhibited, dissasociate from SERCA2 so it can work

adrenergic receptor

GPCR, activated by catecholamines

• B1- Gs, PKA pathway. increased heart rate and output

• B2- bronchodilation and vasodilation

• cholinergic (muscarinic)- Gi, inhibits PKA

beta andrenergic receptors

sympathetic stimulation on heart

• Gs => adylyl cyclase => cAMP => PKA

• stimulated calcium influx

• stimulates RyR2 receptors for SR calcium efflux

• inhibits phospholamban, SERCA2 is more active

cholinergic (muscarinic) receptor

parasympathetic stimulation of heart

• GI => inactivated adenylyl cyclase. Turns PKA off

• decreases heart rate

calmodulin

small calcium binding protein. Will be pre-bound to whatever protein it interacts with, such as ion channels or transcription factors

• activated Ca2+/calmodulin dependent protein kinases

• structure is similar to troponin C

calmodulin dependent protein Kinase 2

• activated by calmondulin triggered by effux through L-type calcium channels. that calmondulin will soon deactivate L-type calcium channel

• CamK2 will help activate RyR2 and phosphorylate phospholamban

vascular smooth muscle cells

• line walls of various organs and blood vessels

• endothelial cells can respond to signals and release factors that will affect smooth muscles cells.

• main regulation is cytosolic calcium- no troponin is used and contraction is activated by Ca- associated calmondulin (Ca2+/CaM)

• Ca2+/CaM activates myosin light chain kinase (MLCK)

• MLCK will phosphorylate subunits on myosin. triggers cross bridge.

• MLCP (myosin light chase phosphatase) will trigger relaxation

vasocontricion modulators

angiotensin 2, thrombin, vasopressin, endothelin will affect endothelial cells that will release factors to smooth muscle

• triggers Gq to release calcium from SR

vasodilation modulators

epinephrine, acetylcholine, bradykinin, mechanical stress

• trigger Gq in endothelial cells, activates calmodulin

• CaM activates endothelial nitric oxide synthase. NO is sent to smooth muscle

• NO activates gyanylyl cyclase, PKG will activate myosin light chain phosphatase

how is cholesterol trasnported

• due to insolubility, it is transported in plasma by lipoprotein particals

• will be up taken by tissues that need them, excess is sent to liver to excretion

lipoproteins particals

how cholesterols are transported

• a hydrophobic lipid core

• outer shell of polar lipids and apolipoproteins

• include chylomicrons, VLDL LDL, and HDL

• chylomicrons initially take up lipids from intestines, will be metabolized down into VLDL,LDL, and HDL as it goes through body

4:10

how are lipoproteins analyzed

not easily adapted for clinical lab setting

• agarose gel electrophoresis- seperate on size and charge

• ultracentrifugation- separates on density

• lipoproteins can be seperated by endothelial cells by flushing system with heparin since the bind to heparin sulfate receptors

apolipoproteins

provide a scaffolding for lipoprotein seembly

• enzyme cofactors

• act as ligands on lipoprotein surface

• facilitate lipid transfer

Apo A-1

found in HDL

• needed for HDL formaopm

• activated LCAT

Apo B-48

found in chylomicrons

• mediates synthesis and secretion of chylomicrons

Apo B-100

found on IDL, LDL, VLDL

• mediates VLDL synthesis and secretions

• binds LDL receptor and mediates LDL endocytosis

Apo C-2

found in chylomicrons, HDL, IDL, VLDL

• binds and activates LPL

Apo E

found in chylomicrons, HDL, IDL, VLDL

• mediates endocytosis of remnants

forward lipid transport pathways

2 of them, exogenous source and endogenous

• exogenous are from diet, will be transported by chylomicrons. will be processes by LPL by tissues that need them.

• endogenous are from liver production of VLDL. will be process by LPL in tissues, and any remnants will be sent to liver as HDL

• Type one hyperlipodemia: chylomicrons can presist in blood if apo C-2 (LPL cofactor) is missing or LPL

exogenous transport pathway

• lipid uptake by small intestines, packaged by chylomicrons with apo B48 and transported through lymph

• will mature and acquire Apo C-2 and Apo E

• LPL in capillaries and tissues releases free fatty acids for uptake. glycerol will be phosphorylated and packaged in VLDL.

• CM remnants are processed by liver

endogenous transport pathway

• liver releases mature VLDL containing Apo: C-2, B-100, E

• LPL will release free fatty acids, will turn into a IDL and

• scitzo!!

Apo C-3

along with apo A-2, will inhibit LPL activity

type one hyperlipidemia

an inability to metabolize chylomicrons due to missing or non-functional apo C-2 (LPL cofactor), LPL, increase LPL inhibiter in blood, mutation in protein anchoring LPL to indothelial cells

• will see a foamy, milky top layer in a blood cample

• start to form xanthomas (yellowish growths on skin)

chylomicron retention disease

when chylomicrons are retained inside intestinal cells. crypt cells will be engorged but blood plasma will be low.

• low ApoB-48

apo B-48 vs B-100

from same gene, B-48 is post transcriptionally modified to change a cytosine to a uracil. this causes transcription to stop early

type 2 hyperlipodema

does not have active LDL receptor

• autosomal dominant

• causes elevated serum cholesterol levels and normal triglyceride levels

• Class 1: no LDLR

• Class 2: transport issues, protein is retained in ER

• Class 3: LDLR cannot interact with Apo B-100

• Class 4: endocytosis issue

• Class 5: endocytosed cholesterol cannot be recycled

type 3 hyerlipidemia

when VLDL remnants accumulate in circulation and become cholesterol enriched.

• particals will have a high cholesterol/TG ratio and cholesterol/ApoB ratio

• abnormal electrophoretic properties

• caused by mutation in APO-E, a single substitution (E-2)

mutations of apoB gene

when lipoproteins cannot be assembled. Low triglycerides and low cholesterol