BPSI 405 Cardiology, Acid-Base Disorders & Liver

Part 2 ayyeee :P

What are the two types of cardiac cells?

Conductive and Contractile cells

Conductive cells

Known as pacemaker cells - responsible for setting rhythm of heart

• Send signals necessary for action potentials

• Found in the SA node and contain Na+ ‘funny channels’

Contractile cells

Known as myocytes - responsible for contraction-relaxation cycle

• Contract to allow for pumping of blood

• Found in the myocardium and have a resting membrane potential

What are the tiny channels that connect cells between cardiac muscles?

Gap junctions, desmosomes, and adherens

How are cardiac muscle fibers connected?

Via intercalated discs at distinct ends

What are the specialized cells that initiate an action potential?

Pacemaker cells <3

What three ions are involved in an action potential?

Calcium, sodium, and potassium

Threshold value of pacemaker cells vs. myocytes

Pacemaker = -40 mV

Myocytes = -70 mV

Pacemaker Action Potential (3 Phases)

Phase 4 (Hyperpolarization) - slow influx of Na+ ions due to funny channels, changes -60 mV to -40 mV

Phase 0 (Depolarization) - Ca2+ voltage-gated channels open, slow influx causes increase to 10 mV and channels close after

Phase 3 (Repolarization) - K+ channels open for slow efflux (leak) of potassium ions

Common symptoms of heart attack for both men and women are chest pain/discomfort. Women also have pain between shoulder blades and fatigue. T/F?

True!

Which treatment is NOT used for regulating blood pressure?

Insulin

Heart attack and cardiac arrest are medically treated the same way. T/F

False!

Heart attacks are a circulation issue (blockage of blood flow) while cardiac arrest is an electrical issue (malfunction in heart’s beating)

Which of the following statements regarding hemoglobin is false?

Each Hgb molecule can bind to one oxygen atom only — False, Hgb can bind up to four oxygen atoms (fully saturated)

Which systolic value is BP categorized as ‘High HP Stage 2’?

140 and/or higher (can lead to hypertensive shock)

A left shift in the Hgb dissociation curve indicates…

• Hgb has higher binding affinity

• Lower release of O2 to tissues (decreased dissociation)

• pH increases (alkalosis)

• Temp decreases

All of the above are true

Which statement is correct about the O2/Hgb dissociation curve?

All of the options are correct

First 3 phases for action potential of contractile cells (myocytes)

Phase 4 - Resting membrane potential (-90 mV)

Phase 0 - Rapid depolarization to -70 mV, voltage-gated Na+ channels open (rapid influx of Na+ ions)

Phase 1 - Repolarization from high membrane potential of +30 mV to 0 mV through opening of voltage-gated K+ channels (slow efflux of K+ ions)

Last 2 phases for action potential of contractile cells (myocytes)

Phase 2 - Plateau maintaining 0 mV where Ca2+ channels slowly open (influx) and K+ channels remain open (efflux)

• Phase where the muscle contraction occurs!

Phase 3 - Repolarization back to resting (-90 mV), Ca2+ channels close but K+ ions continue to flow out

‘Funny’ channels are found in which action potentials?

In pacemaker cell action potentials ONLY

Do pacemaker cells have the absolute refractory period (plateau phase)?

NO, their ‘funny’ channels cause spontaneous depolarization

Gas exchange of oxygen and carbon dioxide is between…

Alveoli and blood of the pulmonary capillaries

Cardiac muscles work all the time. T/F?

True!

They are part of the involuntary nervous system

When an electrical signal is transmitted, what is its pathway?

SA node (made up of pacemaker cells) initiates electrical signal — sends it to the AV node (secondary pacemaker) — signal is transmitted from SA node in atria to the ventricles

How long does the refractory period last (contraction of the heart)?

200 milliseconds

What is the sudden rising phase of the action potential called?

Depolarization

• Sudden influx of positively-charged Na+ ions into the cell

• Membrane potential becomes less negative

Gas exchange

Process that drives cellular respiration through exchange of O2 and CO2 (byproduct)

• High to low concentration gradient of oxygen

Partial Pressures

Amount of gas being dissolved in the body

Alveolar: PAO2 = 100 mmHg at sea level

Arterial: PaO2 = 80-100 mmHg

Hemoglobin saturation

Number of hemes in a Hgb molecule actively carrying oxygen

Arterial: SaO2

Peripheral: SpO2

A right shift in the Hgb dissociation curve indicates…

Lower oxygen binding affinity

Higher dissociation (easier to release O2)

Lower pH (acidosis)

Increase in temp

Bicarbonate’s role in blood pH

Acts as a natural buffer system by removing acidic components in the blood

Lower HCO3 = lower pH; lack of bicarbonate can lead to acidosis

Arterial Blood Gases (ABGs)

pH: acidity of blood

PaCO2: arterial CO2 partial pressure, amount of carbon dioxide in blood

• respiratory component

PaO2: arterial O2 partial pressure, amount of oxygen in blood

HCO3: extracellular blood buffer

• metabolic component

Normal Ranges of ABGs

pH: 7.35 - 7.45

PaCO2: 35 - 45

HCO3: 22 - 28

Respiratory Acidosis

Low pH and high PaCO2

Etiology: Opioids, COPD, hypoventilation

Clinical presentation: Altered mental status, anxiety, headache

Treatment: Treat underlying cause (overdose reversal, bronchodilators)

Metabolic Acidosis

Low pH and low bicarbonate

Etiology: depends on anion gap

Clinical presentation: tachycardia, rapid breathing, fatigue

Treatment: Treat underlying cause (dialysis, diabetic ketoacidosis)

Respiratory Alkalosis

High pH and low PaCO2

Etiology: hyperventilation and altitude

Clinical presentation: lightheadedness and dizziness

Treatment: breathe into paper bag

Metabolic Alkalosis

High pH and high HCO3-

Etiology: depends if Cl- responsive or resistant

Clinical presentation: vomiting/nausea (if Cl- responsive)

Treatment: depends on Cl-

Etiology of Metabolic Acidosis

Depends on anion gap — difference between measured cations and measured anions

Two types: HAGMA and NAGMA

HAGMA

High-Anion Gap

MUDPILES

Methanol, diabetic ketoacidosis, and lactic acidosis (most common)

NAGMA

Non-Anion Gap

Diarrhea and renal acidosis/bicarbonate wasting (most common)

REMINDER

You got this divaaa!!!

Which of the following is NOT a xenobiotic?

Prescription medication, non-prescription medication, food additive, or heme in Hgb

A heme is NOT a xenobiotic

Which substance can inhibit CYP450 metabolism?

Grapefruit juice (it inhibits CYP3A4 enzymes)

What is the space between endothelial cells and hepatocytes called?

Space of Disse

• This where plasma (nutrient-rich fluid with carbs, proteins, and fats) is stored

What is the blood flow that travels through the portal vein after a meal called?

Post Prandial

Is CYP384 affected by genetic polymorphism?

NO - this is true for CYP2D6 enzymes

What is gluconeogenesis?

Process in which the body creates new glucose from non-carb sources such as proteins & amino acids

What is glycogenesis?

Process where excess glucose is stored as glycogen to be used at a later time

Glycogenolysis is where glycogen is reconverted back to glucose in the liver, exported back into the blood of tissues. T/F?

True!

• Glycogen to glucose

Does Phase II use CYP450 enzymes

NO - this superfamily of enzymes is only found in Phase I

Which cells in the liver are responsible for inflammatory response?

Kupffer cells

How many hepatocytes are in the lobule of the liver?

1 million

Process of biotransformation is making less polar xenobiotics into MORE polar ones for easier excretion. T/F?

True!

• More polar = hydrophilic = water-soluble molecules

3 structures in the portal triad

• Portal vein

• Hepatic artery

• Bile duct

Xenobiotic metabolism

Process of removing foreign components from the body through detoxification by the liver

• Goal: to make a lipophilic molecules more hydrophilic

Location of xenobiotic metabolizing enzymes

Smooth Endoplasmic Reticulum (SER)

3 phases of xenobiotic metabolism

Phase I - Modification

Phase II - Conjugation

Phase III - Excretion

3 forms of modification (Phase I)

• Oxidation - addition of polar, reactive groups

• Reduction - addition of less toxic electrons

• Hydrolysis - breakdown of chemical bonds

Warning signs of liver disease

Constant fatigue, sudden weight gain or loss, abdominal pain/swelling, itchy skin, change in urine color