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Physiology

Excitability ( Bathmotropism ) : Excitability means the ability of cardiac muscle to respond to signals. Here we are talking about contractile muscle cells that are excited by the excitatory conductive system and generate an action potential.

Cardiac action potential is similar to action potential in nerve and skeletal muscle tissue , with one difference , which is the presence of plateau phase . Plateau phase is unique for cardiac muscle cells .
The  resting membrane potential for cardiac muscle is about -80 mV.
When the cardiac muscle is stimulated an action potential is generated . The action potential in cardiac muscle is composed of four phases , which are :

1. Depolarization phase (Phase 0 ) :

A result of opening of sodium channels , which increase the permeability to sodium , which will lead to a rapid sodium influx into the cardiac muscle cell.

2. Repolarization : Repolarization in cardiac muscle is slow and triphasic :

a. Phase 1 (early partial repolarization ) : A small fast repolarization , results from potassium eflux and chloride influx.
b. Phase 2 ( Plateau ) : After the early partial depolarization , the membrane remains  depolarized , exhibiting a plateau , which is a unique phase for the cardiac muscle cell. Plateau is due to opening of slow calcium-sodium channels , delay closure of sodium channels , and to decreased potassium eflux.
c. Phase 3  ( Rapid repolarization) :  opening of potassium channels and rapid eflux of potassium.
d. Phase 4 ( Returning to resting level) in other words : The phase of complete repolarization. This due to the work of sodium-potassium pump.


Absolute refractory period:

Coincides wit phase 0,phase1 , and phase 2 . During this period , excitability of the heart is totally abolished . This prevents tetanization of the cardiac muscle and enables the heart to contract and  relax to be filled by blood ..

Relative refractory period : 

Coincides with the rapid repolarization and allows the excitability to be gradually recovered .
Excitation contraction relationship : Contraction of cardiac muscle starts after depolarization and continues about 1.5 time as long as the duration of the action potential and reaches its maximum at the end of the plateau. Relaxation of the muscle starts with the early partial repolarization.

Factors , affecting excitability of cardiac muscle:

I. Positive bathmotropic effect :

1. Sympathetic stimulation : It increase the heart , and thus reduces the duration of the action potentia; . This will shorten the duration of the absolute refractory period , and thus increase the excitability .
2.  Drugs : Catecholamines and  xanthines derivatives .
3. Mild hypoxia and mild ischemia
4. Mild hyperkalemia as it decreases the K+ efflux and opens excess Na+ channels .
5. Hypocalcemia

II. Negative bathmotropic effect :

1. Parasympathetic stimulation: The negative bathmotropic effect is limited to the atrial muscle excitability , because there is no parasympathetic innervation for the ventricles. Parasympathetic stimulation decreases the heart rate , and thus increases the duration of cardiac action potential and thus increases the duration of the absolute refractory period.
2. moderate to severe hypoxia
3. hyponatremia , hypercalcemia , and severe hyperkalemia.

Clinical Physiology : Extrasystole is a pathological situation , due to abnormal impulses , arising from ectopic focus .It is expressed as an abnormal systole that occur during the early diastole .
Extrasystole  is due to a rising of excitability above the normal , which usually occurs after the end of the relative refractory period ( read about staircase phenomenon of Treppe)

The pancreas

The pancreas consists of clusters if endocrine cells (the islets of Langerhans) and exocrine cells whose secretions drain into the duodenum.

Pancreatic fluid contains:

  • sodium bicarbonate (NaHCO3). This neutralizes the acidity of the fluid arriving from the stomach raising its pH to about 8.
  • pancreatic amylase. This enzyme hydrolyzes starch into a mixture of maltose and glucose.
  • pancreatic lipase. The enzyme hydrolyzes ingested fats into a mixture of fatty acids and monoglycerides. Its action is enhanced by the detergent effect of bile.
  • 4 zymogens— proteins that are precursors to active proteases. These are immediately converted into the active proteolytic enzymes:
    • trypsin. Trypsin cleaves peptide bonds on the C-terminal side of arginines and lysines.
    • chymotrypsin. Chymotrypsin cuts on the C-terminal side of tyrosine, phenylalanine, and tryptophan residues (the same bonds as pepsin, whose action ceases when the NaHCO3 raises the pH of the intestinal contents).
    • elastase. Elastase cuts peptide bonds next to small, uncharged side chains such as those of alanine and serine.
    • carboxypeptidase. This enzyme removes, one by one, the amino acids at the C-terminal of peptides.
  • nucleases. These hydrolyze ingested nucleic acids (RNA and DNA) into their component nucleotides.

The secretion of pancreatic fluid is controlled by two hormones:

  • secretin, which mainly affects the release of sodium bicarbonate, and
  • cholecystokinin (CCK), which stimulates the release of the digestive enzymes.

Serum Lipids

 

LIPID

Typical values (mg/dl)

Desirable (mg/dl)

Cholesterol (total)

170–210

<200

LDL cholesterol

60–140

<100

HDL cholesterol

35–85

>40

Triglycerides

40–160

<160

 

  • Total cholesterol is the sum of
    • HDL cholesterol
    • LDL cholesterol and
    • 20% of the triglyceride value
  • Note that
    • high LDL values are bad, but
    • high HDL values are good.
  • Using the various values, one can calculate a
    cardiac risk ratio = total cholesterol divided by HDL cholesterol
  • A cardiac risk ratio greater than 7 is considered a warning.

DNA (Deoxyribonucleic acid) - controls cell function via transcription and translation (in other words, by controlling protein synthesis in a cell)

Transcription - DNA is used to produce mRNA

Translation - mRNA then moves from the nucleus into the cytoplasm & is used to produce a protein . requires mRNA, tRNA (transfer RNA), amino acids, & a ribosome


tRNA molecule

  • sequence of amino acids in a protein is determined by sequence of codons (mRNA). Codons are 'read' by anticodons of tRNAs & tRNAs then 'deliver' their amino acid.
  • Amino acids are linked together by peptide bonds (see diagram to the right)
  • As mRNA slides through ribosome, codons are exposed in sequence & appropriate amino acids are delivered by tRNAs. The protein (or polypeptide) thus grows in length as more amino acids are delivered.
  • The polypeptide chain then 'folds' in various ways to form a complex three-dimensional protein molecule that will serve either as a structural protein or an enzyme.

Carbon Dioxide Transport

Carbon dioxide (CO2) combines with water forming carbonic acid, which dissociates into a hydrogen ion (H+) and a bicarbonate ions:

CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3

95% of the CO2 generated in the tissues is carried in the red blood cells:

  • It probably enters (and leaves) the cell by diffusing through transmembrane channels in the plasma membrane. (One of the proteins that forms the channel is the D antigen that is the most important factor in the Rh system of blood groups.)
  • Once inside, about one-half of the CO2 is directly bound to hemoglobin (at a site different from the one that binds oxygen).
  • The rest is converted — following the equation above — by the enzyme carbonic anhydrase into
    • bicarbonate ions that diffuse back out into the plasma and
    • hydrogen ions (H+) that bind to the protein portion of the hemoglobin (thus having no effect on pH).

Only about 5% of the CO2 generated in the tissues dissolves directly in the plasma. (A good thing, too: if all the CO2 we make were carried this way, the pH of the blood would drop from its normal 7.4 to an instantly-fatal 4.5!)

When the red cells reach the lungs, these reactions are reversed and CO2 is released to the air of the alveoli.

Characteristics of Facilitated Diffusion & Active Transport - both require the use of carriers that are specific to particular substances (that is, each type of carrier can 'carry' one type of substance) and both can exhibit saturation (movement across a membrane is limited by number of carriers & the speed with which they move materials

Abnormalities of Salt, Water or pH

  • Examples:
    • Hyperkalemia: caused by kidney disease & medical malpractice
      • High K+ in blood- can stop the heart in contraction (systole)
    • Dehydration: walking in desert- can lose 1-2 liters/hour through sweat
      • Blood becomes too viscous to circulate well -> loss of temperature regulation -> hyperthermia, death
    • Acidosis: many causes including diabetes mellitus and respiratory problems; can cause coma, death

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