PHYSIOLOGY ASSIGNMENT

TOPIC

1. Excitation - Contraction Coupling

2. Blood Group - ABO & RH
3. Blood Transfusion Hazards - prevention.
4. Immunization Schedule

A.VINOTH KUMAR
FIRST YEAR MBBS
THANJAVUR MEDICAL COLLEGE
THANJAVUR.

1. Excitation - Contraction Coupling (Skeletal, Smooth, Cardiac Muscles)

Aim
To increase the calcium level 10-7 to 2 x 10-4 moles.
Definition
The process by which electrical excitation of surface membrane triggers an increase
of cytosolic calcium concentration in muscle is known as EC coupling/Excitation -
contraction coupling.

Skeletal Muscles
Molecular Mechanisms of Muscle Contraction

The molecular mechanism of muscle contraction is based on the principle that the
sliding motion of the filaments occurs as a result of a cyclic interaction between the myosin
cross bridges and the actin filaments, in the presence of calcium and ATP.
This is known as the cross bridge theory or the ratchet theory as the strokes are
similar to the action of a ratchet.
IMAGE SHOWING TRANSVERSE (T)M TUBULE SARCOPLASMIC RETICULUM SYSTEM

Cross
Bridge Cycle
 The sequence of events that occur during the interaction between the myosin cross-
bridges and the actin molecules is termed as a cross-bridge cycle.
 Events in the Resting Muscle - The cytoplasmic ATP gets attached to its
specific binding site in the head of the myosin molecule and the globular head is not
attached to actin.
 Events in the Stimulated Muscle - When action potential arrives at the T-
tubules, calcium is released from the SR and the myosin-binding sites on actin are
exposed.
 Power Stroke - The binding of myosing head to acting has two effects.
First, Pi is relased from myosin head producing the power stroke, i.e. a
conformational change in which the myosin head bends on the hinge at an angle of
about 45 degrees pulling the acting filament about 11 nm toward the center of the
sarcomere.
- Second, the binding causes the dissociation of ADP
from the myosin head leaving the actomyosin complex in a rigid state. That means
the myosin head stay attached to the actin molecule in the same position and at a
450 angle with respect to the thick and thin filaments.
 Attached State - A new molecule of ATP must bind to the myosin head
and initiate next cycle.
 Detached State - The affinity of myosin for actin resulting in detachment
of cross-bridges from the thin filaments, called as detached state. Soon after, ATP
hydrolysis occurs and the myosin head attains the energized state.
Smooth Muscles
Molecular Mechanisms of Muscle Contraction
  Role of Calcium - The cytosolic calcium concentration is increased mainly
by entry of calcium from the interstitial fluid or to some extent by its release from
cytopiasmic calcium stores (calcium release). However, the concentration of calcium
in cytosol decreases due to calcium to the SR and calcium efflux.
 Calcium Influx - Calcium influx occurs through voltage - gated Ca++
channels, ligand -gated Ca++ channels and a few leaky channels. The ECF calcium
concentration is about 12,000 times higher than that of the cytoplasm (1,200,000
nmol/L versus 100nmol/L). This high inwardly directed gradient favors calcium
entry into the smooth muscle as soon as calcium channels open.
 Calcium Release - Calcium release from the SR takes place by IP3 -
mediated pathway, Calcium - induced calcium release (CICR) mechanism.
 Binding of Calcium to Calmodulin
 Pumping Back of Calcium to the SR
 Calcium Efflux
Major events of smooth muscle contraction and relaxation.
 Ca++ influx into the smooth muscle cell
 Binding of Ca++ with calmodulin - dependent MLCK
 Phosphorylation of myosin
 Increased myosin ATP ase activity.
 Myosin binds with actin resulting in cross-bridge formation
 Contraction of muscle
 Dephosphorylation of myosin by MLCP
 Latch-bridge state (Sustained Contraction)
 Or, slow relaxation
Cardiac Muscles
Molecular Mechanisms of Muscle Contraction

 Muscles present in heart are cardiac muscies. Though they are structurally close to
skeletal muscle they demonstrate many properties of smooth muscles. More than
half of mechanical contraction is over, during absolute Tetanization not seen.
 Duration of muscle twitch - One and half times the total duration of action
potential.
 Excitation contraction coupling - More rapid process time )<10msec).
 All or none law - Applicable, true for whole of the atria or-ventricles.
 Energy - 65% by fats, 25% by carbohydrates; and 10% by
ketones bodies and amino acids.
CARDIAC ACTION POTENTIAL ;
Reason for cardiac muscle action potential ;
1.mode of arrangement of muscle fibres.
2.Auto-rhythmicitity
3.conduction of electric impulses (by intercalated disc)
4. the all or none law in the heart applies to the entire syncytium
5.the action potential in cardiac muscle is prolonged and has a long refractory
period .
6.cardiac muscle contraction is dependent on the initial length of the muscle
fibre (frank-starling law of the heart )
7.cardiac muscles does not fatigue ;
Cardiac muscle has a rich blood supply and the capillary density that is about
4 times greater than skeletal muscles.
Cardiac muscle undergoes aerobic metabolism that prevent the accumulation
of lactic acid in the muscles
Rich in mitochondria that almost account for one-third of the cardiac muscles
by weight.

CONTRACTION;
 When an action potential passes over the cardiac muscle membrane,the
action potential spreads to the interior of the cardiac muscle fibre along
the membrane of the tranverse T tubules.
 The T tubule action potential in turn act on the membranes of the
longitudinal sarcoplasmic tubules to cause release of calcium into the
muscle sarcoplasm from the sarcoplasmic reticulum .
 In another few thousands of second these calcium ions diffuses into the
myofibrils and catalyse the chemical reaction that promote sliding of
the actin and myosin filaments along one another which produces the
muscle contaction .
 In addition to the calcium ions released into the sarcoplasm from the
cisternae of the sarcoplasmic reticulum ,calcium ions also diffuses into
the sarcoplasm from the t tubules themselves at the time of the action
potential, which opens VOLTAGE DEPENDENT –CALCIUM CHANNELS
in the membrane of the T tubules .
 Calcium entering the cell then activate calcium release channels (also
called ryanodine receptor channels in the sarcoplasmic reticulum
membrane, triggering the release of calcium into the sarcoplasm .
 Calcium ions in the sarcoplasm then interact with troponin to initiate
cross bidge formation and contraction by the same process of skeletal
muscle.
 The strength of the contraction of cardiac muscle and quantity of the
calcium ions in t tubule system also depends greatly on the
concentration of calcium ions in the extracellular fluid .
 2.Blood Group - ABO & RH
 Agglutinogens - The blood group antigens.
 Agglutinins - Antibodies against the antigens.
ABO System
 This the most important system in transfusion medicine, as ABo agglutinogens are
highly antigenic.
  In ABO system, in essence there are two antigens, the antigen A and the antigen B.
A antigen has two sub-types. A and A1. The genes for antigens for ABO system are
ABO genes located as chromosome 9.

Occurrence
 These antibodies are found in plasma. Usually, specific antibodies are formed
against a particular antigen, when they are exposed to that antigen. But, Blood group
anti-bodies are naturally occurring antibodies as they are formed without prior
 exposure to the antigens and are present in the blood of individuals in whom the
respective antigens are absent.

Time and Mechanism of Appearance

 Anti-A and Anti-B agglutinins are not formed during fetal life and are absent at birth.
They appear in the second week of neonatal life and increase very slowly in
concentration to attain the peak level at about 10 years of life.

Chemical Nature
 The 𝛼 𝑎𝑛𝑑 𝛽 agglutinins are globulins and belong to ig M category. Therefore, they
do not cross the placenta. They function efficiently at low temperature, i.e., between
5” to 200C. Therefore, they are called cold antibodies.

Occurrence of antigens and antibodies in ABO system

Blood groups Antigen (on RBC) Antibody (in plasma)
A A Anti-B
B B Anti-A
AB A and B Nil
O Nil Anti-A and Anti-B

Rh SYSTEM

The Rh (Rhesus) system is the second most important blood group system in
transfusion medicine. This was first described in Rhesus monkeys in 1940 by Landsteiner
and Weiner, hence it is called Rh system (for Rhesus).

Rh Antigens

In Rh system, there are six antigens, but there are no naturally occurring antibodies.
The antigens are C, D, E, c, d and e. Out of these six antigens, immunologically most active
is the D antigen.
 Thus, in Rh system, there are two blood group: Rh positive (D antigen present) and
Rh negative (D antigen absent).

Inheritance
Rh antigen is inherited as domninant gene:
1. In Indian population, 95 to 98% are Rh+ve and 2 to 5% are Rh-ve.
2. Rh +ve individual may have homozygous (DD) or heterozygous (Dd) genotypes.
Usually, 60% of Rh +ve individuals have Dd genotype and 40% have DD genotype.
The genotype of Rh -ve person is dd.
3. if one of the parents is homozygous positive and the other is homozygous negative,
all offsprings will be heterozygous positives.
4. Similarly, if the father and mother are homozygous negatives, all offsprings will be
homozygous negatives, and when one of the parents is heterozygous positive and
the other homozygous negative, 50% of offsprings will be heterozygous positive and
50% will be homozygous negatives.

Rh Antibody
The antibody in the system is called anti-D antibody, which is produced only when
an Rh negative individual receives the Rh positive blood:
These antibodies develop very slowly in the first encounter, but form rapidly
following subsequent encounter. Rh antibody is of Ig G type, which can cross placental
barrier.

Rh Incompatibility
Rh incompatibility occurs when an Rh negative individual receives Rh positive blood.
 The similar Rh incompatibility occurs in pregnancies when Rh negative mother
bears Rh positive fetus, which leads to erythroblastosis fetalis. The first child does not
suffer, However, subsequent pregnancies carry risk for the fetus. The disorder is called
erythroblastosis fetalis.

3.Blood Transfusion Hazards - Prevention.

Transfusion
Transfusion of whole blood or a component of blood is common in medical practice.

Indications for Transfusion

1. Acute blood loss:
2. Chronic anemia
3. bone marrow failure
4. purpura
5. Clotting factor deficiencies
6. Preparation for surgery and during surgery
7. Burns
8. Anemia
Procedure of Blood Transfusion
i. Selection of appropriate donor
ii. ABo and Rh typing
iii. Cross matching
iv. Antibody Screening of the patient (to detect the presence of clinically significant
antibodies).
Procedure

1. AGE should be 18 - 60 years.

2. Weight more that 45 kg.
3. Heamoglobin level - 13gram/dl male
12 gram/dl female
4. Haematocrit - 35 % to 40%
5. Cross matching - Major cross matching
 Minor cross matching

Collection of Blood

1. Ideally, not more that 350 ml of blood is collected from a single donor at a time.
2. Collection time = 7 to 10 min.
3. COAGULATION Fluid - 50 to 70 ml of anticoagulant consisting of citrate, phosphate
and dextrose (CPD). Disodium hydrogen citrate is used instead of trisodium citrate
as anticoagulant, because this favors fall of pH which is require for survival of red
cells.

Hazards of Blood Transfusion

I. Due to mismatched Transfusion; when as incompatible blood is transfused, the

mismatched transfusion reaction occurs immediately. The complications of mismatched
transfusion are:

1. Shivering and fever (febrile reaction) occur usually

2. Hemoglobinemia and hemoglobinuria
3. Hemoglobinemia jaundice.
4. Acute renal failure.

II. Due to Faulty Techniques of Giving Blood: Due to wrong method of transfusion,
following complications may arise:
1. Thrombophlebitis: This is a common complication is those who receive repeated
transfusions.
2. Air Embolism: Air enters the venous circulation and gets lodged at the outlet of the
right ventricle and blocks the flow of blood to the lungs. Death may occur in severe
cases. Use of plastic bags has reduced this complication.

III. Due to Massive Transfusion: This occurs when more than 10 units of blood are given
within 24 hours or when the total blood volume is exchanged within 24 hours. This leads to
 circulatory overload. Cardiac arrhythmias and even sometimes cardiac arrest occur due to
high potassium level in the stored blood.

IV. Febrile Reaction: The patient feels cold and may get rigor due to rise in body
temperature. The occurs mainly due to presence of pyrogens in the ttansfusion apparatus.

V. Allergic Reactions: This is less frequent and is characterized by itching, erythema,

nausea, vomiting, and in severe cause anaphylactic reactions.
VI. Transmission of Diseases:
1. Hepatitis
2. Malaria
3. AIDS
4. Syphilis.

4. Immunization Schedule
For pregnant women, infants, children’s.
THANK
YOU!