Blood

**Blood** is a specialized **connective tissue**. It consists of a fluid matrix called **plasma** and various living cells and cell fragments collectively called **formed elements**.

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Plasma

**Plasma** is the liquid component of blood, making up nearly **55%** of its volume. It is a straw-coloured, viscous fluid.

Composition of plasma:

• About **90-92% water**.
• About **6-8% proteins**: Major plasma proteins include fibrinogen, globulins, and albumins.
  • **Fibrinogen:** Needed for blood clotting (coagulation).
  • **Globulins:** Primarily involved in the body's defense mechanisms (antibodies are globulins).
  • **Albumins:** Help maintain osmotic balance (regulating water movement between blood and tissues).
• Small amounts of **minerals** (e.g., Na$^+$, Ca$^{++}$, Mg$^{++}$, HCO$_3^-$, Cl$^-$).
• Other substances in transit (being transported): glucose, amino acids, lipids, hormones, etc.

Factors required for blood clotting are also present in plasma in an inactive form. Plasma without the clotting factors (specifically fibrinogen) is called **serum**.

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Formed Elements

The **formed elements** are the cellular components of blood, constituting nearly **45%** of the blood volume. They include erythrocytes, leucocytes, and platelets.

• **Erythrocytes (Red Blood Cells, RBCs):** The most abundant blood cells (5-5.5 million mm$^{-3}$ in healthy adult males). Formed in red bone marrow. In most mammals, mature RBCs are **devoid of nucleus** and are **biconcave** in shape. Contain **haemoglobin**, an iron-containing protein (12-16 g per 100 mL blood) responsible for their red colour and significant role in **transport of respiratory gases** (O$_2$ and CO$_2$). Average life span is 120 days, after which they are destroyed in the spleen (graveyard of RBCs).
• **Leucocytes (White Blood Cells, WBCs):** Colourless (lack haemoglobin), nucleated, and relatively fewer in number (6000-8000 mm$^{-3}$). Generally short-lived. Involved in the body's defense mechanisms. Two main categories:
  • **Granulocytes:** Neutrophils (most abundant WBC, 60-65%), Eosinophils (2-3%), Basophils (0.5-1%). Contain granules in their cytoplasm.
  • **Agranulocytes:** Lymphocytes (20-25%), Monocytes (6-8%). Lack granules.

  **Neutrophils and Monocytes** are **phagocytic** (engulf and destroy foreign organisms). **Basophils** secrete histamine, serotonin, heparin, involved in **inflammatory reactions**. **Eosinophils** resist infections and are associated with **allergic reactions**. **Lymphocytes** (B and T types) are responsible for the body's **immune responses**.

• **Platelets (Thrombocytes):** Small cell fragments produced from megakaryocytes (special cells in bone marrow). Blood contains 1,50,000-3,50,000 platelets mm$^{-3}$. Platelets release substances involved in **coagulation or clotting of blood**. Reduced platelet count leads to clotting disorders and excessive bleeding.

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Blood Groups

Human blood varies, requiring matching before transfusion to avoid adverse reactions. Two major blood grouping systems are ABO and Rh.

• **ABO grouping:** Based on the presence/absence of two surface antigens (A and B) on RBCs and natural antibodies (anti-A, anti-B) in the plasma. Four groups: A, B, AB, and O.

Blood Groups and Donor Compatibility (Table 15.1 in text):

Blood Group	Antigens on RBCs	Antibodies in Plasma	Donor’s Group
A	A	anti-B	A, O
B	B	anti-A	B, O
AB	A, B	nil	AB, A, B, O
O	nil	anti-A, anti-B	O

Individuals with blood group 'O' are **universal donors** as their RBCs have no antigens (neither A nor B), so they won't trigger antibody reactions in recipients. Individuals with blood group 'AB' are **universal recipients** as their plasma has no antibodies (neither anti-A nor anti-B), so they can receive blood from any group without antibody reactions against donor RBC antigens.

• **Rh grouping:** Based on the presence or absence of the Rh antigen on RBCs. Individuals with the antigen are **Rh positive (Rh+ve)**; those without are **Rh negative (Rh-ve)** (about 80% of humans are Rh+ve). An Rh-ve person exposed to Rh+ve blood (e.g., through transfusion) can develop antibodies against the Rh antigen. Rh matching is vital for transfusions.

A special case is **erythroblastosis foetalis**: observed when an Rh-ve pregnant mother carries an Rh+ve fetus. In the first pregnancy, the mother's blood is usually not exposed to fetal Rh antigens. However, during delivery, some fetal blood may enter the mother's circulation, causing her to develop anti-Rh antibodies. In subsequent Rh+ve pregnancies, these antibodies can cross the placenta and destroy fetal RBCs, potentially being fatal or causing severe anaemia and jaundice in the newborn. This can be prevented by administering anti-Rh antibodies to the Rh-ve mother after the first delivery.

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Coagulation Of Blood (Clotting)

**Coagulation or clotting** is the process by which blood forms a solid mass (clot) at the site of injury. This mechanism prevents excessive blood loss. A clot (coagulum) is a dark reddish-brown scum formed mainly of a network of **fibrins**, trapping dead and damaged blood cells.

Clotting is a complex process involving a cascade of enzymatic reactions:

1. Injury or trauma stimulates platelets and damaged tissues to release certain factors.
2. These factors initiate a cascade involving many inactive factors in plasma.
3. This forms an enzyme complex, **thrombokinase**.
4. Thrombokinase converts the inactive plasma protein **prothrombin** into active **thrombin**.
5. Thrombin converts the soluble plasma protein **fibrinogen** into insoluble **fibrins**.
6. Fibrin threads form a network, trapping blood cells to form a clot at the injury site.

**Calcium ions (Ca$^{++}$)** play a very important role in the clotting process.

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Lymph (Tissue Fluid)

**Lymph**, also known as **tissue fluid** or **interstitial fluid**, is a fluid derived from blood that is present in the spaces between the cells of tissues. As blood flows through capillaries, some water and small water-soluble substances (like nutrients, gases, hormones, small proteins) filter out from the plasma into the intercellular spaces, leaving larger proteins and most formed elements within the capillaries. This extracellular fluid surrounding the tissue cells is the tissue fluid.

Tissue fluid has a mineral distribution similar to plasma but contains fewer proteins and lacks RBCs and platelets. Exchange of nutrients, gases, and waste products between blood and cells occurs through this fluid.

An elaborate network of vessels called the **lymphatic system** collects the tissue fluid. The fluid within the lymphatic system is called **lymph**. Lymph vessels eventually drain into major veins, returning the fluid to the bloodstream.

Functions of lymph:

• Transports nutrients, hormones, etc.
• Absorbs fats from the intestine through specialized lymphatic vessels called **lacteals** present in the intestinal villi.
• Contains specialized lymphocytes that are responsible for the **immune responses** of the body.
• Drains excess fluid from the interstitial spaces, maintaining tissue fluid balance.

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Circulatory Pathways

Circulatory patterns in animals can be categorized as open or closed systems.

• **Open Circulatory System:** Blood is pumped by the heart through large vessels into open spaces or body cavities called **sinuses**. Cells and tissues are directly bathed in blood. Found in arthropods and molluscs.
• **Closed Circulatory System:** Blood is always circulated within a **closed network of blood vessels** (arteries, veins, capillaries) and does not directly contact cells/tissues. Found in annelids and chordates (vertebrates). This system allows more precise regulation of blood flow.

Vertebrates have a muscular, chambered heart. The number of chambers increases with evolutionary complexity:

• Fishes: 2-chambered heart (1 atrium, 1 ventricle) - **single circulation**.
• Amphibians and most reptiles: 3-chambered heart (2 atria, 1 ventricle) - **incomplete double circulation** (mixing of oxygenated and deoxygenated blood).
• Crocodiles, birds, and mammals: 4-chambered heart (2 atria, 2 ventricles) - **double circulation** (complete separation of oxygenated and deoxygenated blood).

Let's look at the human circulatory system, which is a closed, double circulatory system.

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Human Circulatory System (Blood Vascular System)

Consists of a muscular, four-chambered **heart**, a network of **closed blood vessels** (arteries, veins, capillaries), and **blood**. The heart is mesodermally derived, located in the thoracic cavity, slightly tilted left, protected by a double-walled pericardium enclosing pericardial fluid.

Structure of the heart (Fig 15.2 in textbook):

• Four chambers: Two small upper chambers (atria), two larger lower chambers (ventricles).
• Septa: Inter-atrial septum separates atria; thick inter-ventricular septum separates ventricles. Atrio-ventricular septum separates atrium and ventricle on the same side, with openings connecting them.
• Valves: Guard openings to ensure unidirectional blood flow and prevent backflow. **Tricuspid valve** (three cusps) between right atrium and right ventricle. **Bicuspid valve** (mitral valve, two cusps) between left atrium and left ventricle. **Semilunar valves** guard openings of right ventricle into pulmonary artery and left ventricle into aorta.

The heart is made of cardiac muscles. Specialized cardiac musculature (nodal tissue) is distributed in the heart, with autoexcitable properties (can generate action potentials without external stimuli).

• **Sino-atrial node (SAN):** Located in the upper right corner of the right atrium. Generates the maximum number of action potentials (70-75/min) and initiates/maintains rhythmic heart activity. Called the **pacemaker** of the heart.
• **Atrio-ventricular node (AVN):** Located in the lower left corner of the right atrium. Receives potential from SAN and conducts it to the ventricles via the AV bundle.
• **Atrio-ventricular bundle (AV bundle):** Continues from AVN, passes through AV septa to inter-ventricular septum, divides into right/left bundles.
• **Purkinje fibres:** Minute fibres branching from bundle branches throughout ventricular musculature. Transmit potential rapidly to ventricular muscles, causing contraction.

Normal heart rate is 70-75 beats per minute (average 72).

Blood vessels are a network of closed branching tubes:

• **Arteries:** Carry blood away from the heart (mostly oxygenated, except pulmonary artery). Have thick, elastic walls due to high pressure blood flow.
• **Veins:** Collect blood from organs and bring it back to the heart (mostly deoxygenated, except pulmonary veins). Have thinner walls, valves to ensure one-way flow.
• **Capillaries:** Smallest vessels (one-cell thick) forming networks in tissues. Site of exchange of materials between blood and cells.

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Cardiac Cycle

The **cardiac cycle** is the sequence of events in the heart that is repeated cyclically. It includes the contraction (systole) and relaxation (diastole) of both the atria and ventricles.

Steps in a cardiac cycle (duration ~0.8 seconds at rest):

1. **Joint Diastole:** All four chambers are relaxed. Tricuspid and bicuspid valves are open; semilunar valves are closed. Blood flows from pulmonary veins and vena cava into left and right ventricles through atria.
2. **Atrial Systole:** SAN generates potential, stimulating atria to contract. Increases blood flow into ventricles by ~30%.
3. **Ventricular Systole:** Potential conducted to AVN and AV bundle, stimulating ventricular muscles to contract. Atria relax (atrial diastole). Ventricular pressure increases, closing tricuspid/bicuspid valves. Ventricular pressure further increases, forcing semilunar valves open, pumping blood into pulmonary artery (from right ventricle) and aorta (from left ventricle).
4. **Ventricular Diastole:** Ventricles relax, pressure falls, closing semilunar valves (preventing backflow). Ventricular pressure declines further, opening tricuspid/bicuspid valves (pushed open by atrial pressure), allowing ventricles to fill again (joint diastole).

This cycle repeats ~72 times per minute. **Stroke volume** is the blood pumped out by each ventricle per cardiac cycle (~70 mL at rest). **Cardiac output** is the volume of blood pumped by each ventricle per minute (Stroke volume $\times$ Heart rate). Cardiac output averages ~5 L in a healthy individual at rest. It can be altered by changing stroke volume or heart rate.

Two prominent **heart sounds** are produced during each cardiac cycle, heard with a stethoscope: First sound (**lub**) from closure of tricuspid/bicuspid valves; second sound (**dub**) from closure of semilunar valves. These sounds are clinically significant.

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Electrocardiograph (Ecg)

An **Electrocardiograph** is a machine used to obtain an **Electrocardiogram (ECG)**, a graphical representation of the electrical activity of the heart during a cardiac cycle. A standard ECG uses leads attached to wrists and ankle to monitor heart activity.

A typical ECG trace (Fig 15.3 in textbook) shows waves and complexes labeled P, Q, R, S, T, corresponding to specific electrical events:

• **P-wave:** Represents atrial depolarization (electrical excitation), leading to atrial contraction (systole).
• **QRS complex:** Represents ventricular depolarization, initiating ventricular contraction (systole). Q is the start of ventricular systole.
• **T-wave:** Represents ventricular repolarization (return to relaxed state). Marks the end of ventricular systole.

Analyzing ECG provides crucial clinical information about heart function and potential abnormalities. Heart rate can be determined by counting QRS complexes per minute.

Double Circulation

In humans, blood flows through two separate circulatory pathways, forming a **complete double circulation**. This ensures complete separation of oxygenated and deoxygenated blood.

The two pathways are:

• **Pulmonary Circulation:** Starts when the **right ventricle** pumps **deoxygenated blood** into the **pulmonary artery**. Pulmonary artery carries blood to the **lungs**. In the lungs, blood is oxygenated and carried back by the **pulmonary veins** into the **left atrium**.
• **Systemic Circulation:** Starts when the **left ventricle** pumps **oxygenated blood** into the **aorta**. Aorta distributes oxygenated blood through a network of arteries, arterioles, and capillaries to all **body tissues**. In tissues, gas exchange occurs. Deoxygenated blood from tissues is collected by venules, veins, and vena cavae and returned to the **right atrium**.

Systemic circulation provides nutrients, O$_2$, and other substances to tissues and removes CO$_2$ and wastes. A unique **hepatic portal system** connects the digestive tract to the liver via the hepatic portal vein before blood goes to systemic circulation. A coronary system supplies blood exclusively to the cardiac muscles.

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Regulation Of Cardiac Activity

Heart activity is primarily regulated intrinsically by the specialized nodal tissue (SAN and AVN), making the heart **myogenic** (originating from muscle tissue itself). However, cardiac function is also moderated by the **neural system** and **hormones**.

• **Neural regulation:** The **autonomic nervous system (ANS)** influences heart activity. Neural signals via **sympathetic nerves** (part of ANS) **increase** heart rate, strength of ventricular contraction, and cardiac output. Neural signals via **parasympathetic nerves** (another component of ANS) **decrease** heart rate, speed of action potential conduction, and cardiac output.
• **Hormonal regulation:** Hormones from the adrenal medulla (e.g., adrenaline) can also increase cardiac output.

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Disorders Of Circulatory System

The circulatory system can be affected by various disorders:

• **High Blood Pressure (Hypertension):** Blood pressure higher than normal (normal is 120/80 mmHg). Repeated readings of 140/90 mmHg or higher indicate hypertension. It increases the risk of heart diseases, stroke, and damage to organs like the brain and kidneys.
• **Coronary Artery Disease (CAD) / Atherosclerosis:** Affects the arteries supplying blood to the heart muscle. Caused by deposits of calcium, fat, cholesterol, and fibrous tissues in the artery lumen, making it narrower and reducing blood flow to the heart muscle.
• **Angina (Angina Pectoris):** Acute chest pain occurring when the heart muscle is not receiving enough oxygen (inadequate blood supply). It is a symptom, not a disease itself, often indicating CAD. More common in middle-aged and elderly individuals.
• **Heart Failure:** The state where the heart is not pumping blood effectively enough to meet the body's needs. Sometimes called congestive heart failure due to lung congestion. It is different from cardiac arrest (heart stops beating) or heart attack (heart muscle sudden damage).

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