THE COAGULATION CASCADE

 

INTRODUCTION: Extrinsic Pathway: The quicker responding and more direct extrinsic pathway, also known as the tissue factor pathway, begins when damage occurs to the surrounding tissues, such as in a traumatic injury. Upon contact with blood plasma, the damaged extravascular cells, which are extrinsic to the bloodstream, release factor III, also known as thromboplastin. Sequentially, Ca²⁺ then factor VII (proconvertin), which is activated by factor III, are added, forming an enzyme complex. Enzymes  

This enzyme complex leads to activation of factor X, also known as Stuart–Prower factor, which activates the common pathway discussed below. The events in the extrinsic pathway are completed in a matter of seconds.

Intrinsic Pathway: The intrinsic pathway, also known as the contact activation pathway, is longer and more complex. In this case, the factors involved are intrinsic to, meaning they are present within the bloodstream. The pathway can be prompted by damage to the tissues, resulting from internal factors such as arterial disease; however, it is most often initiated when factor XII also known as Hageman factor, comes into contact with foreign materials, such as when a blood sample is put into a glass test tube. 

Within the body, factor XII is typically activated when it encounters negatively charged molecules, such as inorganic polymers and phosphate produced earlier in the series of intrinsic pathway reactions.  Factor XII sets off a series of reactions that in turn activates factor XI (antihemolytic factor C or plasma thromboplastin antecedent) then factor IX (antihemolytic factor B or plasma thromboplasmin). In the meantime, chemicals released by the platelets increase the rate of these activation reactions. Finally, factor VIII (antihemolytic factor A) from the platelets and endothelial cells combines with factor IX (antihemolytic factor B or plasma thromboplasmin) to form an enzyme complex that activates factor X (Stuart–Prower factor or thrombokinase), leading to the common pathway. The events in the intrinsic pathway are completed in a few minutes.

COMMON PATHWAY: Both the intrinsic and extrinsic pathways lead to the common pathway, in which fibrin is produced to seal off the vessel. Once factor X has been activated by either the intrinsic or extrinsic pathway, the enzyme prothrombinase converts factor II, the inactive enzyme prothrombin, into the active enzyme thrombin. It should be note that, if the enzyme thrombin were not normally in an inactive form, clots would form spontaneously, a condition that would otherwise not be consistent with life. Then, thrombin converts factor I, the insoluble fibrinogen, into the soluble fibrin protein strands. Factor XIII then stabilizes the fibrin clot.

RELATED;

1.  Blood platelets

2.  Blood and it's components

References

ALBUM OF BIOCHEMISTRY

ALBUM OF BIOCHEMISTRY

MOLECULAR MODEL OF DNA:  DNA is the parent genetic material in life responsible for genetic variations and the process of inheritance.  The memory of inheritance and makeup of the entire body gets information that is transcribed from the DNA to RNA and then functional proteins are translated from the RNA molecule.  In simple terms, this is the source of the slogan that DNA makes RNA and RNA makes proteins which is scientifically known as the Central dogma of molecular biology.  In our discussion here, we are going to look at some of the most common genetic molecules and the way they are related, plus their different roles in the human body.

STRUCTURAL DIFFERENCES

BETWEEN DNA AND RNA

BASIC STRUCTURE OF A NUCLEOTIDE

RELATED;

1.  ALBUM OF PHARMACOLOGY AND THERAPEUTICS

2.  DNA THE GENETIC MATERIAL

3.  RNA AS A MOLECULE OF LIFE

4.  BIOCHEMISTRY TEST QUESTIONS

OPIOID ANALGESICS

 

Introduction: Successful treatment of pain is a challenging task that begins with careful attempts to assess the source and magnitude of the pain. The amount of pain experienced by the patient is often measured by means of a pain Numeric Rating Scale (NRS) or less frequently by marking a line on a Visual Analog Scale (VAS) with word descriptors ranging from no pain (0) to excruciating pain (10). In either case, values indicate the magnitude of pain as: mild (1–3), moderate (4–6), or severe (7–10).  For a patient in severe pain, the administration of an opioid analgesic is usually considered a primary part of the overall management plan. Determining the route of administration, duration of drug action, ceiling effect also known as maximal intrinsic activity, duration of therapy, potential for adverse effects, and the patient’s past experience with opioids all should be addressed.  Use of opioid drugs in acute situations may be contrasted with their use in chronic pain management, in which a multitude of other factors must be considered, including the development of tolerance to and physical dependence on opioid analgesics.

Clinical Use of Opioid Analgesics:  1)  Analgesia: Severe, constant pain is usually relieved with opioid analgesics with high intrinsic activity. This includes the pain associated with cancer and other terminal illnesses. Such conditions may require continuous use of potent opioid analgesics and are associated with some degree of tolerance and dependence. Opioid analgesics are also often used during obstetric labor. Because opioids cross the placental barrier and reach the fetus, however care must be taken to minimize neonatal depression. If it occurs, immediate injection of the antagonist naloxone will reverse the depression.  

2)  Acute Pulmonary Edema: The relief produced by intravenous morphine in dyspnea from pulmonary edema associated with left ventricular heart failure is remarkable. Proposed mechanisms include reduced anxiety and reduced cardiac preloa and afterload. However, if respiratory depression is a problem, furosemide may be preferred for the treatment of pulmonary edema. On the other hand, morphine can be particularly useful when treating painful myocardial ischemia with pulmonary edema.  

3) Cough: Suppression of cough can be obtained at doses lower than those needed for analgesia. However, in recent years the use of opioid analgesics to allay cough has diminished largely because a number of effective synthetic compounds have been developed that are neither analgesic nor addictive.  

4)  Diarrhea: Diarrhea from almost any cause can be controlled with the opioid analgesics, but if diarrhea is associated with infection such use must not substitute for appropriate chemotherapy. Crude opium preparations were used in the past to control diarrhea, but now synthetic surrogates with more selective gastrointestinal effects and few or no CNS effects, such as diphenoxylate or loperamide, are used.  

5)  Shivering: Although all opioid agonists have some propensity to reduce shivering, meperidine is reported to have the most pronounced anti-shivering properties. Meperidine apparently blocks shivering mainly through an action on subtypes of the α2 adrenoceptor.  

6)  Applications in Anesthesia: The opioids are frequently used as premedicant drugs before anesthesia and surgery because of their sedative, anxiolytic, and analgesic properties. They are also used intra-operatively both as adjuncts to other anesthetic agents and, in high doses, as a primary component of the anesthetic regimen . Opioids are most commonly used in cardiovascular surgery and other types of high-risk surgery in which a primary goal is to minimize cardiovascular depression. In such situations, mechanical respiratory assistance must be provided.

RELATED; 

1.  CORTICOSTEROIDS  

2.  CHRONIC INFLAMMATION

3.  MORPHINE

4.  PHARMACOLOGY AND THERAPEUTICS

REFERENCES

CHAMBERS AND CIRCULATION THROUGH THE HEART

 

Introduction: The human heart consists of four chambers: The left side and the right side each have one atrium and one ventricle. Each of the upper chambers, the right atrium and the left atrium, acts as a receiving chamber and contracts to push blood into the lower chambers, the right ventricle and the left ventricle. The ventricles serve as the primary pumping chambers of the heart, propelling blood to the lungs or to the rest of the body. There are two distinct but linked circuits in the human circulation called the pulmonary and systemic circuits. Although both circuits transport blood and everything it carries, we can initially view the circuits from the point of view of gases. The pulmonary circuit transports blood to and from the lungs, where it picks up oxygen and delivers carbon dioxide for exhalation. 

THE SYSTEMIC CIRCUIT:  The systemic circuit transports oxygenated blood to virtually all of the tissues of the body and returns relatively deoxygenated blood and carbon dioxide to the heart to be sent back to the pulmonary circulation. The right ventricle pumps deoxygenated blood into the pulmonary trunk, which leads toward the lungs and bifurcates into the left and right pulmonary arteries. These vessels in turn branch many times before reaching the pulmonary capillaries, where gas exchange occurs: Carbon dioxide exits the blood and oxygen enters. The pulmonary trunk arteries and their branches are the only arteries in the post-natal body that carry relatively deoxygenated blood. 

THE VENOUS SYSTEM:  Highly oxygenated blood returning from the pulmonary capillaries in the lungs passes through a series of vessels that join together to form the pulmonary veins, the only post-natal veins in the body that carry highly oxygenated blood. The pulmonary veins conduct blood into the left atrium, which pumps the blood into the left ventricle, which in turn pumps oxygenated blood into the aorta and on to the many branches of the systemic circuit. Eventually, these vessels will lead to the systemic capillaries, where exchange with the tissue fluid and cells of the body occurs. In this case, oxygen and nutrients exit the systemic capillaries to be used by the cells in their metabolic processes, and carbon dioxide and waste products will enter the blood.

COMPOSTION OF OXYGEN IN THE SYSTEM:  The blood exiting the systemic capillaries is lower in oxygen concentration than when it entered. The capillaries will ultimately unite to form venules, joining to form ever-larger veins, eventually flowing into the two major systemic veins, the superior vena cava and the inferior vena cava, which return blood to the right atrium. The blood in the superior and inferior venae cavae flows into the right atrium, which pumps blood into the right ventricle. This process of blood circulation continues as long as the individual remains alive. Understanding the flow of blood through the pulmonary and systemic circuits is critical to all health professions.

RELATED;

1.  CEREBRAL VASCULAR ACCIDENT  

2.  CAFFEIN AND THE HEART  

3.  CENTRES FOR CONTROL OF BLOOD PRESSURE  

4.  THE CARDIAC CYCLE AND HEART SOUNDS

5.  ANATOMY AND PHYSIOLOGY

REFERENCES

ANEMIA

 

Introduction: Anemia is a condition in which the hemoglobin concentration is lower than normal; it reflects the presence of fewer than the normal number of erythrocytes within the circulation. Erythrocytes  

As a result, the amount of oxygen delivered to body tissues is also diminished. Anemia is not a specific disease state but a sign of an underlying disorder. It is by far the most common hematologic condition. There are several kinds of anemia and, physiologically it can be classified according to whether the deficiency in erythrocytes is caused by a defect in their production a condition known as hypoproliferative anemia, by their destruction a condition known as hemolytic anemia, or by their loss through for example bleeding.

Clinical Manifestations: Aside from the severity of the anemia itself, several factors influence the development of anemia-associated symptoms: the rapidity with which the anemia has developed, the duration of the anemia, the metabolic requirements of the patient, other concurrent disorders or disabilities such as, cardiac or pulmonary disease, and complications or concomitant features of the condition that produced the anemia.

Pronounced symptoms of anemia include the following: 

1) Dyspnea, chest pain, muscle pain or cramping, tachycardia. 

2) Weakness, fatigue, general malaise. 

3) Pallor of the skin and mucous membranes (conjunctivae, oral mucosa). 

4) Jaundice (megaloblastic or hemolytic anemia). 

5) Smooth, red tongue (iron-deficiency anemia) 

6) Beefy, red, sore tongue (megaloblastic anemia) 

7) Angular cheilosis (ulceration of the corner of the mouth). 

8) Brittle, ridged, concave nails and pica (unusual craving for starch, dirt, ice) in patients with iron-deficiency anemia

Assessment and Diagnostic Methods: 1) Complete hematologic studies (eg, hemoglobin, hematocrit, reticulocyte count, and red blood cell (RBC) indices, particularly the mean corpuscular volume [MCV] and RBC distribution width [RDW]) 

2) Iron studies (serum iron level, total iron-binding capacity [TIBC], percent saturation, and ferritin) 

3) Serum vitamin B12 and folate levels; haptoglobin and erythropoietin levels 

4) Bone marrow aspiration 

5) Other studies as indicated to determine underlying illness.

Medical Management: Management of anemia is directed toward correcting or controlling the cause of the anemia; if the anemia is severe, the erythrocytes that are lost or destroyed may be replaced with a transfusion of packed RBCs (PRBCs).

RELATED;

1. BLOOD AND ITS COMPONENTS  

2. THE ABO BLOOD GROUPING  

3.  THE HUMAN RED BLOOD CELLS  

4.  OTHER MEDICAL CONDITIONS

REFERENCES

THE HUMAN RED BLOOD CELLS

 

INTRODUCTION: The erythrocyte, commonly known as a red blood cell (or RBC), is by far the most common formed element: A single drop of blood contains millions of erythrocytes and just thousands of leukocytes. Specifically, males have about 5.4 million erythrocytes per microliter (µL) of blood, and females have approximately 4.8 million per µL. In fact, erythrocytes are estimated to make up about 25 percent of the total cells in the body. The primary functions of erythrocytes are to pick up inhaled oxygen from the lungs and transport it to the body’s tissues, and to pick up some carbon dioxide waste at the tissues and transport it to the lungs for exhalation.  Erythrocytes remain within the vascular network. Although leukocytes typically leave the blood vessels to perform their defensive functions, movement of erythrocytes from the blood vessels is abnormal.

Shape and Structure of Erythrocytes: As an erythrocyte matures in the red bone marrow, it extrudes its nucleus and most of its other organelles. During the first day or two that it is in the circulation, an immature erythrocyte, known as a reticulocyte, will still typically contain remnants of organelles. Reticulocytes should comprise approximately 1–2 percent of the erythrocyte count and provide a rough estimate of the rate of RBC production, with abnormally low or high rates indicating deviations in the production of these cells. These remnants, primarily of networks (reticulum) of ribosomes, are quickly shed, however, and mature, circulating erythrocytes have few internal cellular structural components. Lacking mitochondria, for example, they rely on anaerobic respiration.  This means that they do not utilize any of the oxygen they are transporting, so they can deliver it all to the tissues. They also lack endoplasmic reticula and do not synthesize proteins. Erythrocytes do, however, contain some structural proteins that help the blood cells maintain their unique structure and enable them to change their shape to squeeze through capillaries. This includes the protein spectrin, a cytoskeletal protein element.

Shape of erythrocytes: Erythrocytes are biconcave disks; that is, they are plump at their periphery and very thin in the center. Since they lack most organelles, there is more interior space for the presence of the hemoglobin molecules that, as you will see shortly, transport gases. The biconcave shape also provides a greater surface area across which gas exchange can occur, relative to its volume; a sphere of a similar diameter would have a lower surface area-to-volume ratio. In the capillaries, the oxygen carried by the erythrocytes can diffuse into the plasma and then through the capillary walls to reach the cells, whereas some of the carbon dioxide produced by the cells as a waste product diffuses into the capillaries to be picked up by the erythrocytes. Capillary beds are extremely narrow, slowing the passage of the erythrocytes and providing an extended opportunity for gas exchange to occur.  However, the space within capillaries can be so minute that, despite their own small size, erythrocytes may have to fold in on themselves if they are to make their way through. Fortunately, their structural proteins like spectrin are flexible, allowing them to bend over themselves to a surprising degree, then spring back again when they enter a wider vessel. In wider vessels, erythrocytes may stack up much like a roll of coins, forming a rouleaux, from the French word for “roll.”

RELATED;

1.  BLOOD AND IT'S COMPONENTS

2.  THE ABO BLOOD GROUPING

3.  HEMOGLOBIN

REFERENCES

CLINICAL TRIALS PHASE 2

 

OBJECTIVES OF THE DISCUSSION

By the end of the discussion, the learner/medical student will be able to;

1.  Differentiate between the phases of clinical trials

2.  Outline the rationale for phase II clinical trials

INTRODUCTION TO CLINICAL TRAILS PHASE TWO: Efficacy and side effects: Phase II trials are conducted on larger groups of patients (few hundreds) and are aimed to evaluate the efficacy of the drug and to endure the Phase I safety assessments.  These trials aren‘t sufficient to confirm whether the drug will be therapeutic. Phase 2 studies provide with additional safety data to the researchers. Researchers use these data to refine research questions, develop research methods, and design new Phase 3 research protocols. Around 33% of drugs travel to the next phase. Most prominently, Phase II clinical studies aid to found therapeutic doses for the large-scale Phase III studies.

RELATED;

1.  CLINICAL TRIALS PHASE I

2.  CLINICAL TRIALS PHASE 3

3.  CLINICAL TRIALS PHASE 4

4.  EXPERIMENTAL STUDY DESIGNS

5.  PHARMACOLOGY AND THERAPEUTICS

REFERENCES