DIABETES MELLITUS

 

INTRODUCTION: Diabetes mellitus is a group of metabolic disorders characterized by elevated levels of blood glucose (hyperglycemia) resulting from defects in insulin secretion, insulin action, or both. INSULIN AS A CHEMICAL OF LIFE  Three major acute complications of diabetes related to short-term imbalances in blood glucose levels are hypoglycemia, diabetic ketoacidosis (DKA), and hyperglycemic hyperosmolar nonketotic syndrome (HHNS). Long-term hyperglycemia may contribute to chronic microvascular complications such as kidney and eye disease, and neuropathic complications. Diabetes is also associated with an increased occurrence of macrovascular diseases, including coronary artery disease (myocardial infarction), cerebrovascular disease (stroke), and peripheral vascular disease. [coronaryartery disease]

TYPES OF DIABETES TYPE 1 (FORMERLY INSULIN-DEPENDENT DIABETES MELLITUS): About 5% to 10% of patients with diabetes have type 1 diabetes. It is characterized by destruction of the pancreatic beta-cells due to genetic, immunologic, and possibly environmental factors. In this medical condition, insulin injections are needed to control the blood glucose levels. Type 1 diabetes has a sudden onset, usually before the age of 30 years.

TYPE 2 (FORMERLY NON–INSULIN-DEPENDENT DIABETES MELLITUS): About 90% to 95% of patients with diabetes have type 2 diabetes. It results from a decreased sensitivity to insulin also known as insulin resistance, or from a decreased amount of insulin production. Type 2 diabetes is first treated with diet and exercise, and then with oral hypoglycemic agents as needed. Type 2 diabetes occurs most frequently in patients older than 30 years and in patients with obesity.

Gestational Diabetes Mellitus: Gestational diabetes is characterized by any degree of glucose intolerance with onset during pregnancy (second or third trimester). Risks for gestational diabetes include marked obesity, a personal history of gestational diabetes, glycosuria, or a strong family history of diabetes. High-risk ethnic groups include Hispanic Americans, Native Americans, Asian Americans, African Americans, and Pacific Islanders. It increases their risk for hypertensive disorders of pregnancy. 

Clinical Manifestations: Polyuria, polydipsia, and polyphagia. Fatigue and weakness, sudden vision changes, tingling or numbness in hands or feet, dry skin, skin lesions or wounds that are slow to heal, and recurrent infections. Onset of type 1 diabetes may be associated with sudden weight loss or nausea, vomiting, or stomach pains. Type 2 diabetes results from a slow (over years), progressive glucose intolerance and results in long-term complications if diabetes goes undetected for many years such as in case of eye disease, peripheral neuropathy, or peripheral vascular disease. Complications may have developed before the actual diagnosis is made.

Signs and symptoms of DKA: These include; abdominal pain, nausea, vomiting, hyperventilation, and a fruity breath odor. Untreated DKA may result in altered level of consciousness, coma, and death.

RELATED;

1.  DRUG ADMINISTRATION TECHNIQUES USED IN MEDICINE  

2.  DIABETES INSPIDUS

3.  INSULIN AND THE HUMAN BODY

4.  MEDICINE AND SURGERY 

REFERENCES

PHASES OF METABOLISM

 

INTRODUCTION: The degradation of foodstuffs occurs in three stages. (1) In the first stage, digestion in the gastrointestinal tract converts the macromolecules into small units. For example, proteins are digested to amino acids. This is called primary metabolism.

(2) Then these products are absorbed, catabolized to smaller components, and ultimately oxidized to CO₂. Carbondioxide

(3) The reducing equivalents are mainly generated in the mitochondria by the final common oxidative pathway, citric acid cycle. Thecitric acid cycle

In this process, NADH or FADH₂ are generated. This is called secondary or intermediary metabolism. Then these reduced equivalents enter into the electron transport chain (ETC, or Respiratory chain), where energy is released. This is the tertiary metabolism or Internal respiration or cellular respiration.

Carbohydrates enter the glycolysis pathway, converted to acetyl CoA and are oxidized in the citric acid cycle. Carbohydrate metabolism is centered on glucose, and is mainly used for provision of energy to the body. Lipid metabolism is centered on fatty acids, which are also used for provision of energy. Amino acids are mainly meant for body building purpose. However, most of the amino acids are eventually transaminated, the carbon skeletons are oxidized. This will provide some energy. But energy production is not the main purpose of amino acid metabolism.

RELATED;

1. GLYCOLYSIS

2. THE CITRIC ACID CYCLE

3. PROTEIN ENERGY MULNUTRITION

REFERENCES

PHASES OF CLINICAL TRIALS

 

OBJECTIVES OF THE DISCUSSION:  By the end of this discussion, the learner/medical student will be able to;

1.  List the intentions of phase 1 clinical trials

2.  Continue with the description of following clinical phases

PHASE 1: Safety and dosage: In some of my previous discussions I was talking about a drug being able to cure the intended disease but also have minimal side effects or in simple terms, safer for the patient.  Phase I trials are the first tests of a drug with a lesser number of healthy human volunteers. In most cases, 20 to 80 healthy volunteers with the disease or a condition participate in Phase 1. Patients are generally only used if the mechanism of action of a drug also known as pharmacodynamics, indicates that it will not be tolerated in healthy people. Pharmacodynamics

However, if a new drug is proposed for use in Parkinsonism patients lets say, researchers conduct Phase 1 trials in patients with that Parkinson’s disease. Phase 1 studies are closely monitored and collect information about Pharmacodynamics in the human body.

Researchers adjust dosage regimen based on animal study data to find out what dose of a drug can tolerate the body and what are its acute side effects. As a Phase 1 trial continues, researchers find out research mechanism of action, the side effects accompanying with increase in dosage, and information about effectiveness. This is imperative to the design of Phase 2 studies. Almost 70% of drugs travel to the next phase.

RELATED;

1.  CLINICAL TRIALS PHASE 2  

2.  CLINICAL TRIALS PHASE 3  

3.  CLINICAL TRIALS PHASE 4  

4.  EXPERIMENTAL STUDY DESIGNS

5.  EXPERIMENTAL STUDY DESIGNS

REFERENCES

PHASES OF METABOLISM

 

INTRODUCTION: The degradation of foodstuffs occurs in three stages. 

 (1) In the first stage, digestion in the gastrointestinal tract converts the macromolecules into small units. For example, proteins are digested to amino acids. This is called primary metabolism. 

Physiologyof the gastrointestinal tract  

(2) Then these products are absorbed, catabolized to smaller components, and ultimately oxidized to CO₂. 

Carbondioxide  

(3) The reducing equivalents are mainly generated in the mitochondria by the final common oxidative pathway, citric acid cycle. Thecitric acid cycle  In this process, NADH or FADH₂ are generated. This is called secondary or intermediary metabolism. Then these reduced equivalents enter into the electron transport chain (ETC, or Respiratory chain), where energy is released. This is the tertiary metabolism or Internal respiration or cellular respiration.  

Carbohydrates enter the glycolysis pathway, converted to acetyl CoA and are oxidized in the citric acid cycle. Carbohydrate metabolism is centered on glucose, and is mainly used for provision of energy to the body. Lipid metabolism is centered on fatty acids, which are also used for provision of energy. Amino acids are mainly meant for body building purpose. However, most of the amino acids are eventually transaminated, the carbon skeletons are oxidized. This will provide some energy. But energy production is not the main purpose of amino acid metabolism.

RELATED;

1. GLYCOLYSIS  

2. THE CITRIC ACID CYCLE  

3. PROTEIN ENERGY MULNUTRITION

4.  DIGESTION OF LIPIDS

REFERENCES

PEPTIC ULCER DISEASE

 

Introduction: A peptic ulcer is an excavation formed in the mucosal wall of the stomach, pylorus, duodenum, or esophagus. It is frequently referred to as a gastric, duodenal, or esophageal ulcer, depending on its location. It is caused by the erosion of a circumscribed area of mucous membrane. Peptic ulcers are more likely to be in the duodenum than in the stomach. They tend to occur singly, but there may be several present at one time. Chronic ulcers usually occur in the lesser curvature of the stomach, near the pylorus. Peptic ulcer has been associated with bacterial infection, such as Helicobacter pylori.  The greatest frequency is noted in people between the ages of 40 and 60 years. After menopause, the incidence among women is almost equal to that in men.

PREDISPOSING FACTORS: Predisposing factors include family history of peptic ulcer, blood type O, chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs), alcohol ingestion, excessive smoking, and, possibly, high stress. BLOOD GROUPS

Esophageal ulcers result from the backward flow of hydrochloric acid from the stomach into the esophagus. Zollinger–Ellison syndrome (gastrinoma) is suspected when a patient has several peptic ulcers or an ulcer that is resistant to standard medical therapy. This syndrome involves extreme gastric hyperacidity that is; hypersecretion of gastric juice, duodenal ulcer, and gastrinomas (islet cell tumors). About 90% of tumors are found in the gastric triangle. About one third of gastrinomas are malignant. Diarrhea and steatorrhea (unabsorbed fat in the stool) may be evident. In this condition, the most frequent complaint is epigastric pain. Recent research indicates that over 90% of peptic ulcer disease is caused by H. pylori.  Stress ulcer is a term given to acute mucosal ulceration of the duodenal or gastric area that occurs after physiologically stressful events, such as burns, shock, severe sepsis, and multiple organ trauma. Shock

CLINICAL MANIFESTATIONS: Symptoms of an ulcer may last days, weeks, or months and may subside only to reappear without cause. Many patients have asymptomatic ulcers. Dull, gnawing pain and a burning sensation in the midepigastrium or in the back are characteristic. Pain is relieved by eating or taking alkali; once the stomach has emptied or the alkali wears off, the pain returns. Sharply localized tenderness is elicited by gentle pressure on the epigastrium or slightly right of the midline. Other symptoms include pyrosis (heartburn) and a burning sensation in the esophagus and stomach, which moves up to the mouth, occasionally with sour eructation (burping). Vomiting is rare in uncomplicated duodenal ulcer; it may or may not be preceded by nausea and usually follows a bout of severe pain and bloating; it is relieved by ejection of the acid gastric contents. Constipation or diarrhea may result from diet and medications. Bleeding (15% of patients with gastric ulcers) and tarry stools may occur; a small portion of patients who bleed from an acute ulcer have only very mild symptoms or none at all.

Pharmacologic Therapy: Antibiotics combined with proton pump inhibitors and bismuth salts to suppress H. pylori. H₂-receptor antagonists to decrease stomach acid secretion; maintenance doses of H₂-receptor antagonists are usually recommended for 1 year. Proton pump inhibitors may also be prescribed. Cytoprotective agents to protect mucosal cells from acid or NSAIDs. Antacids in combination with cimetidine or ranitidine for treatment of stress ulcer and for prophylactic use.

Lifestyle Changes: Stress reduction and rest are priority interventions. The patient needs to identify situations that are stressful or exhausting (eg, rushed lifestyle and irregular schedules) and implement changes, such as establishing regular rest periods during the day in the acute phase of the disease. Biofeedback, hypnosis, behavior modification, massage, or acupuncture may also be useful. Smoking cessation is strongly encouraged because smoking raises duodenal acidity and significantly inhibits ulcer repair. Support groups may be helpful. Dietary modification may be helpful. Patients should eat whatever agrees with them; small, frequent meals are not necessary if antacids or histamine blockers are part of therapy. Oversecretion and hypermotility of the GI tract can be minimized by avoiding extremes of temperature and overstimulation by meat extracts. Alcohol and caffeinated beverages such as coffee (including decaffeinated coffee, which stimulates acid secretion) should be avoided. Diets rich in milk and cream should be avoided also because they are potent acid stimulators. The patient is encouraged to eat three regular meals a day.

RELATED;

1.  ANTIEMETIC AGENTS

2.  PROTON PUMP INHIBITORS

3.  MEDICAL CONDITIONS

REFERENCES

CHRONIC INFLAMMATION

 

Introduction: Chronic inflammatory happens when there is a reaction over a prolonged period of time, that is to say, months to years, in which active inflammation plus a healing process occur at a time. This usually proceeded by acute inflammation when the causative agent is not removed and is characterized by the following changes; 

1) Diminished polymorphs cells and presences of macrophages, (epitheliod, and giant cells), plasma cells, and lymphocytes, in addition to vascular budding and formation of new capillaries also known as angiogenesis.  LYMPHOCYTES

In the same case, there is proliferation of fibroblast and fibrosis which is an attempt of healing.  WOUNDHEALING  

2) Cells in the chronic inflammatory process tend to produce substances that add new tissue, such as collagen and new blood vessels, many of these changes also represent the repair process, and there is a blurry continuum between chronic inflammation and the whole repair process.  In general, chronic inflammation is characterized by tissue destruction and attempts at repair, all happening at a time. Comparison between Acute and Chronic Inflammation: Acute inflammation occurs during a short period of time, days or weeks, in the presence of all cardinal signs of inflammation and infiltration of inflammatory cells, mainly neutrophil. While, chronic inflammation occurs in a long period of time, months or years, and is infiltrated with lymphocytes, plasma cells and macrophages associated with formation of fibrous tissue in the periphery of the inflamed tissue.

RELATED;

1.  THE PROCESS OF INFLATION  

2.  CELLULAR EVENTS DURING INFLAMMATION  

3.  PATHOLOGY

references

CORONARY ARTERY DISEASE

Introduction: Acute coronary syndrome (ACS) is an emergent situation characterized by an acute onset of myocardial ischemia that results in myocardial death that is to say, myocardial infarction [MI]) if definitive interventions do not occur promptly.  In unstable angina, there is reduced blood flow in a coronary artery, often due to rupture of an atherosclerotic plaque, but the artery is not completely occluded. This is an acute situation that is sometimes referred to as pre-infarction angina because the patient will likely have an MI if prompt interventions do not occur. In an MI, an area of the myocardium is permanently destroyed, typically because plaque rupture and subsequent thrombus formation result in complete occlusion of the artery. Vasospasm also known as sudden constriction or narrowing, of a coronary artery, decreased oxygen supply such as from acute blood loss, anemia, or low blood pressure, and increased demand for oxygen such as from a rapid heart rate, thyrotoxicosis, or ingestion of cocaine, are other causes of MI.  In each case, a profound imbalance exists between myocardial oxygen supply and demand. An MI may be defined by the type, the location of the injury to the ventricular wall, or by the point in time in the process of infarction (acute, evolving, old).

Clinical Manifestations: In many cases, the signs and symptoms of MI cannot be distinguished from those of unstable angina, hence, the evolution of the term ACS. Chest pain that occurs suddenly and continues despite rest and medication is the primary presenting symptom. Some patients have prodromal symptoms or a previous diagnosis of coronary artery disease (CAD), but about half report no previous symptoms. Patient may present with a combination of symptoms, including chest pain, shortness of breath, indigestion, nausea, and anxiety. Patient may have cool, pale, and moist skin; heart rate and respiratory rate may be faster than normal. These signs and symptoms, which are caused by stimulation of the sympathetic nervous system, may be present for only a short time or may persist.

Assessment and Diagnostic Methods: Patient history (description of presenting symptom; history of previous illnesses and family health history, particularly of heart disease). Previous history should also include information about patient’s risk factors for heart disease. Electrocardiography (ECG) within 10 minutes of pain onset or arrival at the emergency department; echocardiography to evaluate ventricular function. Cardiac enzymes and biomarkers (creatine kinase isoenzymes, myoglobin, and troponin).

Medical Management: The goals of medical management are to minimize myocardial damage, preserve myocardial function, and prevent complications such as lethal dysrhythmias and cardiogenic shock. Reperfusion via emergency use of thrombolytic medications or percutaneous coronary intervention (PCI). Reduce myocardial oxygen demand and increase oxygen supply with medications, oxygen administration, and bed rest. Coronary artery bypass or minimally invasive direct coronary artery bypass (MIDCAB).  

Pharmacologic Therapy: Nitrates (nitroglycerin) to increase oxygen supply. Anticoagulants (aspirin, heparin). Analgesics (morphine sulfate). Angiotensin-converting enzyme (ACE) inhibitors. Beta-blocker initially, and a prescription to continue its use after hospital discharge. Thrombolytics (alteplase [t-PA, Activase] and reteplase [r-PA, TNKase]): must be administered as early as possible after the onset of symptoms, generally within 3 to 6 hour.

RELATED;

1.  CARDIOVASCULAR CONDITIONS

2.  MEDICAL CONDITIONS

REFERENCES

THE ABO BLOOD GROUP

 

Introduction: Although the ABO blood group name consists of three letters, ABO blood typing designates the presence or absence of just two antigens, A and B. Both are glycoproteins. People whose erythrocytes have A antigens on their erythrocyte membrane surfaces are designated blood type A, and those whose erythrocytes have B antigens are blood type B. People can also have both A and B antigens on their erythrocytes, in which case they are blood type AB. People with neither A nor B antigens are designated blood type O. ABO blood types are genetically determined. Normally the body must be exposed to a foreign antigen before an antibody can be produced. This is not the case for the ABO blood group. Individuals with type A blood without any prior exposure to incompatible blood have preformed antibodies to the B antigen circulating in their blood plasma.  These antibodies, referred to as anti-B antibodies, will cause agglutination and hemolysis if they ever encounter erythrocytes with B antigens. Similarly, an individual with type B blood has pre-formed anti-A antibodies. Individuals with type AB blood, which has both antigens, do not have preformed antibodies to either of these. People with type O blood lack antigens A and B on their erythrocytes, but both anti-A and anti-B antibodies circulate in their blood plasma.

RH BLOOD GROUPS: The Rh blood group is classified according to the presence or absence of a second erythrocyte antigen identified as Rh. Although dozens of Rh antigens have been identified, only one, designated D, is clinically important. Those who have the RhD antigen present on their erythrocytes are described Rh positive (Rh⁺) and those who lack it are Rh negative (Rh⁻). It should be noted that, the Rh group is distinct from the ABO group, so any individual, no matter their ABO blood type, may have or lack this Rh antigen. When identifying a patient’s blood type, the Rh group is designated by adding the word positive or negative to the ABO type. For example, A positive (A⁺) means ABO group A blood with the Rh antigen present, and AB negative (AB⁻) means ABO group AB blood without the Rh antigen.

In contrast to the ABO group antibodies, which are preformed, antibodies to the Rh antigen are produced only in Rh⁻ individuals after exposure to the antigen. This process, called sensitization, occurs following a transfusion with Rh incompatible blood or, more commonly, with the birth of an Rh⁺ baby to an Rh⁻ mother. Problems are rare in a first pregnancy, since the baby’s Rh+ cells rarely cross the placenta. However, during or immediately after birth, the Rh− mother can be exposed to the baby’s Rh+ cells. After exposure, the mother’s immune system begins to generate anti-Rh antibodies. If the mother should then conceive another Rh+ baby, the Rh antibodies she has produced can cross the placenta into the fetal bloodstream and destroy the fetal RBCs. This condition, known as hemolytic disease of the newborn (HDN) or erythroblastosis fetalis, may cause anemia in mild cases, but the agglutination and hemolysis can be so severe that without treatment the fetus may die in the womb or shortly after birth. A drug known as RhoGAM, short for Rh immune globulin, can temporarily prevent the development of Rh antibodies in the Rh− mother, thereby averting this potentially serious disease for the fetus. RhoGAM antibodies destroy any fetal Rh+ erythrocytes that may cross the placental barrier. RhoGAM is normally administered to Rh− mothers during weeks 26−28 of pregnancy and within 72 hours following birth.

RELATED;

1.  RED BLOOD CELLS

2.  COMPOSITION OF BLOOD CLICK HERE

3.  SHOCK CLICK HERE

REFERENCES

LUMBER PUNCTURE

INTRODUCTION:  A lumbar puncture (spinal tap) is a diagnostic procedure that involves the removal of cerebrospinal fluid to determine its pressure and constituents. As the name tells us, the removal, using a syringe, is made in the lumbar area. Because the spinal cord ends between the 1st and 2nd lumbar vertebrae, the needle is usually inserted between the 4th and 5th lumbar vertebrae. The meningeal sac containing cerebrospinal fluid extends to the end of the lumbar vertebrae, permitting access to the cerebrospinal fluid with little chance of damaging the spinal cord.

NORMAL PARAMETERS OF CEREBROSPINAL FLUID:  Cerebrospinal fluid is a circulating fluid and has a normal pressure of 70 to 200 mmH₂O. An abnormal pressure usually indicates an obstruction in circulation, which may be caused by infection, a tumor, or mechanical injury. Other diagnostic tests would be needed to determine the precise cause. Perhaps the most common reason for a lumbar puncture is suspected meningitis, which may be caused by several kinds of bacteria. If the patient does have meningitis, the cerebrospinal fluid will be cloudy rather than clear and will be examined for the presence of bacteria and many white blood cells.  A few WBCs in CSF is normal, because WBCs are found in all tissue fluid. Another abnormal constituent of cerebrospinal fluid is red blood cells. Their presence indicates bleeding somewhere in the central nervous system. There may be many causes, and again, further testing would be necessary.

 

RELATED;

1.  BODY FLUIDS

2.  ANATOMY AND PHYSIOLOGY

3.  MEDICAL CONDITIONS

REFERENCES

BCG VACCINATION

 

Introduction: BCG vaccine consists of live bovine tubercle bacilli whose virulence has been attenuated by multiple passages through glycerinated potato. The bacilli of the vaccine are therefore alive, but have lost some of their virulence. BCG is the most widely used vaccine in the world.

EFFICACY OF THE VACCINE: The protection conferred by BCG when it is administered correctly at birth acts mainly on the severe extrapulmonary forms in children. It is currently estimated at between 60-90%.

INDICATIONS: In countries with a high prevalence of TB, BCG vaccination should be administered to infants as soon as possible after birth and in any case before the age of one year.

AVAILABILITY OF VACCINE: The vaccine is available in dry, lyophilised powder that is sensitive to heat, so the vaccine should be kept in a cold chain and away from light. To avoid exposure to light the vaccine is delivered in coloured vials. The vial is accompanied by another vial containing a solvent that must be used cold, by refrigerating it for at least 24 hours before use. After reconstitution the mixture must be kept in the refrigerator and used within 3-4 hours. 

DOSE: The dose of vaccine is 0.05 ml for newborns and children aged upto one year. It is 0.1 ml for children aged over one year. 

REQUIREMENTS: 1 ml syringe and intradermal needle.

SITE OF ADMINISTRATION: Usually same site is recommended for use in the whole of the country so that it is easy to detect the vaccination scar. Usually it is the front of the left upper arm.

ROUTE OF ADMINISTRATION: Vaccine is given intradermally. If by chance the needle goes beyond the dermis, the needle should be withdrawn and inserted at an adjacent spot. The injection should raise a wheal.

RELATED;  

1.  TECNIQUESAND ROUTES OF DRUG ADMINISTRATION  

2.  ACTIVE IMMUNISATION  

3.  ADAPTIVE IMMUNITY  

REFERENCES

GLUCONEOGENESIS

INTRODUCTION: Gluconeogenesis is a metabolic pathway that results in the generation of glucose from certain non-carbohydrate carbon substrates. From breakdown of proteins, these substrates include glucogenic amino acids. From breakdown of lipids such as triglycerides, they include glycerol. From other steps in metabolism they include pyruvate and lactate. PYRUVATE LACTATE 

ROLE OF GLUCONEOGENESIS:  Gluconeogenesis is one of several main mechanisms used by humans and many other animals to maintain blood glucose levels, avoiding low levels also known as hypoglycemia. Other means include the degradation of glycogen also known as glycogenolysis, and fatty acid breakdown.

SITES OF GLUCONEOGENESIS:  Gluconeogenesis is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In vertebrates, gluconeogenesis takes place mainly in the liver and, to a lesser extent, in the cortex of the kidneys. In many other animals, the process occurs during periods of fasting, starvation, low-carbohydrate diets, or intense exercise. 

The process is highly endergonic until it is coupled to the hydrolysis of ATP or GTP, effectively making the process exergonic. For example, the pathway leading from pyruvate to glucose-6-phosphate requires 4 molecules of ATP and 2 molecules of GTP to proceed spontaneously. Gluconeogenesis is often associated with ketosis. Gluconeogenesis is also a target of therapy for type 2 diabetes, such as the antidiabetic drug, metformin, which inhibits glucose formation and stimulates glucose uptake by cells.  In ruminants, because metabolizable dietary carbohydrates tend to be metabolized by rumen organisms, gluconeogenesis occurs regardless of fasting, low-carbohydrate diets, exercise, and many others.

RELATED;

1.  GLYCOLYSIS

2.  GLYCOGEN

3.  BIOCHEMISTRY

REFERENCES