Diabetes Mellitus II. Cardiovascular disease: Diseases which affect the heart & blood vessels. 1. Hypertensive heart disease results in the damage of heart muscles & its valves due to continuous hypertension. It may lead to heart attack in association with damage to renal arteries, blindness & brain stroke (resulting in paralysis; loss of speech & other function). a. Hyper – & hypotension: Refer chapter – Circulation of body fluids, b.
Arteriosclerosis: Degenerative disorder of elderly persons. It is the thickening of arteries & arterioles with consequent loss of elasticity due to hardening & thickening of fibrous tissue. It may result in high blood pressure.
c. Atherosclerosis: It is the narrowing of arteries & arterioles due to insolubilisation & deposition of fats (cholesterol) inside & over the intima. It leads to high blood pressure & also makes the inner surface of arteries irregular which may cause clot formation or thrombosis. 2. Coronary heart disease: Main function of the coronary arteries is to supply oxygen & nutrients to the heart muscle & remove CO2 & other metabolic wastes.
But due to narrowing & hardening of these arteries due to accumulation of fatty deposits, leads to clot formation & resulting in the blockage of blood supply to a part of heart. These include angina pectoris, heart attack & rheumatic heart disease. a. Angina pectoris: Means pain in chest.
It is a severe temporary cardiac pain radiating to arms (especially left arm) due to myocardial ischaemia (deficient oxygen supply) /due to reduced blood supply at the time of physical activity. Angina occurs when the heart needs more blood. Therefore increased physical activity causes heart to beat faster requiring increased blood supply. Fortunately this is not a fatal condition as the pain passes quickly by taking effective vasodilator drug (e.g. Nitroglycerine).
b. Heart attack: Formation of a clot (thrombus) in a narrowed coronary artery stops blood supply to the part of the heart muscle beyond the clot. The muscle cells of this part die due to lack of oxygen and glucose. This condition is called “heart attack” (coronary thrombosis or myocardial infarction) or MI.
It may prove fatal if the area affected is large. The heart attack is characterised by severe pain in the heart, breathlessness, restlessness, and nausea and vomiting. c.
Rheumatic heart disease: The rheumatic heart diseases are common in India under 20 years of age. Rheumatic fever (due to Streptococcal infection, also Cox sackie B-4 virus) produces toxins that cause inflammation of different body parts including joints and endocardium. Repeated fever causes damage to heart walls, heart muscles, scarring and malfunctioning of heart valves, especially atrio-ventricular ones. They give rise to murmur which are pathological (abnormal) heart sounds heard through a stethoscope.
Heart functioning becomes irregular with age. It may give rise to low blood pressure and heart attack. Thus childhood throat infection should be taken seriously.
Prevention of heart disease: Certain precautions can prevent heart diseases. These are as follows:- (i) Avoid tension by keeping cool in all circumstances. (ii) Avoid saturated fats, especially after 35 years of age, to keep cholesterol level of the blood low. (iii) Avoid becoming overweight and obese (bulky). (iv) Take light exercise daily. (v) Avoid smoking, drinking and use of drugs. (vi) Avoid overwork and strain.
(vii) Take preventive measures against infections of respiratory tract. (viii) Consult a doctor in case of any pain in the chest. III. Stroke (Cardiovascular accident, CVA): It is Cerebrovascular (brain blood vessel) damage due to stoppage of blood to a part caused by following reasons :- (a) Clot formation in an artery (cerebral thrombosis) (b) Rupturing of an artery due to weakening of its wall and hypertension (cerebral haemorrhage) (c) Blockage of an artery due to some solid body, fat, air or growth (cerebral embolism) (d) Sustained contraction or spasm of an artery.
The affected brain part does not receive oxygen and nutrients resulting in damage to nerve cells. Such a stroke leads to paralysis, (due to sudden numbness or weakness of face, arm or leg especially on one side of the body) loss of consciousness, loss of speech, hearing or memory and even death. IV. Arthritis: Common disease of old age refers to the inflammation of joints & muscles resulting in pain & stiffness of the joints. When a joint is inflamed it may be swollen, tender, warm to the touch or red. Surrounding each joint is a protective capsule holding a lubricating fluid to aid in motion. Cartilage, a- slippery smooth substance, covers most joints to assure an even, fluid motion of the joint. With joint arthritis, the cartilage may be damaged, narrowed and lost by a degenerative process or by inflammation making movement painful.
Arthritis is of several types:- a. Osteoarthritis: Secretion of the lubricating synovial fluid between the bones at the joint stops the smooth cartilage covering the ends of the bones at the joint wears out due to years of use and is replaced by uneven bony spurs. The joint becomes inflamed, its movement becomes painful, and its function is diminished. Such a stiffness or fixation of a joint is also called ankylosis. The condition of osteoarthritis is more or less permanent. It is common in old persons, mainly affecting weight bearing joints. b. Rheumatoid arthritis: It is a chronic painful inflammation of the synovial membranes of many joints simultaneously.
It usually starts in the small joints in the hand and progresses to other body joint. In severe cases, it eventually results in crippling deformities. There may be other manifestations such as fever, anaemia, loss of weight and morning stiffness. The rheumatoid arthritis involves erosion of joints.
It usually starts at the age of 20-40 years, but may begin at any age. It affects the women more often than the men. c. Gout: It is an inherited disorder of purine metabolism, occurring especially in men. Body forms excess amounts of uric acid and the crystals of sodium urate are deposited in the synovial joints, giving rise to a severe arthritis.
It generally affects one or two joints only. It is very painful, particularly at night, and makes movement difficult. Redness and tenderness may be noticed in and about the affected joint.
Gout generally affects the great toe. Occurrence of gout is related to diet. Persons suffering from gout should avoid meats which are a rich source of nucleic acids including purine. There is no cure for arthritis. However, pain relieving (analgesic) drugs are available to give comfort. Cancer: Cancer is not a single disease. It is a large and complex family of malignancies that can affect virtually every organ in the body. It usually develops from normal cells that has changed or mutated.
It is the result of a continuous, abnormal and relatively autonomous cell proliferation, which is due to the permanent alteration of some cells that gets transmitted to the cell family. It is a disease caused by the loss of control over a cell’s reproduction capacity. Rather than dividing in a controlled and programmed manner, the cell continues to divide and multiply abnormally, until a detectable lump or tumor develops. A single tumor may even have different populations of cells within it with differing processes that have gone away. Malignant versus Benign: A tumor can be classified as malignant or benign. In both cases, there is an abnormal aggregation and proliferation of cells. Malignant tumor, these cells behave more aggressively, acquiring properties of increased invasiveness.
Ultimately, the tumor cells may even gain the ability to break away from the microscopic environment in which they originated, spread to another areas of the body (with a very different environment, not normally conducive to their growth) and continue their rapid growth and division in this new location. This is called metastasis. The rate of cell production in malignant cancerous tissue exceeds the rate of cell death & leads to tumor formation. [Sometimes these outgrow their blood supply & the rapidly increasing number of cells compresses the small blood vessels thereby digging their own graves. This is called ischaemic necrosis]. Once malignant cells have metastasized, achieving cure is more difficult and then chemotherapy plays a more important role than radiotherapy. This spread is accomplished in one of three ways: (i) By directly moving from the tumor to other body parts.
Projections from the main tumor can be seen. (ii) By crossing into the blood vessels and floating along until the cancer cell takes root in another area. (iii) By crossing into the lymph system which normally acts as a filtering system for bacteria and debris. Eventually the lymph system empties into the blood. A cancer cell may be trapped in a lymph node (filtering station) and grows there or it may find its way into the blood stream and the rest of the body. Benign tumors have fewer tendencies to invade due to encapsulated in connective tissue and are less likely to metastasize.
They do divide in an uncontrolled manner, though. Depending on their location, they can be just as life threatening as malignant lesions. An example of this would be a benign tumor in the brain, which can grow and occupy space within the skull, leading to increased pressure on the brain. Characteristics of Cancer Cells: (i) Cancer cells experience uncontrolled and disorganized growth. (ii) Normal cells only divide about 50 (fifty) times before they die, but cancer cells enter the cycle of dividing and reproducing, over and over again and never differentiate.
(iii) Cancer cells have lost all restraint and grow in multiple layers, most likely because of cell surface changes. (iv) The cells are disorganized because they don’t differentiate into the tissue of the organ and they never fulfill the function of the organ. (v) To support their growth, cancer cells release a growth factor that causes neighboring blood vessels to branch into the cancer tissue. This phenomenon has been termed vascularization. (vi) Cancer cells detach from the tumor and spread around the body. To accomplish this, the cells often must make their way across a basement membrane and into a blood vessel or lymphatic vessel.
(vii) Cancer cells have receptors that allow them to adhere to basement membranes; they also produce proteolytic enzymes that degrade the membrane and allow them to invade the underlying tissues. (viii) Cancer cells also tend to be motile. (ix) After travelling through the blood or lymph system, cancer cells start new tumor elsewhere in the body. This process is called metastasis. (x) Benign tumors are those that remain in one place; malignant tumors are those that metastasize. (xi) Angiogenesis (ability to induce blood vessel formation) (xii) Loss of cell cycle control. Stages: Stage generally refers to the degree to which the cancer has spread beyond its original location. Lower stages of cancer (stage I & II) are generally more confined to their site or region of origin than more advanced stage (III & IV).
Stage I, the simplest form, indicates that the tumor is small and confined to the organ or tissue where it began. The best chance for cure is when the tumor is still in Stage I. Also called T stage (tumor stage). Stage II means the tumor has spread to surrounding tissues. Stage III means the tumor has spread into surrounding tissues and lymph nodes also called N stage (nodal stage). Stage IV signifies more extensive spread, often too many organs or parts of the body.
Thus is known as secondary cancer or metastatic diseases also called M stage (stage of metastatic disease). The goal of staging is three fold:- (i) To help select the most important therapy for the patient. (ii) To help predict a patient’s prognosis i.e., how well will the patient respond to the standard treatment; and (iii) To help future patients by assessing your response to therapy and tracking that along with the treatment responses of others with the same stage of cancer. Causes of cancer: I.
Multiple somatic mutations are needed to create a cancerous cell. These mutations can be caused by (a) Carcinogens: Carcinogens (cancer causing factors) are factors, which cause the DNA inside a cell to become altered (also known as mutated). However in order for a mutation to cause cancer, the mutation must cause the cell to do two things: (i) To grow without control and (ii) To become immortal (not die when supposed to). Carcinogens can be physical, chemical or biological Physical mutagens: Physical mutation of DNA can be caused by ionising radiation, ultraviolet radiation and by mineral fibres.
These three mutagens act in very different ways. Ionising radiation literally punches holes in the DNA, breaking the correct genetic sequence. Ionising radiation can come directly from X-rays, cosmic rays (solar radiation) and indirectly from radon gas. Ultraviolet radiation (from sunlight) by contrast causes mutations by causing certain portions of DNA to remain bound together (even when they shouldn’t).
This causes mutations by causing misreading of the DNA. Finally, certain natural mineral fibres like asbestos, because of their size can cause damage directly to DNA resulting in carcinogenic mutations. Chemical mutagens: In the case of chemical mutagens, mutation is caused by foreign molecules binding to a cell’s DNA, causing it to be “misread”.
Examples of chemical mutagens are benzopyrene (found in cigarette smoke) and vinyl chloride (found in the plastics industry), aflatoxin (found in certain moulds) and heterocyclic amines (found in over-cooked food). Biological mutagens: Biological mutagens may be viral or bacterial. Viral mutagens may use a number of different complex mechanisms to cause a cell to become cancerous. Viruses that cause cancer include the human papilloma virus (implicated in cervical cancer), the human T-cell lymphyocytic virus (implicated in lymphoma), and the hepatitis B virus (implicated in liver cancer).
Known bacterial mutagen are Helicobacter pylori (which causes gastric ulcers), implicated in stomach cancer. (b) Viruses (i) Retroviruses a. Rous sarcoma virus: Carries a cellular oncogene (v-src) b. Avian leukosis virus: Activates a cellular oncogene (c-myc) (ii) DNA tumor viruses (insertional mutagenesis): Adenovirus, SV 40, Hepatitis B virus (HBV) (c) A tendency to get cancer can be inherited Individuals inherit one “bad” allele but still need a somatic mutation in the other “good” allele. Retinoblastoma (40% are inheritable), Wilms tumor (100%), breast cancer (only 5% are inheritable). II. Cancer genes: Multiple mutations are needed to create the typical cancer cell.
These mutations are in the genes that i. Regulate cell growth ii. Protect the individual by killing damaged or unneeded cells. iii. Repair the DNA iv. Determine cellular characteristics, and genes to promote angiogenesis (ability to induce local blood vessel formation). Two major factors of gene known to cause cancer are: oncogenes and tumor suppressor genes.
Oncogenes (Induce or maintain uncontrolled growth) The process of activation of oncogenes from proto-oncogenes can include retroviral transduction or retroviral integration, point mutations, insertion mutations, gene amplification, chromosomal translocation and/or protein interactions. The distinction between the terms proto-oncogene and oncogene relates to the activity of the protein product of the gene. A proto-oncogene is a gene whose protein product has the capacity to induce cellular transformation, given it sustains some genetic insult.
An oncogene is a gene that sustained some genetic damage and, therefore, produces a protein capable of cellular transformation. Tumor suppressors: Tumor suppressor genes were first identified by making cell hybrids between tumor and normal cells. On some occasions a chromosomes from the normal cells reverted the transformed phenotype. Tumor suppressor gene normally keeps mitosis in check & prevents cancer from occurring. This gene must be inactivated or removed to eliminate control of cell cycle & initiate cancer. Examples of tumor suppressor genes: (I) Wilms Tumor – involved in Wilms tumor of the kidneys (nephroblastoma) – Appears to shut down division of a small subset of kidney cells during development (II) BRCA1 – inheritable breast cancer (5%) & ovarian cancer – Codes for a protein that binds strongly to DNA, inhibiting an enzyme involved in DNA breakage (III) p53; a transcription factor that blocks entry into S phase if there is DNA damage – If there is too much damage to repair, it causes apoptosis.
Other cancer genes includes (i) Telomerase: Activation of telomerase is necessary for immortality (ii) Angiogensis genes: Tumors need to promote the growth of new blood vessels to support their growth (iii) Metastasis genes: Proteinases to cut through the extracellular matrix, etc. Symptoms of cancer: (i) Thickening or lump in the breast or any other part of the body. (ii) Changes in bowel or bladder habits. (iii) Obvious change in a wart or mole. (iv) A sore that does not heal. (v) Nagging cough or hoarseness. (vi) Indigestion or difficulty in swallowing. (vii) Unexplained changes in weight.
(viii) Unusual bleeding or discharge. Types of cancer (a) Carcinoma: Carcinoma is a malignant neoplasm of epithelial origin. It is a tumor that arises in the tissues that line the body’s organ like the nose, the colon, the penis, breasts, prostate, urinary bladder or the ureter. About 80% of all cancer cases are carcinomas. Carcinoma are commonest cancer and may be: (i) Squamous carcinoma: cancer of epithelial tissue.
(ii) Adenocarncinoma: cancer of glands. (b) Sarcoma: Sarcomas are tumors that originate in mesodermal tissue like bone, connective tissue muscle, cartilage, fibrous tissue or fat. Sarcoma are named according to the tissue in which these are formed like, Fibrosarcoma – fibrous connective tissue Liposarcoma – adipose tissue Chondrosarcoma – cartilage cells Osteosarcoma – bone Leiomyosarcoma – smooth muscles Rhabdomyosarcoma – stripped muscles. Ewing sarcoma (family of tumours) and Kaposi’s sarcoma are the common types of sarcomas. Ewing sarcoma occurs during the rapid bone growth that generally occurs during puberty. It is seldom seen before a child is 10 years old. The tumor may arise in the long bones of the extremities, most often in the femur (thigh bone) or the pelvis.
It may also develop in the skull or the flat bones of the trunk. Kaposi’s sarcoma is a malignant tumor frequently involving the skin of AIDS victims. Treatment decisions depend upon the extent and location of the lesions, as well as the person’s symptoms and degree of immunosuppression. Radiation therapy or cryotherapy can be used for lesions in selected areas.
Combination chemotherapy can also be used. (c) Leukaemia: Leukaemias are cancers of the blood or blood-forming organs. When leukaemia develops, the body produces a large number of abnormal blood cells. In most types of leukaemia, the abnormal cells are white blood cells (200000 – 1000, 000/mm3). The leukaemia cells usually look different from normal blood cells, and they do not function properly.
Leukaemia can either be acute or chronic. In acute leukaemia the abnormal blood cells are blasts that remain very immature and cannot carry out their normal functions. The number of blasts increases rapidly, thus creating a greater and earlier impact on the victim.
In chronic leukaemia, some blast cells are present which are comparatively more mature, and thus can carry out some of their normal function. The number of blasts increases at a slower pace than in acute leukaemia, as a result of which such condition worsens gradually. Leukaemia cells cannot help the body fight infections. Depending on the number of abnormal cells and where these cells collect, patients with leukaemia may have a number of symptoms like: (i) Fever, chills, and other flu-like symptoms (ii) Weakness and fatigue (iii) Frequent infections (iv) Loss of appetite and/or weight (v) Swollen or tender liver, spleen and lymph nodes (vi) Easy bleeding or bruising (vii) Tiny red spots under the skin (viii) Swollen or bleeding gums (ix) Sweating, especially at night; and/or (x) Bone or joint pain. Due to increased neoplastic proliferation of leukocytes these cells infiltrate into various other tissues and organs, producing enlargement of organs or tumors. Leukaemias are treated with chemotherapy. Some also may have radiation therapy and/or bone marrow transplantation (BMT) or biological therapy, e.
g., hormonal treatment. In some cases, surgery to remove the spleen (an operation called splenectomy) may be part of the treatment plan. (d) Lymphomas: Lymphomas affect the lymphatic system, a network of vessels and nodes that acts as the body’s filter. The lymphatic system distributes nutrients to blood and tissue, and prevents bacteria and other foreign “invaders” from entering the bloodstream. There are over 20 types of lymphoma.
Hodgkin’s disease is one type of lymphoma. All other lymphomas are grouped together and are called Non-Hodgkin’s Lymphoma (NHL). Non-Hodgkin Lymphoma may occur in a single lymph node, a group of lymph nodes, or in another organ. This type of cancer can spread to almost any part of the body including the liver, bone marrow and spleen.
Chemotherapy and radiation therapy are the most common treatments for non-Hodgkin’s lymphoma, although bone marrow transplantation, biological therapies, or surgery are sometimes used. Treatment of cancer: The treatment of cancer is a very complex subject. The types of therapies used in cancer treatment depend on several factors:- (i) Type of cancer – Some tumors are more sensitive to radiation others respond better to chemotherapy.
(ii) Location of the tumor – Some tumors can be removed surgically. (iii) Extent or stage of the disease. Types of therapy are – (a) Surgery: Surgery is often the first step in the treatment of cancer. Generally, surgery is done when the cancer is in a limited area.
Sometimes, the goal is to remove the whole tumor and achieve cure. At other times, the surgeon removes the largest portion of tumor so other treatment options can work better. Finally, surgery can be used to make the patient more comfortable, such as removing a blockage of the bowel. (b) Radiation therapy: Radiation is the use of high- energy X-rays to treat cancer. Radiation destroys the ability of cancer cells to grow and divide by damaging the DNA within the tumour cells. Both normal and cancer cells are affected by radiation, but most normal cells recover or repair themselves. Radiation therapy can treat tumors located in a specific area.
Sometimes, radiation helps control the symptoms from a tumor that has spread. Radiation can also be used in certain instances for whole body irradiation, such as for bone marrow transplantation. (c) Chemotherapy: Chemotherapy is the use of chemicals or medicines to treat cancers. Because chemotherapy is generally transported through the blood, it can treat cancers that have spread or are suspected of spreading some distance from the starting place.
Chemotherapy may also be used to enhance the response of localized tumors to surgery & radiation therapy. Eg. in case of cancers of head & neck. (d) Immunotherapy: Immunotherapy is a form of treatment that enhances the body’s ability to recognize cancer cells and destroy them. The body’s immune system can usually destroy or help destroy most infections or other invaders like cancer cells.
It can be given intravenously or by subcutaneous injection. The most research in this area has been conducted on melanoma, though other cancers are also now being targeted. (e) Blood and marrow transplant: High dose chemotherapy or radiation therapy can destroy bone marrow’s ability to make new blood cells. A blood or marrow transplant can be used to replace marrow stem cells which produce blood cells.
Procedure of bone marrow transplantation is usually performed either because a patient has a cancer that is particularly aggressive or because they have a cancer that has relapsed after being treated with conventional therapy. Bone marrow transplantation is a complicated procedure. For a transplant, a patient is treated with high doses of chemotherapy and/or radiation (usually to the whole body) to destroy cancerous cells in the bone marrow and other areas of the body and also to suppress the body’s immune system so that the new donated marrow is less likely to be “rejected”. (Some transplants use marrow that is collected in advance from the actual cancer patient.
These transplants are not associated with the rejection risk).