DM and Acid-Base Disorder Presentation Fall 2024 PDF

DIABETES MELLITUS (DM) AND ACID BASE DISORDER By/ Dr. Abdullah Alshudukhi Fall,2024 outline Introduction to glucose homeostasis Diabetes mellitus Acid-base balance by respiratory system  Glucose homeostasis Glucose occupies a central positi...

DIABETES MELLITUS (DM) AND ACID BASE DISORDER By/ Dr. Abdullah Alshudukhi Fall,2024 outline Introduction to glucose homeostasis Diabetes mellitus Acid-base balance by respiratory system  Glucose homeostasis Glucose occupies a central position in the metabolism of humans, animals, and many microorganisms. After a meal, luminal glucose is transported across the apical membrane into the enterocytes via SGLT1 and subsequently passively transported out of the cell into the circulation through GLUT2 in the basolateral membrane  Cont. Glucose is the primary fuel used for energy (i.e., ATP production) during the digestive phase. Glucose is considered a universal fuel in that most cells can perform the following: 1. import glucose via bidirectional facilitative GLUT transporters. 2. “trap” and “activate” imported glucose by converting glucose into glucose-6-phosphate (G6P). G6P cannot pass through GLUTs. 3. metabolize G6P to pyruvate via the glycolytic pathway, which yields a small amount of ATP without requiring mitochondria or O2.  Insulin Insulin is the primary anabolic hormone that dominates regulation of metabolism during the digestive phase. Insulin is a hormone that belongs to the gene family that includes insulinlike growth factors I and II (IGF-I, IGF- II) and relaxin and produces by pancreas. Primary insulin (proinsulin) is cleaved into insulin and C-peptide.  Serum insulin levels normally begin to rise within 10 minutes after ingestion of food and reach a peak in 30 to 45 minutes. The higher serum insulin level rapidly lowers blood glucose to baseline values.  Insulin has a short half-life of about 5 minutes and is cleared rapidly from the circulation.  Insulin cont. Glucose absorption The principal function of insulin is to increase the rate of glucose transport into certain cells in the body Insulin Insulin promotes glucose uptake and utilization mainly into striated stimulation & secretion (skeletal) muscle. In muscle cells, glucose is either stored as glycogen or oxidized to generate adenosine triphosphate (ATP) and metabolic intermediates needed for cell growth. Insulin binding Abnormalities at various points along this complex signaling cascade, to receptor from synthesis and release of insulin by b cells to insulin receptor interactions in peripheral tissues, can result in the diabetic phenotype Glucose uptake  What is Diabetes mellitus (DM)? Diabetes is metabolic disorders in which there are high levels of sugar in the blood, a condition called hyperglycemia. The ancient Greek word for diabetes means, “passing though; a large discharge of urine. DM is one of the most common metabolic disorders that is increasing at an alarming rate all over the world. DM is primarily characterized by high blood glucose levels (hyperglycemia), polydipsia, and polyphagia Prevalence and epidemiology Diabetes around the world in 2021:537 million adults (20-79 years) are living with diabetes - 1 in 10. This number is predicted to rise to 643 million by 2030. In 2019, diabetes was the direct cause of 1.5 million deaths and 48% of all deaths due to diabetes occurred before the age of 70 years. Diabetes in Saudi Arabia (2021) about 17.7% diabetic adults. Countries with the highest number of diabetic patients worldwide in 2019.  Risk factors for Diabetes Type 1 diabetes : Type 2 diabetes : 1) Family history of diabetes 1) Obesity 2) Disease of the pancreas 2) Family history of diabetes 3) Infection or illness that 3) History of gestational diabetes affects the pancreas 4) Ethnic background - African Americans, Native americans, Hispanic Americans. 5) Old age 6) Hypertension Types of diabetes 1) Type 1 diabetes(T1D)/ Juvenile diabetes/ Insulin dependent diabetes 2) Type 2 diabetes T2D Non-insulin dependent diabetes mellitus 3) Gestational diabetes  Type 1 diabetes (T1D) Is an autoimmune disease characterized by immune attack which destructs pancreatic beta cells and leads to absolute deficiency of insulin. This type of DM is seen in childhood and includes 5–10% of total diabetes patients. Affected individuals depend on daily injections of insulin to maintain normal blood glucose levels. The causes of T1D are not entirely understood however; scientists believe that both genetic and environmental factors are involved.  Type 2 diabetes (T2D) Is caused by a combination of peripheral resistance to insulin action and an inadequate secretory response by pancreatic b cells (“relative insulin deficiency”). T2D is by far the more common form and accounts for 90% of diagnosed cases. T2D is slow to develop (typically in older, obese individuals), and the symptoms are milder and often go unrecognized at first. In T2D, fat, muscle and liver cells do not respond correctly to insulin. This is called insulin resistance. As a result, blood sugar cannot enter these cells to be stored for energy and builds up in the blood. Insulin resistance is a gradual process that develops slowly over time  Signs and symptoms For T1D : For T2D : Frequent urination (polyuria), Same as T1D Thirst (polydipsia), Blurred vision, Weight loss despite Hard to heal skin, an increased appetite (polyphagia) Gum or bladder infections, Tingling or numbness in the hands or feet Gestational Diabetes: Gestational diabetes is any change in blood sugar levels that is diagnosed for the first time during pregnancy, regardless if the condition continues after childbirth or not. In the case of 40–60%, women having GDM can develop DM after 5–10 years of pregnancy.  Pathogenesis of T2D: Type 2 diabetes is a complex disease that involves interactions of genetic and environmental factors. Unlike T1D, it is not an autoimmune disease. The two defects that characterize T2D are: 1. a decreased ability of peripheral tissues to respond to insulin (insulin resistance) 2. b-cell dysfunction that is manifested as inadequate insulin secretion in the presence of insulin resistance and hyperglycemia. Environmental factors, such as a sedentary lifestyle, obesity and dietary habits, clearly play a role. Cont. The most important factor in the development of insulin resistance is obesity. Central obesity (abdominal fat) is more likely to be associated with insulin resistance than is peripheral obesity. The term metabolic syndrome has been applied to a group of findings dominated by visceral obesity accompanied by insulin resistance, glucose intolerance, and cardiovascular risk factors such as hypertension and abnormal lipid profiles. Individuals with metabolic syndrome are at high risk for the development of T2D.  Diagnosis of DM Blood glucose is normally maintained in a narrow range, usually 70 to 120 mg/dL. According to the American Diabetes Association (ADA) and the World Health Organization (WHO), diagnostic criteria for diabetes include the following: 1. fasting plasma glucose 126 mg/dL or 2. random plasma glucose 200 mg/dL (in a patient with classic hyperglycemic signs) 3. 2-hour plasma glucose 200 mg/dL during an oral glucose tolerance test with a loading dose of 75 gm or 4. glycated hemoglobin (HbA1c) level 6.5% Complications of diabetes: 1. Kidney disease ( Diabetic nephropathy) 2. Blindness (Diabetic retinopathy) 3. Heart disease and stroke. Diabetics are 2 to 4 times more likely to have a heart disease and suffer a stroke. 4. Nerve damage 5. Sores on feet and skin possibly resulting in amputations 6. Diabetic coma due to extremely high blood sugar Management of DM Nutritional therapy Exercise Education Pharmacologic Monitoring therapy  Patient education (foot care) Take care of your diabetes  Cont. Inspect your feet every day Wash your feet every day  Cont. Keep the skin soft & smooth Cont. Smooth corns and calluses gently Trim your toenails each week or when needed Cont. Wear shoes and socks at all times Protect your feet from hot and cool Keep the blood fowing to your feet Check with your health care provider. Acid base balance by respiratory system  Introduction Acid Any substance that can yield a hydrogen ion (H+) or hydronium ion when dissolved in water Release of proton or H+ Base Substance that can yield hydroxyl ions (OH-) Accept protons or H+  Introduction pKa Negative log of the ionization constant of an acid pKa is a number that shows how weak or strong an acid is. Strong acids would have a pK 9  Introduction A doctor evaluates a person's acid-base balance by measuring the pH and levels of carbon dioxide CO2 (an acid) and bicarbonate HCO3(a base) in the blood. Blood acidity increases when the level of acidic compounds in the body rises (through increased intake, production, or decreased elimination) Level of basic (alkaline) compounds in the body falls through decreased intake, production, or increased elimination. Blood alkalinity increases when the level of acid in the body decreases or when the level of base increases. Blood is normally slightly basic, with a normal pH range of 7.35 to 7.45. Usually the body maintains the pH of blood close to 7.40.  Producton of acids in human body Acids intake with foods. Cellular metabolism produces CO2. Acids produced by metabolism of carbohydrates CO ,lipids 2 and proteins. Volatile acid H2CO3 CO2+ H2O CO2 CO2 (H+ 15 –20 mol /d) H2SO4 H3PO4 Fixed acid Uric acid Lactic acid Ketone body (H+ < 0.05 –0.10 mol /d) Normal Values – [H+] = 40 nEq/L – pH = 7.40 (7.35-7.45) – PaCO2 = 40 mm Hg* (35-45) – HCO3 = 24 mEq/L (22-26) – pH < 6.8 or > 8.0 * millimetres of mercury  ACIDOSIS / ALKALOSIS An abnormality in one or more of the pH control mechanisms can cause one of two major disturbances in Acid-Base balance – Acidosis –A condition in which the blood has too much acid (or too little base), frequently resulting in a decrease in blood pH Alkalosis –A condition in which the blood has too much base (or too little acid), occasionally resulting in an increase in blood pH  ACIDOSIS / ALKALOSIS pH changes have dramatic efects on normal cell function 1)Changes in excitability of nerve and muscle cells 2)Infuences enzyme activity 3)Infuences K+ levels CO2 + H20  H2CO3 H+ + HCO3-  CHANGES IN CELL EXCITABILITY pH decrease (more acidic) depresses the central nervous system –Can lead to loss of consciousness pH increase (more basic) can cause over- excitability –Tingling sensations, nervousness, muscle twitches INFLUENCES ON ENZYME ACTIVITY  pH increases or decreases can alter the shape of the enzyme rendering it non-functional.  Changes in enzyme structure can result in accelerated or depressed metabolic actions within the cell  Control of Acid-Base Balance The blood's acid-base balance is precisely controlled because even a minor deviation from the normal range can severely afect many organs. The body uses diferent mechanisms to control the blood's acid-base balance. These mechanisms involve the Lungs Kidneys Buffer systems  Control of Acid-Base Balance Role of the lungs 1. This is achieved by changing the pCO2 (or carbonic acid, the denominator in the equation). The CO2 diffuses from the cells into the extracellular fuid and reaches the lungs through the blood. 2. The rate of respiration (rate of elimination of CO2) is controlled by the chemoreceptors in the respiratory centre which are sensitive to changes in the pH of blood.  Role of the lungs 3. When there is a fall in pH of plasma (acidosis), the respiratory rate is stimulated resulting in hyperventilation. This would eliminate more CO2, thus lowering the H2CO3 level. 4. However, this cannot continue for long. The respiratory system responds to any change in pH immediately, CO2 + H20  H2CO3 H+ + HCO3- Role of the lungs The brain regulates the amount of carbon dioxide that is exhaled by controlling the speed and depth of breathing (ventilation). The amount of carbon dioxide exhaled, and consequently the pH of the blood, increases as breathing becomes faster and deeper. By adjusting the speed and depth of breathing, the brain and lungs are able to regulate the blood pH minute by minute Types of Acid-Base Disorders  Respiratory acidosis Defined as a pH less than 7.35 with a PCO2 greater than 45 mm Hg. Hypercapnia – high levels of CO2 in blood  Acidosis is caused by an accumulation of CO2 which combines with water in the body to produce carbonic acid, thus, lowering the pH of the blood  Any condition that results in hypoventilation can cause respiratory acidosis.  Pco2 in the extracellular fluid is increased because CO2 cannot be cleared off by the lungs.  Respiratory Alkalosis Defined as a pH greater than 7.45 with a PCO2 less than 35 mm Hg  Any condition that causes hyperventilation can result in respiratory alkalosis  Causes of Respiratory Alkalosis 1. Psychological responses (such as anxiety or fear) 2. Pain 3. Increased metabolic demands (e.g. fever, thyrotoxicosis, pregnancy) 4. Medications (e.g. respiratory stimulants). 5. Central nervous system lesions