Nikol is a 16 year old female that presents to the emergency department with deep breathing, nausea and vomiting. She also has frequent urination but no hematuria nor dysruia. She is disoriented and holds a can for vomiting, and has acetone smell. What is metabolic acidosis? Metabolic acidosis: clinical disturbance characterized by an increase in plasma acidity; due to increased acid production, loss of bicarbonate, and a reduced ability of the kidneys to excrete excess acids When you have diabetes and don't get enough insulin and get dehydrated, your body burns fat instead of carbs as fuel. Breaking down fatty acids produces ketones, which can make your blood acidic. (diabetic ketoacidosis/ DKA) How does the body respond to metabolic acidosis? *As blood pH drops (becomes more acidic), the parts of the brain that regulate breathing are stimulated to produce faster and deeper breathing (respiratory compensation). Breathing faster and deeper increases the amount of carbon dioxide exhaled. *Respiratory compensation for metabolic acidosis increases the respiratory rate to drive off CO2 and readjust the bicarbonate to carbonic acid ratio to the 20:1 level. *The kidneys also try to compensate by excreting more acid in the urine, which in turn facilitates the excretion of acid and partially restore systemic acid-base balance. Elevated levels of blood glucose and ketone bodies are the hallmarks of untreated T1D. Hyperglycemia is caused by increased hepatic production of glucose via gluconeogenesis, combined with diminished peripheral utilization, Diabetic ketoacidosis (DKA), a type of metabolic acidosis, occurs in T1D. DKA is treated by replacing fluid and electrolytes and administering short-acting insulin to gradually correct hyperglycemia without precipitating hypoglycemia Signs and symptoms of diabetic ketoacidosis include: *Nausea *Vomiting *Abdominal pain *A sweet, fruity smell on your breath *Weight loss. The pancreas the pancreas has 2 systems: the exocrine gland and the endocrine gland *endocrine function; releases juices (enzymes) directly into the bloodstream. *exocrine function; releases juices into ducts. The pancreatic juice has a pH of 8.0- 8.3, and the pH of liver bile is 7.8 pancreatic islets — the islets of Langerhans— secrete the hormones glucagon, insulin, somatostatin, and pancreatic polypeptide (PP) Pancreas endocrine function involves the secretion of insulin, and glucagon; that regulate the rate of glucose metabolism in the body. *The alpha cell produces the hormone glucagon and makes up approximately 20 percent of each islet. Low blood glucose levels stimulate the release of glucagon. *The beta cell produces the hormone insulin and makes up approximately 75 percent of each islet. Elevated blood glucose levels stimulate the release of insulin. *The delta cell accounts for four percent of the islet cells and secretes the peptide hormone somatostatin. Which is also released by the hypothalamus, stomach and intestines. An inhibiting hormone that inhibits the release of both glucagon and insulin. *The pancreatic polypeptide cell (PP cell) accounts for about one percent of islet cells and secretes the pancreatic polypeptide hormone. It plays a role in appetite, and in the regulation of pancreatic exocrine and endocrine secretions. The pancreas is divided into lobules by connective tissue septae. Lobules are composed largely of grape-like clusters of exocrine cells called acini, which secrete digestive enzymes. Exocrine secretions from acini flow through intercalated ducts, intralobular ducts, interlobular ducts and finally into the duodenum through the main pancreatic duct. Vomiting: Vomiting: the forceful expulsion of stomach contents via the mouth or sometimes the nose, also known as emesis. The causes of vomiting are as wide ranging as those for nausea and include anything from food poisoning or gastritis to head injuries and brain cancer. Nausea is the discomfort that is felt before vomiting but not all nausea actually results in vomiting. Vomiting is the means by which the upper gastrointestinal tract rids itself of its contents when almost any part of the upper tract becomes excessively irritated, overdistended, or even overexcitable. Excessive distention or irritation of the duodenum provides an especially strong stimulus for vomiting. The sensory signals that initiate vomiting originate mainly from the pharynx, esophagus, stomach, and upper portions of the small intestines. And the nerve impulses are transmitted by both vagal and sympathetic afferent nerve fibers to the vomiting center. From here, motor impulses that cause the actual vomiting are transmitted from the vomiting center by way of the: 1. fifth, seventh, ninth, tenth, and twelfth cranial nerves to the upper gastrointestinal tract, 2. vagal and sympathetic nerves to the lower tract, 3. spinal nerves to the diaphragm and abdominal muscles. In the early stages of excessive gastrointestinal irritation or overdistention, antiperistalsis begins to occur often many minutes before vomiting appears. (Antiperistalsis: peristalsis up the digestive tract rather than downward) Vomiting Act. Once the vomiting center has been sufficiently stimulated and the vomiting act instituted, the first effects are 1. a deep breath, 2. raising of the hyoid bone and larynx to pull the upper esophageal sphincter open, 3. closing of the glottis to prevent vomitus flow into the lungs, and 4. lifting of the soft palate to close the posterior nares. Next comes a strong downward contraction of the diaphragm along with simultaneous contraction of all the abdominal wall muscles. This squeezes the stomach between the diaphragm and the abdominal muscles, building the intragastric pressure to a high level. 5. Finally, the lower esophageal sphincter relaxes completely, allowing expulsion of the gastric contents upward through the esophagus Thus, the vomiting act results from a squeezing action of the muscles of the abdomen associated with simultaneous contraction of the stomach wall and opening of the esophageal sphincters so that the gastric contents can be expelled. Diabetes leading cause of adult blindness and amputation and a major cause of renal failure, nerve damage, heart attacks, and strokes. Most cases of diabetes mellitus can be separated into two groups: 1. type 1 [T1D] formerly called insulin-dependent diabetes mellitus 2. type 2 [T2D] formerly called noninsulin-dependent diabetes mellitus Other types of diabetes include: -Gestational diabetes is a condition in which blood sugar levels become high during pregnancy -Diabetes insipidus (DI) is a condition characterized by large amounts of dilute urine and increased thirst. The amount of urine produced can be nearly 20 liters per day. Reduction of fluid has little effect on the concentration of the urine. Complications may include dehydration or seizures. Type 1 diabetes: The disease is characterized by deficiency of insulin caused by an autoimmune attack on the β cells of the pancreas. In T1D, the islets of Langerhans become infiltrated with activated T lymphocytes, leading to a condition called insulitis. Over a period of years, this autoimmune attack on the β cells leads to gradual depletion of the β-cell population, symptoms appear abruptly when 80%– 90% of the β cells have been destroyed. At this point, the pancreas fails to respond adequately to ingestion of glucose, and insulin therapy is required to restore metabolic control and prevent life-threatening ketoacidosis. The onset of T1D is typically during childhood or puberty, and symptoms develop suddenly. Patients with T1D can usually be recognized by the abrupt appearance of polyuria (frequent urination), polydipsia (excessive thirst), and polyphagia (excessive hunger). These symptoms are usually accompanied by fatigue and weight loss. The diagnosis is confirmed by 1. glycosylated hemoglobin concentration ≥ 6.5 mg/dl (normal is less than 5.7) 2. fasting blood glucose ≥ 126 mg/dl (normal is 70–99) 3. nonfasting (random) blood glucose level ≥200 mg/dl in an individual with symptoms of hyperglycemia When blood glucose is greater than 180 mg/dl, the ability of the kidneys to reclaim glucose is impaired. This results in glucose spilling into the urine. The loss of glucose is accompanied by the loss of water, resulting in the characteristic polyuria (and dehydration) and polydipsia in diabetics. The metabolic abnormalities of T1D mellitus result from a deficiency of insulin that profoundly affects metabolism in three tissues: liver, muscle, and adipose tissues. Treatment of type 1 diabetes; periodic injection or continuous pump-assisted infusion to control the hyperglycemia and ketoacidosis Contraindications for tight control: Children are not put on a program of tight control of blood glucose before age 8 years because of the risk that episodes of hypoglycemia may adversely affect brain development. Elderly people typically do not go on tight control because hypoglycemia can cause strokes and heart attacks in this population. Type 2 Diabetes: Patients with T2D have a combination of insulin resistance and dysfunctional β cells. but do not require insulin to sustain life, although insulin eventually will be required to control hyperglycemia. T2D is characterized by hyperglycemia; insulin resistance; impaired insulin secretion; and, ultimately, β-cell failure. insulin resistance is characterized by increased hepatic glucose production, decreased glucose uptake by muscle and adipose tissue, and increased adipose lipolysis with production of free fatty acids. Obesity is the most common cause of insulin resistance and T2D, Insulin resistance increases with weight gain and decreases with weight loss, and excess adipose tissue is key in the development of insulin resistance, With obesity, there are changes in adipose secretions that result in insulin resistance. In the long-term, FFAs suppress glucose-induced insulin release. With time β cell becomes increasingly dysfunctional and fails to secrete enough insulin to correct the prevailing hyperglycemia. Hyperglycemia: is caused by increased hepatic production of glucose, diminished peripheral use. Ketosis is usually minimal or absent in patients with T2D because the presence of insulin, even in the presence of insulin resistance, restrains hepatic ketogenesis Dyslipidemia: Because lipoprotein degradation catalyzed by lipoprotein lipase in adipose tissue is low in diabetics, the plasma chylomicron and VLDL levels are elevated, resulting in hypertriacylglycerolemia treating T2D is to maintain blood glucose concentrations within normal limits and to prevent the development of long-term complications Alpha-glucosidase inhibitors These medications help your body break down starchy foods and table sugar. This effect lowers your blood sugar levels; acarbose (Precose), miglitol (Glyset) Biguanides Biguanides decrease how much sugar your liver makes. The most common biguanide is metformin. glucose uptake into muscle cells and adipocytes: Glucose cannot diffuse directly into cells but enters by one of two transport mechanisms: a Na+-independent, facilitated diffusion transport system or an ATP-dependent Na+monosaccharide cotransport system. Sodium-independent facilitated diffusion transport system This system is mediated by a family of 14 glucose transporters found in cell membranes. They are designated GLUT-1 to GLUT-14 Sodium–monosaccharide cotransport system This is an energy-requiring process that transports glucose “against” a concentration gradient, SGLT SYNTHESIS OF GLYCOGEN (GLYCOGENESIS); Glycogen is synthesized from molecules of α-D-glucose. The process occurs in the cytosol and requires energy supplied by ATP (for the phosphorylation of glucose) and uridine triphosphate (UTP). 1. Synthesis of uridine diphosphate glucose 2. Synthesis of a primer to initiate glycogen synthesis 3. ElongFormation of branches in glycogen 4. elongation of glycogen chains by glycogen synthase DEGRADATION OF GLYCOGEN (GLYCOGENOLYSIS); 1. Shortening of chains 2. Removal of branches 3. Conversion of glucose 1-phosphate to glucose 6-phosphate 4. Lysosomal degradation of glycogen Glycolysis; 1. Phosphorylation of glucose 2. Isomerization of glucose 6-phosphate enzyme phosphoglucose isomerase 3. Phosphorylation of fructose 6-phosphate 4. Cleavage of fructose 1,6-bisphosphate 5. isomerization of dihydroxyacetone phosphate 6. Oxidation of glyceraldehyde 3-phosphate 7. Synthesis of 3-phosphoglycerate, producing ATP 8. Dehydration of 2-phosphoglycerat 9. Formation of pyruvate, producing ATP gluconeogenesis; 1. Pyruvate carboxylase converts pyruvate to oxaloacetate in the mitochondrion. 2. Oxaloacetate is converted to malate or aspartate, which travels to the cytosol and is reconverted to oxaloacetate. 3. Phosphoenolpyruvate carboxykinase converts oxaloacetate to phosphoenolpyruvate. 4. Phosphoenolpyruvate forms fructose 1,6-bisphosphate by reversal of the steps of glycolysis. 5. Fructose 1,6-bisphosphatase converts fructose 1,6-bisphosphate to fructose-6-phosphate, which is converted to glucose-6-phosphate. 6. Glucose-6-phosphatase converts glucose-6-phosphate to free glucose, which is released into the blood. Fatty acid synthesis; In adult humans, fatty acid synthesis occurs primarily in the liver and lactating mammary glands and, to a lesser extent, in adipose tissue beta-oxidation catabolic process by which fatty acid molecules are broken down in the cytosol in prokaryotes and in the mitochondria in eukaryotes to generate acetyl-CoA. amino acids synthesis and breakdown; The liver is the only tissue that has all the pathways of amino acid synthesis and degradation. During fasting, the carbon skeletons of amino acids produce glucose, ketone bodies, and CO2; in the fed state the liver can convert intermediates of amino acid metabolism to triacylglycerols; the fate of amino acid carbon skeletons, thus, parallels that of glucose and fatty acids Ketone bodies; produced using acetyl-CoA derived from fatty acid β-oxidation in the liver under specific metabolic conditions. The two ketone bodies are acetoacetate and β-hydroxybutyrat Ketone Body Synthesis Two molecules of acetyl-CoA are condensed to form a cetoacetyl-CoA, which is then conjugated to another molecule of acetyl-coA to form 3-hydroxy-3-methylglutaryl-CoA (HMGCoA). Maintaining blood glucose; Eating a healthy diet with plenty of fruit and vegetables, maintaining a healthy weight, and getting regular physical activity can all help maintaining normal levels of blood glucose 1. Keep track of your blood sugar levels to see what makes them go up or down. 2. Eat at regular times, and don’t skip meals. 3. Choose foods lower in calories, saturated fat, trans fat, sugar, and salt. 4. Track your food, drink, and physical activity. 5. Drink water instead of juice or soda. 6. Limit alcoholic drinks. 7. choose fruit, instead of sweets. 8. Control your food portions (for example, use the plate method: fill half your plate with non-starchy vegetables, a quarter with lean protein, and a quarter with a grain or starchy food). WHY IS IT IMPORTANT TO CONTROL BLOOD-GLUCOSE LEVELS? Maintaining normal blood sugar levels is a very important part of avoiding long-term health issues, managing your weight and just feeling good. Health problems related to blood sugar imbalances are a rapidly growing To avoid; 1. cardiac or vascular event, such as myocardial infarction (heart attack) or stroke; 2. kidney problems that may require dialysis; 3. eye problems, which may lead to loss of vision (blindness); 4. sexual issues, such as erectile dysfunction; 5. problems with circulation and scarring, which can lead to amputation. Glucagon; Receptors in the pancreas can sense the decline in blood glucose levels, such as during periods of fasting or during prolonged labor or exercise. In response, the alpha cells of the pancreas secrete the hormone glucagon, which has several effects: 1. Glucagon stimulates the liver to convert its stores of glycogen back into glucose. This response is known as glycogenolysis. The glucose is then released into the circulation for use by cells throughout the body. 2. Glucagon stimulates the liver to take up amino acids from the blood and convert them into glucose. This response is known as gluconeogenesis. 3. Glucagon stimulates lipolysis, the breakdown of stored triglycerides into free fatty acids and glycerol. Some of the free glycerol released into the bloodstream travels to the liver, which converts the glycerol into glucose. This is also a form of gluconeogenesis. Taken together, these actions increase blood glucose levels. The activity of glucagon is regulated through a negative feedback mechanism; rising blood glucose levels inhibit further glucagon production and secretion. Insulin; The primary function of insulin is to facilitate the uptake of glucose into body cells The presence of food in the intestine triggers the release of gastrointestinal tract hormones such as glucose-dependent insulinotropic peptide (known as gastric inhibitory peptide). This is the initial trigger for insulin production and secretion by the beta cells of the pancreas. Once nutrient absorption occurs, the resulting surge in blood glucose levels further stimulates insulin secretion. Insulin is composed of 51 amino acids arranged in two polypeptide chains, designated A (21 amino acids) and B (30 amino acids), which are linked together by two disulfide bridges. The insulin molecule also contains an intramolecular disulfide bridge between amino acid residues of the A chain. Insulin is degraded by insulin-degrading enzyme, which is present in the liver and, kidneys. Insulin has a plasma half- life of approximately 6 minutes. This short duration of action permits rapid changes in circulating levels of the hormone. Regulation of insulin secretion; Insulin secretion by the pancreatic β cells is closely coordinated with the release of glucagon by pancreatic α cells. The relative amounts of insulin and glucagon released by the pancreas are regulated so that the rate of hepatic glucose production is kept equal to the use of glucose by peripheral tissues In particular, insulin secretion is increased by glucose, amino acids, and gastrointestinal peptide hormones 1. Glucose: Ingestion of a carbohydrate-rich meal leads to a rise in blood glucose, the primary stimulus for insulin secretion 2. Inhibition of insulin secretion: The synthesis and release of insulin are decreased when there is a scarcity of dietary fuels and also during periods of physiologic stress (for example, infection, hypoxia, and vigorous exercise). 3. Secretion is largely controlled by the nervous system. other tissues have insulin-insensitive systems for glucose transport. For example, hepatocytes; erythrocytes; and cells of the nervous system, intestinal mucosa, renal tubules, and cornea do not require insulin for glucose uptake Buffers; A buffer is a system of molecules and ions that acts to prevent changes in H + concentration and thus serves to stabilize the pH of a solution. In blood plasma, the pH is stabilized by reversible reaction involving the bicarbonate ion (HCO 3 – ) and carbonic acid (H 2 CO 3 ): ………………… …………… ……………....HC O 3 – + H + →← H 2 C O 3 The double arrows indicate that the reaction could go either to the right or to the left; the net direction depends on the concentration of molecules and ions on each side. If an acid (such as lactic acid) should release H + into the solution, the increased concentration of H + would drive the equilibrium to the right and the following reaction would be promoted: ...................................... ............ ...........HC O 3 – + H+ → H 2 C O 3 Notice that in this reaction, H + is taken out of solution. Thus, the H + concentration is prevented from rising (and the pH prevented from falling) by the action of bicarbonate buffer. osmotic diuresis; osmotic diuresis is increased urination due to the presence of certain substances in the fluid filtered by the kidneys. This fluid eventually becomes urine. These substances cause additional water to come into the urine, increasing its amount. Osmotic diuresis can be caused by: 1. High blood sugar (glucose) 2. Use of certain medicines, such as Mannitol (used in the treatment of DM) Transport maximum for glucose is expressed by the maximum transporting capacity of the SGLT transportation system. Excessive glucose is not reabsorbed and consequently passes into urine. Transport maximum for glucose tubular transport system in adult humans is about 375 mg/min. Na + and K + levels in plasma; Potassium In hypokalemia, the level of potassium in blood is too low. A low potassium level usually results from vomiting, diarrhea, adrenal gland disorders, or use of diuretics. A low potassium level can make muscles feel weak, cramp, twitch, or even become paralyzed, and abnormal heart rhythms may develop. Potassium affects the way the heart's muscles work. When there is hyperkalemia; too much potassium, the heart may beat irregularly, which may cause heart attacks. Sodium hyponatremia can include altered personality, lethargy and confusion, seizures, coma and even death. Hyponatremia treatments may include 1. changing a medication that affects your sodium level, treating the underlying disease, changing the amount of water you drink or changing the amount of salt in your diet. 2. Intravenous fluids, IV sodium solution to slowly raise the sodium levels in your blood. 3. Medications, to manage the complications of hyponatremia, such as headaches, nausea and seizures People with diabetes are advised to limit sodium, to prevent or control high blood pressure Hyponatremia can result from multiple diseases that affect the lungs, liver, brain, or heart problems like congestive heart failure. the amount of sodium you consume can worsen your condition by causing hypertension (high blood pressure). Vascular diseases that are associated with diabetes; Diabetes mellitus increases the risk of developing coronary, cerebrovascular, and peripheral arterial disease. The pathophysiology of vascular disease in diabetes involves abnormalities in endothelial, vascular smooth muscle cell, and platelet function. The metabolic abnormalities that characterize diabetes, eg; hyperglycemia, increased free fatty acids, and insulin resistance, each provoke molecular mechanisms that contribute to vascular dysfunction. These abnormalities contribute to the cellular events that cause atherosclerosis and increase the risk of the adverse cardiovascular events that occur in patients with diabetes and atherosclerosis. Expression of both glycoprotein Ib and IIb/IIIa is increased, augmenting both platelet–von Willebrand factor and platelet–fibrin interaction. Hyperglycemia further changes platelet function by impairing calcium homeostasis and thereby alters aspects of platelet activation and aggregation, including platelet conformation and release of mediators. Vascular complications in diabetics; 1. Peripheral artery disease, known as PAD, occurs when plaque builds up in the arteries and reduces blood flow to the feet and legs 2. Diabetic eye disease. Diabetes' effect on the vascular system is what causes diabetic eye disease. The tiny blood vessels in the retina become swollen, which blocks the oxygen supply to the retina. If the condition becomes severe, it can cause blindness. The endocrine system; series of glands that produce and secrete hormones that the body uses for a wide range of functions. These control many different bodily functions, including: 1. Respiration 2. Metabolism 3. Reproduction 4. Sensory perception 5. Movement 6. Sexual development 7. Growth Hormone- producing glands are; 1. Hypothalamus: responsible for body temperature, hunger, moods and the release of hormones from other glands; also controls thirst, sleep and sex drive. Hormones of the Hypothalamus *Thyrotropin-releasing hormone (TRH) *Gonadotropin-releasing hormone (GnRH) *Growth hormone-releasing hormone (GHRH) *Corticotropin-releasing hormone (CRH) *Somatostatin *Dopamine. 2. Pituitary: master control gland, the pituitary gland controls other glands and makes the hormones that trigger growth. Hormones produced by the pituitary gland *Adrenocorticotrophic hormone (ACTH) *Thyroid-stimulating hormone (TSH) *Luteinising hormone (LH) *Follicle-stimulating hormone (FSH) *Prolactin (PRL) *Growth hormone (GH) *Melanocyte-stimulating hormone (MSH) 3. Parathyroid: controls the amount of calcium in the body. produces the *parathyroid hormone, which plays a role in regulating your body's levels of the minerals calcium and phosphorus. Hyperparathyroidism is when your parathyroid glands create too much parathyroid hormone in the bloodstream 4. Pancreas: This gland produces the insulin that helps control blood sugar levels. *insulin, *somatostatin, *gastrin, and *glucagon, play an important role in maintaining sugar and salt balance in our bodies 5. Thyroid : The thyroid produces hormones associated with calorie burning and heart rate. *triiodothyronine (T3) and *thyroxine (T4). It also stores these thyroid hormones and releases them as they are needed. 6. Adrenal : produce the hormones that control sex drive and cortisol, the stress hormone. * Cortisol *Aldosterone *DHEA *Androgenic Steroids *epinephrine (adrenaline) *norepinephrine (noradrenaline) 7. Pineal: This gland produces *melatonin which affects sleep. 8. Ovaries: Only in women, the ovaries secrete *estrogen, *testosterone and *progesterone, the female sex hormones. 9. Testes:Only in men, the testes produce the male sex hormone, *testosterone, and produce *sperm. Laboratory findings explanaition; Sodium: helps keep the water and electrolyte balance of the body Complications of hyponatremia include altered personality, lethargy and confusion. Severe hyponatremia can cause seizures, coma and even death. Hypernatrenia can lead to high blood pressure, heart disease, and stroke. It can also cause calcium loss. Potassium: helps the nerves to function and muscles to contract and helps the heartbeat stay regular. If left untreated, both severe hypokalemia and severe hyperkalemia can lead to paralysis, cardiac arrhythmias, and cardiac arrest. mild cases of hyperkalemia may not produce symptoms and may be easy to treat, but severe cases that are left untreated can lead to fatal cardiac arrhythmias. Hyperkalemia, hads a higher risk of morbidity and mortality if left untreated. Severe hypokalemia may also cause respiratory failure, constipation and ileus( lack of movement somewhere in the intestines that leads to a buildup and potential blockage of food material.) Chloride: helps keep the amount of fluid inside and outside of the cells in balance. It also helps maintain proper blood volume, blood pressure, and pH of body fluids. Hypochloremia is an electrolyte imbalance that occurs when there's a low amount of chloride in your body. Symptoms include: fluid loss. Dehydration. weakness or fatigue. difficulty breathing. diarrhea or vomiting, caused by fluid loss. Hyperchloremia complications include: excessive fatigue, muscle weakness, breathing problems, frequent vomiting, prolonged diarrhea, excessive thirst, high blood pressure. Bicarbonate : help maintain the acid-base balance (pH) and to work with sodium, potassium, and chloride to maintain electrical neutrality at the cellular level. A low CO2 level can be a sign of several conditions, including: Kidney disease. Diabetic ketoacidosis Low bicarbonate levels in the blood are a sign of metabolic acidosis. 1. Long and deep breaths. 2. Fast heartbeat. 3. Headache and/or confusion. 4. Weakness. 5. Feeling very tired. 6. Vomiting and/or feeling sick to your stomach (nausea) 7. Loss of appetite. High bicarbonate levels may cause: 1. Confusion (can progress to stupor or coma) 2. Hand tremor. 3. Lightheadedness. 4. Muscle twitching. 5. Nausea, vomiting. 6. Numbness or tingling in the face, hands, or feet. 7. Prolonged muscle spasms (tetany) Urea : Urea is made when protein is broken down in your body. Urea is made in the liver and passed out of your body in the urine, high urea in the blood indicates kidney dysfunction. Uremia may cause (high urea) 1. extreme tiredness or fatigue. 2. cramping in your legs. 3. little or no appetite. 4. headache. 5. nausea. 6. vomiting. 7. trouble concentrating. Low urea levels are not common and are not usually a cause for concern. They can be seen in severe liver disease creatinine : High levels of creatinine in the blood can be caused by several conditions; 1. Chronic kidney disease 2. Kidney obstruction 3. Dehydration 4. Increased consumption of protein 5. Intense exercise 6. Certain medications High creatinine levels in the blood cause several complications; 1. Nausea. 2. Chest Pain. 3. Muscle Cramps. 4. Vomiting. 5. Fatigue. 6. Changes in urination frequency and appearance. 7. High blood pressure. 8. Swelling or fluid retention low creatinine complications; Low muscle mass: Lack of strength, difficulty exercising, a thin or frail body. Liver disease: Inflamed liver, which may cause pain in the upper right-side of the abdomen, fatigue or nausea. Diet-related: Feeling faint or dizzy, losing weight. Glucose: Hyperglycemia can damage the vessels that supply blood to vital organs, which can increase the risk of heart disease and stroke, kidney disease, vision problems, and nerve problems. Hypoglycemia may cause other complications; 1. An irregular or fast heartbeat 6. sweating 2. Fatigue 7. Hunger 3. Pale skin 8. Irritability 4. Shakiness 9.Anxiety 5. Tingling or numbness of the lips, tongue or cheek
