Metabolism: nutrients metabolized into individualized chemicals that can be utilized by cells to maintain life -produce energy, repair

cells, and maintain life -through release of hormones, endocrine system controls cellular activity that regulates bodys metabolism -hormones are chemical messengers secreted by various glands that exert controlling effects on the bodys cells Diabetes Mellitus, DM (endocrine disorder) -Systemic metabolic disorder characterized by chronic hyperglycemia due to: 1. decrease in secretion or production of insulin (Type I) 2. Decrease in cells ability to utilize insulin (cell receptors, Type II) -Incidence: 12-15 million Americans; higher in Blacks, Hispanics, American Indians; Increase in Finland, Norway, Denmark, Germany, Poland, Israel; Very low incidence in Japan -Impaired use of carbs, fats, and proteins -Chronic hyperglycemia causes structural abnormalities (vasculature of organs) -Lock and Key: insulin key unlocks cells that allows glucose to be utilized inside the cell (cells starved of glucose, the excess glucose is found in bloodstream instead and causes problems) -Pancreas beta cells of the islets of Langerhans: insulin synthesized and released in response to eating food -Steps in the normal activity of insulin and blood glucose: 1. Pancreas (Beta-cells) causes 2. Insulin to be synthesized and released 3. Insulin stimulates GLUT4 (glucose transporter protein) in cytoplasm to move to tyrosine kinase receptors, allows facilitated diffusion of glucose across membrane -Both insulin and glucose bind to tyrosine kinase receptors on cells membrane
Type I Incidence Age of Onset Etiology Pathophys 10% Before 30 probably multiafactorial Beta cells destroyed by inappropriate autoimmune response, this theory is most widely accepted and supported by presence of islet cell antibodies in 85% of newly diagnosed, inherited susceptibility, viruses possibly either trigger immune response or cause inflammation which leads to Beta cell destruction, end result is little or no production of endogenous insulin usually abrupt Type II 85-90% After 30, trend is changing multifactorial resistance to insulin in cell membrane receptors, or decrease in # of receptors, can result in normal or increased production of endogenous insulin

Type of onset Body weight at onset Insulin

Ideal body weight or thin Little/no insulin produced

Insidious: rarely go in for symptoms related to diabetes, diagnosed when ppl go in for other reasons Obese: gained weight over time Insulin present, but not utilized by cells

clinical manif

polyuria, polydipsia, polyphagia, weight loss (fats and proteins breakdown and used for energygluconeogenesis [liver make glycogen from fats/proteins]), weakness/fatigue (poor use of food products) Exogenous insulin, diet, exercise, acute complications common, chronic ocmplications occur at early age more difficult 'brittle' hard to control, wide fluctuations in Blood sugar

polyuria, polydipsia, polyphagia, weakness, fatigue, but may be asymptomatic

mngmnt

diet, exercise, oral hypoglycemic medication (acts at receptor level), insulin possibly

control

usually easily controlled if adhere to diet

Polyruia: increase urine output, glucose pulls water into bloodstream, increase volume through kidneys Polydipsia: increase thirst, high osmolarity stimulates thirst in hypothalamus Both of above related to Osmotic action of glucose in the blood! Polyphagia: increase in hunger (Related to cellular starvation, as well as weight loss and weakness/fatigue) Diagnoses: 1. FBS (fasting blood sugar) >126mg/dl on more than one test 2. Presence of islet cell antibodies 3. Glycosylated hemoglobin >5.5% (Hgb A1C: gives better picture than FBS, avg. glucose that binds w/ Hgb, life or RBC ~2months) 4. Glucose tolerance test: drink glucose, look at BS, look at fluctuations in BS every 30 min. Criteria for good control: 1. Maintain optimal weight and in good health 2. Glycosylated Hgb <7% Hgb A1C 3. FBS <140mg/dl 4. Postprandial BS <=180 mg/dl ACUTE COMPLICATIONS 1. Diabetic Ketoacidosis (Diabetic coma): hyperglycemia of 300-800mg/dl w/ ketonuria (ketones in urine) Pathophys: 1. Marked decrease in insulin (not enough for food taken in or not enough produced) 2. illnesses 3. Psychological stress -Too little insulin leads to decrease glucose transport to cells -Body senses low cellular glucose (high in bloodstream) causes glycogenolysis and gluconeogenesis (breaking down fats/proteins to make glucose) MAKES THINGS WORSE! -High blood sugar: osmotic diuresis, pulls fluid toward sugar in bloodstream, increases intravascular volume, increases loss thru kidneys (dehydrated, polyuria, polydipsia) -Increased lipolysis: ketone acid production and accumulation (leads to keonuria and acidosis: excretion of ketone acids by lungs, b/c of breathing hard, fast, and deep) -Acidosis: hyperkalemia (increases K+ level), electrolyte changes -Increased proteolysis & lipolysis: increases gluconeogenesis Clinical Manifestations: hyperglycemia, ketonuria, polyuria, polydipsia, polyphagia, N/V, abdominal pain, Kussmauls Respirations (hard, fast, deep), can lead to hypotension, tachycardia, shock, and cardiac arrhythemias Management: 1. Shift from fat catabolism to CHO catabolism by giving insulin 2. correct fluid intake and electrolyte imbalances 3. correct the cause

2. Hypoglycemia (Insulin reaction): BS level <60mg/dl, insulin shock Results from: overdose of insulin, inadequate food intake, increase amounts of exercise Clinical manifestations: 1. Neurogenic reaction when the hypothalamus senses decreased glucose levels: increase in heart rate, respiratory rate, diaphoresis, pallor (pale), cool skin, tremors (cant store glucose, not enough fuel) 2. Cellular malnutrition (mostly brain): headache, dizziness, irritability, confusion, fatigue, vision changes, hunger, seizures, coma Management: 1. Give glucose 2. correct fluid intake and electrolyte imbalances 3. correct the cause CHRONIC COMPLICATIONS 1. Macrovascular degenerative changes: >1 yr, probably related to lipolysis-hyperlipidemia-athersclerosisCAD (coronary artery disease), PVD (peripheral vascular disease), CVA (stroke) 2. Microvascular disease (degenerative changes): affects the capillary, thickens its basement membrane 1. Glycosylation of proteins/collagen: formation and deposits of AGEs [Advanced Glycosylation End Products] in vessel walls, making it harder to diffuse out, this thickens the basement membrane in capillaries 2. Protein kinase C (enzyme): is activated (inappropriately) by high blood sugar -BOTH 1 & 2, leads to vascular cell proliferation-thickens basement membrane-decrease perfusion of nutrients & O2-hypoxia, ischemia Major places affected: retina (diabetic retinopathy), fine capillaries affected, no perfusion, poor vision Kidneys (nephropathy, renal failure) Periphery (feet) 3. Neuropathy: related to microvascular disease, occurs in feet 1st, nerve arent getting perfusion (death of nerve endings) Etiology: vascular ischemia leads to nerve endings destroyed in ischemic areas 1. Peripheral: pain and tingling in extremities, decrease in sensation 2. Autonomic Nervous system: a. Gastroparesis: GI emptying b. Neurogenic bladder: poor bladder emptying c. Sexual dysfunction d. CV-no HR variability (HR doesnt vary upon exercise, rest, etc) 4. Infection/poor wound healing: glucose is a good media for growth, decrease sensation, decrease possible prevention, hypoxia (O2 insufficiency to tissues)/ischemia (blood insufficiency to tissues) causes poor wound healing 5. Metabolic Syndrome: under endocrine in later chapters ACID-BASE BALANCE pH=[H+]=ratio of (HCO3-)/(H2CO3) Normal=20/1 Acid: H+ producing Base: accepts H+ Buffer: absorbs excess H+ or OH-, pH regulation Three mechanisms regulating a-b balance: 1. Plasma buffer systems (fast): HCO3-/H2CO3, protein buffers (Hgb), phosphate (PO4-), cellular ion exchange 2. Repiratory system (minutes to hours): lungs regulate retention or elimination of CO2 thru changes in rate of retention (rate & depth) 3. Renal system (hours to days): kidneys absorb (back into bloodstream) more HCO3- or H+ OR excrete

more HCO3- or H+ our of body into urine Arterial Blood gases (ABGs): pH=7.35-7.45 pCO2: 35-45 mmHg respiratory indicator (<35alkalosis, >45 acidosis) HCO3-: 22-28 mEq/L metabolic indicator Acidosis: pH<7.35; systemic increase in [H+] or decrease in HCO3Alkalosis: pH>7.45; systemic decrease in [H+] or increase in HCO3Respiratory Acidosis: anything depressing ventilation or gas exchange; not breathing deep b/c of lung disorders Compensation: by kidneys: retain more HCO3- or excrete more H+ Respiratory Alkalosis: hyperventilation: blow off more CO2 Compensation: by kidneys: excrete more HCO3- or retain more H+ Metabolic Acidosis: loss of base (HCO3-) or gain of acid due to 1. Renal failure: kidneys unable to retain HCO32. Lactic acidosis 3. DB ketoacidosis 4. Diarrhea 5. Ingestion of acids Compensation: by lungs: hyperventilate to get rid (blow off) of more CO2 Metabolic Alkalosis: loss of metabolic acids (prolonged vomiting), excess HCO3- intake (sipping Maalox) Compensation: by lungs: hypoventilate to retain more CO2
Respiratory Acidosis Alkalosis Initial ABGs pH pCO2 HCO3Compensated ABGs low high normal high low normal Metabolic Acidosis Alkalosis low normal low high normal high

pH pCO2 HCO3-

normal, acid side of normal high high

normal, base side of normal low low

normal, acid side of normal low low

normal, base side of normal high high

PEDIATRIC RESPIRATORY DISORDERS UPPER TRACT 1. Aspiration: inhalation of fluid or solid objects into tracheobronchial system a. Etiology: impaired gag reflex or swallowing, tubes in epiglottis, communication between esophagus and trachea tracheoesophageal fistula, High risk: young kids who cant chew adequately and unconscious pts b. Pathology: epiglottis protects trachea from foreign objects, depending on content may only be trauma, irritation, or inflammation; chemicals can erode and destroy trachea or lung tissue; solid object may block bronchi, bronchiole, alveoli (decreasing inhaled air) c. Manifestations: infants: prevention is best; suction babys airway, control us of baby powder, avoid overfeeding, cut toddlers food in small pieces, avoid toys w/ small pieces, remove object by suction or Heimlich 2. Croup: syndrome of upper airway resulting in narrowing of airway

a. Etiology: bacterial or viral microorganisms b. Pathophysiology: inflammation of larynx, pharynx, or epiglottis; swelling leads to air narrowing, increased mucous production c. Manifestations: i. Acute laryngotracheo-bronchitis: gradual onset, rhinitis/fever, inspiratory stridor, harsh, high crowing noise ii. Viral croup: sudden onset at night, afebrile, high pitch stridor, muffled voice iii. Acute epiglottitis: sudden onset (life-threatening), fever, inspiratory wheezing, restlessness, drooling, difficulty swallowing d. Management: high humidity and antibiotics, treat laryngeal spasms, respiratory emergency (tracehostomy) and antibiotics LOWER TRACT 1. RDS: Respiratory distress syndrome: affects 5-10% of premies, 30-50% neonatal deaths, 70% of premature infants deaths a. Etiology: decreased surfactant production, immature lung tissue (underdeveloped and uninflatable alveoli) i. 24 weeks: very small amount of surfactant, few developed terminal sacs ii. 26-28 weeks: sufficient surfactant and lung development to permit survival b. Pathology: i. Premature infants lungs not mature, atelectasis (no exchange of O2 and CO2) ii. Pulmonary blood flow limited by decreased vasculature development iii. Decreased surfactant iv. Alveoli cant expand v. Need for increased respiratory effort to inhale air and prevent alveoli collapse at expiration vi. Increase pCO2 & decreased pO2, cant cross alveolar-capillary membrane; hypoxemia leads to respiratory acidosis vii. Development of fibrin clots or film (hyaline membrane) decreases gas diffusion c. Manifestations: increased RR, intercostals retractions, labored breathing (expiratory grunting, nasal flaring), decrased pH, increased pCO2, decreased pO2 (resp. acidosis), chest x-rayatelectasis 2. Bronchopulmonary Dysplasia (BPD): associated w/ chronic lung disease in infants and young kids a. Etiology: premature birth, RDS, prolonged mechanical ventilation, O2 toxicity b. Pathology: mechanical ventilation w/ O2 acts as lung tissue irritant (inflammation), scarring and stiffening of lung tissue, alveoli fail to multiply, chronic inflammation result in increased mucus and plugging of alveoli and shunt unit c. Manifestations: hypoxemia, CXR (atelectasis, low pH, high pCO2, low O2), respiratory infections and acidosis d. Management: mechanical ventilation, oxygenation (weaning off), adequate nutrition and calories, treat acidosis, maintain fluid balance, bronchodilators 3. Asthma: reactive airway disease in kids; inflammatory disease characterized by: increased mucus pro., edema, bronchospasms that leads to narrowing of airways a. Factors that trigger: viral respiratory tract infections, allergens, genetics (30%), irritants in air, exercise, sulfites b. Prevalence: 5-10% of all kids to some degree, 80% of affected have symptoms beyond 5yo c. Pathophysiology: both large & small airways affected; allergens trigger release of IgE (mast cell degranulation) resulting in: edema of bronchial mucosa, bronchospasm, increased mucus pro. i. Air trapped in lungs results in inadequate ventilation, hypoxemia, hypercapnia, respiratory acidosis, and respiratory failure d. Manifestations: wheezing on expiration, cough (vomiting), irritability, restlessness, dyspnea, chest tightness, tachypnea, nasal flaring, anxious facial expressions, diaphoresis

e. Treatment: avoid contact w/ triggering factors, increase fluid intake, administer aerosol tx, bronchodilators, inhaled or systemic corticosteroids, encourage exercise and prophylactic medications 4. Cystic Fibrosis: chronic exocrine gland disorder, autosomal recessive gene (chrom. 7) disorder results in excessive, thick mucous production results in obstruction of respiratory and pancreatic ducts a. 2500 children, most common fatal genetic disease b. Pathology: production and stasis of thick, tenacious mucous (obstructive pulmonary disease); pancreatic exocrine deficiency of trypsin, amylase, and lipase (malabsorption); chronic respiratory disease; elevated NaCL in sweat due to ineffective Cl movement out of cell and high reabsorption of Na into cell; complications of CF affect all organ systems c. Manifestations: i. Respiratory: thick mucus blocks airways, air trapping, atelectasis; frequent respiratory infections and inflammatory response; chronic cough/sputum production; barrel chest; chronic rhinitis; clubbing of finger (chronic hypoxia) ii. GI tract: emaciated (thin) malabsorption of calories; stereatorrhea-fatty, foul smelling BMs d. Diagnosis: sweat test e. Management: replace pancreatic enzymes (orally), treat respiratory tract infections (postural drainage), lung transplants, gene therapy in progress, survival age is 30 years, cause of death is respiratory involvement GENETICS Gene: fundamental unit of information storage; blueprints of protein synthesis Chromosomes: made up of genes Deoxyribose nucleic acid (DNA): genetic info stored, genes composed of DNA sections Two gametes make an organism (23 pairs of chromosomes, 46 chromosomes total) Backbone composed of sugar-phosphoric acid Centers are nitrogenous pairs: AU (purines, 2 H-bonds) & GC (pyrimidines, 3-H bonds) DNA inside chromosomes, each chromosome has thousands of genes Somatic cells (non-sex cells) have 46 chromosomes Gametes (sex cells) only one member of each chromosome pair Genetic Mutations: error in duplication of DNA 1. Single gene (most common) a. Base-pair substitution: different pair is substituted for normal pair in DNA b. Frameshift mutation: either insertion or deltion of 1+ base pairs to DNA Genotype: genetic constitution of individual Phenotype: measurable expression of genes in an individual Chromosomes found in pairs in somatic cells w/ matching genes Alleles: alternative forms of a gene at a give place on the pair of chromosomes Homozygous: identical pair of alleles (TT or tt) Heterozygous: two different alleles at a given place (Tt) Dominant traits: traits for which only 1 pair of alleles is necessary for expression Recessive traits: traits for which both alleles of a pair are necessary for expression 1. Autosomal dominant: abnormal allele is dominant a. Males=Females b. No skipping of generations c. Affected heterozygous: individual transmits the trait to ~50% of offspring 2. Autosomal recessive: abnormal allele is recessive a. Males=Females b. Usually skips a generation

c. Both parents of an affected child are carriers X-Linked inheritance: Of 23 chromosome pairs in karyotype, 22 are autosomes, one pair is sex chromosomes Females inherit two X-chromosomes Males inherit one X-chromosomes (always from mom) 1. X-Linked Dominant: 1 allele present for expression a. Males=Females b. On males, traits either dominant or recessive are expresses as phenotype c. Affected males have non-affected sons & affected daughters d. Affected heterozygous females have a 50% risk of transmitting the abnormal gene to each daughter or son 2. X-Linked Recessive: a. Males>Females b. Affected males cant transmit gene to sons, but transmit to ALL daughters c. Sons of female carriers have a 50% risk of being affected d. Daughters of female carriers have a 50% risk of being carriers CHROMOSOME DISORDERS May be either numeric or structural, may affect either autosomes or sex chromosomes 1. Numerical Aberrations: nondisjunction: loss/gain of chromosomes 2. Trisomy 21 (Downs Syndrome): 1/700 live births, increased with materal age, 20-30% of paternal origin Sex Chromosome Aberrations: 1. Turners syndrome: only have 45 chromosomes, XO sex chromosomes a. 1/2500 female births; have no Y, problems w/ reproduction, female phenotype 2. Klinefelter Syndrome: 47 chromosomes, XXY a. 1/1000 male births: male phenotype, female characteristics, infertility Multifactorial Inheritance: polygenic: many genes play a part in diseases + environment -Many genes, each w/ a small effect acting additively -Intelligence, cleft lip/palate, Coronary artery disease