Midterms LAB

• Ovarian Hyperstimulation Syndrome

  • Multiple ovarian follicular cysts
  • Increased capillary permeability

  
• Ovarian Hyperstimulation Syndrome

  A complication of ovulation-induction therapy for infertility, although it rarely may develop in an otherwise normal pregnancy
• Most common cause of Ovarian Hyperstimulation Syndrome

  • Fertility medications
  • Pregnancy
• Hormones involved in the pathophysiology of Ovarian Hyperstimulation Syndrome

  • Estradiol
  • Luteinizing hormone
  • Human chorionic gonadotropin (hCG)
  • Vascular endothelial growth factor (VEGF)
  • Renin
• Connection between the hormones and the development of OHSS

  1. Ovulation induction therapy poses a risk

  2. hCG stimulation of vascular endothelial growth factor (VEGF) expression in granulosa-lutein cells, leading to greater permeability

  3. Can lead to ascites, pleural or pericardial effusion, hypovolemia with acute kidney injury, and hypercoagulability
• Clomiphene

  A partial agonist of estrogen receptors, causing the increase secretion of gonadotropins and estrogens by inhibiting estradiol's negative feedback on the release of gonadotropins
• Clomiphene

  Used in the treatment of disorders of ovulation in patients who wish to become pregnant
• How Clomiphene affects the pituitary gland and hypothalamus

  1. Affects directly the pituitary gland

  2. Affects the hypothalamus

  3. Without the negative feedback, hypothalamus continue to produce GnRH

  4. Release FSH and LH

  5. Continue to stimulate ovaries

  6. The surge of gonadotropins will cause ovulation

  
• Diabetic Ketoacidosis

  • Results from an insulin deficiency combined with an excess in counterregulatory hormones such as glucagon
  • Leads to gluconeogenesis and ketone body formation
• Diabetic ketoacidosis is caused by increased fatty acid metabolism and the accumulation of ketoacids (acetoacetate and ß-hydroxybutyrate)
• DKA usually occurs in insulin-dependent diabetes mellitus in association with cessation of insulin or an intercurrent illness such as an infection, gastroenteritis, pancreatitis, or myocardial infarction, which increases insulin requirements temporarily and acutely, and is characterized by hyperglycemia, ketonemia, and a high-anion gap acidosis
• Main trigger for DKA

  Lack of insulin - Pseudostate of starvation - Catabolism of fat stores
• Hormones involved in the pathophysiology of DKA

  • Insulin
  • Glucagon
  • Cortisol
  • Epinephrine (catecholamines)
• Connection between hormones and pathophysiology of DKA

  1. Insulin deficiency (excess of the counterregulatory hormones) causes excessive amounts of acetoacetic acid to be formed in liver cells

  2. In the absence of insulin but in the presence of excess fatty acids in the liver cells, the carnitine transport mechanism for transporting fatty acids into the mitochondria becomes increasingly activated

  3. In the mitochondria, beta-oxidation of the fatty acids then proceeds rapidly, releasing extreme amounts of acetyl-CoA

  4. A large part of this excess acetyl-CoA is then condensed to form acetoacetic acid, which is then released into the circulating blood

  5. Most of this acetoacetic acid passes to the peripheral cells, where it is again converted into acetyl-CoA and used for energy in the usual manner

  6. The absence of insulin also depresses utilization of acetoacetic acid in peripheral tissues

  7. So much acetoacetic acid is released from the liver that it cannot all be metabolized by the tissues

  8. The concentration of acetoacetic acid rises during the days after cessation of insulin secretion, sometimes reaching concentrations of 10 mEg/L or more, which is a severe state of body fluid acidosis

  9. Some of the acetoacetic acid is also converted into B-hydroxybutyric acid and acetone

  10. These two substances, along with the acetoacetic acid, are called ketone bodies, and their presence in large quantities in the body fluids is called ketosis

  11. In DKA, the ketone body, B-hydroxybutyrate, is synthesized at a threefold greater rate than acetoacetate; however, acetoacetate is preferentially detected by a commonly used ketosis detection reagent (nitroprusside)
• Symptoms of Diabetic Ketoacidosis

  • Nausea/vomiting
  • Thirst/polyuria
  • Abdominal pain
  • Shortness of breath
• Precipitating events for Diabetic Ketoacidosis

  • Inadequate insulin administration
  • Infection (penumonia/UTI/gastroenteritis/sepsis)
  • Infarction (cerebral, coronary, mesenteric, peripheral)
  • Pancreatitis
  • Drugs (cocaine)
  • Pregnancy
• Physical findings in Diabetic Ketoacidosis

  • Tachycardia
  • Dehydration/hypotension
  • Tachypnea/Kussmaul respirations
  • Abdominal tenderness (may resemble acute pancreatitis or surgical abdomen)
  • Lethargy/obtundation/cerebral edema/possible coma

  
• Other clinical manifestations of Diabetic Ketoacidosis

  • Hyperglycemia (Glucose: >250 mg/dL)
  • Presence of ketones in blood and urine (leading to a fruity odor in the breath)
  • Metabolic acidosis (low blood pH and low bicarbonate concentration)
  • Generalized weakness and fatigue along with dry mucous membranes
• Myxedema

  • Advanced hypothyroidism, a condition that develops in persons who almost lack thyroid hormone function
  • Refers to the dermal deposition of mucopolysaccharides, causing the affected area such as the skin and soft tissues to swell
• Myxedema Coma

  Occurs when the body's compensatory responses to hypothyroidism are overwhelmed by a precipitating factor such as infection
• Clinical manifestations of Myxedema Coma

  • Reduced level of consciousness, sometimes associated with seizures
  • Bagginess under the eyes and swelling of the face
  • Fatigue and extreme somnolence, with persons sleeping up to 12 to 14 hours a day
  • Extreme muscular sluggishness
  • Slowed heart rate
  • Decreased cardiac output
  • Decreased blood volume
  • Sometimes increased body weight
  • Constipation
  • Mental sluggishness
  • Failure of many trophic functions in the body as evidenced by depressed growth of hair and scaliness of the skin, development of a froglike, husky voice

  
• Precipitating events for Myxedema Coma

  • Typically occurs
• Myxedema coma

  Dermal deposition of mucopolysaccharides, causing the affected area such as the skin and soft tissues to swell
• Myxedema coma occurs when the body's compensatory responses to hypothyroidism are overwhelmed by a precipitating factor such as infection
• Clinical manifestations of myxedema coma

  • Reduced level of consciousness, sometimes associated with seizures
  • Bagginess under the eyes and swelling of the face
  • Fatigue and extreme somnolence, with persons sleeping up to 12 to 14 hours a day
  • Extreme muscular sluggishness
  • Slowed heart rate, decreased cardiac output, decreased blood volume
  • Sometimes increased body weight
  • Constipation
  • Mental sluggishness
  • Depressed growth of hair and scaliness of the skin
  • Development of a froglike, husky voice

  
• Precipitating events for myxedema coma

  • Medications like sedatives, anesthetics, and antidepressants
  • Illnesses like pneumonia, congestive heart failure, heart attacks, gastrointestinal bleeding, or strokes
  • Sepsis
  • Cold exposure
• The primary mechanism of myxedema coma involves reduced ventilation leading to low oxygen levels and high carbon dioxide levels
• Hypoglycemia and dilutional low sodium levels also contribute to the onset of myxedema coma
• Thyroid hormones

  Thyroxine (T4) and triiodothyronine (T3), synthesized in the thyroid gland and stimulated by thyroid-stimulating hormone (thyrotropin)
• In myxedema coma, greatly increased quantities of hyaluronic acid and chondroitin sulfate bound with protein form excessive tissue gel in the interstitial spaces, causing the total quantity of interstitial fluid to increase
• The edema in myxedema coma is the nonpitting type due to the gel nature of the excess fluid
• Nucleotide

  Composed of a purine or pyrimidine base, a pentose sugar, and one or more phosphate groups

  
• DNA vs RNA nucleotides

  DNA has deoxyribose sugar, RNA has ribose sugar

  DNA has adenine, thymine, cytosine, guanine, RNA has adenine, uracil, cytosine, guanine

  
• Genetic code

  Matches sequences of nucleotide bases with sequences of amino acids, with each 'word' (codon) being 3 nucleotide bases

  
• Properties of the genetic code

  • Specificity (unambiguous)
  • Universality (conserved across evolution)
  • Degeneracy (redundant)
  • Nonoverlapping (read from fixed starting point)
  • Commaless (read 3 bases at a time)

  
• Stop/termination codons for humans

  • UAA, UAG, UGA
  • AGA, AGG (in mammalian mitochondria)
• The UGA codon codes for tryptophan in mammalian mitochondria

  
• Codons for leucine

  6 codons, due to the degeneracy of the genetic code

  
• Reading frame

  The open reading frame (ORF) of the mRNA, where the order of codons determines the amino acid sequence of the protein