PBL #2

Question 1

How do you interpret arterial blood gases?

Answer 1

• pH
  
  • normal = 7.35 - 7.45
  • <7.35 → Acidemia
  • >7.45 → Alkalemia
• P_CO2
  
  • normal = 34-45 mmHg (think 40)
  • <40 → respiratory alkalosis
  • >40 → respiratory acidosis
• P_O2
  
  • normal: >90 mmHg
  • <90 → hypoxia
• HCO₃^-
  
  • normal = 22-32 mEq/L (think 24)
  • <24 → metabolic acidosis
  • >24 → metabolic alkalosis

Question 2

How do you calculate the anion gap and relate it to the mechanisms of fluid and electrolyte disorders?

Answer 2

• Anion Gap = Na⁺ – (Cl^- + HCO₃^-)
  
  • normal = 8-12
  • Metabolic Acidosis with Anion Gap:
    
    • M: methanol
    • U: Uremia
    • D: DKA
    • P: Paraldehyde, Propylene Glycol
    • I: Iron pills, Isoniazid
    • L: Lactic acidosis
    • E: Ethylene glycol
    • S: Salicylates
  • Metabolic Acidosis with normal Anion Gap:
    
    • H: Hyperalimentation, post-Hypervenitlation
    • A: Addison disease
    • R: Renal Tubular Acidosis (RTA)
    • D: Diarrhea
    • A: Acetazolamide
    • S: Spironolactone
    • S: Saline infusion
  • Low anion gap think → Multiple Myeloma

Question 3

What are the major body fluid compartments?

Answer 3

• Human total body water= 60% H₂O Males, 50% H₂O Females
  
  • 2/3 of total H₂O → Intracellular
  • 1/3 of total H₂O → Extracellular
    
    • 3/4 of Extracellular H₂O → Interstitial
    • 1/4 of Extracellular H₂O → Intravascular (Plasma volume)
• If 70 kg male:
  
  • Total body water = 42 L
    
    • Total intracellular water = 28 L
    • Total extracellular water = 14 L
      
      • Total interstitial water = 11 L
      • Total intravascular water = 3 L

Question 4

What is the role of osmotic and hydrostatic pressure in determining the volume of the major bodily fluid compartments?

Answer 4

• Osmotic Pressure
  
  • will want to draw fluid into the capillary
• Hydrostatic Pressure
  
  • will want to push fluid away/out of capillary
• These two forces will balance each other out throughout the body with Albumin driving osmotic pressure primarily and your BP driving your hydrostatic pressure.
  
  • Only spot where these don’t balance out is in the renal corpuscle…driving filtration!

Question 5

What is osmotic diuresis? When does it occur?

Answer 5

• Occurs when the normal tight coupling between sodium and water reabsorption in the proximal tubule is disrupted.
  
  • Osmotic diuresis →
    
    • increased urine flow due to abnormally high amount of any solute that is not reabsorbed (e.g. mannitol)
    • solute is filtered at such a high rate that much is left in the tubule (e.g. very high plasma glucose), leaving large amounts of solute in the lumen (INCREASE OSMOLARITY → More stuff)

Question 6

What is the the physiology behind orthostatic hypotension?

Answer 6

• Stand up → blood goes to legs, shifts out of central venous compartment to peripheral venous compartment → decreased stroke volume → decreased BP
  
  • Reflex to decreased BP → decreased baroreceptor firing → increased sympathetic nervous system → increased RAAS in kidneys & increased heart rate

Question 7

What is the mechanism of Tm (transport maximum) transport of glucose?

Answer 7

• Normally 100% of filtered glucose is reabsorbed in the proximal tubule
  
  • BUT → Na⁺/Glucose transporters (SGLT’s) have a saturation point = Transport maximum (Tm)
    
    • once this is reached, any additional glucose will NOT be reabsorbed → pee out in urine
      
      • Tm = 15 mM glucose → about 200 mg/dL
        
        • GLUCOSURIA!

Question 8

Describe potassium homeostasis.

Answer 8

• 98% is stored intracellularly
• Low extracellular (plasma)
• K⁺ Regulation:
  
  • Insulin → increases activity of Na⁺/K⁺ ATPase
    
    • drives K⁺ into cells
  • Catecholemines → activate ß₂ receptors → stimulate Na⁺/K⁺ ATPase
    
    • drives K⁺ into cells
  • pH → increase [H⁺] → H⁺ pumped into cells, K⁺ pumped out to buffer metabolic acidosis after HCO₃^- is depleted
  • Exercise → muscle cells release K⁺
• Renal excretion:
  
  • Passive movement of K⁺ into lumen driven by concentration gradient
  • Physiologic regulator: Aldosterone
    
    • ​stimulates Na⁺/K⁺ ATPase
    • increases presence of ROMK channel
      
      • Inhibited by Angiotensin II & Mg²⁺
  • BK channel present in High K⁺ states
• Renal reabsorption:
  
  • Alpha-Intercalated cell in Collecting Duct
    
    • K⁺/H⁺ ATPase (H⁺ exchanged for K⁺)

Question 9

What are the mechanisms and rationale for potassium movement across cell membranes in DKA?

Answer 9

• Acidosis buffer mechanism:
  
  • After blood bicarbonate is depleted, compensation for low blood pH occurs by pushing H+ into cells → need to balance this incoming charge → K+ is antiported out into the serum → Hyperkalemia
  • occurs at the cost of her body cells losing their K+ → her cells are hypokalemic and K+ will need to be repleted during treatment

Question 10

How does the respiratory system compensate for metabolic acid-base disorders?

Answer 10

• Body wants to get rid of CO₂ (acid)
  
  • to do this you breath more → Kussmaul breathing (rapid, deep, and labored breathing)
• CO₂ + H₂O ⇔ H₂CO₃ ⇔ HCO₃^- + H⁺
  
  • Le Chatelier’s Principle
    
    • Breathe off some CO₂, pull equation to the left → gets rid of H⁺, decreasing the acidity caused by ketoacids

Question 11

The following are what type of insulin?

insulin lispro, insulin aspart, insulin glulisine

Answer 11

Rapid Acting (ultra rapid)

fast onset, very short duration

Question 12

The following are what type of insulin?

Insulin glargine, Insulin detemir

Answer 12

Long Acting

(slow onset)

Question 13

What type of insulin is NPH insulin?

Answer 13

Intermediate-acting

(not used very often)

Question 14

What type of insulin is Regular Insulin?

Answer 14

Short acting

(slower onset than the rapid acting, but longer duration)

Question 15

What are the signs and symptoms typical of diabetic ketoacidosis?

Answer 15

• Kussmaul respirations (rapid/deep breathing)
• N/V
• abdominal pain
• psychosis/delirium
• dehydration
• fruity breath (exhaled acetone)
• Chief concerns: polyuria, polydipsia, polyphagia, fatigue, dyspnea, abdominal pain, N/V, HA, confusion, lethargy

Question 16

What are the preventive care and disease-related risk management strategies appropriate for patients with diabetes?

Answer 16

• cigarette smoking → cessation
• blood pressure → <130/80
• LDL → <100 mg/dL
• HDL → raise HDL (no set goal)
• prothrombotic state → low dose aspirin therapy
  
  • (esp. patients with CHD and other risk factors)
• glucose → HbA1C < 7%
• overweight/obesity → decrease BMI
• exercise prescription based on patient’s status
• nutrition

Question 17

What is the prevalence of Type I diabetes in the United States?

Answer 17

• Prevalence of newly diagnosed Type I diabetes per 1,000 persons
  
  • 1.93 overall (95% CI 1.88-1.97)
  • 2.55 in whites (95% CI 2.48-2.62)
  • 1.62 in blacks (95% CI 1.5-1.75)
  • 1.29 in Hispanics (95% CI 1.21-1.37)
  • 0.35 in American Indians (95% CI 0.26-0.47)

Question 18

What are the risk factors for Type I Diabetes?

Answer 18

• high birth weight
• childhood obesity
• increasing maternal age at birth may be associated with increased risk of childhood type 1 diabetes

Question 19

What is the role of genetics in Type I Diabetes?

Answer 19

• Type 1 has a hereditary component but inheritance pattern is unknown.
  
  • Mutations in HLA-DR3 and HLA-DR4 are associated with increased risk of developing type 1 diabetes
    
    • (HLA complex helps the immune system distinguish the body’s own protein from proteins made by foreign invaders)
  • Onset of type 1 diabetes by age 60 years reported in 65% of monozygotic twins of persons with type 1 diabetes. This is based on cohort studies.

Question 20

What is the mechanism of action of insulin, emphasizing receptors and signal transduction pathways?

Answer 20

• Insulin binds to → Insulin receptors
  
  • Metabolic:
    
    • activation of phosphatidylinositol-3-kinase→ activation of serine/threonine kinase Akt
    • Akt activation → glucose transporter (GLUT) 4–containing vesicles into cell membrane → increases glycogen and lipid synthesis → stimulates protein synthesis through the activation of mTOR.
  • Mitogenic signaling pathway:
    
    • activation of Ras → cascade of activating phosphorylations in MAP kinase pathway → cell growth and proliferation.

Question 21

What is the difference between primary gain and secondary gain?

Answer 21

• Primary gain:
  
  • positive reasons to use treatments (take insulin→ not sick/acidotic)
    
    • e.g. Tx of medical condition
• Secondary gain:
  
  • reasons that a patient would want to NOT take treatment (no insulin → attention from boyfriend and others)
    
    • e.g. attention from boyfriend