Ketone Bodies - Biochemistry - Medbullets Step 1

Overview

Structure
- two types
  - acetoacetate
  - β-hydroxybutyrate
    - β-hydroxybutyrate + NAD+ → acetoacetate + NADH
    - ↑ NADH:NAD+ ratio results in ↑ β-hydroxybutyrate:acetoacetate ratio
- 1 ketone body = 2 acetyl-CoA
Function
- produced by the liver
  - brain can use ketones if glucose supplies fall
    - >1 week of fasting
- can provide energy to body in prolonged energy needs
  - prolonged starvation
    - glycogen and gluconeogenic substrates are exhausted
- can provide energy if citric acid cycle unable to function
  - diabetic ketoacidosis
    - cycle component (oxaloacetate) consumed for gluconeogenesis
  - alcoholism
    - ethanol dehydrogenase consumes NAD+ (converts to NADH)
    - ↑ NADH:NAD+ ratio in liver reduces pyruvate and oxaloacetate levels available for gluconeogenesis (both are products of reactions where NAD+ is required for as cofactor)
- RBCs cannot use ketones as they lack mitochondria
Synthesis
- occurs in hepatocyte mitochondria
  - liver cannot use ketones as energy
    - lacks β-ketoacyl-CoA transferase (thiophorase) which converts acetoacetate to acetoacetyl
- under normal conditions acetoacetate = β-hydroxybutyrate
- HMG CoA synthase is rate limiting enzyme
Clinical relevance
- ketoacidosis
  - pathogenesis
    - ↑ ketone levels
    - caused by
      - poorly controlled type I diabetes mellitus
        
        liver ketone production exceeds ketone consumption in periphery
      - possible in type II diabetes mellitus but rare
      - alcoholism
        
        chronic hypoglycemia results in ↑ ketone production
  - presentation
    - β-hydroxybutyrate > acetoacetate
      - due to ↑ NADH:NAD+ ratio
    - acetone gives breath a fruity odor
    - polyuria
    - ↑ thirst
  - tests
    - ↓ plasma HCO₃
    - hypokalemia
      - individuals are initially hyperkalemic (lack of insulin + acidosis) because K leaves the cells
      - overall though the total body K is depleted
        
        replete K in these patients once the hyperkalemia begins to correct
    - nitroprusside urine test for ketones may not be strongly +
      - does not detect β-hydroxybutyrate
        
        state favored by ↑ NADH:NAD+ ratio
      - should use a test specific for β-hydroxybutyrate

Blood, Plasma, Serum	Reference Range
ALT	8-20 U/L
Amylase, serum	25-125 U/L
AST	8-20 U/L
Bilirubin, serum (adult) Total // Direct	0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca²⁺)	8.4-10.2 mg/dL
Cholesterol, serum	Rec: < 200 mg/dL
Cortisol, serum	0800 h: 5-23 μg/dL //1600 h: 3-15 μg/dL 2000 h: ≤ 50% of 0800 h
Creatine kinase, serum	Male: 25-90 U/L Female: 10-70 U/L
Creatinine, serum	0.6-1.2 mg/dL
Electrolytes, serum
Sodium (Na⁺)	136-145 mEq/L
Chloride (Cl^-)	95-105 mEq/L
Potassium (K⁺)	3.5-5.0 mEq/L
Bicarbonate (HCO₃^-)	22-28 mEq/L
Magnesium (Mg²⁺)	1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)
24-28 wks // 32-36 wks	30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks	40-220 ng/mL // 80-350 ng/mL
Ferritin, serum	Male: 15-200 ng/mL Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma	Male: 4-25 mIU/mL Female: premenopause: 4-30 mIU/mL midcycle peak: 10-90 mIU/mL postmenopause: 40-250
pH	7.35-7.45
PCO₂	33-45 mmHg
PO₂	75-105 mmHg
Glucose, serum	Fasting: 70-110 mg/dL 2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation	Fasting: <5 ng/mL Provocative stimuli: > 7ng/mL
Immunoglobulins, serum
IgA	76-390 mg/dL
IgE	0-380 IU/mL
IgG	650-1500 mg/dL
IgM	40-345 mg/dL
Iron	50-170 μg/dL
Lactate dehydrogenase, serum	45-90 U/L
Luteinizing hormone, serum/plasma	Male: 6-23 mIU/mL Female: follicular phase: 5-30 mIU/mL midcycle: 75-150 mIU/mL postmenopause 30-200 mIU/mL
Osmolality, serum	275-295 mOsmol/kd H₂O
Parathyroid hormone, serume, N-terminal	230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C)	20-70 U/L
Phosphorus (inorganic), serum	3.0-4.5 mg/dL
Prolactin, serum (hPRL)	< 20 ng/mL
Proteins, serum
Total (recumbent)	6.0-7.8 g/dL
Albumin	3.5-5.5 g/dL
Globulin	2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma	.5-5.0 μU/mL
Thyroidal iodine (¹²³I) uptake	8%-30% of administered dose/24h
Thyroxine (T4), serum	5-12 μg/dL
Triglycerides, serum	35-160 mg/dL
Triiodothyronine (T3), serum (RIA)	115-190 ng/dL
Triiodothyronine (T3) resin uptake	25%-35%
Urea nitrogen, serum	7-18 mg/dL
Uric acid, serum	3.0-8.2 mg/dL

Hematologic	Reference Range
Bleeding time	2-7 minutes
Erythrocyte count	Male: 4.3-5.9 million/mm³ Female: 3.5-5.5 million mm³
Erythrocyte sedimentation rate (Westergren)	Male: 0-15 mm/h Female: 0-20 mm/h
Hematocrit	Male: 41%-53% Female: 36%-46%
Hemoglobin A1c	≤ 6 %
Hemoglobin, blood	Male: 13.5-17.5 g/dL Female: 12.0-16.0 g/dL
Hemoglobin, plasma	1-4 mg/dL
Leukocyte count and differential
Leukocyte count	4,500-11,000/mm³
Segmented neutrophils	54%-62%
Bands	3%-5%
Eosinophils	1%-3%
Basophils	0%-0.75%
Lymphocytes	25%-33%
Monocytes	3%-7%
Mean corpuscular hemoglobin	25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration	31%-36% Hb/cell
Mean corpuscular volume	80-100 μm³
Partial thromboplastin time (activated)	25-40 seconds
Platelet count	150,000-400,000/mm³
Prothrombin time	11-15 seconds
Reticulocyte count	0.5%-1.5% of red cells
Thrombin time	< 2 seconds deviation from control
Volume
Plasma	Male: 25-43 mL/kg Female: 28-45 mL/kg
Red cell	Male: 20-36 mL/kg Female: 19-31 mL/kg

Cerebrospinal Fluid	Reference Range
Cell count	0-5/mm³
Chloride	118-132 mEq/L
Gamma globulin	3%-12% total proteins
Glucose	40-70 mg/dL
Pressure	70-180 mm H₂O
Proteins, total	< 40 mg/dL

Sweat	Reference Range
Chloride	0-35 mmol/L
Urine
Calcium	100-300 mg/24 h
Chloride	Varies with intake
Creatinine clearance	Male: 97-137 mL/min Female: 88-128 mL/min
Estriol, total (in pregnancy)
30 wks	6-18 mg/24 h
35 wks	9-28 mg/24 h
40 wks	13-42 mg/24 h
17-Hydroxycorticosteroids	Male: 3.0-10.0 mg/24 h Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total	Male: 8-20 mg/24 h Female: 6-15 mg/24 h
Osmolality	50-1400 mOsmol/kg H₂O
Oxalate	8-40 μg/mL
Potassium	Varies with diet
Proteins, total	< 150 mg/24 h
Sodium	Varies with diet
Uric acid	Varies with diet
Body Mass Index (BMI)	Adult: 19-25 kg/m²

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