Metabolic Complications of Home Parenteral Nutrition

Jeremy Nightingale Consultant Gastroenterologist

St Mark’s Hospital

Metabolic Complications

• Most in very short bowel – Little oral absorption

• Can result from undernutrition

• More if renal or liver disease

• Acute or chronic

Metabolic Complications Acute • Hypoglycaemia • Cramps - low [Na+] • Refeeding

Chronic • Metabolic acidosis (hyperchloraemic, lactic) • Mineral / vitamin deficiency and excess • Renal failure / stones / hyperamonaemia • Bone disease

Refeeding Biochemistry

Na/K Pump

Na+

K+ (Mg2+)

Glucose

PO4-

Insulin

Glycolysis

TCA Cycle

ATP synthesis Thiamine

Cell

Main Problems of Refeeding

• Low phosphate DEATH • Thiamine deficiency (Wernicke’s encephalopathy) LOSS OF SHORT TERM MEMORY • Re-activation of Na+/K+ pump

OEDEMA / LVF

High Risk of Developing Refeeding Problems NICE 2006

One or more BMI <16 kg/m2

Weight loss >15% in 3-6/12 Little or no intake >10 days Low K, P or Mg

Two or more BMI <18.5 kg/m2

Weight loss >10% in 3-6/12 Little or no intake >5 days Alcohol or drug abuse Insulin, chemotherapy, antacids, diuretics

Metabolic Acidosis

• Acidic PN solution – Hyperchloraemic acidosis (use acetic acid) – Amino acids

• Renal / Respiratory failure

• GI loss of bicarbonate

D - Lactic Acidosis • Fermentation of CHO in the colon • Jejuno-colon patients

• Suspect if

• Treatment – Diet: ↓ mono- & oligo-saccharides ↑ polysaccharides – Oral broad spectrum antibiotic (neomycin / vancomycin) – Thiamine – Rarely fasting and PN

Acidosis Large anion gap

Normal blood L- lactate

• Sodium Cramps • Magnesium Tremor, ?fits • Vit D Osteomalasia • Selenium Muscle function reduced • Iron Microcytic anaemia • Essential fatty acids Dry flaky skin

• Zinc Psoriatic like rash

Poor wound healing • Copper Microcytic anaemia Neutropaenia • Chromium Diabetes • Biotin Sore nose / mouth

Mineral / Vitamin Deficiency

Hypomagnesaemia in patients with less than 200 cm jejunum

Nightingale JMD et al. Gut 1992; 33: 1493-7

Receiving magnesium or low serum magnesium n % Jejunostomy 31 / 40 78 Jejunum-colon 15 / 31 48

Dehydration (hyperaldosteronism)

Fatty acids Resection of Ileum / colon

Low Mg2+

Parathormone Secretion / function

Renal Mg2+ reabsorption 1α hydroxylase activity

Gut magnesium absorption

1, 25 - hydroxycholecalciferol

Treatment of Hypomagnesaemia

• Correct dehydration • Magnesium oxide • 1-alpha hydroxycholecalciferol • Subcutaneous / intravenous magnesium sulphate

Mineral / Vitamin Excess

• Manganese Parkinsonism Depression Poor memory

Renal Failure and HPN

• Oxalate nephropathy (jejunum-colon)

• Chronic dehydration (jejunostomy)

• Chronic obstruction (hydronephrosis)

• Analgesic drugs

25 % Jejunum – colon patients develop symptomatic renal stones Nightingale JMD et al. Gut 1992; 33: 1493-7

Ca-oxalate

FFA’s

Ca-FFA

Oxalate

Formation of Calcium Oxalate Renal Stones

Bile acids

Dehydrated Low citrate

Oxalobacter Formigenes

Dehydrated Low citrate

Oxalate Content of Food after Tomson CRV 2001

mg / 100 gm Rhubarb 537 - 860 Spinach 571 - 750 Beetroot 675 Okra 264 Wheat bran 240 Peanuts 116 - 185 Bran flakes 141 Almonds 131 Rice bran 123 Chocolate 117 - 366 Parsley 100 Tea 55 - 280 mg / 100ml

Prevention of Oxalate Renal Stones 1. Fat restriction Nordenvall B et al. Acta Chir Scand 1983;149:89-91 Andersson H and Jagenburg R. Gut 1974;15:360-6

2. Oral calcium Barilla DE et al. Am J Med 1978; 64: 579-85 Lindsjo M et al. Lancet 1989; ii: 701-4

3. Cholestyramine Smith LH et al. N Engl J Med 1972; 286: 1371-5 Stauffer JQ et al. Ann Intern Med 1973; 79: 383-91

Hyperammonaemia Yamada E et al. Lancet 1993; 341: 1542-3.

Yokoyama K et al. Nephron 1996; 72: 693-5

• Confusion in patients with a short bowel +/- colon.

• Inadequate citrulline to detoxify ammonia.

• Problem if renal impairment.

• Arginine (an intermediary in urea cycle) can correct.

PN Associated Metabolic Bone Disease

Normal Osteoporosis

Bone Disease General causes Older age / female Smoking / alcohol Reduced exercise or sunlight

Underlying disease /IF Steroids / heparin Period of immobility Vitamin D deficiency Low Magnesium

Treatment Parenteral Nutrition

Parenteral Nutrition Osteopathy

• Osteopenia / osteomalasia in 50% when PN starts. Epstein S et al. J Parenter Enteral Nutr 1986; 10: 263-4

• 165 patients having PN for more than 6 months • T score of less than –2.5 in 41% • 35% had bone pain and 10% a fracture. • Young age starting PN and low BMI - highest risks Pironi L et al. Clin Nutr 2002;21: 289-96

Long-term Bone Disease 65 patients Repeat DEXA after 18.1±5.5 months Mean Z score

- ↑ femoral neck - unchanged at lumbar spine

Multiple regression highest risk - Female sex - Age starting HPN

HPN not associated with reduced bone density Low bone density relates to general risk factors

Pironi et al, Clin Nutr 2004:23,1288-1302

Parenteral Nutrition Osteopathy

AA infusions > 2 gm / kg /day Acidosis Vit D toxicity Aluminium Loss of diurnal parathormone rhythm

Prevention / Treatment of Osteoporosis in Intestinal Failure

1. Life style Stop smoking / little alcohol / exercise / sunlight

2. DEXA scan every 2 - 3 years

3. Adequate vit D, Ca, Mg

4. Biphosphonate infusions*

5. Daytime feeding

*: Beware osteonecrosis of jaw

Metabolic Complications of HPN

• Know your formulations • Very short bowel most likely to have

problems • Acidosis worse if renal failure • Low oxalate diet if jejunum-colon • DEXA scan every 2 - 3 years

Intestinal Adaptation

The process that attempts to restore the total gut absorption of macronutrients, macrominerals and water to that of before a resection.

Adaptation

• Hyperphagia Crenn P et al. Gut 2004; 53: 1279-86

• Structural adaptation

• Functional adaptation

Structural Jejunal Adaptation in Man

Jejunostomy • None (n=9) O’keefe SJD. Gastroenterology 1994; 107: 379-388

Jejunum-colon • Epithelial hyperplasia (n=4) Porus RL. Gastroenterology 1965; 48: 753-59 Weinstein D et al. Arch Surg 1969; 99: 560-2

• Epithelial atrophy (n=7) De Francesco A et al. Transplant Proc 1994; 26: 1455-6

Functional Adaptation in Man Jejunostomy (or ileal resection) • None Hill GL et al. Gut 1974; 15: 982-7 Nightingale JMD et al. Gut 1992; 33: 1493-7

Jejunum-colon • Increased absorption of macronutrients (glucose), water, sodium and calcium * • Ability to stop parenteral nutrition Althausen TL et al. Gastroenterology 1950; 16: 126-34 * Dowling RH & Booth CC. Lancet 1966; ii: 146-7 * Gouttebel MC et al. Dig Dis Sci 1986; 31: 718-23 Gouttebel MC et al. Dig Dis Sci 1989; 34: 709-15 * Nightingale JMD et al. Gut 1992; 33: 1493-7 Cosnes J. Eur J Gastrenterol Hepatol 1994; 6: 197-202 * Carbonnel F et al. J Parenter Enteral Nutr 1996; 20: 275-80 Messing B et al. Gastroenterology 1999; 117: 1043-50

Jejunostomy No structural or functional adaptation Jejunum-colon Functional adaptation

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