hypoalbuminemia and low total lymphocyte count (tlc) · kwashiorkor hypoalbuminemia ... marasmus...

Hypoalbuminemia and Low Total Lymphocyte Count (TLC): Are they malnutrition markers or simply disease and inflammation markers

Agussalim Bukhari Departement of Nutritional Sciences, Faculty of Medicine

Hasanuddin University, Makassar

Background

Traditionally: Energy Deficit Marasmus Specifically Protein Deficit Kwashiorkor Hypoalbuminemia Recently: Kwashiorkor mostly related to

inflammation Still many clinicians use Hypoalbuminemia

and Low TLC as markers of Malnutrition only Recently They both are also used as

prognostic markers

1

Background

Consequently many Clinicians hope that after Nutritional Therapy Albumin and TLC must be improved

By understanding the mechanism of Low albumin and TLC in many patients, a holistic approach would be applied including nutritional therapy to achieve optimal outcomes

2

MARASMUS

KWASHIORKOR

Background

3

KWASHIRKOR MARASMIC-KWASHIORKOR 4

Metabolic Response to Starvation and Trauma

Metabolic rate

Body fuels

Body protein

Urinary nitrogen

Weight loss

Starvation

conserved

conserved

slow

Trauma or Disease

wasted

wasted

rapid

The body adapts to starvation, but not in the

presence of critical injury or disease.

Popp MB, et al. In: Fischer JF, ed. Surgical Nutrition. 1983.

P= 0.028 (p<0.05) (Anova)

3.443

3.153

2.678

0.000

0.500

1.000

1.500

2.000

2.500

3.000

3.500

4.000

normal kurang buruk

AL

BU

MIN

LLA

Fathin et al, unpublished data, 2015

Plasma Albumin is associated with Nutritional Status (LLA/MUAC)

7

Syahir et al, unpublished data, 2015

TLC is associated with Nutritional Status (LLA/MUAC)

8

Malnutrition without inflammatory state (Non catabolic state): Low intake due to poverty or voluntarily (anorexia nervosa, bulimia) marasmus type (Chronic PEM) without hypoalbuminemia (oedema)

Malnutrition with inflammatory state kwashiorkor (Acute PEM) or marasmic-kwashiorkor type Usually wirh hypoalbuminemia (Oedema) – Acute inflammation (high grade inflammation): Sepsis, Burn,

pneumonia, typhoid fever

– Chronic Inflammation (Low grade inflammation): TB, Liver Cirrhosis, Chronic kidney disease, Cancer, HIV-AIDS, Colitis.

9

Revised Malnutrition Category

NORMAN, K., PICHARD, C., LOCHS, H. & PIRLICH, M. 2008. Prognostic impact of disease-related malnutrition. Clin Nutr 27, 5-15. 10

Revised Malnutrition Category

Oedema in kwashiorkor

Traditionally considered as direct result of low albumin and associated with low protein intake with normal calorie intake

Inflammation is currently regarded responsible for the oedema via 3 mechanisms: Transcapillary loss of albumin due to increase

vascular permeability Increased albumin catabolism Decreased albumin synthesis

11

Mechanism of Hypoalbuminemia

Hypoalbuminemia

Increased Catabolism

Transcapillary Loss

Gut Loss

Urinary Loss

Hemodilution

Decreased Synthesis

12

Mechanism of Low TLC

LOW TLC

Increased Apoptosis

HIV

Stress Congenital Immunodefi

ciency

Malnutrition

13

Malnutrition Inflammation/Infection

14

Gershwin, ME et al, Handbook of Nutrition and Immunity, 2004

15


Mechanisms by which infection can affect nutrient status.

16


Am J Clin Nutr, 83, 735-743.(Morley et al., 2006)

Pengaruh mediator inflamasi pada penurunan asupan makanan dan peningkatan pengeluaran energi (katabolisme)

TILG, H. & MOSCHEN, A. 2008. Mol Med, 14, 222-231.

17

PREGNANCY

AGING MEDICINE

FIRST YEAR OF LIFE

INFECTION

MALNUTRITION

PHYSIOLOGIC

ACQUIRED

RADIATION

SEVERE DISEASE

STRESS

EXHAUSTED

Immunodeficiency

18

Abbas et al, Cellular and Molecular Immunology, 2016

0

10

20

30

40

50

60

CD4+ CD8+

well-nourished malnourished

The proportion of T Lymphocyte subsets in children with PEM and well-nourished controls. The CD4/CD8 ratio is decreased

Lym

phoc

ytes

(%

)

19


CD4 NUMBER

STRESS

SHORT TIME (MINUTES)

LONG TIME (HOURS)

CORTICO STEROID EXOGEN

CORTICO STEROID

ENDOGEN

B ADRENERGIK INCREASED

RACE,SEX, AGE

HIV/ID PRIMER

- -

-

+

+ -

20

Abbas et al, Cellular and Molecular Immunology, 2016

Surgical stress

Release of stress hormone and inflammatory markers – Decrease the action of insulin – Mobilisation of energy substrate – Negative Nitrogen balance

Suppression of the immune system

Noblett SE, Watson DS, Huong H, et al. (2006) Pre-operative oral carbohydrate loading in

colorectal surgery: a randomized controlled trial. Colorectal Dis 8, 563-569. 21

• Patients at risk– Trauma

– Surgery

– Wounds

• More trauma patients develop infection than surgical

patients

• Infection occurs in 34% of ICU patients

Applegren P et al: Acta Anaesthesiol Scand 2001;45:710-719Angus DC et al: Crit Care Med 2001;29:1303-1310Wallace WC et al: Am Surg 1999;65:987-990

Immune

SuppressionInfection RiskAnti- inflammatory

mediators predominate

Immune SuppressionImmune Suppression

22

Immune SuppressionElective surgery, Trauma, Wound healing

Immune enhancing nutrients:Arginine,Glutamine,

Nucleotides

Normal Inflammatory ResponseHomeostasis of pro- and anti-inflammatory mediators

Anti-inflammatorymediators predominate

Immune Stimulating NutrientsImmune Stimulating Nutrients

(Risk for infection)

23

Noblett SE, Watson DS, Huong H, et al. (2006) Pre-operative oral carbohydrate loading in

colorectal surgery: a randomized controlled trial. Colorectal Dis 8, 563-569. 24


Immune enhancing nutrients:Arginine,Glutamine,

Nucleotides



Immune Stimulating NutrientsImmune Stimulating Nutrients


25


Uncontrolled Inflammation

Pro-inflammatorymediators predominate

Uncontrolled InflammationUncontrolled Inflammation(SIRS)

Risk for ALI, ARDS, MODS and Death

SIRS occurs in:• 33% of all hospitalized patients• > 50% of ICU patients• > 80% of surgical intensive care

26

Inflammatory trigger-

Uncontrolled inflammatory response

Severe Shock

MODS- (Lungs fail first)

MODS – Multi Organ Dysfunction Syndrome

SIRS

Risk for ALI/ARDS

Sepsis, Infection (i.e. Pneumonia)

Uncontrolled InflammationUncontrolled Inflammation

Death

27


Immune enhancing nutrientsArginine, Glutamine, Nucleotides


Uncontrolled InflammationSIRS, ALI, Sepsis

Inflammation modulating nutrientsEPA, GLA, Antioxidants



Summary


(SIRS)

28

Malnutrition and its Consequences

Changes in intestinal barrier

Reduction in glomerular filtration

Alterations in cardiac function

Altered drug pharmacokinetics

Roediger 1994; Green 1999; Zarowitz 1990 29

Malnutrition and its Consequences

Loss of weight

Slow wound healing

Impaired immunity

Increase Complication

Increase in length of hospital stays

Increased treatment costs

Increase in mortality

Roediger 1994; Green 1999; Zarowitz 1990 30

Albumin Replacement

Hypoalbuminemia is a common phenomenon in patients with serious illness

Treatment should focus on the underlying cause

No improvement on mortality and even worse with albumin treatment

31

N Engl J Med. 2014 Apr 10. 370 (15):1412-21

Cochrane Database Syst Rev. 2011 Nov 9

Some evidences showing effects of Nutritional Therapy on

Malnourished patients

32

Increase Calorie intake after Nutritional treatment

51.72

69.74 81.74

89.35

Awal Hari 7 Hari 14 Hari 20

% Calorie intake

33 SMF Gizi Klinik RS Wahidin Sudirohusodo tahun 2014

DayO Day7 Day14 Day20

Improved Lenght of Stay (LOS) After Nutritional Therapy

34

16.7

10.38 6.68

LOS Pasien Malnutrisi LOS Malnutrisi setelah Rawat

bersama di RSUP Dr.Wahidin

Sudirohusodo

LOS pasien di RSUP Dr Wahidin

Sudirohusodo

LENGHT OF HOSPITAL STAY 2014 Series1

SMF Gizi Klinik RS Wahidin Sudirohusodo tahun 2014

44.8 41.7

23.1

55.2 58.3

76.9

hari 7 hari 14 hari 20

IMMUNITY menurun atau tetap (%) meningkat (%)

35

Improved Immunity After Nutritional Therapy

Day7 Day14 Day20

Increased (%) Decreased/unchanged (%)

EPA and GLA EPA and GLA ––Do They Work?Do They Work?

Gadek JE et al: Crit Care Med 1999:1409-142036

Gadek JE et al: Crit Care Med 1999;(27):1409-1420

EPA and GLA EPA and GLA ––Do They Work?Do They Work?

37

Conclusions: The meta-analysis showed a significant reduction in the risk of mortality as well as relevant improvements in oxygenation and clinical outcomes of ventilated patients with ALI/ARDS given EPA + GLA.

(JPEN J Parenter Enteral Nutr. 2008;32:596-605) 38

Conclusions: Early intravenous FO may not decrease the number and degree of organ failures in patients with septic shock from abdominal infection. Future tri- als are needed before FO supplementation in septic shock from abdominal infection can be recommended.

(JPEN J Parenter Enteral Nutr. 2010;34:431-437) 39

Submitted 18 June 2015 Accepted 22July2015 Published

13 August 2015 40

Conclusions Hypoalbuminemia and Low TLC are affected by

both Nutritional factor, inflammation, and diseases

Treatment should focus on the underlying cause rather than simply replacing albumin or Lymphocyte

The most effective method of minimizing hypoalbuminemia and low TLC is with nutritional therapy to create improved nitrogen balance, by provision of substrate for synthesis, counteracting stress-induced catabolism and damping down inflammation 41

THANK YOU

42

Terima Kasih

45

STRATTON, R., GREEN, C. & ELIA, M. 2003. Disease related malnutrition: an evidence based approach to treatment, Cambridge, CABI Publishing

SOETERS, P., ALLISON, S. & SABOTKA, L. 2011. Simple and Stress Starvation In: SOBOTKA, L. (ed.) Basic in Clinical Nutrition. 4th

VAN-DER-SCHUEREN, M. V. B. D., SOETERS, P. & ALLISON, S. 2011. Influence of Malnutrition on function In: Basic in Clinical Nutrition. In: SOBOTKA, L. (ed.) Basics 48

SOETERS, P., ALLISON, S. & SABOTKA, L. 2011. Simple and Stress Starvation In: SOBOTKA, L. (ed.) Basic in Clinical Nutrition. 4th

VAN-DER-SCHUEREN, M. V. B. D., SOETERS, P. & ALLISON, S. 2011. Influence of Malnutrition on function In: Basic in Clinical Nutrition. In: SOBOTKA, L. (ed.) Basics 49

51 Journal of Cachexia, Sarcopenia and Muscle© Springer-Verlag Berlin Heidelberg 2012

Zinc and Glucocorticoids

Zn Defic. ----raises glucocorticoids levels and in part mediate thymic atrophy

Zn Defic. Reduces IgM and IgG response with 50% loss of T-helper function before increased glucocorticoid

52

Fatty acids and immune function

High fat diets -----diminished innate immune responses and T-cell proliferation

Human NK cells activity is increased by reduced fat intake to < 30% energy intake

Diets deficient in n-6 or n-3 fatty acid---decrease innate immune function

Excess intakes of n-3 FA have also similar negative effects (15 g/day)

53

n-3 PUFA (Fish oil)

Posses anti-inflammatory properties Have been used to treat autoimmune

disorders such as rheumatoid arthritis, SLE, inflammatory bowel diseases, and allergic diseases

54

PERLU KEBIJAKAN RUMAH SAKIT

Angka Kejadian Malnutrisi Di Rumah Sakit Masih Tinggi

Efek klinis MALNUTRISI menjadi beban

Rumah Sakit

57

Prevalensi Malnutrisi di Rumah Sakit

(Indonesia)

41.42

68

37.14

Prevalensi Malnutrisi

58

59

↓ sistim imunitas memperlambat penyembuhan dan meningkatkan risiko

komplikasi

↑ morbidity and ↑ mortality

McWhirter J P and Pennington C R. Incidence and recognition of malnutrition in hospital BMJ 1994;308:945-948

59

Efek klinis MALNUTRISI menjadi beban

Rumah sakit

59

Penggunaan Clinical Pathway

Malnutrisi RS

Kerjasama Tim

Panduan Praktik Klinis (PPK)

60

Penelitian di RSUP Dr. Wahidin Sudirohusodo

61

RSUP Dr. Wahidin Sudirohusodo (2014)

Sumber data : SMF Gizi Klinik

46%

36%

10% 7%

1%

Perawatan Gizi Klinik

gizi buruk gizi sedang gizi ringan gizi baik gizi lebih

4%

96%

Persentase Konsul Gizi Klinik

Jumlah Konsul Gizi Jumlah pasien Rawat Inap

4%

62

Perbandingan asupan energi pada hari ketujuh pasien yang dirawat bersama dibanding tanpa rawat bersama (2011)

0

200

400

600

800

1000

1200

1400

1600

1800

konsul gizi tidak konsul

KET

asupan hari ketujuh

75%

54%

Analisis Asupan Energi

63

KESIMPULAN Angka kejadian malnutrisi termasuk kanker

kaheksia di RS masih cukup tinggi. Malnutrisi menjadi beban Rumah sakit karena

LOS bertambah, biaya RS bertambah. Semakin cepat mendeteksi malnutrisi melalui

skrining awal maka akan semakin cepat pelayanan komprehensif.

Pelayanan Komprehensif di Rumah Sakit melibatkan terapi medis, terapi gizi, asuhan keperawatan dan asuhan gizi.

64

KWASHIORKOR MARASMIC-KWASHIORKOR

65

Efek penurunan BB pada median survival (dalam Minggu)

67


Pro-inflammatory Mediators

Anti-inflammatory Mediators

The Inflammatory ResponseThe Inflammatory Response

69

Immune Suppression



Immune SuppressionImmune Suppression


70


Uncontrolled Inflammation


Uncontrolled InflammationUncontrolled Inflammation

(SIRS)

71

72

TNFa

NFKB

MyoD <<

synthesis protein <<

TNFa

NFKB

Ubiquitin-Proteasome

Proteolisis

TNFa

NFKB

Perilipin <<

HSL

Lipolisis

Hospital malnutrition

Malnutrition characterized by

HYPOALBUMINEMIA is associated with

：

Increased morbidity,

Increased mortality and

Prolonged hospital length of stay

73

How common is Malnutrition in surgical patients?

25% of surgical patients are malnourished on admission! Does it matter?

McWirther, BMJ 1994;308:945-8. Baker, N Engl J Med 1982;306:969-72

0 10 20 30 40 50 60 70 80

Infections (%) LOS (days)

Well nourished Moderately malnourished Severly malnourished

P<0.005 (infections) P<0.0001 (LOS)

74

Larter, C.Z., Farrel, G.C. 2006. Journal of hepatology. 44 (2): 253-261.

76

Plasma Albumin is associated with Nutritional Status (LLA/MUAC)

42.9%

33.3%

0.0%

57.1%

66.7%

100.0%

0.0%

20.0%

40.0%

60.0%

80.0%

100.0%

120.0%

baik kurang buruk

AL

BU

MIN

LLA

ALBUMIN NORMAL

ALBUMIN KURANG

ALBUMIN

LLA/MUAC

NORMAL KURANG TOTAL

BAIK 3 (42.9%) 4 (57.1%) 7

KURANG 5 (33.3%) 10 (66.7%) 15

BURUK 0 9 (100%) 9

TOTAL 8 23 31

Fathin et al, unpublished data, 2015 77

33.3% 33.3%

16.7%

66.7% 66.7%

83.3%

0.0%

10.0%

20.0%

30.0%

40.0%

50.0%

60.0%

70.0%

80.0%

90.0%

baik kurang buruk

AL

BU

MIN

SGA

NORMAL

KURANG

ALBUMIN

SGA NORMAL KURANG TOTAL

BAIK (A) 1 (33.3%) 2 (66.7%) 3

KURANG (B)

5 (33.3%) 11 ( 66.7%) 16

BURUK (C)

2 (16.7%) 10 (83.3%) 12

TOTAL 8 23 31


Plasma Albumin is associated with Nutritional Status (SGA)

78

p= 0.557, (p>0.05) tidak terdapat hubungan yang

signifikan antara albumin dan SGA.

3.367

3.119

2.958

2.700

2.800

2.900

3.000

3.100

3.200

3.300

3.400

NORMAL KURANG BURUK

AL

BU

MIN

SGA


Plasma Albumin is associated with Nutritional Status (SGA)

79

Syahir et al, unpublished data, 2015

TLC is associated with Nutritional Status (SGA)

80

Revised Definition of Malnutrition

Not only based on Anthropometric measures

Weight Loss, Lean Mass Loss, LOSF, and Body Composition

Hence patient with BMI 20 (normal) with

> 5% weight loss in 3 mo or > 10% in 6 mo are diagnosed malnutrition.

Konsensus dari Academy of nutrition and Dietetic (AND) dan ASPEN, 2012 81

hypoalbuminemia and low total lymphocyte count (tlc) · kwashiorkor hypoalbuminemia ... marasmus...

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