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Veterinary PathophysiologyStudent’s Lectures, 5th Semester

Department of Clinical Pathology and Oncology,University of Veterinary Medicine

Metabolic disorders 1.General aspects. Disturbances of protein metabolism

METABOLIC DISORDERS

Disorders of:

1. Supply (intake) of nutritive materials (overfeeding and starvation)

2. Protein and amino-acid metabolism

3. Carbohydrate metabolism

4. Lipid metabolism

5. Vitamin metabolism - see Biochemistry, Animal Nutrition6. Water, acid-base and electrolyte balance – see alterations of

homeostasis7. Metabolism of macro- and microelements – see also

alterations of homeostasis

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DEVELOPMENT OF METABOLIC DISEASES

intake utilization,demand/output

HEALTHY STATE

Interm. metabolism

decreased increased increased decreasedintake demand/utilization intake utilization

e.g. starvation, e.g. primary ketosis, e.g. overfeeding e.g. diabetes secondary milk fever, toxicosis mellitus –

ketosis, lipid mobilisation ammoniatoxicosis, hyperglycaemia,baby pig disease, syndrome lactate poisoning storageFe-deficiency salt poisoning diseases eg. anaemia PRODUCTION copper

DISEASES

Deficiency Excess

OVERFEEDING AND OBESITY– feeding centers, regulation

4Loftus JP, Wakshlag JJ: Canine and feline obesity: a review of pathophysiology, epidemiology,

and clinical management Veterinary Medicine: Research and Reports 2015:6

Herbivores –seasonal POMC outpourunder pituitary pars intermedia(PI) control

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OVERFEEDING AND OBESITY

Overfeeding = energy intake > absolute/relative demand

Causes: endogenous: ie. Hypothyreosis (less frequent…)

exogenous: ie. available tasty and/or highly energetic food

Pathophysiology not completely understood - multifactorial:

1. Glucostatic model: glucose and glucostatic hormones (amylin, glucagon-like peptide-1 [GLP-1]) drive insulin secretion andstimulate the hunger centers

2. Lipostatic model: it appears that fatty acids in the diet are the primary driving factor for increasing GI hormone secretion andfeed-back to appetite centers

3. Set point theory: assumes that there is control of eating based on an energy set-point that slowly maladjusts

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OVERFEEDING AND OBESITY

Development and types:

Dynamic phase – active weight gain

Increased energy expenditure: metabolic activity increased

moving increased body weight „costs” more energy

Static phase – no active weight gain, excessive body-fat maintaned

Hyperplastic obesity: excessive weight gain in childhood characterized by the creation of new fat cells.

Hypertrophic obesity: excessive weight gain in adulthood characterized by expansion of already existing fat cells.

(http://medical-dictionary.thefreedictionary.com)

Fat tissue undergoes „turn-over” – adipocytes undergo mitosis and apoptosis throughout life.

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OVERFEEDING AND OBESITY

1. Local consequences: fat is an endocrine organ – over 100 proteins,

peptides and cytokines (IL-6, IL-8, TNFα, resistin, CRP, leptin,

adiponectin) released

2. General effects of obesity

- „Inflammation of obesity” – all species- „metabolic syndrome” with insulin resistance and hypertension

humans, swine, cats, horses and herbivores typically yes (dogs not characteristic)

3. Disorders of specific organ-functionshypertension; thermoregulation – decreased heat tolerance;reproductive functions (dystocia); locomotor functions (arthrosis) etc.

Consequences: obesity is associated with a dysregulatedand dysfunctional adipose tissue

STARVATION, FASTING(deprivation of food)

Types and causes:

Absolute: rare

on course of severe diseases

due to local causes

animal abuse

Aim of the organism: to maintain energy balance (importance of glucose!) via maximized utilization of body stores and minimizing losses (importance of protein!)

Relative: frequent

decreased intake of food, bad quality/composition of food, maldigestion/malabsorption, increased loss (GI, kidney),increased demand!

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• Decrease of blood glucose within 24 to 72 hours

• release of glucagon, reduction in insulin secretion

• Glycogenolysis - glycogen stores last max. 72 hours

• Gluconeogenesis: from muscle protein alanine• fatty acid oxidation in hepatocytes generates

ketone bodies• loss of body fat and protein accompanied by

depletion of potassium, phosphate and magnesium

CONSEQUENCES OF STARVATION

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CONSEQUENCES OF STARVATION

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...and REFEEDING

• rapid decline in both gluconeogeneisand anaerobic metabolisms• rapid increase in serum insulin• stimulates the movement of extracellular potassium,phosphate, magnesium to the intracellular compartment• enhanced by depletedintracellular stores and large concentration gradient• rapid ly occusinghypokalaemia, hypophosphataemia and hypomagnesaemia• to maintain osmotic neutrality - sodium and water retention

CONSEQUENCES OF DECREASED NUTRIENT INTAKE

General consequences:

Decreased:• production• reproductive function,• defense mechanisms• metabolic disorders• altered bloodcomposition• cachexia• edema

Organs affected:

• liver: altered carbohydrate, lipid, protein metabolism• endocrine function• muscles• circulatory system• bone marrow• skeletal system• adipose tissue

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Cat Dog Man

Bones 10.4 5 -

Muscles 57.9 4240.7 (whole

body)

Brain and spine 2.2 22 6.9 (Brain)

Heart 34 16 40.4

Spleen 68.5 57 18.4

Liver 59.8 50 28.6

Pancreas 55.1 62 48.8

Kidneys 50.9 55 49.2

Lungs 20.5 29 28.6

Percentage loss of fresh organs during starvation

Based on work by Sedlmair (cats), Voit (cats), Voit (dogs) and Meyers (man) (summarized by MEYERS, 1917).

SPECIAL ASPECTS OF STARVATION IN RUMINANTS

Consequences are similar but more severe than in non-ruminants

Rumen: motility and VFA production decreases →NH3 and pH increases

Liver: more urea is produced (up to a limit i.e. availability of ATP)

blood urea

urea in milk and in urine

and gluconeogenesis and ketogenesis increasesBlood: immediate hypoglycaemia

shortly followed by FFA-increase,ketone body production increases (secondary ketosis)compensated metabolic acidosis

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ENERGY STORES OF A DAIRY COW(Stöber and Dirksen, 1982)

STORED COMPOUND

TOTAL AMOUNT,

kg

VELOCITY OF MOBILI-

ZATION

TRANSPOR-TED FORM

Carbohydrate (liver and muscle glycogen)

2-3

very fast

glucose

Lipid (adipose tissue triacyl-glycerol)

40-60

fast

FFA, glycerol

Protein (muscle) 50-70 slow amino acids

Amino acid (AA) and proteinmetabolism

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IMBALANCES OF AMINO ACID METABOLISM

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1. Primary disorders and their causes:

Imbalance/Deficiency Antagonism Overload and toxicity

decreased intake similar chemical characteristic,increased loss structure (?) sometimes life-

threatening symptomsImportance of:- S and -CH3 Leucine - Isoleucine Methionine (hepatotox.)

containing Leucine - Valine Phenylalanine (neuro.)amino acids Lysine - Arginine Tyrosine - Tryptophan (niacin) Tryptophan - Threonine Tryptophan (pneumo.)- Lysine (pigments) etc.

2. Secondary causes:Alteration of protein metabolism

Most common backgrounds of abnormal AA metabolism

• In farm animals: due to inadequate intake (pigs, poultry, dairy cows!)

• Pet animals: due to liver malfunction/portosystemic shunts

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1. Decreased intake/synthesis

- lack of available proteins/aminoacids

- Decreased digestion/absorption

2. Decreased protein synthesis

- Mostly liver dysfunction

3. Increased loss

- via intestines (protein-loosing enteropathy)

- due to renal failure (increased filtration/decreased absorption: protein-loosing nephropathy)

- Parasites; - burns; - bleeding (chronic)

CAUSES OF PROTEIN DEFICIENCY

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CONSEQUENCES OF PROTEIN DEFICIENCY 1.

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1. Decreased performance/production:retarded growth, weakness of muscles,decreased milk or egg production,loss of body weight,retarded embryonic development

2. Impairment of the defense mechanisms – high morbidity

decreased: - antibody and white blood cell production- phagocytic activity- collagen formation- wound healing

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CONSEQUENCES OF PROTEIN DEFICIENCY 2.

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3. Alteration in blood constituents – important fordiagnosis

decreased production of blood cells,decreased plasma protein synthesis hypoproteinaemia

hypoalbuminaemia (consequent decrease in the total calcium level, relative increase in ionised calcium content)

CONSEQUENCES OF PROTEIN DEFICIENCY 3.

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4. Decreased organ-functions

Liver function:

- decreased synthesis of coagulation factors, later albumin

- decreased deamination and detoxification

GI tract: - digestive enzyme deficiency- anorexia, dyspepsia (=disturbed digestion)

Endocrine functions: - adrenocortical hyperfunction, lack ofgonadotropic hormones and TSH

Cornified tissues: - disorders in pigmentation, feather formation, wool quality

Bones: - osteoporosis

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CAUSES AND CONSEQUENCES OF PROTEIN OVERLOAD/EXCESS

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Causes:

• Increased protein or NPN intake

• Neoplasms (tissue necrosis)

• Inflammation (including immune mediated disorders)

Consequences: physiol.: athletic condition,pathol.: alterations in plasma proteins

(paraproteinaemia)

Carnivores – if healthy, protein overload does not existHerbivores – excessive ammonia production in the rumen/large

intestine; diarrhoea, (ruminal) and metabolic alkalosis,

PLASMA PROTEINS

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Importance of the albumin/globulin (A/G) ratio

Protein fractions of blood plasma (electrophoresis):- albumin,- 1, 2, ß1, ß2, -globulins,- fibrinogen

Good markers even in case of mild injuries without any alteration in total protein content.

• Acute phase proteins

• Peptide mediators

• Transport proteins• Factors of coagulation, fibrinolytic, kinin and complement

systems.

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Serum proteins (electrophoresis)

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DISORDERS OF PLASMA PROTEINS 1.

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Quantitative:

1. normal total protein concentration but altered fractions:

dysproteinaemia i.e. decreased albumin,increased globulins(providing partial compensation)

2. total protein concentration as well as fraction(s) are altered:

hypoproteinaemia i.e.: decreased albumin,normal globulins

hyperproteinaemia i.e.: normal albumin,increased globulin or

increased albumin andglobulins (as in dehydration)

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DISORDERS OF PLASMA PROTEINS 2.

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Qualitative changes:

paraproteinaemia (presence of abnormal proteins)

Consequence: according to the functions of proteins in question

When A/G decreases:- erythrocyte sedimentation rate increases- serum colloid lability increases- (edema)

Glutaraldehid- (GLUTARSEL-) test

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Erythrocyte sedimentation rate (ESR)

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IMPAIRMENT OF NITROGEN METABOLISM DURING LIVER AND

RENAL FAILURE

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Decreased hepatic Decreased renalfunction function

↓detox. ↓ synthesis ↓urea and creatinineexcretion

↑protein (alb.) loss

↓urea ↓ protein ↑urea and creatinine↑NH3 ↑ amino acid protein

AMINOACIDURIA PROTEINURIA

← ORGANS →

BLOOD

URINE

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