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Disorders of carbohydrate/lipid metabolism

Márton Márialigeti

Department of Clinical Pathology and Oncology

University of Veterinary Medicine, Budapest

14 October 2019

Veterinary PathophysiologyStudent’s Lectures, 5th Semester

Glucose – an overview

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Absorption

• Monogastric: small intestines

• Ruminants:• Rumen: lined by stratified squamous epithelium• Absorption: VFA (acetate, propionate, butyrate), lactate, water (along conc

gradient)• Elimination of VFAs is necessary to maintain rumen pH; elimination through the

portal vein• VFAs:

• Acetate: oxidized to generate ATP, fat building• Propionate: removed by liver, used to synthetise glucose (virtually no small intestinal

absorption!!)• Butyrate (in the form of BHB): oxidised in tissues as an energy source

For example:

• 100 kg goat producing about 1550 kg milk in 305 days of lactation• 4% lactose, 3,5 % protein, 3,6 % fat• 250 g lactose, 180 g protein, 185 g

fat EVERY SINGLE DAY• In chocolate equivalents: about the

fat/sugar contents of 4,5 whole milk chocolate bars (100 g)

• Half of that lactose (the glucose half) is made of propionate• All the fat from acetate• 1,3 days =

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Distribution• Monogastric animals: BG around 5 mmol/L

• Ruminants (domestic): BG around 3,5 mmol/L• VFAs: accounting about 70% of energy supply; tissue use of glucose is still

present (accounting for about 10% of CO2 production)

• Birds: higher BG(hummingbird: 17 mmol/L)

Storage

• In the form of glycogen

• In the form of body fat

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Storage

• Glycogenesis in the liver/muscles• hexoses freely move through the liver

cell membrane, where they are transformed into glucose

• Phosphorylation by glucokinase is dependent on glucose and insulin concentration

• Glucose reenters the circulation and also covers the need of the liver; excess is stored in the form of glycogen

• Glycogen half-life is about a day (interrupted eating patterns)

• Muscles: presence of hexokinase – high G affinity, phosphorylation (and absence of G-6-Pase)

Energy mobilisation

• Glycogenolysis• In the liver: initiated by epinephrine AND

glucagon which promotes glyconeogenesisas well (G-6-Pase)

• In the muscles: initiated by epinephrine; G-6-Pase is absent, therefore the end product is lactate and pyruvate (glycolysis)

• Cori-cycle• Epinephrine and glucagon stimulation test

• Glycogen in disease• Generally depleted• Starvation, diabetes mellitus (DM), bovine

ketosis, ovine pregnancy toxaemia, any form of nutritional carbohydrate deficiency or increased turnover

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Endocrine regulation

Endocrine regulation - insulin

• Insulin receptors are found on liver, muscle, fet and mammary tissue• Insulin effect on sensitive tissues: increased GLUT-4 expression,

facilitation of glucose entry into the cells• Liver: independent of glucose transport, glucose regulation is based

on increased glucokinase activity (eliminating G and creating a concentration gradient)• Insulin promotes glucose uptake/energy storage

• Glycogenesis• Lipogenesis by increasing LPL activity• Antiglyconeogenic• Antiketogenic

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Endocrine regulation - glucagon

• Effects: acts on the liver

• Stimulates the release of glucose: glycogenolysis, glyconeogenesis

• Production is stimulated by hypoglycaemia, decreased by FFAs and ketones

• Plasma glucagon concentration increases in starvation then decreases as FFAs and ketones become the major sources of energy

• Effects:• Glyconeogenic• Glycogenolytic• Ketogenic

Endocrine regulation – insulin to glucagon ratio

• In the liver: regulating glucose release/storage

• In felids/ruminants: higher glucagon levels lead to ‘starving’ mode in the liver while insulin increases glucose uptake in other tissues (diet-lower hexose levels absorbed)

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Endocrine regulation: other hormonal effects

• Glucocorticoids: stimulate hepatic gluconeogenesis and decrease peripheral insulin sensitivity

• Growth hormone: direct anti-insulin actions

Hypoglycaemia - causes

• Preanalytical error:• Pseudohypoglycemia

• Decreased carbohydrate source or uptake• Starvation• Piglet neonatal hypoglycaemia – glyconeogenetic enzyme defect• Ruminant ketosis• Maldigestion, malabsorption

• Increased insulin levels• Iatrogenic• Insulinoma (insulin producing tumor)• Paraneoplastic (usage, IGF-1 secretion, insulin receptor upregulation etc)

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Hypoglycaemia - causes

• Hormonal• Hypoadrenocorticism, hyposomatotropism

• Decreased hepatocellular glycogen synthesis• Glycogen storage disease (defect in enzyme function, maltese and other dogs)• Liver insufficiency, portosystemic shunts• Septic processes

• Increased demand• Exercise (greyhounds, hunting breeds)• Hyperthyroidism• Tumors• Hypercatabolic status, end stage (septic, traumatic etc)

Hypoglycemia - causes

• Increased losses• Renal glucosuria

• Medication/toxins• Insulin

• Oral antidiabetic drugs

• Mitotane

• Beta blockers

• xylitol

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Hypoglycemia: symptoms

• Nervous system:• Desorientation, weakness, ataxia, paresis

• Sympathicotonia:• Mydriasis, myoclonus, anxiety

• Polyphagia, weight gain (long term)

Hypoglycemia in neonatal piglets

• Low lipid – and glycogen stores

• Underdeveloped GNG enzymes (20-40%

• Lack of nutrition (decreased milk consumption due to littermates, diseases etc)

• Lower amylase/insulin secretion

• Increased heat need

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Hypoglycemia in neonatal toy breed dogs

• Essentially the same as in piglets

• B1-vitamin deficiency contributes

Hyperglycemia - causes

• Alimentary• Postprandrial

• Increased glycogen catabolism• Catecholamine effect (alarm reaction, pheochromocytoma)• Hypercatabolic states, beginning phase (sepsis, trauma, shock)

• Lack of insulin or insulin resistance (decreased tissue use)• Diabetes mellitus• Hypercortisolism (Cushing’s)• Acromegaly• Diostrus in the bitch• Glucagonoma

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Hyperglycemia - causes

• Iatrogenic/pharmacologic• Corticosteroids

• Gestagenes

• Iv glucose

• Thiazides

• Parenteral nutrition

• Adrenerg medication

Diabetes mellitus

• Relative or absolute lack of insulin• Type I: decreased insulin

production

• Type II: insulin receptor problems (damage, insensitivity)

• Type III: I/II precursor stages

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Daibetes mellitus -pathophisiology

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