Post on 23-Mar-2020
2019-10-16
1
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
1
2
2019-10-16
2
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 =
3
4
2019-10-16
3
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
5
6
2019-10-16
4
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
7
8
2019-10-16
5
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
9
10
2019-10-16
6
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)
11
12
2019-10-16
7
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)
13
14
2019-10-16
8
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
15
16
2019-10-16
9
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
17
18
2019-10-16
10
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
19
20
2019-10-16
11
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
21
22