Patologi Klinik VeterinerGangguan Metabolisme Karbohidrat, Protein & Lemak

GANGGUAN METABOLISMESegolongan penyakit akibat gangguan metabolisme dan bersifat sistemikPenyakit ini ada 3 golongan:Gangguan metabolisme karbohidratGangguan metabolisme proteinGangguan metabolisme lemakDapat menimbulkan kelebihan atau kekurangan zat bersangkutan

Glukosa dalam Darahconcentration is influenced by hormones modifying glucose uptake by cells (for energy production), promoting/inhibiting gluconeogenesis, or affecting glycogenesis (glycogen production) and glycogenolysis.Insulin most important hormone involved in glucose metabolismInsulin release is stimulated by glucose, amino acids and hormones (e.g. glucagon, growth hormone, adrenaline). Release is inhibited by hypoglycemia, somatostatin, and noradrenaline.

Several hormones oppose the action of insulin and, therefore, will increase blood glucose.The table below summarizes the effects of these different major hormones on physiologic processes that affect blood glucose concentrations.

Hipoglikemia penurunan produksi (e.g. inherited disorders, liver disease) penggunaan yang meningkat (e.g. insulinomas, sepsis)

Decreased production 1)Inherited defects: Hypoglycemia is a feature of certain glycogen storage diseases: Pompe disease and von Gierke's disease. 2)Idiopathic: Juvenile hypoglycemia (usually affects small breed dogs). 3)Liver disease: Severe liver disease and portosystemic shunts can produce hypoglycemia. More than 70% of the functional liver mass must be lost before hypoglycemia ensues. 4)Decreased intake: Starvation, malabsorption. In horses, glucose decreases if they are fed a high grain diet, with little roughage.

Increased utilization 1)Idiopathic: Hypoglycemia of hunting dogs and endurance horses. 2)Neoplasia: Insulin-secreting tumors (insulinoma) or tumors secreting insulin-like growth factors (mesenchymal tumors, hepatic tumors). 3)Sepsis: Hypoglycemia occurs due to liver dysfunction, impairment of insulin degradation and enhanced glucose utilization. 4)Bovine ketosis, ovine pregnancy toxemia 5)Addison's disease: Hypoglycemia occurs due to decreased gluconeogenesis and increased insulin-mediated glucose uptake by skeletal muscle.

Lain-lain :Pemakaian insulin berlebihan pada diabetes, pengobatan psykosis dengan shock hipoglikemikHipoglykemia

HyperglycemiaPhysiologic: Physiologic hyperglycemia occurs post-prandially and in response to stress in all species. This can be mediated by epinephrine (and is transient, lasting 4-6 hours) or corticosteroids (results in a more sustained increase in glucose). Cats and cattle tend to produce marked stress hyperglycemias. In cattle, a very high glucose (> 500 mg/dL) is a poor prognostic indicator. In liver disease, a prolonged postprandial hyperglycemia may be observed.Therapeutic agents: Glucocorticoids, dextrose-containing fluids, thyroxine, xylazine, megesterol acetate etc.

Disease:1)Diabetes mellitus: (inherited in Keeshonds & Golden Retrievers). Cats are prone to non-insulin dependent diabetes mellitus. 2)Hyperadrenocorticism: In dogs and horses, hyperglycemia is due to insulin resistance. 3)Acromegaly: Hyperglycemia is due to insulin resistance.

4)Hyperglucagonemia: Hyperglycemia is due to insulin resistance. 5)Hyperthyroidism in cats: Increases in glucose are often transient. The exact mechanism is unknown (? defective insulin secretion, ? enhanced sensitivity to catecholamines). 6)Acute pancreatitis: Hyperglycemia, which is usually transient, may occur due to stress, glucagon secretion and decreased insulin production.

GANGGUAN METABOLISME KARBOHIDRATDiabetes melitus (Hiperglykemia)Dasar penyakit adalah defisiensi insulin

Gejala klinis penyakit :Hiperglikemia Glikosuria Dapat diikuti gangguan sekunder metabolisme protein dan lemak Dapat berakhir dengan kematian

Penyakit ini diturunkan secara autosomal resesif

Etiologi:Sebab tepat belum diketahui berhubungan dgn kelainan hormonal InsulinGrowth hormon Hormon steroid Keadaan diabetes timbul akibat ketidak seimbangan dalam interaksi pankreas, hipofisis dan adreanal

PankreasPankreas mempunyai pulau Langerhans : sel beta dan sel alphaSel beta : hormon insulinSel alpha : menghasilkan hormon glukagon Efek anti insulin berfungsi sebagai faktor hiperglikemik dan glikogenolitik meningkatkan kadar gula darah

Cara kerja insulinAda 2 teori cara kerja insulinTeori 1 = Teori Levine : Insulin mentransfer glukosa melalui membran sel otot serat lintang, tetapi tidak menggangu perpindahan glukosa melalui sel membran hatiTeori 2Insulin diperlukan untuk fosforilasi glukosa dalam sel glukosa 6 posfatase Untuk pengikatan ini dibutuhkan enzim hexokinase yang dihasilkan oleh sel hati Kelenjar hipofisis menghasilkan zat inhibitor hexokinase Insulin merupakan zat antagonis terhadap hexokinase

Kelenjar HipofisisGrowth hormon Hormon ACTH Efek menghambat enzim hexokinase. Bila kelenjar hipofisis hiperaktif menyebabkan terjadi diabetes

Kelenjar AdrenalGlukoneogenesis yaitu perubahan bentuk protein menjadi karbohidrat. Karena pengaruh hormon steroid yang dihasilkan oleh kortex adrenal Bila berlangsung terus menerus menekan sel beta pankreas menimbulkan defisiensi insulin permanenAktivitas adrenal bergantung kepada kelenjar hipofisis anterior

KOMPLIKASI DIABETES MELITUSMerupakan gangguan biokimia. Cedera morfologik sebenarnya tidak dapat untuk menegakkan diagnosis Tidak selalu sebagai dasar dari pada gangguan metabolisme

PankreasBeberapa dengan pankreas normalPada umumnya kerusakan pada sel beta ringan tidak mungkin menimbulkan gangguan produksi insulinBila ada : HialinisasiFibrosis Vakoalisasi hidropik yang sebenarnya merupakan penimbunan glikogen

Pembuluh darahBila gangguan metabolisme karbohidrat terlalu lama, hiperglikemik menahun, pada otot, hati dan jantung terjadi difisiensi. Lemak dimobilisasi sebagai sumber tenaga lemak dalam darah bertambah. Lipaemia dan cholestrolimia gangguan vaskular, dengan komplikasi aterioskelosis merata skeloris pembuluh darah arteri coronaria, ginjal dan retina

MataSkelosis arteri retina retinitis diabetika. Berupa perdarahan kecil-kecil tidak teratur pelebaran pembuluh darah retina dan berkeluk-keluk kapiler-kapiler membentuk mikroaneurisma

JantungSklerosis arteri coronaria infrak otot jantung

Ginjal Kelainan degeneratif pada alat vaskular glomeruler tubular pyleonepritis akut maupun kronis

KulitPenimbunan lipid dlm makropag-makropag pada dermis xantoma diabetikum

Susunan syarafPada syaraf tepi dan kadang medula spinalis Perubahan degeneratif Demyelinisasi Fibrosis Mungkin berhubungan dengan skelosis pembuluh darah

Hati Perlemakan hepatomegali dan infiltasi glikogenDisebabkan karena defisiensi karbohidrat sumber tenaga dari lemak imobilisasi lemak berlebihan defisiensi lipotropik lemak tidak dapat diangkut dari sel penimbunan lemak berlebihan

KlinisPolyphagia : tubuh tidak dapat memetabolisme karbohidrat yg dimakan penderita banyak makanPolidipsia : glycosuria (diuresis osmotik) kompensasi: penderita banyak minumPolyuria : glycosuria (diuresis osmotik) penderita banyak kencing

GANGGUAN METABOLISME PROTEIN.Penyakit akibat kelebihan protein (-)Defisiensi proteinTerjadi pada pemasukan protein kurang kekurangan kalori, asam amino, mineral, dan faktor lipotropikAkibatnya :Pertumbuhan tubuhPemeliharaan jaringan tubuhPembentukkan zat anti dan serum protein akan terganggu.Penderita mudah terserang penyakit infeksi, perjalanan infeksi berat, luka sukar sembuh dan mudah terserang penyakit hati akibat kekurangan faktor lipotropik

Hyperalbuminemia Overproduction of albumin is not known to occur.Relative: Hyperalbuminemia is a relative change seen with dehydration. Globulins will also increase in this situation, resulting in hyperproteinemia with no change in A:G ratio.Drugs: Increases in albumin are reported in experimental studies in dogs administered corticosteroids. It is not clear if this is due to increased production of corticosteroids or dehydration secondary to free water losses from corticosteroid-induced polyuria.

MACAM-MACAM PENYAKIT DEFISIENSI PROTEIN.HipoproteinemiaSebab : Exkresi protein darah berlebihan melalui air kemihPembentukan albumin terganggu spt pada penyakit hatiAbsorpsi albumin berkurang akibat kelaparan atau penyakit usus, juga pada penyakit ginjal

HypoalbuminemiaPhysiologic: Excessive fluid administration (overdilution).Decreased production 1) Decreased production can occur if there are insufficient amino acids available for hepatic production of albumin. This occurs in cases of chronic severe malnutrition due to dietary deficiency or starvation. 2) The liver is the main site of albumin production. Chronic hepatic disease will result in hypoalbuminemia when there is a > 80% reduction in functional mass. 3) Acute phase reactions stimulate downregulation of albumin production.

Increased loss of albumin This occurs with the following:1) Protein-losing glomerulopathy: 2) Severe hemorrhage:3) Protein-losing enteropathies. 4) Severe exudative dermatopathies.

Other cause of hipoalbuminemia:Sequestration sequestration of albumin within body cavities, e.g. peritonitis.Catabolism This is not a well-characterized mechanism for low albumin.

GlobulinTP albumin = globulinHipo dan AgammaglubulinemiaAda 3 jenis :Hipoagammaglobulinemia kongenitalPenyakit herediterMudah terserang infeksi. Kematian sering terjadi akibat infeksiPlasma darah tidak mengandung gamma proteinDapat terjadi penyakit hipersensitivas (ex: penyakit artritis)

2. Hipo/ (a) gammaglobulinemia didapatPenderita mudah terkena infeksiTerjadi hiperplasi konpensatorik sel retikulum mengakibatkan limfadenopathi dan splenomegaliFPT results when neonates fail to suckle or if dams leak colostrum pre-parturition. For diagnosis of FPT, determination of IgG is recommended within 24 to 48 hours of birth.

3. Hipoagammaglobulinemia sementaraMerupakan peralihan pada waktu gamma globulin yang didapat dari induk habis dan anak harus membentuk gamma globulin sendirihas been reported in Arabian horses and dogs. They have a delayed onset of post-natal immunoglobulin synthesis and are susceptible to adenoviral and bacterial infections.

Pirai atau GoutAkibat gangguan metabolisme asam urat asam urat serum meninggi pengendapan urat pada berbagai jaringanAsam urat merupakan hasil akhir dari pada metabolisme purin.Secara klinis :Arthritis akut yg sering kambuh secara menahunPada jaringan ditemukan tonjolan-tonjolan disebut tophus Di sekitar sendiBursaTulang rawanTelingaGinjalKatup jantung

A:G RatioThis is the ratio of albumin present in serum in relation to the amount of globulin. The ratio can be interpreted only in light of the total protein concentration. Very generally speaking, the normal ratio in most species approximates 1:1. For example, high total protein with a normal A:G ratio suggests dehydration, while the same protein with a low A:G ratio would indicate hyperglobulinemia

GANGGUAN METABOLISME LEMAKKelebihan lemak (Obesitas)Terjadi kalori didapat > kalori yg dimetabolisme (hipometabolisme)Terjadi pada hipopituitarisme dan hipotiroidisme. Kalori yg dibutuhkan menurun berat badan naik, meskipun diberi makan tidak berlebihan Lemak ditimbun pada:Jaringan subkutisJaringan retroperitoneumPeritoneumOmentumPericardiumPankreasObesitas memperberat hipertensi, diabetes, penyakit jantung

HiperlipemiaJumlah lipid darah total dan kholesterol meningkatTerdapat pada :Diabetes melitus tidak diobatiHipotiroidisme Nefrosis lupoidPenyakit hati Sirhrosis biliaris XantomatosaHiperlipidemiHiperkholesterolemiPenimbunan lemak terjadi di dinding pembuluh darah arteriosklerosis

Defisiensi lemakTerjadi pada Kelaparan (starvation)Gangguan penyerapan (malabsorption)Tubuh terpaksa mengambil kalori dari simpanannya krn intake kurangYang mula-mula dimobilisasi : karbohidrat dan lemak, dan hanya pada keadaan gizi buruk akhirnya protein diambil dari jaringanPada penyakit Whipple selain difisiensi lemak, juga difisensi protein, karbohidrat dan vitamin.

TrigliseridaHormones involved in fat metabolismLipoprotein lipase (LPL) found in vascular endothelium, activated by insulin, ACTH, TSH, glucagon & thyroid hormone. activity is enhanced by heparin. hydrolyzes CM and VLDL to free (non-esterified) fatty acids and glycerol for tissue use.Hepatic lipase hydrolyzes surface phospholipids on lipoproteins and is responsible for removing triglycerides from LDL (and helps the liver remove LDL from circulation).

Hormone sensitive triglyceride lipase responsible for lipolysis stimulated by catecholamines, glucagon, growth hormone, thyroxine, ACTH, corticosteroids and prostaglandins. inhibited by insulin (most active in the absence of insulin).

HypertriglyceridemiaPhysiologic:Postprandial hypertriglyceridemia is due to an increase in CM. A fat layer will form on refrigeration of the sample.Diabetes mellitus:Hyperlipemia is due to a marked increase in triglycerides, with a concurrent mild to moderate increase in cholesterol. There is increased CM, VLDL and LDL. This is from a deficiency or lack of insulin, resulting in decreased activation of lipoprotein lipase (decreases CM and VLDL hydrolysis), increased lipolysis (enhances VLDL production) and downregulation of LDL receptors (increases LDL). Pancreatitis:Hyperlipemia is mostly associated with hypertriglyceridemia with a mild increase in cholesterol. This is due to increased CM and VLDL from decreased lipoprotein lipase activity.

Hepatic lipidosis:Anorexia induces increased lipolysis and hypertriglyceridemia (from increased VLDL production).Hypothyroidism, cholestasis, hyperadrenocorticism:Hypercholesterolemia is more common in these disorders, although triglycerides may be mildly increased (from increased VLDL production).Familial hyperlipidemias:These are usually due to defects in lipoprotein lipase and have been reported in dogs (Miniature Schnauzers, Beagles, Brittany Spaniels) and cats (inherited hyperchylomicronemia in Siamese, domestic shorthair and Himalayans).

Excessive negative energy balance:In states of excessive negative energy balance (e.g. starvation, anorexia) particularly when energy demands are high (e.g. late pregnancy, early lactation), lipolysis of fat stores in adipocytes will increase VLDL concentrations.Drugs:Estrogens and progesterone acetate (the latter has been used in cats for treatment of miliary dermatitis).

CholesterolCholesterol occurs in blood as part of low density (LDL) and high density lipoprotein fractions (HDL). Low density lipoproteins contain 42% cholesterol, whereas HDLs contain between 21 and 36% cholesterol. LDLs are formed from very low density lipoproteins (VLDL) by hepatic lipase.

Causes of hypercholesterolemiaInherited disorders of lipid metabolism:Briards, Rottweilers, Shetland Sheepdogs, and Dobermans. Other inherited lipid disorders, e.g. hyperlipidemia of Miniature Schnauzers, hyperchylomicronemia of cats, usually result in increased triglycerides primarily, but you may also see increased cholesterol.Diabetes mellitus:Insulin stimulates lipoprotein lipase, which is responsible for hydrolysis of chylomicrons (CM) and VLDL. Insulin also antagonizes hormone sensitive lipase. Insulin lack results in elevated concentrations of CM and VLDL in the blood, with high triglyceride and cholesterol concentrations

Hypothyroidism:In dogs,Nephrotic syndrome characterized by edema, hypoalbuminemia, hypercholesterolemia and albuminuria and is caused by glomerular damage, e.g. amyloidosis, immune-complex glomerulonephritis. Hyperadrenocorticism:Cholestasis:Pancreatitis:Miscellaneous:Drugs (e.g. corticosteroids, methimazole), post-prandial (mild increases in cholesterol may be seen, although values will usually not be elevated outside reference intervals).

Causes of abnormally low cholesterol levelsDecreased absorption:Malabsorption and maldigestion problems, e.g. protein losing enteropathies, exocrine pancreatic insufficiency.Decreased production:Since the liver is the main site of cholesterol production, low cholesterol values can be seen in chronic liver diseases (e.g. cirrhosis), synthetic liver failure (acute or chronic), and portosystemic shunts (acquired or congenital).

Altered metabolism: Inflammatory cytokines can reduce the cholesterol content of lipoproteins by decreasing lecithin-cholesterol acyltransferase activity Increased uptake of lipoproteins: Upregulation of LDL-receptors on cells (peripheral tissues and liver) can potentially lower cholesterol values. occurs in rapidly proliferating tumor cells (e.g. acute myeloid leukemia in human patients) response to inflammatory cytokines (some acute phase proteins in human patients, such as serum amyloid A, enhance LDL removal from the circulation in acute phase reactions).

TERIMAKASIHhttps://ahdc.vet.cornell.edu/clinpath/modules/chem/chempanl.htm