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Patologi Klinik Veteriner

Gangguan Metabolisme
Karbohidrat, Protein &
Lemak

GANGGUAN
METABOLISME

Segolongan penyakit akibat gangguan


metabolisme dan bersifat sistemik
Penyakit ini ada 3 golongan:
1.
2.
3.

Gangguan metabolisme karbohidrat


Gangguan metabolisme protein
Gangguan metabolisme lemak

Dapat menimbulkan kelebihan atau


kekurangan zat bersangkutan

Glukosa dalam Darah

concentration 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
metabolism
Insulin 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 insulinmediated glucose uptake by skeletal muscle.

Hipoglykemia

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

Hyperglycemia
Physiologic: Physiologic hyperglycemia occurs postprandially 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, dextrosecontaining fluids, thyroxine, xylazine, megesterol acetate
etc.

Disease:
1) Diabetes mellitus: (inherited in Keeshonds &
Golden Retrievers). Cats are prone to noninsulin 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
KARBOHIDRAT
Diabetes 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
Insulin
Growth hormon
Hormon steroid
Keadaan diabetes timbul akibat ketidak seimbangan dalam
interaksi pankreas, hipofisis dan adreanal

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

Cara kerja insulin

Ada 2 teori cara kerja insulin

Teori 1 = Teori Levine :

Insulin mentransfer glukosa melalui membran sel


otot serat lintang, tetapi tidak menggangu
perpindahan glukosa melalui sel membran hati
Teori 2

Insulin 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 Hipofisis

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

Kelenjar Adrenal

Glukoneogenesis 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 permanen
Aktivitas adrenal bergantung kepada kelenjar hipofisis anterior

KOMPLIKASI DIABETES MELITUS

Merupakan gangguan biokimia.


Cedera morfologik sebenarnya tidak dapat untuk menegakkan
diagnosis
Tidak selalu sebagai dasar dari pada gangguan metabolisme

Pankreas

Beberapa dengan pankreas normal


Pada umumnya kerusakan pada sel beta ringan tidak
mungkin menimbulkan gangguan produksi insulin
Bila ada :
Hialinisasi
Fibrosis
Vakoalisasi hidropik yang sebenarnya merupakan
penimbunan glikogen

Pembuluh darah

Bila 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

Mata

Skelosis arteri retina retinitis diabetika.


Berupa

perdarahan kecil-kecil tidak teratur


pelebaran pembuluh darah retina dan berkeluk-keluk
kapiler-kapiler membentuk mikroaneurisma

Jantung

Sklerosis arteri coronaria infrak otot jantung

Ginjal

Kelainan degeneratif pada alat vaskular glomeruler tubular


pyleonepritis akut maupun kronis

Kulit

Penimbunan lipid dlm makropag-makropag pada dermis


xantoma diabetikum

Susunan syaraf

Pada syaraf tepi dan kadang medula spinalis


Perubahan degeneratif

Demyelinisasi
Fibrosis
Mungkin berhubungan dengan skelosis pembuluh darah

Hati

Perlemakan hepatomegali dan infiltasi glikogen


Disebabkan karena defisiensi karbohidrat sumber tenaga
dari lemak imobilisasi lemak berlebihan defisiensi
lipotropik lemak tidak dapat diangkut dari sel
penimbunan lemak berlebihan

Klinis

Polyphagia : tubuh tidak dapat memetabolisme karbohidrat


yg dimakan penderita banyak makan
Polidipsia : glycosuria (diuresis osmotik) kompensasi:
penderita banyak minum
Polyuria : glycosuria (diuresis osmotik) penderita banyak
kencing

GANGGUAN METABOLISME
PROTEIN.

Penyakit akibat kelebihan protein (-)


Defisiensi protein
Terjadi pada pemasukan protein kurang kekurangan
kalori, asam amino, mineral, dan faktor lipotropik
Akibatnya :
Pertumbuhan tubuh
Pemeliharaan jaringan tubuh
Pembentukkan 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.

Hipoproteinemia

Sebab :

Exkresi protein darah berlebihan melalui air kemih

Pembentukan albumin terganggu spt pada penyakit hati

Absorpsi albumin berkurang akibat kelaparan atau penyakit


usus, juga pada penyakit ginjal

Hypoalbuminemia
Physiologic: 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.

Globulin
TP albumin = globulin

Hipo dan Agammaglubulinemia


Ada 3 jenis :
1. Hipoagammaglobulinemia kongenital

Penyakit herediter

Mudah terserang infeksi. Kematian sering terjadi akibat


infeksi

Plasma darah tidak mengandung gamma protein

Dapat terjadi penyakit hipersensitivas (ex: penyakit


artritis)

2. Hipo/ (a) gammaglobulinemia didapat

Penderita mudah terkena infeksi


Terjadi hiperplasi konpensatorik sel retikulum
mengakibatkan limfadenopathi dan splenomegali

FPT 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 sementara

Merupakan peralihan pada waktu gamma globulin yang


didapat dari induk habis dan anak harus membentuk
gamma globulin sendiri

has 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 Gout

Akibat gangguan metabolisme asam urat asam urat serum


meninggi pengendapan urat pada berbagai jaringan
Asam urat merupakan hasil akhir dari pada metabolisme purin.
Secara klinis :
Arthritis akut yg sering kambuh secara menahun
Pada jaringan ditemukan tonjolan-tonjolan disebut tophus

Di sekitar sendi
Bursa
Tulang rawan
Telinga
Ginjal
Katup jantung

A:G Ratio
This 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
LEMAKlemak (Obesitas)
Kelebihan

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 subkutis
Jaringan retroperitoneum
Peritoneum
Omentum
Pericardium
Pankreas
Obesitas memperberat hipertensi, diabetes, penyakit jantung

Hiperlipemia

Jumlah lipid darah total dan kholesterol meningkat


Terdapat pada :

Diabetes melitus tidak diobati


Hipotiroidisme
Nefrosis lupoid
Penyakit hati
Sirhrosis biliaris
Xantomatosa
Hiperlipidemi
Hiperkholesterolemi

Penimbunan lemak terjadi di dinding pembuluh


darah arteriosklerosis

Defisiensi lemak

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

Trigliserida
Hormones involved in fat metabolism
Lipoprotein 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).

Hypertriglyceridemia

Physiologic: 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).

Cholesterol

Cholesterol 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 hypercholesterolemia
Inherited 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 levels


Decreased 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 LDLreceptors 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).

TERIMAKASIH

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