Trastornos endocrinos y metabólicos Flashcards
First two autoantibodies that appear in patient with T1DM
antiinsulin and antiGAD65
Autoantibody in T1DM that usually disppears by age 5
antiinsulin
Most common age for T1DM
<15 years old
What factor influences the risk of a faster progresion to the symptomatic phase in T1DM
The number of autoantibodies and the age of seroconversion of the first antibody
Theory of production of autoantibodies in T1DM
By a continuous exposition to beta-cell autoantigens
What autoantibody is associated with the haplotype HLA-DR3-DQ2
anti-GAD65
What autoantibody is associated with the haplotype HLA-DR4-DQ4
antiinsulin
The appearance of which autoantibody increases the risk of reaching the symptomatic phase
anti-IA2
How do polymorphisms affect the development of immune tolerance in the fetal thymus
They lead to inadequate deletion of autorreactive T cells or insufficient generation of T reg cells
What characterizes the progression from phase 1 to phase 2 in T1DM
dysglucemia
How is dysglucemia detected when T1DM progresses from phase 1 to phase 2
Oral glucose tolerance test or intravenous glucose tolerance test
How does the intravenous glucose tolerance test work
It detects the preformed insulin granules before they are secreted
Common age, ethnicity and BMI for patients with type 1b diabetes
<20 years, of african or asian origin, and greated BMI
Drugs that can cause diabetic ketoacidosis
antipsychotic agents, illicit drugs, alcohol, thiazide diuretics, corticosteroids, etc
How does insulin deficiency lead to ketoacidosis
Glucose usage will decrease, therefore increasing lipolysis and free fatty acids. This will cause an increase of ketone body production and lead to hyperketonemia, until reaching ketoacidosis
How does insulin deficiency lead to hyperosmolarity
Gluconeogenesis will be increased, causing hyperglycemia which will also cause glycosuria, electrolyte loss, and volume depletion, causing hyperosmolarity
Diagnostic criteria in diabetic ketoacidosis for ketosis
concentration of b-hydroxybutyrate > 3 mmol/L or urine ketone strip >2+
Diagnostic criteria in DKA for metabolic acidosis
pH <7.3 or HCO3- <18 mmol
Diagnostic criteria in hyperglycemic hyperosmolar state for hyperglycemia
plasma glucose >600 mg/dL
Diagnostic criteria in hyperglycemic hyperosmolar state for hyperosmolarity
Calculated effective serum osmolality >300 m0sm/kg or total serum osmolality >320 m0sm/kg
What defines the severity of DKA
Whether the mental status is alert, drowsy or coma
What is usually given as treatment for DKA
Fluids
Causes of hypoglycemia in adults
Insulin secretagogue, alcohol, hepatic/renal/cardiac failure, hypocortisolism, etc
Sympathoadrenal response in the presence of hypoglycemia
increase of oxygen consumption, which increases heart work load and causes heart rate variability and ECG changes
Effects of hypoglycemia in the eye
Diplopia, decrease of retinal sensitivity and response, loss of vision
Effects of hypoglycemia in the brain
Neurocognitive dysfunction, increase of seizures, brain injury
Pathways that cause oxidative stress and loss of insulin actions
Polyol, hexosamine, protein C kinase, AGE
Main sensory tests for diabetic neuropathy
Vibration, pain, pressure, light touch, temperature
Events that occur at earliest stage of diabetic retinopathy
Microaneurysms
What causes changes to the appearance of the retina in moderate diabetic retiniopathy
Distortion of blood vessels in retina
What could cause retinal detachment in diabetic retinopathy
Angiogenesis inside retinal surface increases risk of their leakage, in that case it could peel the retina from the underlying tissue
Normal value of glomerular filtration rate
> 90
Normal value of albuminuria
<30 mg/g
Value of GFR that is considered kidney failure
<15
Value of albuminuria considered severely increased
> 300 mg/g
Cotransporter in proximal tubules responsible for reabsorption of glucose and sodium
SGLT1 (proximal) and SGLT2 (distal)
How are SGLT1 and SGLT2 upregulated under hyperglycemic conditions
hypatocyte nuclear factor 1 (HNF1a) and glucocorticoid-induced kinase-1 (SGK1) stimulate them
How does hyperglycemia lead to glomerular hyperfiltration
Reabsorption of glucose in the proximal tubule will cause a decrease of hydraulic pressure in Bowman’s capsule and concentration of NaCI in macula densa, leading to a decreased vasoconstrictor tone and a efferent arterial dilation
How does hyperglycemia lead to podocyte death
Promotion of ROS can react with NO (produced by podocytes to prodtect glomerulus), creating oxidative stress and inducing apoptosis
How does insulin regulate protein synthesis and cell growth in the glomerulus
It activates PI3K and mTOR pathways
What are the effects of angiotensin II, endothelin 1, ROS, and thromboxane A2 on the efferent arteriole of the glomerulus
Vasoconstriction
What are the effects of insulin resistance, COX2, prostanoids on the afferent arteriole of the glomerulus
Vasodilation
Therapies that could slow the progression of DKD
SGLT2 inhibitors, RAS blockers, GLP-1RAs
How does the polyol pathway promote hyperglycemia
Increases intracellular oxidative stress
How does the hexosamine pathways promote hyperglycemia
Activation of serine and threonine residues of transcription factors cause pathologic gene expression
How does the PKC activation promote hyperglycemia
Increased expression of NFKB, PAI1, and TGFb
Most common type of diabetic neuropathy
Chronic distal symmetric sensory poly-neuropathy
Criteria for confirmed neuropathy
Abnormal nerve conduction and symptoms or signs of neuropathy
How are NE and 5HT involved in pain
Modulate descending inhibitory pain pathways
What are some symptoms of cardiac autonomic neuropathy
Resting tachycardia, exercise intolerance, orthostatic hypotension, QT prolongation
Symptoms of a GI autonomic neuropathy
Gastroparesis, diarrhea, constipation
How does hyperglycemia lead to the collapse of arch (Charcot Arthropathy)
Oxidative stress and ischemia cause a progressive localized inflammatory response and impaired vascular smooth muscle
How does hyperglycemia lead to an ulcer formation on the foot
Decreased blood supply will cause impaired healing, so when the skin degrades it won’t be healed properly
The simultaneous or sequential appearance of diverse metabolic and inflammatory conditions associated with insulin resistance and accumulation of fat tissue, refers to:
Metabolic syndrome
How does the Semmes-Weinstein Monofilament test work to detect diabetic foot
Apply pressure to several spots of the foot with a monofilament
Diagnostic criteria for abdminal obesity
Waist circumference >102cm in men and >88cm in women
