202 ES - Biochemistry Flashcards
Hormonal regulation of pituitary gland is primarily ______ feedback
negative
Polyuria
Excretion of large volume of dilute urine
Central vs nephrogenic DI
Central: deficiened ADH
Nephrogenic: ADH normal but renal resistance
Polydipsia
Abnormal great thirst
The majority of hypothyroidism cases are?
Primary causes
3 types of primary hypothyroidism
Iatrogenic - drugs/radiotherapy
Autoimmune - chronic autoimmune thyroiditis
Other - postpartum thyroiditis
Patients of chronic autoimmune thyroiditis (Hashimoto’s thyroiditis) have ______ levels of thyroid peroxidase (TPO) & thyroglobulin (Tg) antibodies
high
Causes of iatrogenic hypothyroidism
Amiodarone
Lithium
TSH & fT4 levels of primary, subclinical, secondary/tertiary hypothyroidism
Primary - ↑ TSH, ↓ fT4
Subclinical - ↑ TSH, normal fT4
Secondary/tertiary - normal/↓ TSH, ↓ fT4
Hyperthyroidism more commonly affects which gender?
Women
Most common cause of hyperthyroidism
Grave’s disease
- autoimmune disorder involving the production of autoantibodies against TSH receptor
Toxic multinodular goitre
2nd most common cause of hyperthyroidism
Caused by iodine deficiency
TSH & fT4 levels of primary, subclinical, pituitary adenoma hyperthyroidism
Primary - ↓ TSH, ↑ fT4
Subclinical - ↓ TSH, normal fT4
Secondary/tertiary (Pituitary adenoma) - ↑ TSH, ↑ fT4
4 stages of nonthyroidal illness
- Low T3
- High T4
- Low T4
- Recovery
Physiological functions of calcium (6)
Bone formation Brain function & neurotransmission Heart function Muscle function Blood clotting Cellular metabolism
______ dissolve bone;
______ form new bone.
Osteoclast; Osteoblast
Where is intracellular calcium stored?
Endoplasmic reticulum (ER) Sarcoplasmic reticulum (SR) Mitochondria
Factors affecting blood Ca2+
Changes in plasma protein concentration
Changes in anion concentration
Acid-base abnormality
Causes of hypercalcemia
Hyperparathyroidism
Malignancy
Vitamin D intoxication
Medication-induction
Causes of hypocalcemia
Hypoalbuminemia Hypoparathyroidism Poor intake or impaired absorption of calcium Vitamin D deficiency/low calcitriol Liver & renal diseases Osteoblastic metastases
Hypothalamus-pituitary-adrenal gland (HPA) axis regulates?
Cortisol
Renin-angiotensin system regulates?
Aldosterone
The sympathetic system regulates?
Hormones secreted from adrenal medulla
Adrenal gland disorders of too much hormones
Cushing’s syndrome
Congenital adrenal hyperplasia
Pituitary tumor
Hyperaldosteronism
Adrenal gland disorders of too little hormones
Addison’s disease
Diagnostic strategies of adrenal hormone disorders
- Suspected hypofunction
- Suspected hyperfunction
Suspected hypofunction - Stimulation test
Suspected hyperfunction - Suppression test
What is Addison’s disease?
Long-term disorder
Insufficient production of all steroid hormones
Lack of aldosterone & cortisol
Presentation of gluocorticoid (cortisol) insufficiency (Addison’s disease)
Weight loss & long-fasting fatique
Weakness & malaise
Low bp
Androgen insufficiency (Addison’s disease)
- male
- female
Male: do not express signs of ↓ androgens Female: - ↓ body hairs - reduced libido - hot flushes
Presentation of mineralcorticods (aldosterone) insufficiency (Addison’s disease)
Hypotension
Hyponatremia & hyperkalemia
Shock
Clinical features of Addison’s disease
Pigmentation - bc excess ACTH
- sun-exposed & pressured areas
Knuckles, elbow, knees, palmar creases
Diagnostic strategy for Addison’s disease (3 stages)
- Demonstration of inappropriately low cortisol level
- Determination the level of adrenal dysfunction (primary vs secondary)
- Identification of specific cause of adrenal insufficiency
In Addison’s disease:
Cortisol levels are ______; ACTH levels are ______
low; high
Presentation:
Cushing’s vs Addison’s
Cushing’s:
- hypotension
- hypernatremia
- weight gain
- hair overgrowth
Addison’s:
- hypotension
- hyponatremia
- weight loss
- hair loss
Diagnostic strategy for Cushing’s disease (2 stages)
- Confirmation of raised blood cortisol
2. To establish cause of observed cortisol excesss
Normal fasting blood sugar level?
72 - 99 mg/dL
How is glucose transported into the cell?
Na+ & ATP-independent transporter
Na+ & ATP-dependent transporter
- glucose cannot diffuse into cell directly
- once inside cell, glucose phosphorylated to G6P and cannot leave cell
Na+ & ATP-independent transporter
GLUT1-GLUT14
Facilitated transport, uniporter
Low Km, ______ affinity;
High Km, ______ affinity
high; low
Na+ & ATP-dependent transporter
SGLT1
SGLT2
on epithelial cells of intestine, renal tubules, choroid plexus
Secondary active transport, energy required, symporter
Which 3 hormone regulates blood sugar?
Glucagon - ↑ blood glucose
Insulin - ↓ blood glucose
Stress hormones (epinephrine) - “fight or flight”
Synthesis of insulin
Preproinsulin (ER) → proinsulin (Golgi apparatus) → insulin + C-peptide (stored in secretory vesicles)
How is insulin secretion regulated?
- high blood glucose
- low blood glucose
High blood glucose:
ATP ↑ → K+ efflux ↓ → hyperpolarization↓ → Ca2+ influx ↑ → insulin release ↑
Low blood glucose:
ATP ↓ → K+ efflux ↑ → hyperpolarization↑ → Ca2+ influx ↓ → insulin release ↓
How is insulin degraded?
Insulinase (found in liver & kidney)
Insulin effect on glucose transporters
Insulin ↑ glucose transport into insulin-sensitive cells - GLUT4
GLUT4 mechanism
- Insulin binds to receptor
- Signal transduction cascade
- Exocytosis
- Glucose enters cell
Insulin effect on carbohydrate metabolism
Stimulation
- Glucose uptake by cells through GLUT4
- glycogenesis
Inhibit
- glycogenolysis
- gluconeogenesis
Insulin effect on fat metabolism
Stimulation
- transport of FA into adipose tissue
- conversion of excess glucose into FA
- synthesis of FA & TAG
Inhibit
- FA release from adipose tissue
- ketogenesis
Insulin effect on protein metabolism
Stimulation
- a.a. entry to cells
- protein synthesis (translation)
Inhibit
- protein catabolism & a.a. release from cells
- gluconeogenesis
What depends on insulin for glucose uptake?
GLUT4
- found in muscle & adipose
Type 1 DM
Deficiency of insulin
- destruction of β cells in islets of Langerhans by T-cells & autoantibodies
- insulin-dependent DM
Type 2 DM
Insulin resistance
- failure of insulin receptors to response
- body unable to use insulin
- non-insulin-dependent DM
Insulinoma
High secretion of insulin due to β cell tumor
- associated with type 2 DM
rT3 in nonthyroidal illness & hypothyroidism
Nonthyroidal illness: rT3 ↑
Hypothyroidism: rT3 ↓
