Pathophysiology 2 Exam 2

What do hormones regulate?

- Reproduction

- Growth/Development

- Fluid homeostasis

- Metabolism

- Responses to stress

What are the targets of cAMP

Protein kinase A: ADH, ACTH, TSH, FSH, LH, Epinephrine (beta receptors), Parathyroid hormone, Glucagon

Receptor specificity

Molecular "fit" of a hormone within a receptor binding pocket

What is the target tissue for oxytocin?

Mammary glands & uterine muscles

What is the target tissue for ADH?

Kidney tubules

Where is ADH produced?

In the supraoptic neurons of the hypothalamus

What triggers the release of ADH?

- Hyperosmolality, osmoreceptors in the hypothalamus detect altered osmolality

- Hypotension, baroreceptors (in carotid sinus & aortic arch) detect low BP & hypovolemia

What effects does ADH have on the body?

Water retention due to increased water reabsorption by renal collecting duct

True or false?

Steroid hormones travels in circulation bound to proteins: Corticosteroid-binding globulin (transcortin), albumin

True

What produce & secrete thyroid hormones?

Follicular cells of the thyroid glands

What is the endocrine system composed of?

Cells and organs that are specialized to synthesize and secrete hormones into the bloodstream to act at distant target cells

What are hormones?

Blood-borne chemical messengers that affect target cells anatomically distant from the secreting cell

What type of hormones are lipid soluble?

Thyroid & Steroid hormones

Which hormones do their action by attaching to surface protein kinase receptor?

Insulin, Prolactin, and Growth hormone receptors

What does the Gs receptor do?

Increases production of 2nd messenger, cAMP

Where are endocrine hormones made?

Rough endoplasmic reticulum and stored in vesicles w/ in cells

True or False?

Knowing the cyclical nature of hormone release is important when interpreting the hormone concentration and when providing hormone replacement therapy.

True

Negative feedback control

Maintains hormone activity w/in normal range or set point of normal activity

Receptor affinity

The inclination of the hormone to remain bound to receptor, How tight/ strong is the receptor-hormone bond

What are the hormones of the posterior pituitary?

Oxytocin & ADH

What is the primary target organ of GH?

Liver

Describe the normal actions on liver cells of Growth Hormone (anterior pituitary)?

- Liver metabolism

- Induces production of insulin-like growth factor-1

- Increases lean body mass, reduces fat mass

What is GH controlled by?

Hypothalamus: GHRH & GHIH (somatostatin)

Is prolactin an anterior or posterior pituitary hormone?

Anterior

What are the trophic effects that prolactin has on breast tissue?

Development of breast tissue & lactation

What inhibits prolactin secretion?

Dopamine produced by hypothalamus

What do drugs that block dopamine receptors cause?

- Gynecomastia (enlargement of male breast)

- Galactorrhea (milky discharge unrelated to normal milk production)

What stimulates GH secretion?

- Hypoglycemia

- Rise in amino acids

- Starvation

- Exercise

What are all steroid hormone synthesized by?

Cholesterol

What are steroid hormones essential for regulating?

Body's response to normal/abnormal lvls. of physiologic and psychologic stress

What inhibits the release of gonadotropins?

Negative feedback from sex steroids

ACTH stimulates the production of what?

- Cortisol

- Adrenal androgens

What are the significant diurnal pattern of ACTH and CRH

- Peak on wakening in the morning

- Valley in the evening

True or false?

Thyroid hormones remain attached to thyroglobulin until stimulated by TSH

True

TSH is secreted in response to?

TRH

What is TSH inhibited by?

Negative feedback regulation of TRH & TSH through concentration of circulating T3

What steroid hormone does the adrenal cortex (zona glomerulosa) secrete in response to stimulation by angiotensin II?

Mineralocorticoids (aldosterone)

What regulates aldosterone?

Angiotensin II

Renin-angiotensin system

1. Juxtaglomerular cells of kidney release renin

2. Angiotensinogen converts to angiotensin I

3. ACE turns angiotensin I to angiotensin II in the lungs

4. Angiotensin II causes adrenal cortex to release aldosterone

Aldosterone is released in response to what?

- Low BP

- Reduced renal perfusion

- High serum potassium level

What is the difference b/t primary and secondary endocrine disorders?

Primary usually is due to a problem w/ the endocrine gland itself but secondary is due to too much or too little levels of trophic hormones by anterior pituitary gland

Clinical manifestation of growth hormone deficiency

- Diminished lean body mass

- Hypercholesterolemia (High lvls. of cholesterol in blood increasing risk of heart attack/ stroke)

- Decreased bone density

Pituitary gigantism

- Growth hormone excess

- Occurs in childhood before the skeletal epiphyses are closed

Acromegaly

Growth hormone excess in adults

Where is thyroid hormones produced?

In follicular cells of thyroid

True or False?

Thyroid hormones and catecholamines both have a permissive effect on each other

True

What is found in >90% of patients w/ Hashimoto's thyroiditis?

Anti-thyroglobulin

Etiology of primary hypothyroidism

Thyroid failure

Etiology of secondary hypothyroidism

Pituitary failure, Decrease TSH

Clinical manifestation of thyroid storm

- Elevated temperatures

- Tachycardia

- Arrhythmias

- Congestive heart failures

- Agitation

- Psychosis

What are the precipitating event of thyroid storm?

Stress & gland manipulation

How can Hashimoto thyroiditis cause hyperthyroidism?

Due to damage to the thyroid gland, stored hormones release and cause hyperthyroidism and then progress to hypothyroidism.

Clinical manifestation of Congenital adrenal hyperplasia?

- Feminization in males

- Masculinization in females

What is congenital adrenal hyperplasia (adrenogenital Sx)?

Specific enzymatic defects in the biosynthesis of cortisol by the adrenals that causes severe & life-threatening symptoms in newborns

How does aldosterone facilitate salt and water retention?

By the kidney w/ resultant potassium secretion

Secondary hyperaldosteronism etiology?

Poor kidney perfusion that stimulates the renin angiotensin-aldosterone cascade leading to heart failure, reduced kidney perfusion and liver cirrhosis

Hyperaldosteronism clinical manifestation?

- Hypertension

- Hypervolemia

- Hypokalemia

Treatment for hyperaldosteronism?

- Spironolactone to increase sodium excretion & potassium retention

- Sodium restriction

- Potassium replacement

What is the most common cause of Cushing syndrome in the US?

Exogenous steroid use

Cushing disease etiology

Pituitary hyperstimulation of adrenal cortex causing excess secretion of cortisol

What is needed in order for calcium to be absorbed?

Vitamin D, if vit D deficient then calcium absorption is impaired

Function: Osteoclast? Osteoblast?

- Osteoclast break & make calcium

- Osteoblasts uses calcium to make bones

What produces calcitonin?

Thyroid parafollicular cells

Clinical manifestation of hypoparathyroidism

- Circumoral numbness

- Muscle cramps, spasms

- Paresthesia of distal extremities

- Prolonged Q-t intervals- Increased intracranial pressure

- Severe symptoms: carpopedal spasm, laryngospasm, & seizures

- Tetany: Chvostek & Trousseau sign

Management of parathyroid hormone deficiency:

- IV calcium & calcitriol (activated form of vit. D)

- Oral calcium supplement w/ vit. D (long term treatment)

How does high serum calcium levels affect neuromuscular excitability?

Decreases it

Hypercalcemic crisis is caused by?

Rarely because of hyperparathyroidism and more frequently due to malignant cells that release PTH-Like hormones.

Treatment for hypercalcemic crisis?

Rapid volume expansion w/ 0.9% NS and diuretics to increase Ca excretion (except thiazide)

What is diabetes insipidus?

Insufficient ADH activity causing excessive loss of water in urine

Central diabetes insipidus

Involves hypothalamus or pituitary gland

Nephrogenic diabetes insipidus

Involves kidneys, problem w/ receptor not the cells producing ADH

Clinical manifestation of diabetes insipidus

- Polyuria, polydipsia (hallmark)

- Nocturia

- Hypernatremia b/c of water deficit

- Dry mucous membrane

- Poor skin turgor

- Decreased saliva & sweat production

- Disorientation, lethargy, seizures

What test is done to differentiate from central diabetes insipidus from nephrogenic diabetes insipidus?

Water deprivation test w/ vasopressin

If a pt has nephrogenic diabetes insipidus what would the water deprivation test w/ vasopressin show?

Little or no response

Syndrome of inappropriate antidiuretic hormone (SIADH)

Excessive ADH stimulates renal tubules to reabsorb water despite decreased blood osmolality

Clinical manifestation of SIADH

- Hyponatremia

- High urine osmolality

- Low serum osmolality

- Postural BP changes

- Muscle cramp, weakness

- Seizures, coma, confusion

What does GLUT 4 do in the absence of insulin?

GLUT4 is stored in intracellular vesicle until insulin presents which will trigger the exocytosis of GLUT 4 & it translocate to membrane

Pancreas: beta cells (islet of langerhans) function

Produce proinsulin

Pancreas: alpha cells function

Produce glucagon

Pancreas: F/ gamma cells

produce pancreatic polypeptide

Pancreas: delta cells

Produce somatostatin

Diabetes mellitus (DM)

An endocrine disorder diagnose by the presence of chronic hyperglycemia

Classic signs of type 1 DM?

- Polyuria

- Polydipsia

- Polyphagia

Type 1 diabetes mellitus

Destruction of beta cells of the pancreas

- Absolute insulin deficiency

Diabetes mellitus is diagnosed if anyone of these conditions occurs:

- Random sampling of blood glucose ≥200 mg/dL with classic signs and symptoms (polyuria, polydipsia, polyphagia)

- Fasting blood glucose level of ≥126 mg/dL

- Blood glucose concentration ≥200 mg/dL 2 hours after a 75-g oral glucose load

- HgbA1C level ≥ 6.5% (glycated hemoglobin test)

What is Gestational DM?

Glucose intolerance w/ onset during pregnancy

OGTT one step

Perform a 75g OGTT:Diagnosis of GDM is made with any of the following plasma glucose values:

- Fasting: ≥ 92 mg/dL

- 1 hour: 180 m g/dL

- 2 hour: ≥ 153 mg/dL

OGTT two step

Step 1: Perform a 50g GLT (non-fasting) if the plasma glucose levels measured 1 hour after the load is 130/ 135/ or 140 mg/dL proceed to a 100g OGTT

Step 2: Done at least after 3 days, 100g OGTT, GDM confirmed if 2** of the following four plasma glucose levels:

- Fasting: ≥ 95 mg/dL

- 1 h: ≥180 mg/dL

- 2 h: ≥155 mg/dL

- 3 h: ≥140 mg/dL

Why does hypoglycemia occur in newborn if mom is hyperglycemic?

Mother is hyperglycemic but the insulin cannot pass through the placenta, only glucose can, therefore the baby was producing more insulin due to excess glucose causing hypoglycemia

What age should people start screening for for diabetes (T2)?

40 to 70 y/o who do not have diabetes and are overweight/ obese (BMI ≥ 25-30/ ≥30), if they have risk factors they should screen earlier

Diabetic ketoacidosis (type 1 DM)

Insulin deficiency causes lipolysis of body tissues leading to free fatty acids, which are then transformed into ketones causing ketoacidosis

Important signs of diabetic ketoacidosis

Deep, labored respiration that are fruity in odor (Kussmaul respiration)

Nonketotic hyperglycemic hyperosmolar coma (NHHS) are more common in?

Older adults, type 2 DM

What is the earliest sign of glomerular nephropathy?

Microalbuminuria

Goal for treating chronic hyperglycemia?

- Pre-prandial blood glucose level between 70 and 130 mg/dL

- Post-prandial blood glucose level less than 180 mg/dL

What is the first line drug (treatment) for T2 DM?

Metformin, to sensitize the insulin receptors to get HbA1C

During what time period of pregnancy does insulin needs increase sharply?

24th to 28th weeks of gestation

Treatment for acute hypocalcemic crisis?

IV calcium & calcitriol (activated form of vit. D)

Which is a major glucose transporter at the blood-brain barrier (Erythrocytes)?

Glut 1

Pre-diabetes

- Impaired glucose tolerance (2 hour post glucose value of 140-200 mg/dL)

- Impaired fasting glucose tolerance (fasting plasma glucose value of 100-125 mg/dL

- HgbA1C level 5.7% - 6.4%