PATHO EXCAM 3: endocrine

General characteristics 

• Hormones excreted from ____ + deactivated by _____

• Specific rate and rhythm of secretion depends on time of the day, cycles, stress patterns, etc…

• Hormones are receptor-specific 

Endocrine glands and their hormones 

• ____: master gland that releases either STOP or GO signals towards anterior pituitary 

• ____: prolactin, GH, TSH, ACTH, FSH, LSH

• ____: Oxytocin, ADH

• Thyroid gland: what hormones released?

• Parathyroid glands: what hormones released?

• Pancreas: what hormones released?

• Adrenal medulla: what hormones released?

• Adrenal cortex: what hormones released?

• kidneys

• liver or other cells

• hypothalamus

• anterior pituitaty

• posterior pituitary

• TH, calcitonin

• PTH, calcitrol

• insulin, glucagon

• epinephrine, norepinephrone, aldosterone

• mineralcorticoids, glucocorticoids

Regulation of hormone 

• Hormones are regulated by:

1. Chemical factors (ex: insulin released from pancreas) 

2. Endocrine factors (ex: cortisol released from adrenal cortex causes hyperglycemia, which compensatorily stimulates insulin release from pancreas)

3. Neural factors (ex: nervous system directly stimulates pancreas to release insulun in resonse to stress-induced hyperglycemia from cortisol)

• Positive feedback loop

  • example?

• Negative feedback loop: inhibtory response when smth is too high

  • example?

• oxytocin which triggers uterine contractions during childbirth

• thyroid hormone cascade from hypothalamus > anterior pituitary > thyroid gland

Hormone receptors 

• Target cells: either plasma membrane OR intracellular hormone receptors

  • Will recognize + bind with hormone → initiate signal to intracellular effectors

• ____: low hormone concentration increases receptor numbers/affinity 

  • to allow a wanted response!

• ____: high hormone concentration decreases receptor numbers/affinity 

  • to prevent excessive response!

• hormone upregulation

• hormonw downregulation

Lipid VS Water soluble hormones

Lipid soluble 

• what hormones does this include?

• are these bound to carrier?

• diffuse across membrane?

• Rapid or slow onset?

• Short or long duration?

Water soluble 

• what hormones does this include?

• are these bound to carrier?

• diffuse across membrane?

  • describe the 1st and 2nd messengers

• Rapid or slow onset?

• Short or long duration?

• steroid hormones (thyroid hormones, estrogen, androgen, glucocorticoids, mineralcorticoids)

• yes bound to carrier when circulating

• small size + slips easily through membrane

• rapid onset

• long duration

• proteins and catecholamines (epinephrine, norepinephrine)

• not bound to carrier when circulating

• cant diffuse accross membrane freely

• 1st messenger is the hormone itself. 2nd messenger (activated by 1st messenger’s binding) is the intracellular molecule that carries the 1st messenger into the cell. examples of 2nd messenger are cAMP and cGMP.

• slow onset

• short duration

____: Hypersecretion of ADH → results in hella retained water 

***think: soaked inside***

Caused by

• 3 main things?

• also medications (ex:_____)

Clinical manifestations

• ?

Treatment 

• Fluid restriction

• what type of saline? 

• AVOID raising the Na level by _____ within 24 hrs —> or else deadly _____ (damage to pons of brainstem caused by rapid Na correction too fast = brain shrivels = seizure = death  )

• syndrome of inappropriate ADH

• small cell lung cancer, viral pneumonia or meningitis, severe brain trauma/injury

• carbamazepine

• all SX related to hyponatremia (slow HR, high BP, confusion, altered mental, fatigue, cramps)

• hypertonic saline

• 8-10 points

• pontine demylelination

 ____: ADH insufficiency → losing too much water when peeing

***think: DI = dry inside***

2 types

• ____: insufficiency ADH secretion from posterior pituitary  

• ____: adrenal gland poorly responds to ADH

Caused by

• ?

Manifestations

• ?

Treatment

• meds like ______

• Manage electrolytes

• Treat underlying disorder (ex: stop taking the causative-drug)

• diabetes insipidus

• neurogenic

• nephrogenic

• head problems (surgery, tumor, meningitis) OR meds like Phenytoin’

• polyuria, nocturia, polydipsia + low BP, high HR

• Desmopressin

THYROID DISORDERS

• describe the pathophysiology of thyroid disorders that will eventually lead to hypothyroidism?

• describe the pathophysiology of thyroid disorders that will eventually lead to hyperthyroidism?

• environment or gene > autoimmunity > Tcell cellular autoimmunity > thyroid gland DESTROYED > hashimotos disease > hypothyroidism

• environment or gene > autoimmunity > Bcell humoral autoimmunity > thyroid gland STIMULATED > graves disease > hyperthyroidism

Hyperthyroidism (Thyrotoxicosis)

• results in excess TH levels

Caused by

1. Primary hyperthyroidism:

• main cause?

• other causes?

2. Secondary hyperthyroidism

• caused by?

Manifestions

• 2 key manifestations of Graves disease?

• Fine straight hair 

• Goiter

• Heat intolerance 

• Weight loss

• Diarrhea 

• Sweating 

• Tachycardia, palpitations

• graves disease (igE mediated autoimmunity aka type 2 hypersensitivity —> igE mimics TSH —> body continues secreting TH)

• toxic mulitnodular goiter or adenoma

• excess synthroid or adenoma

• exphtalamos (also vision issues, eye irritation) + swelling of anterior tibial portion of legs (caused by excess hylauronic acid accumulation in SQ tissue)

Nodular disease-induced hyperthyroidism

• Thyroid gland naturally enlarged during puberty, pregnancy, iodine deficient-states + immune, viral, or genetic disorders

• Toxic multinodular goiter (toxic adenoma): several hyperfunctioning nodules 

Treatment

• Radioactive iodine 

• Anti-thyroid drugs

• Removal (which risks parathyroid gland damage → hypocalcemia)
  

Thyrotoxic crisis

• Aka thyrotoxic storm 

• Rare, dangerous worsening of thyrotoxic state from dramatic TH level rise → DEATH within ___ hours

Caused by 

• ?

Manifestations

*** worsened hyperthyroidism vibes***

• Hyperthermia, tachycardia, heart failure, altered mental ( agitation, delirium), GI distress

Treatment

• Anti-thyroid drugs

• Iodine 

• BB

• Glucocorticoids

• 48

• undiagnosed or partially treated Graves disease patient who is subjected to physiologic stress (infection, injury, surgery, etc…)

Hypothyroidism

Types

1. Primary:

• main cause?

2. Secondary

• caused by?

Manifestations

• Cold intolerance 

• Myxedema of face

• Hair loss + brittle hair, nails

• Dry scaly skin

• Blank facial expression + periorbital edema 

• Decreased mental acuity 

• weight gain

• Bradycardia

• Constipation

• loss thyroid tissue either from Hashimotos or ablation

• anterior pituitary dysfunction (high TRH, low TSH, low TH) OR hypothalamus dysfunction (low TRH, low TSH, low TH)

_____: Autoimmue disease causing gradual inflammatory destruction of thyroid tissue 

• Most common cause of hypothyroidism!

Manifestations

• hallmark manifestation?

• Decreased LOC

• hypothermia without shivering

• hypoventilation

• lactic acidosis

• hypotension

• hypoglycemia

Treatment

• medication?

• Ventilation support 

• Circulatory support

• hashimotos

• myxedema: life threatening; due to altered skin composition

  • SX: nonpitting edema at eyes, hands, feet, supraclavicular area + thick mucous lining mouth/throat = slurred speech and hoarse voice

• synthroid (T4 specifically)

Thyroid carcinoma 

• Most common cause of endocrine cancer

• Mainly which type of thyroid carcinoma is most common?

Caused by

• ?

Manifestations

• ?

Treatment

• Removal

• Suppressio therapy (via meds)

• Radiation and chemotherapy 

• follicular and papillary thyroid carcinomas

• ionizing radiation

• manifestations

  • Small thyroid nodule

  • OR tumor in lungs, brain, or bone

  • OR voice/swallowing changes with difficulty breathing due to tumor growth impinging on trachea or esophagus

Endocrine pancreas 

• Primary stimulus for insulin secretion is high glucose levels in blood___ hours after meals

• Insulin is an anabolic hormone that promotes glucose uptake via ____ (glucose transporters) into liver + muscle + adipose tissue → synthesizes carbs/proteins/lipids/nucleic acids

• which organ is the body’s main glycogen reservoir 

• Facilitates K, Mg, and Phosphate to move into cells

• 2 hrs

• GLUT

• liver

Diabetes mellitus

Diagnosis 

• Hba1C ___

• Random glucose ___

• Fasting glucose _____

Caused by

• Genetic, autoimmune, or idiopathic

• above 6.5%

• above 200

• above 126

Type 1 DM

Pathophysiology  

• ?

Manifestations

Acute 

• Classic hyperglycemia SX: polydipsia, polyuria, polyphagia

• Weight loss (bc we cant build fat)

• Fatigue 

• Recurrent infxns and delayed wound healing 

• Genital yeast infection

• Visual changes

• Neuropathy 

• Chest pain (due to atherosclerotic plaque buildup)

Complications 

• Dehydration

• Life threatening complication is?

  • whats the blood sugar range of this complication?

  • pathophysiology?

• Genetic or environment factors > antigens form on beta cells then circulates in bloodstream > acitvation of cellular immunity AND humoral immunity against beta cells > destroyed/apoptosis of beta cells > NO insulin can be made

• Diabetic ketoacidosis w/ Kussmaul breathing + fruity breath

• 200-350

• insulin deficiency > breakdown fat for energy = forms beta hydroxybutyric + acetoaceticacids > ketotic state (ketones in urine + diabetic ketoacidosis) > Kussmaul breathing as compensatory mechanism

Type 2 Diabetes mellitus: conditon where person STARTS with ____ → LATER loss of _____

Caused by

• ?

• Risk factors: genetics, age, lifestyle (obesity, hypertension, poor diet, physical inactivity)

Pathophysiology 

• ?

Manifestations

• Classic hyperglycemia trifecta: polydipsia, polyuria, polyphagia

• Abdominal obesity

• Hypertension

• Lipid profile?

Acute complications of type 2 DM

• ____: basically thick syrupy blood + hyperglycemia —> develops into COMA!!!

  • Blood glucose range is ____

Chronic complications of type 2 DM

• infection → potential amputation

• ____: when hyperglycemia causes thickened basement membrane + endothelial hyperplasia —> poor perfusion 

  • Results in?

***think: micro-vascular = where in the body you have tiny vessels***

• ____: when hyperglycemia causes fibrous plaque proliferates in sub-endothelial layer of arterial wall 

  • Results in?

***think: big picture/systemic issue***

Treatment

• Based on disease progression 

  • Lifestyle modifications first > Metformin next > GLP1 and -agliflozins last

• insulin resistance

• beta cells

• insulin resistance from beta cell dysfunction

• Genetics or environment > hormone changes, obesity, decreased insulin sensitivity, inflammation > insulin resistance > metabolic toxicity, high free fatty acids, inflammation, oxidative stress > destroyed Beta cells > low insulin secretion, decreased amylin, decreased incretin, increased glucagon, > hyperglycemia

• high triglycerides + low HDL

• hyperosmotic hyperglycemic non-ketotic syndrome

• 600+

• microvascular disease

• retinopathy (eye issues), nephropathy (kidney), neuropathy (sensory issues) —> potential limb amputation

• macrovascular disease

• CV disease, peripheral vascular disease, stroke —> potential limb amputation

Metabolic syndrome and type 2 DM 

• having Metabolic syndrome → NOT ONLY puts u higher risk of developing type 2 diabetes but also _____

• 3 of 5 criteria to be diagnosed metabolic syndrome

  • Waist circumference ____

  • Triglycerides ____

  • HDL ____

  • Systolic BP ____ or Diastolic BP _____

  • Fasting glucose ____

Role of GI hormones in DM

• ____ is reduced in both DM types

• External GLP1 agonists drugs control glucose levels via ____

Role of Kidneys in DM

• Proximal tubule absorption of glucose via ____ is an important controller of blood glucose level 

• Drugs that block SGLT2 (-Agliflozin drugs) prevent ____ → causing you to ____→ reduced preload + lowered glucose level 

  • Adverse SE of this drug: yeast infections, UTI, euoglycemic diabetic ketoacidosis (EDKA)

  • pathophysiology of EDKA?

• sudden cardic death (just imagine dropping dead bruh)

• >40 for men, > 35 for women

• >150

• <40 for men, <50 for women

• 130 systolic

• 85 diastolic

• >100

• GLP1

• promoting glucose-dependent insulin secretion

• SGLT2

• diabetic heart failure

• pee sugar water

• if u pee sugar water → less glucose available in blood → less insulin secreted → breakdown fat → diabetic ketoacidosis → kussmaul breathing 

Cushings syndrome 

• High cortisol > increased vascular sensitivity catecholamines > Hypertension

Manifestations

• counts as as Metabolic Syndrome too

• Moon face, buffalo hump

• Increased Infection risk (from immunosuppression)

• Skinny/arms legs but abdominal weight gain

• Stretch marks

• blood sugar?

• Na status?

• K status?

  • thus metabolic alkalosis or acidosis?

• hyperglycemia + sugar pee

• hypernatremia

• hypokalemia

• metabolic alkalosis

Adrenal insufficiency

Primary adrenal insufficiency: due to issue with ____

Secondary adrenal insufficiency: due to issue with ____ OR can be from abrupt withdrawal of steroids

• so basically HIGH steroid use → cortisol does DOWN (low CRH, low ACTH)

• interupts the negative feedback loop w/hypothalamus

• adrenal gland

• pituitary gland

Primary adrenal insufficiency 

• aka _________

  • president JFK had this disease!

Pathophysiology 

• ?

Types

1. Congenital

• Usually caused by ______

2. Acquired 

• From infection (TB, HIV, fungal infecton), hemorrhagic infarction, cancer, or Drugs

Manfestations 

• Hyperpigementation (bronze skin) ← due to high ACTH levels

• Changes in body hair distribution

• GI distress

• Weight loss

• Orthostatic hypotension

• Glucose status?

• Na status?

• K status?

• addisons disease

• High CRH (from hypothalamus) > high ACTH (from anterior pituitary)> uh oh something attacked adrenal cortex > low corticosteroid + low aldosterone 

• hypoglycemia

• hyponatremia

• hyperkalemia

Secondary adrenal insufficiency 

***Professor wants u to focus on primary adrenal insufficiency ****

Pathophysiology 

• ?

Manifestations

• Similar to Addisons disease EXCEPT for what 3 things that are different?
  

• High CRH (from hypothalamus) > Uh oh smth attacked my anterior pituitary > Low ACTH > Low cortisol (from adrenal cortex) 

• NO bronze skin (bc we got low ACTH here) + adrenal gland is unaffected so normal K + normal Na

Hyperaldosteronism 

Types

1. Primary (Conn syndrome): due to ____

2. Secondary: due to excess stimulation (too much ACTH, angiotensin 2, hyperkalemia) causing excess alosterone secretion  

Manifestations

• ?

• Na status?

• K status

  • metabolic _____

Treatment 

• Aldosterone antagonist medication (ex: ____)

• adrenal cortex tumor

• hypertension, hypervolemia

• hypernatremia

• hypokalemia

• metabolic acidosis

• spironolactone

Tumors of adrenal medulla

• tumors cause excessive secretion of ____

Manifestations

• ?

• glucose status?

• catecholamines (glucocorticoids, mineralcorticoids)

• hypertension —> hypertensive crisis + chest pain, high HR, palpitations, tachycardia + hyperglycemia + high metabolism + sweating + vision issues

• hyperglycemia

White adipose tissue

• Primary type of fat in body; mainly functions to store energy

Peripheral adiposity VS Visceral adiposity 

Peripheral = healthy

• Hyperplasia + high energy storage capacity

• low inflammatory cytokines

• low insulin resistance

• involves high estrogen (high estrogen enhances healthy peripheral fat + inhibits visceral fat)

 Visceral (abdominal) = unhealthy 

• Hypertrophic + low energy storage capacity

• increased inflammatory cytokines

• increased insulin resistance

• Increased chance of developing into cancer  

• involves low estrogen (ex: post-menopausal women)

___: chronic low grade inflammation

• Develops when caloric intake > caloric expenditure

• Obesity is a major cause of death bc can develop into → CV disease, Type 2 DM, or Cancer

Pathophysiology 

• ?

• obesity

• Adipocytes > accumulated white adipose tissue alters adipokine signals which tell CNS we are still hungry/not full/alters energy balance > macrophage infiltrates the adipocytes = releases more inflammatory cytokines, adipokines, more inflammation > chronic inflammation > insulin resistance, hyperglycemia, hypertension, diabetes

Starvation

Short term starvation

• Therapeutic use for fast weight loss

• Body will PROTECT protein

  • via using carb source first via Glycogenolysis (breaksup glycogen stored in liver = energy yay) → then use stored fat via Gluconeogenesis (breaksup fat to into ketones = energy yay)

Long term starvation

• Begins after several days of starvation 

• Therapeutic use for morbidity obese people

• But is Pathological when in poverty, disease, anorexia nervosa

• Can result in DEATH from proteolysis (loss protein stores = bad asf)

• _____: protein malnutrition 

  • Results in loss muscle mass + loss body fat 

• ____: protein malnutrition BUT maintains carbohydrate intake 

  • Results in loss muscle mass BUT retained body fat + abdominal edema

• ____: physical wasting; weight loss + muscle atrophy 

  • Due to inflammation and increased catabolic response 

  • Seen in patients with cancer, AIDs, tuberculosis, and other major chronic progressive inflammatory diseases

• _____: life-threatening condition thay occurs in malnourished individuals when you try to re-feed too fast with food WITHOUT first replenishing their B9 (thiamine)

  • need to re-introduce feeding slowly 

• marusmus

• kwashikor

• cachexia

• re-feeding syndrome