Part 23 Flashcards

(145 cards)

1
Q

Irritable Bowel Syndrome definition

A

Chronic condition of the digestive system with abdominal pain and changes in bowel habits (constipation/diarrhea), sees functional disturbance in intestinal motility and visceral perception strongly influenced by emotional factors either 1 of 4 subtypes

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2
Q

Diagnostic criteria Rome IV for Irritable bowel syndrome

A

Recurrent abdominal pain occurring at elast 1 day a week for 3 months associated with relatioship to defacation, change in stool frequency, and associated change in stool form/appearance

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3
Q

Irritable bowel syndrome prevalence

A
  • most commonly diagnosed GI condition
  • up to 50% of all GI referrals
  • onset in late 20’s, rarely over 40
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4
Q

Irritable bowel syndrome signs and symptoms (4)

A
  • abdominal pain usually lower quadrant, RELIEVED by defacation
  • bloating/distention
  • mucus in stools
  • constipation or diarrhea
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5
Q

4 IBS subtypes

A
Predominant constipation (most common)
Predominant diarrhea
Mixed bowel habits
Unclassified
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6
Q

Red flags that something is NOT simple as IBS (6)

A
  • onset after age 50
  • weight loss
  • recent travel preceding
  • blood in stool
  • nocturnal pain
  • unexplained vomiting
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7
Q

Low FODMAP diet

A

Diet used to help alleviate IBS symptoms by limiting diets in fermentable oligo/di/monosaccharides that can cause colon bloating and pain

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8
Q

Constipation definition

A

Less than 3 stools per week, but more specifically any alteration in consistency, motility, or caliber in the process of rectal evacuation

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9
Q

3 types of chronic constipation

A
  • Extracolonic (low fiber, inadequate water, anorexia, atonia, medication)
  • mechanical (narrowing due to tumor, hemorrhoids, colitis, stricture)
  • functional (slow transit or normal transit)
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10
Q

First 2 choice medications to treat constipation

A
  • mirilax (polyethylene glycol)
  • fiber
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11
Q

Best source of fiber

A

Bran (about 40% fiber raw)

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12
Q

Indications for laxative use (4)

A
  • reduce painful elminiation associated with episiotomy, hemorrhoids and other anorectal lesions
  • patients with CV disease to prevent straining
  • compensate for loss of tone in abdominal and perineal muscle in geriatric patients
  • empty bowel prior to procedure or those on narcotics
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13
Q

Rapid acting laxatives definition and examples (2)

A

Act within 2-6 hours but impart watery consistency to stool, useful for diagnostic procedures or surgery

  • saline laxatives
  • polyethylene glycol
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14
Q

Bulk forming agents mech of action

A

Effects identical to dietary fiber, form stool 1-3 days after treatment initiated, swell in water and form gel softening fecal mass and increasing bulk

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15
Q

Bulk forming agents ADR’s (1)

A

-administration with full glass of water to prevent esophageal obstruction

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16
Q

Bulk forming agents examples (3)

A
  • psyllium
  • methylcellulose
  • polycarbophil
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17
Q

Surfactants mech of action

A

Produce soft stool after several days of treatment, alter consistency by lowering surface tension facilitating passage of water into feces

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18
Q

Surfactant examples (1)

A

-docusate sodium/potassium/calcium

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19
Q

Stimulant (irritant) laxatives mech of action

A

ACt on intestinal wall to produce net increase in amount of fluid and electrolytes within the intestinal lumen, promote accumulation by increasing secretion of water and ions into intestine and reducing water and electrolytes absorption, most act on colon within 6-12 hours

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20
Q

Bisacodyl (dulcolax) drug class and function

A

Stimulant laxative, indicated for intermittent use to treat constipation or as bowel prep

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21
Q

Senokot (x lax) drug class, mech of action, and ADR (1)

A

Anthraquinone derivative, thought to stimulate aurbach’s plexus, changes urine color

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22
Q

Osmotic laxatives mech of action

A

Poorly absorbed salts draw water into intestinal lumen increasing fecal mass stretching intestinal wall stimulating peristalsis

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23
Q

Osmotic laxatives function, ADRs (3)

A

low dose produce semisoft stool in 6-12 hours, high dose in 2-6 hours for bowel prep

-Dehydration, renal dysfunction, heart failure

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24
Q

Polyethylene glycol (miralax) function and ADR’s (3)

A

Osmotic laxative relatively safe for occasional constipation,

  • N/V
  • bloating
  • flatulence
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25
Mineral oil drug class and function
Lubricant laxative given orally or rectally posesses greater potential adverse effects than docusate and thus routine use should be discouraged
26
Laculose and sorbitol function
Saccharides used orally or rectally as having an osmotic effect allowing fluid to retain in colon, resulting in soft stool in 1-3 days, reserved as second line for patients who do not respond to bulk forming laxatives, can enhance intestinal excretion of ammonia (useful for portal hypertension)
27
dicyclomine drug class and function, ADR's (3)
anti-spasmodic used to treat irritable bowel syndrome, dry mouth, urinary retention, blurry vision
28
TNF inhibitors 3 examples and funcion
-infliximab (remicade) -adalimumab(humira) certolizumab (cimizia) Treatment for moderate to severe ulcerative colitis and crohns and RA
29
Most common esophageal cancer globally vs in the US
Globally is squamous cell, adenocarcinoma in the US
30
Clinical presentation of esophageal cancer (2)
- dysphagia often progressive - unintentional weight loss
31
Esophageal cancer treatment options (3) and prognosis
- endoscopic mucosal resection (stage T1a) - esophagectomy with lymphadenectomy (stage T1b) - most of time palliative chemo, stents, brachytherapy, etc. 5 year survival rate only about 50% even without metastasis
32
Eosinophilic esophagitis and presentation
Chronic inflammation due to allergic process resulting in increased eosinophils in esophageal tissue, presents with reflux symptoms, solid food dysphagia, and impactation of food bolus, symptoms do NOT improve with acid suppression****
33
Eosinophilic esophagitis diagnosis (3)
- EGD with esophageal biopsy with pathology report showing >15 eosinophils per hpf not otherwise explained - eosinophilia persists after trial of PPI - characteristic tears on endoscopy
34
Eosinophilic esophagitis treatment options (3)
- first line inhaled corticosteroid (complication is candida, fluconazole might help) - allergy testing - esophageal dilation
35
Esophageal webs
-tissue membrane protruding into lumen most common in cervical esophagus, can be associated with iron deficiency anemia - plumme vinson syndrome
36
Triad of plummer vinson syndrome
Anemia Cervical esophageal webs dysphagia
37
Esohpageal rings
Concentric ring protruding into lumen that is typically in the distal esophagus and asymptmatic mostly but sometimes causees intermittent dysphagia for solids esp when the tube become <13 mm in diameter*******
38
Zenker diverticulum and gold standard diagnosis (1) and treatment (1)
- Herniation of esophageal mucosa, rare typically in elderly populations who regurgitate undigested food stuffs - barium swallow - surgical technique if necessary
39
Up to __% of scleroderma patients with have esophageal involvement, resulting in...
90%, resulting in atrophy, sclerosis, absent peristalsis
40
Achalasia
Inadequate peristalsis in the lower esophagus due to a tight lower esophageal sphincter that leads to progressive dysphagia for solids and liquids***
41
Achalasia diagnostic studies (2)
- bird beak sign on barium esophogram - EGD
42
Achalasia treatment options (3)
- surgical myotomy - pneumatic dilation of LES (risky and loses efficacy over time) - botox injections
43
Odynophagia definition
Painful swallowing, often medication induced esophagitis, pill becomes lodged and causes mucosal injury, can also be infectious
44
Alarm symptoms with GERD that indicate need for EGD to check for barrett's esophagus (3)
- GI bleed - new onset dyspepsia >60 - unexplained weight loss
45
GERD treatment options (step up therapy)
Step up from bottom - Lifestyle mods - PRN H2 blockers - H2 blocker daily - PPI gradual increase -antacids and sucrlfate should be used prn for mild symptoms and pregnancy but not otherwise
46
Barrett's esophagus
REplacement of stratified squamous epithelium in distal esophagus with metaplastic columnar epithelium, increases risk for esophageal cancer more than 30 fold, with short segment being more prevalent but long segment causing more severe reflux and risk for cancer
47
Barrett's esophagus treatment options (3)
- indefinite PPI therapy - ongoing surveillance - radiofrequency ablation
48
Caustic esophageal injury common ingestions (4), what 2 things do you always do and what 2 do you NOT do?
- battery liquid - drain cleaner - hair relaxers - bleaches Preserve the airway and get a chest x ray, Do not induce vomiting this will cause more injury, do not do endoscopy if more than 24 hours to prevent perforation
49
Alkaline vs acidic caustic esophageal injury
Liequefactive necrosis with severe injury rapidly vs coagulation necrosis more limiting
50
Obesity hypoventilation syndrome (OHS) Pickwickian syndrome
A BMI greater than 30 that has limited chest mobility resulting in chronic alveolar hypoventilation worsening CO2 levels and right sided heart failure
51
Grehlin
Hormone released by stomach to promote hunger
52
Leptin
Hormone released from adipose signal to send to the brain to promote satiety
53
Bariatric surgery
Effects weight loss thru reducing stomachs reservoir capacity (restriction), shortening length of intestine (malabsorption), or a combo of both of these (roux en y gastric bipass)
54
Recall the ligament of trietz represents the transition from...
...duodenum to jejunum
55
EGD prep (2)
- NPO after midnight - no anticoagulation (preferred if have to biopsy will bleed) - local anesthetic spray or sedation (normally sedation is preferred due to how uncomfortable it is)
56
Z line
Visible transition point on EGD at the lower esophagus that divides the esophageal tissue above and gastric tissue below, should be clean transition
57
How far from the incisors from the Z line?
35-40cm
58
Schatzki ring
An inflamed ridge where the Z line should be in the lower esophagus
59
Barrett's esophagus classic description
"salmon colored fingerlike projections into the esophagus past the z line)
60
Vast majority of stomach is supplied by what vessel?
The celiac trunk
61
Where is the most common part of the duodenum for ulcer disease to occur?
Right after the pyloric sphincter, the duodenal bulb
62
Anterior ulcers of the duodenum vs posterior
Anterior perforate into the peritoneum of the open abdomen, posterior erode the pancreas behind it
63
Hyperplastic polyp of the colon
Inflammatory polyp of the colon that is very normal and will not become neoplastic and does not need to be removed on colonoscopy
64
Sessile polyp
Flat polyp with a wide base
65
Tubular vs tubulovillous vs villous adenoma
3 types of adenoma that are at increased risk of being cancerous (<5% to 20% to 40%, respectively)
66
Diarrhea
Passage of frequent (3 or more a day) small volume loose stools
67
Acute vs chronic diarrhea
Acute is a day up to 2 weeks, usually due to infection and self limiting or drugs, chronic is at least 4 weeks and is more often associated with irritable bowel syndrome, inflammatory bowel disease, intolerances, certain medications
68
Osmotic diarrhea
Occurs when too many solutes retained in the intestines which inhibits water absorption, often due to sugar malabosrption (lactose, fructose, etc) however electrolyte absorption is NOT impaired, often resolves upon cessation of ingestion of irritating substance
69
Secretory diarrhea
Diarrhea that occurs when excretion of water in intestine exceeds absorption, frequently involves electrolyte loss, usually does not resolve if fasting, infections are the #1 cause
70
Fatty diarrhea
Often steatorrhea, caused by malabsorption (damage or loss of absorptive ability either due to surgery, giardia, mesenteric ischemia, or maldigestion, etc.
71
#1 cause of parasitic diarrhea in US and how to you test for it? How do you treat it?
-Giardia, stool ova and parasite, metronidazole
72
Cryptosporidiosis infection, diagnosis, and treatment
Can survive chlorine disinfectants and be a cause of chronic diarrhea in HIV/immunocompromised, diagnosed via stool culture, treated with nitazoxanide
73
2 most common viral causes of gastroenteritis
- norwalk virus rotavirus
74
Staphylococcus food poisoning characteristics
- often ingesting foods contaminated with toxin - lasts 24 hours - lacks fever - cannot be passed to others - self limiting - n/v/d
75
Clostridium perfringens infection characteristics
- foods kept warm before serving (catering) - fever absent - lasts 24 hours
76
E coli 0157 enterohemorrhagic (shiga toxin producing) infection characteristics
- usually raw foods or contaminated water - can spread person to person - mild to severe diarrhea - may cause hemolytic uremic syndrome (anemia, uremia, thrombocytopenia) - do NOT use antibiotics
77
Salmonella typhi infection characteristics
- severe form of salmonella - life threatening, progressive fever, abdominal pain, rose spots - stool culture/blood culture - treatment needed with cipro or ceftriaxone otherwise severe complications - can be asymptomatic carriers
78
Shigella infection characteristics
- spread thru any contact with stool that has shigella germs - greatest risk children under 5 in daycare centers - highly infectious - usually self limiting
79
Camplyobacter jejuni infection characteristics
- common bacterial cause of diarrhea in the US from undercooked meats, dairy, freshwater - very high fever - sea gull wing rods on gram stain - reactive arthritis or guillan barre syndrome
80
Vibrio cholera infection characteristics
- normally uncomplicated - rice stool, can get from shellfish - need to keep hydrated
81
Toxic megacolon and treatment options (2)
Rare but severe complication of colonic inflammation, characterised by distension of total or segment of colon and associated with systemic toxicity, treated with antibiotics or surgery
82
Patient presents with acute onset of watery, nonbloody, volumous diarrhea accompnaied by nausea and vomiting, does not have a fever. What organism?
-enterotoxigenic E coli
83
Patient has had chronic diarrhea. Stool cultures grow out cryptosporidium. What is important to do next?
-test patient for HIV
84
Crohn's disease description***
-Inflammation and ulceration (eventually fistula) somewhere along any point of the GI tract (but most often the terminal ileum and right colon) that involves the full thickness of the bowel in a patchy, non-continuous distribution (skip lesions), although the rectum is relativey spared. Chronic recurring condition marked by remissions and exacerbations
85
Crohn's disease etiology (3)****
- strong genetic component - autoimmune response to evironmental factors/bacteria - cigarette smoking increases susceptability in genetically susceptible
86
Crohns disease typical presentation (6)
- female - urban (processed food) - teenage to young adulthood - RLQ pain - mass effect in the lower abdomen (firmness in intestine) - high fever
87
Bloody diarrhea should make you think of this type of IBD ____ and ___ as backup
ulcerative colitis, crohns
88
Crohn's disease often results in...
....fistulas (colo-bladder, colo-vaginal, etc.)
89
Pyoderma gangrenosum
Cutaneous ulcerations caused by fistula tracts indicative of internal disease of the body
90
Tests to help differentiate between crohn's and ulcerative colitis other than colonoscopy
-p-ANCA neg + ASCA = crohn's p-ANCA positive 40-80% of the time = UC
91
Ulcerative colitis description
Chronic, recurrent condition marked by exacerbations and remissions where inflammation is localized primarily to the mucosa of the colon only and the rectum and is uniform and continuous with bloody diarrhea and tenesmus often as presenting symptoms
92
Ulcerative colitis typical presentation (4)
- any age - more common in industrialized urban areas (processed food) - worsening bloody diarrhea - bowel shortening on colonsocopy as well as continuous erythema only affecting the mucosa
93
For quick immediate relief of IBD, use these drugs (2)
- prednisone/steroids (IV or PO) budenoside | -
94
Untreated IBD increases risk for...
....colon cancer
95
Endocrine system definition
Intercellular communication network where hormones travel cell to cell thru the blood stream and regulate complex phenomena including stress, growth, electrolyte and fluid balance, and reproduction
96
Exocrine vs endocrine glands
Exocrine glands have ducts that carry secretions to the body surface or other organ cavity, endocrine are ductless and release hormone into tissue fluids with dense capillary networks (the bloodstream)
97
Autocrine signaling
Released by a cell to have local effects on the same cell type in which the chemical is released without being transported in the bloodstream
98
Paracrine signaling
Released by cells that affect other cell types locally without being transported in the bloodstream
99
Example of steroids, peptides and glycoproteins, and monoamines
- Sex hormones (derived from cholesterol) - ADH/vasopressin - Catecholamines (all tyrosine derived)
100
What 2 types of hormone must bind to transport proteins for transport because they are hydrophobic?
Steroid and thyroid hormones (half life increased when bound and protected from degrading enzymes and kidney filtration)
101
Monoamines and peptides are hydrophilic so they mix easily with...
....blood plasma in circulation without plasma carrier proteins
102
Nervous system and endocrine systems relationship and an example of this relationship
Interactions between allows for coordinated communication function to regulate several body systems Ex) autonomic parasympathetic stimulation of the pancreas enhances insulin release
103
Elevated blood K+ stimulates the adrenal cortex to release ___ which causes ___ to promote excretion of K+ (and the retention of Na+)
Aldosterone, kidneys
104
What gland releases melatonin?
Pineal gland
105
What structure provides neural control of circadian rhythm?
Suprachiasmatic nucleus of the hypothalamus
106
Suprachiasmatic nucleus of hypothalamus and mechanism of action
- Cluster of nerve cell bodies in the hypothalamus above optic chiasm that acts as the master biological clock serving as a pacemaker for body's circadian rhythm - self induced firing establishes many inherent daily rhythms using clock protein release and accumulation until "critical mass" reached when transported back into nuclei blocking more production genetically resulting in levels gradually declining as degraded, removing inhibitory effects on the machinery. Then genes that are no longer blocked begin producing more proteins resetting the cycle
107
Melatonin function
The "hormone of darkness", released 10x more during darkness than in light from the pineal gland to help body system become entrained to light dark cues and therefore regulate sleep-wake cycle
108
Pituitary gland/hypophysis location, lobes
- Housed in sella turcica of the sphenoid bone - - Anterior lobe (adenohypophysis) and posterior lobe (neurohypophysis)
109
ADH/vasopressin mech of action
- Hypothalamus detects increased osmolarity of blood thru osmoreceptors (indicating dehydration) or thru peripheral baroreceptors decreased firing (indicating lower blood pressure volume) - ADH released fro post. pituitary in response - H2O permeability of late distal tubule and collecting duct increased - constriction of vascular smooth muscle occurs - Fluid reabsorption by the kidneys and increased BP occurs
110
Oxytocin uterine contraction pos. feedback mech of action
- Labor begins,cervix of uterus is stretched - signal sent to hypothalamus causing posterior pituitary to release oxytocin - causes strong contraction of uterine smooth muscle - more signals sent to hypothalamus because of uterine stretching, repeating the cycle
111
Suckling reflex mech of action
- suckling or other physiological stimuli (crying, etc) sends afferent fiber impulses to spinal cord and up to brain - hypothalamus triggered by dopamine levels dropping and releases oxytocin from posterior pituitary, anterior pituitary triggered to release prolactin (to produce more milk) - oxytocin stimulates contraction of smooth muscle around mammary ducts causing milk let down in response
112
Growth hormone is also known as...
...somatotropin
113
FSH impact in females vs males
- Stimulates development of eggs and follicles | - stimulates testes and production of sperm
114
LH impact on females vs males
- Stimulates ovulation and corpus luteum to secrete progesterone and estrogen - stimulates interstitial cells of testes to secrete testosterone
115
Growth hormone and IGF-1 functions (3)
- Protein synthesis - enhance amino acid transport into cells - stimulate lipid metabolism
116
Growth hormone release mech of action
- Exercise/stress/fasting/sleep stimulate hypothalamus to increase GHRH secretion and decrease somatostatin secretion - This causes increased GH release from anterior pituitary - Plasma GH acts on the liver and other cells to increase IGF-1 secretion - these act on the muscles and other organs - these negatively inhibit further release of GHRH and GH in the hypothalamus and the anterior pituitary
117
Acromegaly definition
Condition due to GH secreting pituitary adenoma that can lead to headache, visual distrubances, hyperglycemia, and increased lean body mass with thickening of bones and soft tissues
118
Treatment for acromegaly (2)
- Hypophysectomy - - irradiation of tumor
119
Prolactin function and 3 things an excess of it can result in
- Released from anterior pituitary and has trophic effects on the breast, inhibits GnRH and suppresses release of LH and FSH (inhibits ovulation and spermatogenesis) - when in excess can result in amenorrhea, infertility, or galactorrhea
120
What inhibits release of prolactin, what enhances it?
- Dopamine - - TSH
121
Bromocriptine
suppresses activity of prolactin
122
ACTH release and function
Secretion from the anterior pituitary, increased by corticotropin releasing hormone (CRH) from the hypothalamus, stimulates release of cortisol from the adrenal cortex
123
What stimulates release of FSH and LH?
GnRH release from hypothalamus
124
Primary vs secondary endocrine disorders
Primary are due to dysfunction of target gland vs secondary are due to dysfunction of the pituitary gland or hypothalamus
125
Primary vs secondary hyperthyroidism hormone levels
Primary sees increased T3/T4 with low TSH, while 2ndary sees increased T3/T4 with high TSH
126
Cushings syndrome vs disease
-Syndrome is a problem with suppressed ACTH and elevated cortisol while disease is a problem at the level of the pituitary producing excess ACTH AND elevated cortisol (think primary vs secondary definitions of endocrine disorders)
127
3 common etiologies of hyperfunction endocrine disorders
- autoimmune stimulation - secreting tumors - idiopathic
128
5 common etiologies of hypofunction endocrine disorders
- autoimmune inhibition - nonsecreting tumors - surgical removal - ischemia and infarct - receptor defects
129
Thymus
Organ present at large size at birth in mediastinum superior to the heart that devolves after puberty and is responsible for hormone secretion that regulate development and later activation of T lymphocytes
130
Thyroid gland definition and what does it produce and where (2)
-Largest endocrine organ with high rate of blood flow, has 2 lobes connected by an isthmus with follicular cells -T3 and T4 production in follicular cells (enhances bodies metabolic rate and O2 consumption, heat production, and increase heart rate and respiratory rate) and calcitonin in parafollicular cells (reduce ca2+ in blood)
131
T3 vs T4
Most released from thyroid is T4, the only usable form in the body is T3 so it is converted in the body to its active form T3
132
Synthesis of T3 and T4 mech of action
- synthesis of thyroglobulin and exocytosis into follicle - active uptake of I- by follicle cells to colloid, activity increased by TSH - oxidation of I- to I2 - I attaches to tyrosines on thyroglobulin - T3 and T4 formed - Endocytosis of colloid - Enzymatic removal of T3/4 from thyroglobulin by hydrolysis of peptide bond - Enters blood stream and binds to thyroid binding globulin (TBG)
133
Excess iodine levels in bloodstream actually cause ___, caused by the ____ effect
decreased T3/T4 synthesis, the wolff-chaikoff effect
134
Cretinism definition
Infantile low TH causing abnormal bone development, thickened facial features, low temp, lethargy, and brain damage
135
Myxedema definition
Adult onset hypothyroidism causing sluggishness, sleepiness, weight gain, constipation, increased cold sensitivity and tissue swelling. IF severe and untreated can result in myxedema coma
136
Endemic goiter cause
Due to dietary iodine deficiency resulting in low T3/4 and high TSH and an enlarged thyroid gland full of thyroglobulin not being used
137
Toxic goiter (graves disease) and 2 signs of it
- Development of autoantibodies against TSH receptors on the thyroid - elevated T3/4 and exopthalmos
138
Hypoparathyroidism treatment and 1 severe complication of it
- Surgical excision during thyroid surgery - - can result in fatal tetany in 3-4 days post op
139
Pancreas hormonal vs digestive function by mass
98% dedicated to exocrine digestion
140
a cells vs B cells vs Delta cells of the pancreas
- a cells release glucagon (low carb or fasting) - B cells release insulin (high carb to promote uptake into cells and stimulate glycogen synthesis) - Delta cells release somatostatin (secreted with rise in blood glucose and amino acids after meal to act paracrine modulating secretions of a and B cells)
141
Hormones that raise blood glucose (5)
- glucagon - epi/norepi - cortisol - Growth hormone - Thyroid hormone
142
Insulin receptor definition and action upon binding insulin
Found on the target tissues for insulin, upon insulin binding causes tyrosine kinase to autophosphorylate the B subunits which then phosphorylate intracellular proteins to activate glucose transporters (GLUT4), glucose, K+, phosphate, and magnesium enter the cell
143
Somatostatin (delta cells)
Produced by delta cells of the pancreas, essential in carb, fat, and protein metabolism and homeostasis of ingested nutrients, different from hypothalamic somatostatin which inhibits growth hormone release at the anterior pituitary
144
Mineralcorticoids (aldosterone) is secreted from what part of adrenal cortex? What about glucocorticoids (cortisol)? What about androgens?
- Zona glomerulosa - zona fasciulata - zona reticularis
145
Cortisol release mech of action
- Stress or non stress neural inputs cause increased CRH release from hypothalamus - hypophyseal portal system takes that and releases ACTH from the anterior pituitary - This stimulates release of cortisol from the adrenal cortex - this acts at target cells for cortisol and has a negative impact on both CRH and ACTH release