Endocrine/Metabolism/GI Flashcards
Vitamin A Overdose
-acute- N/V, vertigo, blurred vision
chronic- alopecia, dry skin, hyperlipidemia, hepatotoxicity, hepatosplenomegaly, visual difficulties, papilledema/cerebral edema
teratogenic- microcephaly, cardiac anomalies, fetal death
Vitamin B1 Deficiency
- thiamine
- infantile and adult beriberi (dry with peripheral neuropathy or wet with cardiac sx)
- Wernicke-Korsakoff syndrome in alcoholics
Vitamin B12 Deficiency
- cobalamin
- pernicious anemia
- presentation: older, mentally slow women of northern Euro descent who is lemon colored (anemic and icteric), and has a smooth/shiny tongue indicative of glossitis w/ shuffling, broad based gait
Vitamin B3 Deficiency
- Niacin
- 3 Ds of pellagra: dementia, dermatitis, diarrhea
Vitamin C Overdose
- false negative stool guaiac results
- diarrhea, abdominal bloating
Vitamin E Overdose
-higher mortality rate due to hemorrhagic stroke in adults and higher rates of necrotizing enterocolitis in infants
Vitamin B2 Deficiency
- riboflavin
- cheilosis (cracks at corners of mouth), stomatitis, glossitis, dermatitis, corneal vascularization, and ariboflavinosis
Cholecystekinin
- stimulates digestion of fat and protein
- secreted by I cells in duodenum
- causes secretion of digestive enzymes from pancreas and gall bladder contraction
Gastrin
- released by G cells
- stimulates HCl secretion by promoting histamine release
Somatostatin
- hormone that inhibits gastrin release
- secreted by delta cells
- raises pH in duodenum
Indirect Indicators (Labs) of Chronic EtOH Consumption
- macrocytosis (vitamin/folate deficiency)
- AST:ALT ratio >2
GLUT4
- transmembrane glucose transport protein
- responsive to insulin
- expressed in skeletal muscle cells and adipocytes
- provides facilitated diffusion of glucose across membrane
- steroselective for D-glucose
GLUT2
- present in hepatocytes (liver), pancreatic B cells, renal tubules, small intestine
- provides facilitated diffusion of D-glucose across membrane
GLUT3
-present in placenta and neuronal cells
Amylase
- secreted by parotid gland
- hydrolyzes starch into sugars
- elevated in acute bacterial parotits (caused by Staph a.)
Chymotrypsin
- secreted by pancreas
- inactive precursor is chymotrypsinogen
- activated by trypsin
Phospholipase A2
- can damage cell membranes
- secreted by pancreas as inactive precursor prophospholipase A2
- activated by trypsin
Elastase
- secreted by pancreas
- inactive precursor is proelastase
- activated by trypsin
Trypsin
- activates chymotrypsin, phopholipase A2, carboxypeptidase, and elastase
- inactive form is trypsinogen
- inappropriate activation is a central path to necrotizing pancreatitis
- converted to trypsin by enteropeptidase (enterokinase)
Lipase
-converts triglycerides to fatty acids and glycerol
Wilsons Disease
- AR WD gene mutation in copper transporting ATP-ase
- kayser fleischer ring on eye
- basal ganglia atrophy
- disorder of copper metabolism causing liver disease
- dx: dec. serum ceruloplasmin and inc. tissue copper levels
- tx: D penicillamine or trientine, transplant is curative
C Peptide
Released with endogenous release of insulin. Will not be present of insulin supply is exogenous.
Elevated alk phos… What now?
Test for gamma glutamyl transpeptidase. If high, this indicates hepatic issue, but if low, this indicates bone issue.
Secretin
Secreted by duodenal S cells and inc. bicarbonate secretion from the pancreas.
Small intestine bacterial overgrowth is associated with increased:
Vitamin K and folate (because these are made by gut bacteria)
Budd Chiari Syndrome
Thrombotic occlusion of hepatic veins, leading to portal HTN, ascites, and hepatosplenomegaly.
Ceruloplasmin and Copper Elimination
- major copper carrying protein in the blood
* copper eventually ends up in bile and is excreted in poop
VIPoma
- pancreatic islet cell tumors that secrete VIP
- inc. VIP inc. intestinal Cl loss
- VIP also inhibits gastric acid secretion
- somatostatin inhibits secretion of VIP and is used to tx VIPoma
- watery diarrhea, hypokalemia, achlorydria
Pompeii Disease
Deficiency of a-1-4 glucosidase (acid Maltese)
Cardiomegaly, macroglossia, and muscular hypotonia with hepatomegaly.
MEN1
- primary hyperparathyroidism (hypercalcemia)
- pituitary tumors (prolactin, visual defects)
- pancreatic tumors (gastrinomas)
- associated with zollinger ellison due to gastrin
- protein is menin
- also called Werner syndrome
MEN2a
- medullary thyroid cancer (calcitonin) with amyloid
- pheochromocytoma
- parathyroid
- also called sipple syndome
- RET genes
MEN2b
- medullary thyroid cancer (calcitonin) w/ amyloid
- pheochromocytoma
- mucosal neuromas/marfinoid habitus/neurofibroma
- RET gene
Niemann-Pick
- sphingomyelinase deficiency causes accumulation of lipid sphingomyelin
- hepatospelenopmegaly
- neurologic regression
- cherry red macular spot in infancy
Tay-Sachs
- deficiency in B-hexosaminidase A
- leads to GM2 accumulation in neurons
- neurologic regression
- cherry red spot on macula
- NO hepatosplenomegaly
Gauchers
- glucocerebrocidase accumulation
- B-glucocerebrocidase deficiency
- hepatosplenomegaly, pancytopenia, skeletal problems
- tissue paper macrophages
Fabry Disease
- a-galactocidase A deficiency
- globotriaosylceramide (ceramide trihexoside) accumulation
- neuropathic pain and dermatologic pathology in childhood
Krabbe Disease
- galactocerebrocidase deficiency
- accumulation of galactocerebroside and psychosine
- infants have developmental delay and/or regression, hyptotonia, optic atrophy, and seizsures
Zollinger Ellison
- gastrin secreting tumor of the pancreas
- causes GI mucosal ulceration
- high acid
- big folds
Menetrier Disease
- hyperplasia of surface mucous cells in stomach
- parietal cells dec (dec. acid)
- enlarged rugal folds
- dec. acid production, inc. risk gastric cancer
HLA associated with Celiac?
HLA-DQ 2 or 8
Whipple Disease
- infectious dz involving any organ
- caucasian males who work on farms
- tropheryma whipplei
- lamina propria of gut is filled with macrophages stuffed with PAS positive, gram +, rod shaped bacilli
- malabsorption, weight loss, diarrhea
- tx with antibiotics
Whipple Disease
Tropheryma whipplei.
Small bowel filled with macrophages stuffed with PAS positive, gram positive, rods.
Pts present with malabsorption, weight loss, and diarrhea.
Tx with antibiotics.
Caucasian males thirty to fifty.
NOD2
-genetic association for crohns
HLA-B27
- genetic association with ulcerative colitis
- (also ankylosing spondylitis)
Gardner Syndrome
- AD
- familial adenomatous polyposis
- multiple osteomas
- epidermal inclusion cysts
Turcot Syndrome
- brain tumor (glioma)
- familial adenomatous polyposis
- AR
- APC mutation
Hereditary Nonpolyposis Colorectal Carcinoma
- no polyps
- lynch syndome
- CEO: colon cancer, endometrial cancer, ovarian cancer
Peutz Jagher
- AD
- lips with black pigment
- hamartomatous polyps
- inc risk cancer
- serine threonine kinase gene mutation
Gastrointestinal Stromal Tumor (GIST)
- sarcoma of GI tract
- KIT mutation
- tx: resection, and tyrosine kinase inhibitor (-tinib)
Gilbert
- unconjugated bili inc.
- yellow when stressed
- UGT coding region deficiency (UDP glucuronosyltransferase)
- benign and present after periods of stress
- tx: is phenopbarbitol
Crigler-Najjar
- unconjugated bili
- UGT promotor region deficiency
- type 1-deadly, need liver transplant
- type 2: phenobarbitol is used to tx
Dubin Johnson
- conjugated bili inc.
- black liver
- AR
- transporter that transports bili also transports catecholamines and those make liver black
Rotor Syndrome
- conjugated bili
- AR
- no liver pigmentation
Primary Sclerosing Cholangitis
- men 20-40
- associated with ulcerative colitis
- associated with cholangiocarcinoma
- concentric, onion skin fibrosis around bile ducts
- beaded bile duct appearance
Primary Biliary Cirrhosis
- women age 40-50, pruritic, fatigue, pale stools
- granulomas
- xanthomas
- inc. AMA
- associated with other autoimmune dz
- lymphocyte infiltration and granulomatous destruction of interlobular bile ducts
Hemochromatosis
- inc. level of iron
- primary: ch. 6, AR, HFE gene, inc. small intestine absorption of iron
- secondary: following transfusion
- hyperpigmented skin
- secondary DM
- Prussian blue stain and genetic test
- total iron binding capacity dec. (want to dec. Fe)
- men>women
- tx: phlebotomy
What causes exophthalmus and pretibial myxedema?
-glycosaminoglycans (myxoid tissue) attract water and cause eye movement forward
Hurthle cells?
- present in Hashimoto and other diseases
- epithelial cell change
Orphan Annie Eye Cells are diagnostic for?`
- cell with big empty nuclei
- papillary carcinoma
- may also see psammoma bodies
Medullary Carcinoma of Thyroid
- arises from parafollicular C cells
- secretes calcitonin
- associated with MEN2a and 2b
- RET mutation common (codes transmembrane tyrosine kinase)
- amyloid stroma
Stones, bones, and psychic groans mean?
-hyperparathyroidism
Effect of primary hyperparathyroidism on Ca and P?
-Ca is inc, P is dec.
Effect of secondary hyperparathyroidism on Ca and P?
-Ca and P are inc.
Effect of hypoparathyroidism on Ca and P?
-dec. Ca and inc. P
How to tx prolactinoma?
- DA agonist like bromocryptine
- resect
How to tx GH tumor?
- octreotide somatostatin analog
- or resect via transphenoidal
Conn Syndrome
-adrenocortical neoplasm (adenoma)
Waterhouse Friderichsen
- acute adrenal insufficiency due to hemorrhagic infarction of adrenal glands)
- associated with sepsis (N. meningiditis)
- DIC
- tx: antibiotics and steroid replacement
Addisons
- chronic adrenocortical insufficiency
- destruction of adrenal cortex
- dec. in cortisol, aldo, and androgens
- weakness, skin hyperpigmentation, hypotension, poor response to stress, loss of libido
Best test for pheo?
-free metanephrines
How to tx for pheo prior to surgery?
- start with alpha blocker to prevent unopposed HTN (phenoxybenzamine)
- then beta blocker
What HLAs are associated with DM type 1?
-HLA DR3, DR4, and DQ
What type of immune rxn is type 1 DM?
-type 4 T cell rxn against pancreatic B cells
What is RANK-L?
-RANK-L is a RANK ligand on osteoblasts that have been activated by PTH, which binds on osteoclasts and activates them also
Markers of bone breakdown?
-hydroxyproline and alk phos
Watershed areas of colon?
-splenic flexure and rectosigmoid colon
Linear, shallow ulceration of lower esophagus with enlarged cells and intranuclear inclusions?
-CMV esophagitis
Lactase Deficiency
- undigested lactose results in osmotic diarrhea
- may be primary or acquired (more common)
- bowel mucosa are normal
Ulcerative Colitis
- rectum is always involved
- inflammation is limited to mucosa and submucosa only
- mucosal damage is continuous
Crohn’s Disease
- transmural inflammation
- perianal fistula due to transmural inflammation
- non-caseating granulomas
- skip lesions
Newborn GI Issues with CF
- ileal meconium obstruction
- inspissated meconium consistency (thick)
- negative squirt sign (explosive diarrhea after digital rectal exam)
Newborn GI Issues with Downs
- hirschsprung disease
- rectosigmoid obsrtuction
- meconium consistency normal
- squirt sign is positive (explosive diarrhea after digital exam)
Pituitary Apoplexy
- caused by acute intrapituitary hemorrhage
- most common with preexisting adenoma
- sever HA, bitemporal hemianopsia, panhypopituitarism
Porcelain Gall Bladder
Inc. risk of gall stones and sign of chronic cholecystitis and adenocarcinoma of the gall bladder.
Crohns Dz is associated with what type of kidney stone?
Oxalate stones: fat is not absorbed in gut, and Ca binds to fat and is excreted in waste. Ca should bind to Oxalate and get absorbed. Unbound Oxalate is absorbed and leads to kidney stones.
What is the definition of erosive in regard to gastric erosions?
- do not fully extend through the muscularis mucosa
- (through the muscularis would be an ulcer)
Papillary Carcinoma
- orphan annie eye cells (ground glass appearance)
- large, overlapping nuclei
- intranuclear inclusions and grooves
- psammoma bodies
How does leptin affect GnRH?
Dec. leptin (starvation) inhibits pulsatile release of GnRH, dec. FSH/LH, and dec. estrogen.
What vitamins/nutrients are absorbed in the duodenum/proximal jejunum?
- iron
- B12
- folate
- fat soluble vitamins (ADEK)
- Ca
- may be dec. after gastrojejunostomy
What causes large rugal folds?
- gastrin hypersecretion
- often due to Zollinger Ellison
Intrinsic Factor
- produced by parietal cells of stomach
- necessary for absorption of vit B12 (cobalamin) where it is absorbed in distal half of ileum
Peripheral T4
- binds thyroid bind globulin in circulation
- T4 is steroid (lipid soluble) so binds nuclear receptor
Best diet for weight loss?
-low calorie
Abetalipoproteinemia
- AR
- dec. apo B48 and B100
- not able to make lipoproteins
- leads to vitamin def (A, D, E, K)
- diarrhea, acanthocytosis (spiny RBCs), ataxia, degeneration of retina
- low cholesterol
Hepatic Encephaolopathy
- precipitated by GI bleeding
- inc. nitrogen delivery to the gut is coverted to ammonia and absorbed
- ammonia enters liver and is detoxified to urea if the liver is functional
- if liver is damaged ammonia accumulates, causing inc. inhibitory neurotransmission and impaired ecitatory neurotransmitter release
- tx: lactulose
- lactulose helps trap excess ammonia so it is pooped out
Thyrotoxic Myopathy
- neuromuscular disorder due to overproduction of thyroxine
- associated w/ hyperparathyroidism
Phosphorylation of what residues of insulin receptors leads to insulin resistance?
-phosphorylation of serine and threonine residues by TNFa, catecholamines, glucocorticoids, and glucagon leads to temporary insulin resistance
D-xylose Test
- monosaccharide which can be absorbed directly at brush border without pancreatic enzyme involvement
- can differentiate between pancreatic vs. mucosal causes of malabsorption
Enteropeptidase
-converts trypsinogen to trypsin
Pepsin
- activated from pepsinogen to pepsin by acidic pH and preexisting pepsin
- initiates the digestive process of proteins that is completed by trypsin and other enzymes in small intestine
Hashimoto Thyroiditis
- lymphocytic thyroiditis
- women (45-65)
- mononuclear infiltrate with germinal centers
- follicles surrounded by Hurthle cells
What do pancreatic alpha cells secrete?
-glucagon
VIP
- increases water and electrolyte secretion
- increases relaxation of intestinal smooth muscle and sphincters
- VIP is inc. by vagal stimulation
What enzyme does cortisol activate in the catacholamine synthesis pathway?
-activates phenylethanolamine-N-methyltransferase that converts norepi to epi
