Robbins - Chp 9 & 10 Flashcards
Vitamin A Functions
Vision - used in synthesis of rhodopsin
Cell proliferation -> activation of retinoic acid receptors (RARs) by their ligands (squamous metaplasia of epithelium if deficient)
Lipid Metabolism - fatty acid oxidation (RXR activated by 9-cis-retinoic acid)
Immunity - gut epithelium, stimulates immune system
Vitamin A deficiency
Celiac, Chrohn’s Caused by bariatric surgery Xeropthalmia Night blindness Dry, scaly skin Corneal degeneration Immunosuppression
Vitamin A Excess
Acute toxicity - nausea, vomiting, vertigo, blurred vision
Chronic toxicity - alopecia, dry skin, hepatic toxicity and enlargement, arthalgias, and pseudotumor cerebri
Teratogenic (cleft palate, cardiac abnormalities)
Vitamin D functions
Increases Ca absorption with TRPV6
Interaction with PTH (enhance RANKL on osteoblasts -> binds RANK on osteoclasts and activates them -> breakdown bone for resorption)
Vitamin D deficiency
Rickets
- frontal bossing, square head, rachitic rosary, pigeon breast deformity, lumbar lordosis, leg bowing
Osteomalacia
- persistent osteoid bone is weak and vulnerable to fractures of vertebral body and femoral neck
Vitamin C function
(Ascorbic acid)
- antioxidant - facilitate iron absorption by reducing it to the Fe2+ state
- necessary for hydroxylation of proline and lysis in collagen synthesis
- necessary for dopamine beta-hydroxylase, which converters dopamine to NE
Vitamin C deficiency
Scurvy - swollen gums, bruising, petechiae, hemarthrosis, anemia, poor wound healing, corkscrew hair
Vitamin C excess
Nausea, vomiting, diarrhea, fatigue
Can increase iron toxicity in predisposed individuals by increasing dietary iron absorption
Zinc deficiency
- rash around eyes, mouth, nose, and anus called acrodermatitis enteropathica
- anorexia and diarrhea
- growth retardation in children
- depressed mental function
- depressed wound healing and immune response
- impaired night vision
- infertility
Iron deficiency
Hypochromic microcytic anemia
B12 deficiency (cobalamin)
Megaloblastic pernicious anemia and degeneration of posterolateral spinal cord tracts
B3 Deficiency (niacin)
Pellagra - the three Ds: dementia, dermatitis, diarrhea
B1 Deficiency (thiamine)
Dry and wet beriberi, Wernicke syndrome, Korsakoff syndrome
Folate deficiency (B9)
Megaloblastic anemia, neural tube defects
BMI categories
18-25 -> good
25-30 -> overweight
>30 -> obese
POMC and CART
- increase MSH and MC3/4R -> increased TSH and CRH -> increased energy expenditure (increase BMR)
NPY and AgRP
Increase Y1/5R -> increase MCH and orexin -> increases appetite (orexigenic)
Leptin
Made by fat cells
Stimulates POMC/CART, inhibits NPY/AgRP
Stimulates energy expenditure
Can be a proinflammatory cytokine
Adiponectin
Produced by adipocytes
Binds to AdipoR1:muscle and AdipoE2:liver
Ghrelin
Only hormone that increases food intake
Stimulates NPY/AgRP
PYY
Secreted by ileum
Depresses appetite
Low in Prader Willi
Stimulates POMC/CART
Hydrops fetalis
Edema of fetus during intrauterine growth
- immune or nonimmune
Immune hydrops fetalis
- type II hypersensitivity
- blood group incompatibility (Rh)
- consequences:
— hemolytic anemia -> hypoxic injury to heart and liver -> decrease proteins and heart failure -> edema
— jaundice -> kernicterus
— erythroblastosis fetalis
— extramedullary hematopoiesis in the liver
— hepatosplenomegaly
Nonimmune hydrops fetalis
- CV defects
- Chromosomal abnormalities
- fetal anemia
— alpha-thalassemia (most common cause of non immune)
Clinical features: pallor, hepatosplenomegaly, jaundice, neuro injury, edema, extramedullary hematopoiesis in the liver
PKU
- autosomal recessive
- due to decreased phenylalanine hydroxylase of decreased BH4 (malignant PKU)
- Symptoms: intellectual disability, growth retardation, seizures, fair complexion, eczema, musty body odor
- Treatment: decrease phenylalanine and increase tyrosine
- malignant treatment: supplement BH4
Maternal PKU
Due to improper dietary therapy during pregnancy
Symptoms in infant: intellectual disability, growth retardation, congenital heart defects
Galactosemia
- galactokinase Deficiency or classic galactosemia
- galactokinase deficiency
— autosomal recessive; milder
— symptoms: galactosemia, galactosuria, infantile cataracts - classic galactosemia
— absence of galactose-1-phosphate uridyltransferase
— autosomal recessive
— symptoms develop when infant begins feedings
— symptoms: failure to thrive, jaundice, hepatomegaly, infantile cataracts, intellectual disability, predisposed to E. Coli sepsis
Cystic Fibrosis
- bicarb cannot be excreted -> acidic fluids -> increased mucin/plugging of ducts/increased bacteria -> pancreatic insufficiency
- Meconium ileus
- class II most common
- heterozygote is at risk for pancreatic issues, pulmonary disease, obstructive azoospermia
Wilms tumor is associated with what syndromes?
WAGR, Denys-Drash, Beckwith-Wiedemann
WAGR syndrome
Wilms tumor, Aniridia (absence of iris), Genitourinary malformations, mental retardation/intellectual disability (WT1 deletion)
- autosomal dominant PAX6
Denys-Drash syndrome
Wilms tumor, diffuse mesangial sclerosis (early onset nephrotic syndrome), dysgenesis of glands (male pseudohermaphroditism), WT1 mutation
- At risk for: gonadoblastoma
Beckwith-Wiedemann Syndrome
Wilms tumor, macroglossia, organomegaly, omphalocele, large cells, genomic imprinting, hemipheryplasia (WT2 mutation)
- IGF2 - solely expressed on paternal allel when maternal is silenced, uniparental disomy = overexpression of IGF2 (growth factor)
- at risk for: hepatoblastoma, pacreatoblastoma, adrenocortical tumors, rhabdomyosarcomas
Morphologic features of Wilms tumor
Sheets of small blue round cells
Anaplastic cells: large hyperchromatic pleomorphic nuclei
Large circumscribed mass
Tumor is soft, tan to gray color with cysts and hemorrhage
Class triphasic combo: blastemal cells, stromal cells, epithelial cell types observed
- clinical course: abdominal mass, hematuria, pain in abdomen, intestinal obstruction, HTN, increased risk of developing second primary tumors
