Path- Nutritional Pathology

Question 1

What are the 4 ways to assess protein-energy malnutrition?

Answer 1

1. Body weight for a given height
   marasmus
2. Midarm circumference
   - measures somatic protein compartment –>marasmus
3. Serum proteins [albumin, transferrin]
   - measures visceral protein compartment–> kwashiorkor

Question 2

What is the difference between primary and secondary energy malnutrition?

Answer 2

Primary- they do not have access to nutrition

1. Marasmus
2. Kwashiorkor

Secondary- supply of nutrients is adequate but:

1. malabsorption
2. impaired use/storage
3. excess losses [cancer, AIDS]
4. increased need [huntingtons]

Question 3

What is marasmus a deficiency in?
What protein compartment is most affected?
What compartments of the body are maintained?
What will the patient look like?
What other problems are associated with the poor nutrition?

Answer 3

Deficiency in total calories.
Somatic protein compartment [skeletal muscle] and subcutaneous fat are lost.
Albumin/serum proteins are maintained.

The child will be emaciated [

Question 4

What is kwashiorkor a deficiency in?
What protein compartment is most affected?
What compartments of the body are maintained?
What will the patient look like?
What other problems are associated with this?

Answer 4

Deficiency in protein.
Visceral compartment [serum, liver proteins] are most affected.
Somatic [skeletal] and subcutaneous fat are maintained.

The patient will have low serum albumin and transferrin, so they will have a protruberant belly due to hepatosplenomegaly and ascites. Weight loss is masked by fluid retention.

They will experience:

1. immune deficiencies
2. skin lesions -flaky paint, flag sign

Question 5

Sometimes children with kwashiorkor are still so skinny that it is tough to see edema. Where should you look to see if they are edematous?

Answer 5

1. back of hands/feet

2. around the eyes

Question 6

What are 4 major causes of secondary protein-energy malnutrition?

Answer 6

1. cachexia
2. cancer, AIDS
3. cytokines [IL1/6, TNF, IFNg]
4. chronic GI disease, elderly, severe trauma, sepsis

Question 7

What are the 3 main assessments of obesity?

Which one corresponds to central/visceral obesity and is associated with higher risk of obesity-associated diseases?

Answer 7

1. BMI- weight in kg/height in sq meters
2. Skin fold thickness
3. Waist:Hip Circumference ratio ** higher the ratio, the more central/visceral obesity and more complications

Question 8

What percent of adults in the US are overweight?

Obese?

Answer 8

50% are overweight and an additional 30% are obese

Question 9

What are the major health complications associated with obesity?

Answer 9

1. DM
2. HTN
3. atherosclerotic coronary artery disease
4. DVT
5. metabolic syndrome [insulin resistance, hypertriglyceridemia, low HDL, HTN, CAD]
6. stroke
7. NAFLD
8. hypoventilation/OSA
9. osteoarthrosis
10. cancer
11. dementia

Question 10

How is the energy balance maintained in the body?

Answer 10

1. Afferent arm [adipose, GI, pancreatic signals]
2. Central sensor [hypothalamus]
3. Effector arm [feeding behavior, energy expenditure]
4. communication via neuropeptides/hormones

Question 11

Describe the orexigenic arm of energy balance.
What is the effect of grehlin on this pathway?
What is the effect of leptin?

Answer 11

Orexigenic neurons –> neuropeptide Y–> melanin-concentrating hormone–> increased food intake, decreased energy expenditure.

Grehlin activates the orexigenic pathway [tells you to eat]
Leptin inhibits the orexigenic pathway [tells you to stop eating]

Question 12

Describe the anorexigenic arm of energy balance.

What is the effect of grehlin? leptin?

Answer 12

Anorexigenic neurons–> MSH, cocaine, amphetamines–>thyrotropin releasing hormone, corticotropin releasing hormone–> decreased food intake, increased energy expenditure.

Grehlin decreases anorexigenic pathway
Leptin stimulates anorexigenic pathway

Question 13

What mutation is associated with 4-5% of MASSIVELY obeses patients?

Answer 13

Melanocortin 4 receptor [target of anorexigenic neurons]

Question 14

What are the fat soluble vitamins?
What do they need to be absorbed?
Are they stored in the body?
Are they more likely to cause pathology from excess or deficiency?

Answer 14

ADEK
They need bile to be absorbed
They are stored in the body
They can cause toxicity in excess [because they are stored so well, they rarely cause deficiency]

Question 15

What are the water soluble vitamins?
Are they stored in the body?
Are they more likely to cause pathology from excess or deficiency?

Answer 15

C and B complexes
They are not stored in the body, except for B12 [cobalamin]
Deficiencies develop faster because they are not stored in the body

Question 16

What is the storage/transport form of vitamin A?

Answer 16

Retinol

Question 17

What are sources of vitamin A?

Answer 17

1. Liver
2. green leafy vegetables
3. dairy
4. dark orange/yellow fruits

Question 18

What are the 4 functions of vitamin A?

Answer 18

1. Beta-carotene [pro-vitA] = photo-protective, antioxidant
2. retinal = visual pigments [rhodospsin, photopsin]
3. Retinoic acid = cell growth and differentiation
4. immunity to infections

Question 19

What are the 5 manifestations of vitamin A deficiency?

Answer 19

1. night blindness [earliest manifestation]
2. Xerophthalmia [dryness from inability to produce tears]
3. Squamous metaplasia of respiratory/urothelial mucousa
4. follicular dermatosis
5. immune deficiency

Question 20

Acute toxicity with which vitamin presents like pseudotumor cerebri with headache, irritability, vomiting, stupor and papilledema?

Answer 20

vitamin A

Question 21

Chronic toxicity with which vitamin presents with nausea, vomiting, weight loss, lip dryness, peeling skin, osteoporosis and bone pain, and hepatomegaly with fibrosis?

Answer 21

Vitamin A

Question 22

What is the most severe side effect of isoretinoin/vitamin A toxicity?

Answer 22

Teratogen:

1. cleft palate, small/missing ears
2. cardio defects
3. renal defect
4. limb defects
5. thymic agenesis
6. embryonic lethality

Question 23

What are the 2 forms of vitamin D?
Where does each come from?
Which is the major source of vit D in humans?

Answer 23

D2 - ergocalciferol form plant sterols, fish, grains

D3 - cholecalciferol made in skin from 7-dehydrocholesterol on exposure to UVB [animal sterol] *major source in humans

Question 24

How is ergocalciferol and cholecalciferol processed in the body?

Answer 24

1. 25-hydroxylation in the liver –>25-hydroxyvitaminD

2. 1-hydroxylation in kidneys–>1,25 dihydroxyvitamin D

Question 25

What are the 4 major sources of vitamin D for humans?

Answer 25

1. sunlight [UVB] 2. fortified foods [milk,grain] 3. fatty fish/fish oil 4. plants, grains

Question 26

What are the 3 major functions of vitamin D?

Answer 26

1. intestinal absorption of calcium and phosphorus 2. mobilization of calcium from bone 3. parathyroid hormone dependent distal renal tubular reabsorption of Ca

Question 27

What is the effect of vit. D deficiency in children? | Adults?

Answer 27

Deficiency causes excess unmineralized osteoid. So you make extra bone, it just doesn't harden Children --> rickets 1. frontal bossing 2. genu valgus, varus 3. rachitic rosary 4. Harrison's groove [thoracic cage is wierd] 5. kyphoscoliosis 6. greenstick fractures 7. widened wrists, ankles Adults--> osteomalacia 1. deranged bone remodeling 2. gross fractures, microfractures

Question 28

A patient presents with anorexia, nausea, and vomiting. He has polyuria, polydipsia. He is weak and nervous and itchy. He has low specific gravity urine, proteinuria, casts and azotemia. X-ray shows metastatic calcifications. What vitamin toxicity is likely?

Answer 28

Vit D

Question 29

What is the most active/abundant form of vitamin E? | What is the main function?

Answer 29

Alpha-tocopherol is an antioxidant and free radical scavenger

Question 30

What are sources of vit E?

Answer 30

1. vegetables 2. grains/fortified cereal 3. nuts and oils 4. milk, fish, meat 5. vitE supplements

Question 31

What are the 4 major antioxidant nutrients?

Answer 31

ACE, selenium

Question 32

What are the 2 major problems associated with the RARE deficiency of vitamin E?

Answer 32

1. neuropathy - posterior column, spinocerebellar degeneration 2. hemolytic anemia

Question 33

What are 3 problems with the RARE toxicity of vitamin E?

Answer 33

1. muscle weakness, fatigue 2. nausea, diarrhea 3. antagonizes vit K and enhances coumadin/anticoagulants

Question 34

What are 3 major sources of vitamin K?

Answer 34

1. intestinal flora 2. dietary 3. efficiently recycled

Question 35

What is the main function of vitamin K?

Answer 35

It is a cofactor for microsomal g-glutamyl carboxylase that turns glutamine to glutamate to facilitate calcium binding 1. procoagulant - 2, 7,9,10 2. anticoagulant - protein C, S, Z 3. proteins for bone metabolism - osteocalcin, calcification inhibiting matrix 4. cell growth regulating arrest proteins

Question 36

Vitamin K deficiency is really rare because it is in the diet, gut flora, and is recycled. What 4 scenarios present with vit K deficiency?

Answer 36

1. fat malabsorption, biliary tract disease 2. broad spectrum antibiotics [destropy gut flora making vit K] 3. neonates have a small reserve 4. warfarin anticoagulant blocking Vit K epoxide reductase so it doesn't get recycled

Question 37

What are the 2 negative effects associated with Vit K deficiency?

Answer 37

1. bleeding diathesis | 2. hemorrhagic disease in newborns

Question 38

Of vitamin K1, K2, and K3 which are toxic?

Answer 38

``` K1 = phylloquinine = NOT toxic K2 = questionable k3 = toxic, menaquinones [precursors] ```

Question 39

An infant has anemia, hyperbilirubinemia, and kernicterus. What vitamin toxicity is associated with this?

Answer 39

Vit K [menaquinones]

Question 40

What are the sources of vitamin C?

Answer 40

Ascorbic acid in citrus fruit, liver, milk

Question 41

What are the 4 functions of vit C?

Answer 41

1. activate prolyl and lysyl hydroxylase which is important for cross-linking and collagen stability 2. antioxidant [scavenge free radicals, regenerate vit E] 3. synthesize dopamine, NE, Epi 4. synthesize carnitine

Question 42

A patient presents with various hemorrhages: - purpura, eccyhmoses on skin and mucousa - subperiosteal hemorrhages - retrobulbar, subarachnoid, intracerebral She also has poorly formed osteoid matrix from cartilegenous overgrowth. Her legs are bowed and she has sternal depression. There is a perifollicular rash, hyperkeratotic, papular rash ringed by hemorrhage. Her wounds have impaired healing. What vitamin is deficient?

Answer 42

Vit C - Scurvy

Question 43

What is Vit B1? What are the sources? What is the function?

Answer 43

Thiamine- available in the diet, but deficient in refined foods. Function: 1. carb/glucose metabolism 2. pentose phosphate pathway 3. maintain neural membranes and nerve conduction

Question 44

Chronic alcoholics are usually deficient in what vitamin?

Answer 44

B1 - Thiamine

Question 45

What are the 5 syndromes associated with deficient thiamine [B1]?

Answer 45

1. dry beriberi 2. wet beriberi 3. wernicke encephalopathy 4. korsokoff psychosis 5. megaloblastic anemia, DM, sensineural deafness

Question 46

A patient presents with symmetric peripheral neuropathy. They have mixed motor and sensory symptoms. On exam they demonstrate food drop, toe drop and wrist drop. What is this called? What vitamin are they deficient in?

Answer 46

Dry beriberi and they are deficient in thiamine [B1]

Question 47

A patient presents with heart failure and peripheral edema. She has a cariomyopathy, and the heart is enlarged, globular, with 4 chamber dilation and thin ventricle walls. What is this presentation? What vitamin is she deficient in?

Answer 47

Wet beriberi--> B1 thiamine deficiency

Question 48

An alcoholic sustaining his diet with refined foods presents with opthalmoplegia, nystagmus, ataxia, and global confusion, apathy and disorientation. On imaging you see focal hemorrhage and necrosis of the mamillary bodies [as well as some periventricular thalamus, floor of 4th ventricle, anterior cerebellum]. What disorder does he have? What vitamin is he deficient in? Is this problem reversible or irreversible?

Answer 48

Wernicke's encephalopathy - thiamine deficiency [B1] - REVERSIBLE

Question 49

An alcoholic sustaining diet with refined foods presents with retrograde amnesia with confabulation as well as anterograde amnesia [can't learn new info]. Imaging shows lesion in the medial dorsal nucleus of the thalamus. What disorder is this? What vitamin is he deficient in? Reversible or irreversible?

Answer 49

Korsakoff Psychosis - B1/thiamine deficiency - IRREVERSIBLE

Question 50

A malnourished alcoholic is in the hospital. The nurses decide to refeed him with IV glucose. What must you make sure they deliver WITH the glucose so as not to exacerbate a deficiency?

Answer 50

B1-thiamine

Question 51

What are sources of vitamin B2?

Answer 51

B2/riboflavin is found in: 1. milk 2. leafy veggies 3. liver 4. fortified foods 5. coloring agents [yellow/orange]

Question 52

What is the main function of riboflavin [B2]?

Answer 52

riboflavin is a component of FMN and FAD so it is necessary for oxidation-reduction reactions to produce energy from carbs, fat, protein

Question 53

A patient presents with angular stomatitis [cheilosis], glossitis, interstitial keratitis, and dermatitis of cheeks scrotum and vulva. What vitamin are they likely deficient in?

Answer 53

B2/riboflavin

Question 54

What are the 4 main sources of B3/niacin?

Answer 54

1. meats/coloring 2. grains, legumes 3. seed oils 4. endogenously synthesized from tryptophan [which also synthesizes serotonin, so a niacin def--> depression]

Question 55

What is the main function of niacin/B3?

Answer 55

It is a component of NAD and NADP so it is involved in dehydrogenation reactions in energy metabolism

Question 56

What are the 3 signs of a B3 deficiency?

Answer 56

Pellagra** 1. Diarrhea [atrophy/ulcerations] 2. Dermatitis [photosensitive, glossitis] 3. Dementia [degeneration of neurons]

Question 57

What 3 naturally occuring substances comprise B6? | What are sources?

Answer 57

1. pyridoxine 2. pyridoxal 3. pyridoxamine Source: widely available in diet, so primary deficiency is rare.

Question 58

Primary deficiency is rare for B6, but what are 3 major causes of secondary deficiency?

Answer 58

1. long term use of pyridoxine antagonists like ISONIAZID, ESTROGEN, PENICILLAMINE 2. chronic alcoholism 3. pregnancy

Question 59

What is the function of B6?

Answer 59

pyridoxal 5-phosphate participates in transamination, carboxylation and deamination in lipid, AA metabolism

Question 60

A women on long term estrogens begins experiencing the following symptoms: 1. cheilosis 2. dermatitis 3. glossitis 4. peripheral neuropathy 5. convulsions. What vitamin is it likely she is deficient in?

Answer 60

B6 [estrogens, penecillamine, isoniazid]

Question 61

What 5 things cause secondary deficiency of B9/folic acid?

Answer 61

1. OCP, anticonvulsant, ethanol 2. cigarettes 3. malabsorption 4. chemo [methotrexate--I DHFR] 5. B12 deficiency [needed to convert methylTHF to THF]

Question 62

What is the main function of folic acid/B9?

Answer 62

synthesis of nucleic acids

Question 63

Deficiencies in which 2 vitamins leads to megaloblastic anemia?

Answer 63

B9 and B12 [huge cells, immature nuclei with 6 or more lobes]

Question 64

What are the 3 major problems associated with B9 deficiency?

Answer 64

1. megaloblastic anemia 2. GI problems - sore tongue/taste bud atrophy - small bowel villous/crypt atrophy - diarrhea 3. Fetal neural tube defects

Question 65

A woman gives birth to a baby that has anencephaly, meningocele, spina bifida. What was she deficient in?

Answer 65

folate / vitamin B9

Question 66

What is the only water-soluble vitamin to be stored in the human body? What are sources?

Answer 66

B12-cobalamin [cobalt atom in a heme ring] Meat Fortified foods

Question 67

Describe the absorption of B12.

Answer 67

1. digestion in stomack releases B12 2. B12 binds salivary biding proteins [R-binders] 3. Pancreatic protease releases B12-R in duodenum 4. B12 binds IF secreted from gastric parietal cells 5. IF-B12 attaches to receptors in distal ileum and is absorbed into enterocytes

Question 68

What is pernicious anemia?

Answer 68

Ab : 1. attack parietal cells 2. block attachment of IF to B12 3. prevent binding of B12-IF in the distal ileum

Question 69

What is the function of B12?

Answer 69

Cofactor in the folic acid pathways

Question 70

What are the 4 major presentations of B12 deficiency?

Answer 70

1. megaloblastic anemia 2. GI symptoms - sore tongue/taste bud atrophy - small intestine crypt/villous atrophy - diarrhea 3. neural tube defects [anencephaly, meningocele] 4. Subacute Combined Degeneration of the spinal cord [dorsal column & corticospinal tracts]

Question 71

A patient presents with a hypochromatic, microcytic anemia. What trace element are they deficient in?

Answer 71

Iron: 1. blood loss [chronic] 2. inadequate diet

Question 72

A patient presents with a goiter and hypothyroidism. What trace element are they deficient in?

Answer 72

Iodine

Question 73

A patient presents with muscle weakness, neurological symptoms and abnormal collagen cross-linking. What trace element may they be deficient in?

Answer 73

Cu

Question 74

A patient presents with dental caries. What trace element might they be deficient in?

Answer 74

Fluoride

Question 75

A patient presents with myopathy and cardiomyopathy. What element might they be deficient in?

Answer 75

Selenium [antioxidant with vit E]