Episode 102: This is a sample of the Master the USMLE audio program online at MMC.works

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NUTRITION

I. Eating disorders – includes obesity, anorexia, bulimia


Difference between anorexia and bulimia?

A. Anorexia

Distorted body image; women with anorexia can have distorted image; control issue; they have lost control of everything in their life, and the only thing that they can control over is what they put in their mouth. With a decrease of body fat and wt, GnRH decreases, therefore FSH and LH also decrease, leading to low estrogen; as a result, amenorrhea occurs, AND predisposes to osteoporosis, as if pt is postmenopausal.  Anorexic people will eventually develop osteoporosis. Rx – convince person to gain enough wt to bring period back; not birth control. (ie first step in management of HP/diabetes = wt loss; as you lose adipose,  you upregulate insulin resistance). In anorexia, usually die to cardiac dz (heart failure: heart just stops).

B. Bulimia Nervosa

1. Metabolic Alkalosis: It’s not a body image problem – they can be obese, normal or thin (no weight issue); however, they binge (eat a lot), then force themselves to vomit. Pic on boards: from vomiting, wear down enamel on teeth; so, brownish stuff seen on teeth is just dentine (erosions seen on teeth). Metabolic alkalosis from forced vomiting will be seen. Metabolic alkalois is bad b.c there is a left shift curve, and the compensation is resp acidosis, which drops pO2, therefore will get hypoxia with metabolic alkalosis, and the heart do not like that. The heart already with low O2 will get PVC’s (pre-mature ventricular  contractions), R-on-T phenomenon, then V-fib, then death. Therefore, met alkalosis is very dangerous in inducing cardiac arrythmias, and this commonly occurs in bulimics due to forced vomiting. Pt can also vomit out blood – Mallory Weiss Syndrome – tear in distal esophagus or proximal stomach.

2. Borhave syndrome, which is worse. In the syndrome, there is a rupture and air and secretions from the esophagus get into the pleural cavity; the air will dissect through subcutaneous tissue, come around the anterior mediastinum, which leads to Hemimans crunch – observed when dr looks at pt’s chest, puts a stethoscope down, and you hear a ‘crunch’. The “crunch” is air that has dissected through interstial tissue up into the mediastinum, indicating that a rupture occurred in the esophagus; this is another common thing in bulimics. So, there are 2 things imp in bulimics: 1) Metabolic alkalosis from vomiting (which can induce arrthymias 2) Borhave’s syndrome

C. Obesity

With obesity, using a diff method: BMI: kg’s in body wt/meters in body ht’2. If your BMI is 30 or greater, you are obese; if your bmi is 40 or greater, you are morbidly obese. Main complication of obesity = HTN; with HTN, leads to LVH, and potentially heart failure. MCC death in HTN = cardiac dz. Other complications of obesity include: gallbladder dz, cancers with a lot of adipose, you aromatize many  17-ketosteroids like androstenedione into estrogens. Therefore, will hyperestrinism (all obese women have hyperestrinism), you are at risk for estrogen related cancers – ie breast cancer, endometrial carcinoma, colon cancer.

II. Malnutrition

Protein-calorie malnutrition:

1. Marasmus – total calorie deposition, and wasting away of muscle; however, high chance of survival if they get food

2. Kwashiorkor – prob gonna die; have carbs, but no protein; also have anemias, cellular immunity probs (ie no rxn to ags), low albumin levels, ascites, fatty livers. These kids are apathetic and need to be  force-fed; therefore, kid with kwashiorkor is more likely to die than child with Marasmus. Example: kid with edema, flaky dermatitis, reddish hair (Cu def) – kwashiorkor

III. Vitamins

A. Difference between fat and water soluble vitamins:

1. Fat soluble vitamins dissolve in fats, indicating that they are taken up by chymlomicrons. The chymlomicron will have A, D, E, and, K b/c these are the fat soluble vitamins. Fat soluble are more likely to be stored in fat, so the toxicity is much greater, b/c if it is water soluble, we just pee it out. MCC bright yellow urine = vitamins

2. Water soluble vitamins are all cofactors for biochemical rxn’s.

B. Fat soluble vitamins:

1. Vitamin A

a. Function: Is very imp in children for growth and can have failure to thrive in vit A def. Very important in iodopsin/rhodopsin within the eye and the first sign of vit A def is night blindness which is called nictolopia. Vit A also prevents sq metaplasia.

b. Example of Vit A def: eye with sq metaplasia, goose bumps on back of arm called follicular hyperkeratois. Eye is lined with cuboidal epithelium; when you get sq metaplasia, will get white spots on the eye. If become extensive, grow over eye, and can lead to softening of the cornea (keratomalacia), and leads to blindness. 2nd MCC blindness globally = vit A def. MCC blindness globally = trachoma; MCC blindness in USA = diabetes. Therefore, vit A will prevent sq metaplasia, if you are Vit A deficient and a nonsmoker, a person can end up with sq metaplasia in mainstem bronchus and bronchogenic carcinoma.

c. Toxicity: Hypervitaminosis A – ex. big game hunter that eats bear liver and has headaches. Increased vit A causes cerebral edema, also get papilloedema (which causes the headache), can alsp lead to herniation and death. There is also an increase of retinoic acid (used from treating acne and acute progranulocytic anemia). The retinoic acid toxicity can lead to severe liver toxicity. Therefore,  hypervitaminosis of vit A affects 2 areas: 1) cerebral edema (brain) 2) liver. Example: if have young lady pt on retinoic acid for acne, need to check liver enzymes and ask for headaches (can be developing papilloedema or cerebral edema related to vit A toxicity). Massive amount of vit A in bear livers, and hunter dies with massive headaches or liver failure.

2. Vitamin D = VERY imp on the boards; MC source of vit D is from sunlight.

a. Cholesterol is the

1. Main component of our cell membranes

2. Starting point for making bile salts and bile acids

3. First compound that starts the synthesis of steroid hormones in the adrenal cortex

4. And the 7-dehydrocholesterol in the skin is photoconverted to vitamin D. Therefore we need cholesterol! (makes bile salts, hormones, cell membranes, and vit D).

b. Source: Sun is the most imp source of vit D. take baby out to expose to sunlight (no vit D or vit K in breast milk, therefore must be supplemented – expose to sun for vit D).

c. Synthesis of Vitamin D: Reabsorbed in the jejunum. Undergoes 2 hydroxylation steps; first is in the liver, where it is 25 hydroxylated and the 2nd is in the kidney and its 1 alpha hydroxylase. What hormone puts 1-alpha hydroxylase in the proximal tubule? PTH. PTH is responsible for synthesis of 1-a-hydroxylase and is synthesized in the proximal tubule. (ACE is from the endothelial cells of the pulmonary capillary, EPO is from the endothelial cells of the peritubular capillary). 1-a-hydroxylase is the 2nd hydroxylation step, and now it is active (the first was in the kidney).

d. Vit D function: reabsorb Ca and phosphorus from the jejunum. It HAS to reabsorb both of these, b/c its main job is mineralizing bone and cartilage. Have to have appropriate solubility product to be able to do that; Ca and phosphorus are necessary to mineralize cartilage and bone (like the osteoid making bone). Therefore, it makes sense to reabsorb Ca and phosphorus b/c it needs to make sure that both of them are present in adequate amounts to have an adequate solubility product to mineralize bone.

e. Parathyroid Hormone (PTH) – Functions:

(1)is somewhat related to Vitamin D metabolism, it helps last step for hydroxylation of vit D syn.

(2) PTH will lead to reabsorption of Ca in the early distal tubule (this is also where Na is reabsorbed, and thiazides block this channel). At that location, there is a Ca channel; PTH helps reabsorption of the Ca in this location. Ca has to ‘take turns’ with Na, usually more Na, reabsorbed; therefore Ca has to sneak through channel, with help of PTH. Therefore, with thiazides, Na is blocked, leaving the Ca channel completely open, and the thiazides will lead to hypercalcemia. Therefore, use in Ca stone formers – most of stone formers have hypercalciurea; these pts have too much Ca in their urine; when they are on thiazides, the drug takes Ca OUT of the urine, so they do not form stones.

(3) PTH will decrease reabsorption of phosphorus in the prox tubule, and

(4) decrease the reaccumulation of bicarb, too.

f. Vitamin D and PTH and how they work together:

Vit D’s main function is mineralizing bone, and osteoblasts (bone builders) are involved with this process, therefore the receptor for Vit D is located on the osteoblast. When vit D hooks into the receptor, it causes the release of alkaline phosphatase. So, when you are growing bone or rehealing of a fracture, you expect to see an increase in alkaline phosphatase, which makes the appropriate solubility product to mineralized cartilage and bone. Knowing that PTH breaks down bone (maintains Ca levels in the blood stream) you would think that its receptor would be on the osteoclast (cell normally breaks bone down). However, only one hormone has a receptor on ostoeclasts and that is calcitonin. When calcitonin hooks into the osteoclast receptor, it inhibits the osteoclast, and therefore is used to treat hypercalcemia. Calcitonin also used in treating osteoporosis. The receptor for PTH is on the osteoblast, but not sharing the same one as vit D. When PTH hooks on the osteoblast, it releases IL-1. Another name for IL-1 is osteoclast activating factor (other functions of IL-1 are also involved in fever, stimulates Ab synthesis, and B cell stimulation). So, IL-1 (released from the osteoblast) activates osteoclasts via IL-1 release from osteoblast, and osteoclast is signaled to break down bone to maintain Ca levels in our bloodstream. Sex hormones keep IL-1 in check; in women, estrogen levels keep a check on IL-1 (do not want too much  osteoclast activation); in men, it is testosterone that keeps IL-1 in check (puts inhibitory effect on IL-1 release from the osteoblast after PTH hooks in). Therefore, in women, can see why they get osteoporosis – lack of estrogen = IL-1 not in check and breaking more bone down than making (this is the mechanism of postmenopausal osteoporosis). PTH is more involved in maintaining Ca levels in our blood, while Vit D is more involved in mineralizing our bones and cartilage.

g. Vitamin D deficiency: Many reasons: lack of sun, poor diet, liver dz, renal dz.

Example: Pt on phenytoin and pt has hypocalcemia, why? Phenytoin, alcohol, barb’s, rifampin all induce the cyt p450 system located in the SER. Therefore, get SER hyperplasia; therefore, you metabolize drugs and other things made in the liver, including 25-hydroxyvitamin D. Therefore, anything that rev’s up the p450 enzymes will cause a decrease in vit D, and any other drugs being taken.

Example: woman on birth control pills and taking phenytoin, and she got pregnant, why? The phenytoin rev’ed up the p450 system, which increased the metabolism of estrogen and progesterone in the birth control pills, therefore not enough levels to prevent pregnancy.

Example: what is the enzyme in the SER that increases when the p450 is rev’d up? Gamma glutamyl transferase (GGT) – enzyme of SER! (look at in alcoholics)

Example: MCC chronic renal dz in USA: diabetes mellitus – tubular damage, so no 1-ahydroxylase, therefore inactive vit D. Therefore, pts with chronic renal failure are put on 1-25-vit D.

Example: if someone gets OTC vit D, what steps does it go through to become metabolically active? 25 hydroxylated in liver, and 1-a-hydroxylated in your kidney (it is NOT 1, 25 vit D – this is a prescription drug, and extremely dangerous). Many people have the misconception that the vitamin D is already working. This is not the case; pt must have a functioning liver and kidney. With vit D def in kids = rickets; vit D def in adults = osteomalacia (soft bones). If you can’t mineralize bone, you cannot mineralize cartilage, and they will both be soft, therefore pathologic fractures are common. Kids have different a few things that are different in rickets – ie craniotopies, soft skulls (can actually press in and it will recoil). They can also get ricketic rosaries, b/c the osteoid is located in the costochondral junc, and b/c they are vit D def, there is a lot of normal osteoid waiting to be mineralized, but not an appropriate Calcium/phosphorus solubility product; will have excess osteoid with little bumps, which is called ricketic rosary. Not seen in adults’ b/c they are getting fused. So, 2 things you see in kids and not adults: 1) craniotopies 2) ricketic rosaries; rhe rest is the same, with pathologic fractures being the main problem.

h. Toxicity/Hypervitaminosis of vit D: hypercalcemia, therefore risk of having too many stones in the urine, and stones is a MCC complication.

  • Type 1 rickets – missing the 1-a-hydroxylase
  • Type 2 rickets – missing the receptor for vit D

3. Vitamin E

a. Main function: maintain cell membranes and prevent lipid peroxidation of the cell membranes; in other words, it protects the cell membranes from being broken down by phospholipase A (lipid peroxidation, which is free radical damage on the cell membrane, and is prevented with vit E). Other function: neutralized oxidized LDL, which is far more atherogenic than LDL by itself. When LDL is oxidized, it is way more injurious to the cell then when it is not oxidized. Vit E will neutralize oxidized LDL, therefore is a cardioprotectant (vit E and C both neutralize oxidized LDL). In summary: vit E func = 1) protects cell mem from free radical damage. 2) Oxidizes free LDL (this is the LDL that macrophages phagocytose to produce foam cells, and leads to atherosclerotic plaques).

b. Deficiency of vitamin E: Is seen but is very uncommon, and if seen if would be in kids with cystic fibrosis; from birth, kids have resp probs and pancreas problems. (look at in robbins, too). A kid that has cystic fibrosis will have malabsorption problems; therefore what four vitamins should you give him? Cystic fibrosis pt has a malabsorption of fat; therefore they will have malabsorption of fat soluble vitamins – A, D, E, and K. Vit E def in USA is usually seen in cystic fibrosis patients.

c. Clinical presentations: One of the features of vit E def is hemolytic anemia (vit E normally maintains the integrity of the membrane); this pt is now susceptible to free radical damage, damaged mem of RBC leads to hemolysis of RBC and hemolytic anemia. Another feature of vit E are things related to myelin: posterior column dz, spinal cerebellar probs. Therefore, with vit E def, have neurological problems and hemolytic anemia.

d. Vitamin E toxicity: anything more than 1100 units (average capsule is 400 units, therefore, if take 3 pills, already toxic). Vitamin E toxicity will inhibit synthesis of Vit K dependent Coagulation factors (2, 7, 9, 10, protein C, protein S); in other words, you are antiCoagulated. Example: pt with MI – take antioxidants, and aspirin; with anterior MI, they antiCoagulate the pt, and pt goes home on three months of warfarin. Normal INR ratio, and takes lots and lots of vit E and other vitamins. Take a lot of vit E and will help warfarin, leading to over antiCoagulated state, (remember that warfarin blocks gamma carboxylation of  vitamin K dep factors). Vit E will prevent the SYNTHESIS of these factors. Therefore, vit E toxicity is synergistic in activity with warfarin. Example: pt on warfarin, came home from MI, INR ratio is huge; why? Taking vit E.

4. Vitamin K

a. Sources: Can come from what we eat, but most is synthesized by our colonic bacteria (our anaerobes in our gut) – this is why we give vit K injections to our baby when they are born; they only have 3 days worth of vit K from mom, but after that, they won’t have any b/c its not in breast milk; therefore, a very low level of vit K between days 3-5; also, they don’t have bacteria to make the vit K. Therefore, can get hemorrhagic dz of the newborn (this is why we give vit k when they are born); after 5 days, the bacteria colonize, and vit is made by the baby.

b. Metabolism: Bacteria make vit K in an inactive form – K2. K2 (inactive form must be converted by epoxide reductase to K1 (K1 is the active form of vitamin K). K1 will gamma carboxylates the vit K dependent factors (2, 7, 9, 10, protein C and S). Gamma carboxylates requires the same understanding as Vitamin C, in vit C If you don’t hydroxylate pro and lys then the crosslinks are weaker (anchor pt). Gamma carboxylation of vit K dep factors actually activates them to become functional. Vit K dep factors all have something in common: (1)have to be activated by vit K1 and (2) they are the only Coagulation factors that are bound to a clot by Calcium (Ca); so they have to be bound by Ca in order to work and form a clot; if you can’t bind, then you are antiCoagulated. That is what gamma carboxylation: glutamic acid residues are gamma carboxylated on the vit K dep factors (which is done with K1), and allows Ca to bind the factors; therefore, it keeps them together and you are able to form a clot; therefore, if they are not gammacarboxylated, they are useless b/c Ca can’t grab them to form a clot (so, gammacarboxylation is the anchor pt, so Ca can bind to form a clot, similar to hydroxylation of proline and lysine in collagen synthesis). Warfarin blocks epoxide reductase, so all the vit K pt has is K2 and no gammacarboxylation will occur. Therefore, the patient is anticoagulated.

c. Vitamin K deficiency: MCC vit K def (in hospital) = broad spectrum Ab’s. 2nd MCC = poor diet, being a newborn, malabsorption. Def vit K = hemorrhagic diathesis (bleeding into skin or brain). Know why newborn has vit K def: Example: kid with rat poison –rat poison is warfarin; when rats eat it, they get antiCoagulated and die. Treat with intramuscular Vitamin K. Example: kid lived with grandparents and developed hemorrhagic diathesis: why? B/c the elderly were on warfarin, and kid ate the warfarin, and led to toxic levels.

C. Water Soluble Vitamins: all are cofactors in major biochemical pathway

1. Vitamin C:

a) Classic example of Vitamin C deficiency: older person on tea and toast diet – indicating that they are malnourished; pt gets bleeding of the gums = scurvy, due to vit C def. Vit C is responsible for hydroxylation of proline and lysine, and this occurs in the Golgi apparatus b/c that’s where post-translational modification occurs. Pts have weak Type I collagen b/c cannot crossbridge it; therefore, BV’s are unstable and gums bleed. Get bleeding of the gums, inflammation, and may loose teeth.

b) Associated question: what complication is associated with severe hemophilia A? Hemearthroses, and caused by Vit C deficiency (b/c the BV’s are unstable and they rupture).

c) Physical diagnosis of Vitamin C deficiency: Along with the tea and toast diet, there is also perifollicular hemorrhage (hemorrhage around the hair follicles). See ring sideroblast (nucleated RBC, and has too much iron in the mitochondria), ring around the hair follicle and also see cork screw hairs due to vit C def. The tongue looks like it hurts and patients with vit C have a smooth tongue – glossitis, with kelosis around ankles, plus a hemorrhagic diathesis = scurvy.

d) Excess vitamin C: very common b/c pts take way too much vit C (6-8gm), main complication is Renal stones (increased uric acid stones, and other kinds of stones). Vitamin C and D both have toxicity stones.

e) Vitamin C is used in ancillary Rx for methemoglobinuria; it is a reducing agent and a great scavenger hunter for free radicals (knocks them off).

f) Cofactor in biochemical pathway: Vit C is a cofactor for converting the catecholamine NE into Epi.

2. Vitamin B1 (Thiamine):

a) Involved in many biochemical reactions: transketolase rxn’s in the pentose phosphate shunt; and pyruvate dehydrogenase; alpha keto glutarate dehydrogenase; and alpha keto acid dehydrogenase. All the dehydrogenase rxns require thiamine as a cofactor. Pyruvate dehydrogenase is the main rxn that converts pyruvate into acetyl CoA. Pyruvate can also be converted to OAA with a carboxylase enzyme. When you combine acetyl CoA with OAA, you make citrate, and you are in the TCA cycle.

b) So, if thiamine def, b/c it is involved in the pyruvate dehydrogenase rxn (which converts pyruvate to acetyl CoA), you will not have a lot of acetyl CoA around, therefore, won’t have much citrate around, therefore, you won’t have the TCA cycle working efficiently, and LESS ATP. Therefore, the problem with thiamine def is ATP depletion. When you go from pyruvate to acetyl CoA, you generate 2 NADH’s and since this is in the mito, you get 6 ATP (so, just from going from pyruvate to acetyl-Coa, gives 6 ATP); and then with TCA, get 24 ATP’s. 6 + 24 = 30 ATP; the total you can get from completely metabolizing glucose is 38 ATP; so, if you are thiamine def, you are out 30 ATP’s; so, the main prob of thiamine def is ATP depletion.

c) In thiamine def you’ll see foot drop (dry beriberi), and pitting edema (wet beriberi).

How does this explain wet/dry beriberi?

1) Dry beriberi = peripheral neuropathy, and refers to Wernicke’s korsakoff psychosis (can’t remember old and new things – like an exam – ie “used to know that, but can’t remember now”; a memory problem). It takes a lot of ATP for synthesis of myelin; without myelin, you will get peripheral neuropathy and foot drop (due to common peroneal palsy), can get wrist drop (radial nerve palsy), and claw hand (ulnar nerve palsy). Wernicke’s encephalopathy is confusion, ataxia, and nystagmus. All of these are due to demyelization.

2) Wet beriberi = heart failure; MCC thiamine def = alcohol (not polished rice). Alcoholics are the MC people with thiamine def. Wet beriberi is referring to cardiomyopathy – cause: LHF went into RHF which lead to pitting edema. Heart needs ATP to function, therefore, the pt with have congestive cardiomyopathy; their heart will have biventricular enlargement (the whole chest will be heart), with left and right HF (pitting edema is a sign of right HF due to increased hydrostatic pressure behind the failed heart). If you give IV thiamine, can reverse; and in some cases it’s related to toxicity of alcohol, and cannot work.

d) Example: pt in ER given IV of 5% dextrose and normal saline; all of sudden, pt develops confusion, nystagmus, and ataxia, and opthalmaplegia. Diagnosis: subclinical thiamine deficiency. As soon as the glucose was hung up, the pyruvate went to acetyl CoA and used the rest of thiamine…then went into acute Wernicke’s encephalopathy. Therefore, moral of the story: give IV thiamine before hanging up IV glucose, especially in ER.

f) When people come in comatose or semicomatose, several things you always do: 1) 50% glucose if a hypoglycemia problem 2) naloxone (OD) 3) IV thiamine

3. Vitamin B3 (Niacin):

Rash in sun exposed area = pellagra (aka dermatitis), due to niacin def (also diarrhea, dermatitis, dementia); hyperpigmentation in sun-exposed areas = Cassel’s necklace (dermatitis/pellagra); NAD/NADP rxns  (N stands for nicotinamide, and the nicotinamide was derived from niacin). Therefore, all the oxidation rxns rxn’s are niacin dependent. Example: pyruvate to acetyl CoA = went from NAD to NADH and niacin is involved here. Tryptophan can used in synthesizing niacin and serotonin (why it’s an essential aa); but it’s not the main source of niacin, but a good source.

Nicotinic acid = least expensive lipid lowering drug; see the flushing assoc with it; supposed to take aspirin with it to remove the flushing related to nicotinic acid (used in treating familial hyperlipidemia), it is the DOC for elevated hyperTGemia.

4. Vitamin B2 (Riboflavin):

FAD/FMN – rxns are riboflavin cofactor rxns (therefore, whenever you have FAD and FMN rxns, these are riboflavin cofactor rxns). (Niacin for NAD/NADP rxns, and riboflavin for FAD/FMN rxns). Also, the first rxn: glutathione reductase converts oxidized glutathione into glutathione which riboflavin is a cofactor for.

5. Vitamin B6 (Pyridoxine):

We’re talking about microcytic anemia. First rxn in the synthesis of heme involves succinyl Coa, plus glycine. The enzyme is ALA synthase, and the cofactor is B6. Therefore, it is imp to the synthesis of hemoglobin and heme proteins. The cytochrome system is the heme system, too. Myoglobin is different from Hb (has one heme group), while Hb has four heme groups. There is also heme in the liver, in the cytochrome system. Pyridoxine is involved in the synthesis of heme, which is in porphyrin. Pyridoxine is in the transaminases rxn. Most abundant substrate from making glucose in the fasting state = alanine (aa from muscle – aa’s broken down from muscle to get glucose, via gluconeogenesis). How can an aa be used to make glucose? Transamination. Transaminations (SGOT, SGPT) from the liver can take transaminases; they take amino groups out and put them into other things; if you take the amino group out of alanine, this produces pyruvate (an alpha keto acid). If you take aspartate and take the aa out, you have OAA, which is a substrate for gluconeogenesis. If you take pyruvate, and add an amino group, can synthesize alanine. If you take OAA, and add an amino group, you can make aspartate. This is what the transaminases do, with B6 as a cofactor. B6 is also involved in the synthesis of neurotransmitters. Therefore, a child that is B6 deficient, they end up with severe neurological problems b/c no neurotransmitters (B6 imp to synthesizing the neurotransmitters). Important in transamination, neurotransmitter, and heme synthesis. MCC def B6 def = isoniazid; without B6, will develop neurologic problems and sideroblastic anemia related to heme problem.

D. Other important co-factors

1. Pantothenic acid is related to FA synthase; not the rate limiting rxn, but imp in making palmitic acid (a 16 C FA), and helps in making CoA (ie acetyl CoA, HMG CoA); pantothenic acid is the cofactor for these rxns.

2. Biotin

Cofactor for other rxn of pyruvate to acetyl Coa via pyruvate dehydrogenase = thiamine is the cofactor, while biotin is the cofactor for Pyruvate decarboxylase to OAA. Therefore, thiamine helps form acetyl CoA from pyruvate, while biotin helps form OAA from pyruvate. If you are def, need to eat 20 raw eggs/day. Deficiency: get a rash and go bald (alopecia). If biotin def, cannot form OAA, and cannot from citrate either (this is the first step in gluconeogenesis, therefore you can end up with fasting hypoglycemia). If you build pyruvate, it will be forced to go to lactic acid.

3. Trace elements

a) Chromium = glucose tolerance factor, and helps insulin do its job. Oatmeal can also decrease glucose with all the fiber; good for a type II diabetic to be on chromium.

b) Copper – lysl oxidase – puts crossbridge between collagen fibrils and elastic tissue. Therefore, if Cu def, have weak collagen and weak elastic tissue, predisposing to dissecting aortic aneurysm. Red hair in kwashiorkor also due to Cu def.

c) Fluorine needed to prevent dental carries; too much fluorine leads to white, chalky teeth, also in Colorado b/c water has too much fluorine. It will also get calcification of the ligaments, where ligaments go into bone; the calcified ligaments are subject to rupture; any good radiologist can detect fluorine toxicity.

d) Selenium – in pentose phosphate shunt, form glutathione, and have riboflavin helping that enzyme. Glutathione can neutralize peroxide, and this requires glutathione peroxidase; selenium is the cofactor for this reaction. Therefore, in other words, it is an antioxidant b/c if you are def in it; the glutathione cannot breakdown the peroxide. (Vit E usually comes with selenium – so one works on glutathione, while the other protects the lipid membrane from free radical damage and scavenges oxidized LDL).

e) Zinc – Example: older person with dysgusia (abnormal taste) and anosmia (lack of sell); smell and taste are both def in zinc def. Zinc is a metalloenzyme; therefore it has a trace metal as a cofactor. Collagenase  is a metalloenzyme b/c it has zinc in it, and it breaks down the type 3 collagen, so you can form type 1 collagen. Therefore, if deficient in it, will have poor wound healing, and you get a rash on the face. So, rash on face, dysgusia, anosmia, poor wound healing = zinc deficiency!!! Diabetics are zinc def, unless taking supplements.

4. Dietary fiber (insoluble and soluble) – soluble fiber can lower cholesterol (not the insoluble fiber). How it works (ie oatmeal): oatmeal has insoluble fiber, when it’s in the gut, it will suck up water into it from the colon, and also suck up bad things – lipopolic acid. 95% of bile acids and bile salts are reabsorbed in the terminal ileum. The 5% are lipopolic acids, which are carcinogenic (produces colon cancer). So, fiber (insoluble and soluble), it sucks the lipopolic acid up, into the interior of the stool, so it has no contact with the bowel mucosa. Plus, defecate more often and therefore lipopolic acids have even less contact with the stool. Women are lucky b/c they recycle estrogens; main way of excreting estrogens is in bile and out of your stool, but a small % of estrogens are recycled back into the system. You may not necessarily need that, so, when on fiber, increased estrogen is passed out, therefore, decreasing chance of breast cancer, ovarian cancer, and uterine cancer b/c fiber in the diet.

IV. Special diets – protein restriction

What 2 dz’s would you restrict protein in?

1) Renal failure b/c excess protein broken down to ammonia and other things – the ammonia is metabolized in the urea cycle, will have increase urea and the kidney will have to get rid of more urea.

2) Cirrhosis of the liver – defective urea cycle therefore cannot metabolize ammonia; most of the ammonia that we have in our bodies comes from bacteria in our colon that have urease in them (H. pylori); and they breakdown urea to ammonia in our colon. Ammonia is reabsorbed, and supposed to go back to our liver and go into the urea cycle, become urea and get rid of it. But with cirrhosis, no urea cycle, so the ammonia levels increase in the blood, leading to hepatic encephalopathy, mental status abnormalities, asterixis; also caused by octpaneme, benzoic acid, neurotransmitters. So, two situations to restrict protein. cirrhosis and chronic renal failure.

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