Final Diseases Flashcards
Vitamin B1 Deficiency (less than 1.2mg/day)
- Beriberi - lack of meat or lots of polished rice causes insufficient ATP, muscle wasting causes cardiovascular damage, CNS- confusion, loss of reflex, edema, mostly plagues alcoholics and sailors.
- Wernicke-Korsakoff - usually associated with alcoholism and poor diet. In these patients, ethanol prevents uptake of B1 causing dry Beriberi (CNS dysfunction), and wet Beriberi (cardiac dilated myopathy, edema)
Vitamin B2 deficiency (less than 1.2mg/day)
Lack of fortified cereals leads to glossitis and cheilosis. In alcoholics, you usually see cracked lips, dark red tongue, dermatitis, normocytic anemia, confusion.
Vitamin B3 deficiency (less than 14-16 mg/day
Lack of cereal, meat, or legumes in diet can lead to Pellagra which consists of diarrhea, dermatitis, dementia. Some diseases like Hartnup’s which prevents absorption of Tryptophan can also cause Pellagra.
Vitamin B3 excess (greater than 35mg/day)
Can be caused by a statin alternative via GPCR that reduce lipolysis (cholesterol)flushing, burning face, stomach irritation
Vitamin B6 excess (more than 500mg for months)
If you eat too much eggs, nuts, fish, yeast, legumes, Vitamin B6 can be toxic and cause peripheral neuropathy.
Vitamin B6 deficiency
Usually related to alcoholics or TB drug use that effects transaminases, decarboxylases, glycogen phosphorylases, and ALA. This can lead to stomatitis, peripheral neuropathy, glossitis, irritability, sideroblastic anemia, seizure
Biotin deficiency
Only get when you eat 20 raw egg whites because avidin of egg binds to biotin preventing it’s absorption.
THF deficiency
If you don’t eat enough fruit or leafy greens Megaloblastic anemia which is where protein synthesis is normal, but without DNA synthesis in bone marrow, so there’s growth without division.
Folate deficiency (less than 400 ug/day)
Can be caused by lack of B12 which rescues the pool of THF. Causes spina bifida, anencephaly
B12 deficiency (less than 2.4 ug)
Need to be made by microorganisms. Can be caused by lack of intrinsic factor from parietal cells (bariatric surgery), autoimmune disease, or lack of transcobalamine (malabsorption) which prevents it from being degraded. Causes folate deficiency, neurological demyelination (not seen in folate deficiency) megaloblastic anemia from lack of folate, and pernicious anemia from lack of intrinsic factor
Vitamin C deficiency
Can’t make collagen because no hydroxylation (no tyrosine or dopamine hydroxylase), scurvy, hemorrhagic gingival mucosa, catecholamine deficiency, no carnitine, more free radicals because vitamin C picks them up.
Vitamin A deficiency
Important to form prosthetic group for rhodopsin. Without it you get night blindness. Also need for growth and differentiation of epithelial because Vitamin A makes hormones that binds to zinc finger.
Vitamin D deficiency (lack of sunlight)
In children causes rickets because it is important for calcium reabsorption and mineralizing the bones. In adults causes osteomalacia
Vitamin D excess
Hypervitaminosis D is when vitamin D isn’t absorbed well leading to hypercalcemia, hypercalciuria, and metastatic calcification
Deficiency of Vitamin E
Abetalipoproteinemia which causes neurological abnormalities, fragile RBCs
Vitamin K deficiency
Extended bleeding, hemorrhage, neurological problems
Vitamin K excess
can cause clogging so you treat with anti clotting inhibitors of vitamin K epoxide redctase like dicumarol, coumarin, warfarin
Lipid malabsorption (steatorrhea)
Can be caused by Crohn’s, cystic fibrosis, celiac, cirrhosis, small bowel, abetaliopoproteinemia, which can lead to problems with liver, blocked bile duct, blocked pancreatic duct, or defective absorptive cells. Treat with low LCFAs, avoid starvation, and plenty of carbs.
Abetalipoproteinemia
malabsorption and deficient transport of fats, cholesterol, fat soluble vitamins, Leads to fatty stool (steatorrhea), or fat vitamin deficiency.
Biliary atresia
blockage of bile ducts carrying bile from the liver to the gallbladder
Celiac disease
immune disease where people cant eat gluten because it damages their small intestine due to flat microvili. Symptoms are diarrhea, bloating.
Cystic fibrosis
affects sweat and mucus glands caused by mutation in CFTR that causes thick mucus. This thick mucus causes the pancreatic ducts to get blocked, problems absorbing fats and fat soluble vitamins, and fatty stool Treat with no LCFA and vitamin supplements
Cholestasis
reduction or stop of bile flow from liver causing itching, dark urine, light stool. Treat with medication or surgery
Chronic pancreatitis
inflammation of the pancreas, reducing digestive enzymes to digest fat, protein, and carbohydrates in small intestine.
Crohn’s disease
IBD, can affect either mouth or anus, but usually affects small/large intestine. Symptoms are diarrhea, abdominal pain, weight loss, fatigue
Lactose intolerance
the inability to digest lactose in dairy products because of lack the enzyme lactase
Whipple disease
bacterial infection in digestive system that affects how body breaks down fats and carbs
Side effects of Bile sequestrants
Bile sequestrants are another way to lower cholesterol. They prevent bile acid and cholesterol from being recycled which lowers LDL. Can cause bloating, constipation, and TG increase
Defects in this purine degradation enzyme cause immune deficiencies
Purine nucleoside phosphorylase
Defects in this purine degradation enzyme causes SCID
adenosine deaminase
What 5 things can cause gout?
Gout is caused by accumulation of uric acid. Underexcretion of uric acid, overproduction of uric acid, increase in PRPP synthetase, defects in glucose 6 phosphatase (von gierke), defects in HGPRTase for purine salvage.
What two defects in protein degradation can cause SCID
defect in adenosine deaminase or purine nucleoside phosphorylase
Acute and Chronic Gout
Acute you can treat with anti-inflammatories, and drugs. Chronic the goal is to decrease uric acid, example is to use allopurinol to inhibit xanthine oxidase
ADA Deficiency
Adenosine deaminase deficiency causes SCID, “bubble boy”. Leads to toxic build up of adenosine leading to death of lymphocytes. Usually diagnosed as baby
Purine Nucleoside Phosphorylase deficiency
mostly affects T cells, increased dGTP
Orotic Aciduria types 1 and 2
Defect in UMP synthase (either the oroate phosphoribosyl transferase or the orotidylic acid decarboxylase). This is autosomal recessive and causes orotic aciduria, megaloblastic anemia, growth failure, development delays.
Defect in Beta aminoisobutyrate
causes beta aminoisobutyric aciduria
APRT deficiency
autosomal recessive, impacts kidneys, urinary tract, and causes renal stones or DHA nephropathy
HGPRT mutation or deficiency
Partial mutation you get gout. But if you’re deficient you have Lesch Nyhan which is X linked recessive and leads to over production of uric acid and overexcretion.
Lesch Nyhan
HGPRT deficiency. Causes inability to salvage hypoxanthine or guanine. This causes increased purine degradation and more uric acid produced. Leads to hyperuricemia, hyperuricosuria, megaloblastic anemia, gouty arthritis, mental retardation, and self mutalation
Methotrexate
a structural analog of DHF to limit tetrahydrofolate availability for dTMP synthesis; can treat psoriasis and rheumatoid arthritis
What’s difference between B12 deficiency and folate deficiency?
Even though both cause megaloblastic anemia, only B12 has neurological dysfunction with it. Folate deficiency you get spina bifida.
Which enzyme defect in pyrimidine degradation causes no problems, and appears most in Asian populations?
B-aminoisobutyric transaminase
Sulfanomides
Inhibits dihydropteroate synthase to inhibit folate synthesis.Often prescribed with Trimethoprim which inhibits DHF reductase.
6-Mercatopurine
Competes with hypoxanthine and guanine for hypoxanthine-guanine phosphoribosyl transferase (HGPRTase). Product (thioIMP) inhibits reactions involving IMP to block de novo purine nucleotide synthesis; antimetabolite
Which nucleotide analog is used for treatment of rheumatoid and psoriatic arthritis, and suppresses T-cell proliferation?
Leflunomide
Which population of patients can benefit from Hydroxyurea?
patients with myeloproliferative disorders and sickle cell because it causes inhibition of ribonucleotide reductase
Mycophenolate & Ribavarin
Inhibit synthesis of guanine nucleotides by competitively inhibiting IMP dehydrogenase.
Hypocalcemia
extremely low extracellular calcium leads to tetany/muscle spasm; treat with Vitamin D to increase intestinal calcium absorption, or release of PTH to do bone/kidney reabsorption and phosphate release.
Hypercalcemia
Kidney stones
Hematochromatosis
A disease caused by iron overload due to mutation in hepcidin gene. Iron absorption is not inhibited so iron accumulates in liver; Liver damage (primary), Diabetes (secondary). Treat with:
Phlebotomy
Blood donation
Iron Deficiency
One of the most common micronutrient deficiencies
Causes of iron deficiency: Acute massive hemorrhage, blood loss, Growth, Pregnancy, Replacing iron cookware with aluminum and Teflon-coated pots.
Or Microcytic hypochromic anemia:
Small RBC
Low hemoglobin content
Coper deficiency-mediated iron deficiency
Zinc deficiency
Acrodermatitis enteropathica,Poor wound healing,
Hair loss, Neuropsychiatric implications, Decreased taste acuity, and in children causes poor growth and testicular atrophy
Wilson Disease
An Autosomal recessive disease when Intestinal absorption biliary excretion (ATP7B) is blocked.
Causes Copper accumulation, Liver (liver damage)
Brain (Neurological degradation), Gold or greenish ring in cornea, Hepatolenticular degeneration
Treated with penicillamine
A Rare X-linked recessive ATP-dependent transporter (ATP7A) deficiency that blocks copper from entering through portal vein. Causes: Growth retardation, Mental deficiency, Seizure, Arterial aneurysm, Bone demineralization, and death
Iodine deficiency
can cause spontaneous abortion, birth defects, irreversible impairment of brain and physical development
Genetic sideroblastic anemia
X-linked mutation in ALA synthase
Aquired sideroblastic anemia
Vitamin B6 deficiency: inadequate diet, alcoholism, isoniazoid
porphyria
abnormal build ups of toxic heme intermediates. Nervous system dysfunctions, abdominal pain, photosensitivity, treat with heme, lots of carbs, and no metabolizing drugs
Lead poisoning
Inhibits ALA dehydratase and ferrochetalase. Causes increased ALA in the blood, anemia, and competes with Ca2+ so inhibits NT release and build up on bone
Genetic porphyria
dominant, but low penetrance: caused by stress, hormones, or drugs that metabolize P450
porphyria cutanea tarda
most common, dominant but low penetrance. Can be caused by liver damage, alcoholism. You get photosensitivity and dark urine, NO neurological or abdominal problems. Treat with phlebotomy and sun avoidance.
Acute Intermittent Porphyria
acute attacks of constipation, muscle weakness, neurological changes, colored urine and stool
jaundice
deposits of bilirubin in skin and sclerae due to increased production or decreased excretion of Bilirubin
Pre hepatic jaundice
Hemolysis leads to excess production of bilirubin exceeding liver conjugating capacity, indirect hyperbilirubinemia, increased urobilinogen in blood, and increased urine from high conjugated Br in intestine
Hepatic (intrahepatic) jaundice
Ca be either direct, or indirect hyperbilirubinemia caused by deficient uptake, or excretion by hepatocytes, bilirubin in the urine.
Neonatal jaundice
due to lack of bilirubin gluronyl transferase before 4 weeks, accumulation causes encephalopathy and kernicterus. treat with phototherapy that makes Br more soluble
Genetic conditions that cause intrahepatic jaundice
- Crigler Najjar - deficient of bilirubin glucuronyl transferase (type 1 and 2), autosomal recessive,
- Gilbert Syndrome - common, mild elevated indirect bilirubin
- Dublin Johnson - defect in conjugated bilirubin exiting hepatocyte due to mutation in MRP2
Posthepatic jaundice (obstructive)
direct hyperbilirubeinmia, caused by bile acid accumulation, conjugated bilirubin in urine, can cause liver damage ad increased indirect Br
hypoxia
when going from altitude change , right away there is an increase i 2,3BPG (glycolytic intermediate) and it decreases the transport of O2 to tissues
Barts Syndrome
all 4 alpha globin genes are deleted, so there’s only four gamma, ususally fatal at birth due to fetalis hydrops which is accumulation of fluid in fetus
H disease
3 alpha globin deleted gives you 4 beta globin and disease can be moderate.
Beta Thalassemia minor
usually asymptomatic
Beta thalassemia major (Cooley)
need transfusions for severe anemia, and often suffer from iron overload
Sickle cell
Most common hemoglobinopathy, autosomal recessive, there’s missense of hemoglobin S gene causing glu to val in a beta globin. this decreases solubility of deoxy hemoglobin causes sickling. symptoms are hemolytic anemia, occlusion, painful crises, increased risk of stroke; heterozygotes have advantage against malaria
Hemoglobin C
HbC have mild hemolytic anemia, less severe sickling
Acquired hemoglobinopathies
- CO poisoning - binds and increase O2 affinity so it can’t drop off
- Methemoglobinemia - oxidation exceeds reduction caused by drugs that metabolize cytochrome b5; causes chocolate blood, high metHb, treat with methylene blue
Cushing’s syndrome
Hypercortisolism causes increased lipolysis, protein degradation, and gluconeogenesis, this leads to lack of muscle causing thin legs and arms and a round belly.
Hyperthyroidism
Grave’s disease, causes excessive sweating, anxiety, fast heart rate, hypermetabolic rate, due to antibody that looks like TSH binding to TR
Hypothyroidism
Hashimoto’s, cold intolerance, slow weight gain, fatigue, auto immune attack against cells of thyroid gland
Where can glucose 6 phosphate go?
glycogenesis, glycolysis, PPP
Where can pyruvate go?
It can go back and forth to become lactate or alanine, it can become OXA which becomes glucose 6 phosphate, which then becomes pyruvate. Or it can become irreversibly acetyl CoA
Where can acetyl CoA go?
Comes from oxidation of pyruvate, fatty acids, and AA and becomes HMG CoA- which can become cholesterol or ketone bodies, CO2, and fatty acids
What’s main source of energy in fed state?
Glucose, it’s being stored as glycogen in liver and muscle. Made into proteins in muscle, and the liver sends AcetylCoA for TG synthesis via VLDL to adipose.
what is main source of energy in Basal post absorptive state?
fatty acids are main fuel source after the glycogen is depleted in 24hrs. Liver uses lactate, glycerol and AA to make glucose for brain and RBCS. Muscle uses glycogen, FAs, and KBs
What is main source of energy in prolonged starvation.
FAs are still main source of fuel until depleted, then you get muscle breakdown. Brain is using KB (2-3 weeks), adipose is still making fat, muscle starts proteolysis which eventually decrease
what does pyruvate kinase deficiency cause?
erythrocytes are more vulnerable because of decreased ATP, increased 2,3 -bisphosphoglycerate which cause hemolytic anemia, pale skin, fatigue, treat with splenectomy or marrow transfusion
What happens in lactate dehydrogenase deficiency?
hemolysis and cramping during exercise because you cannot generate more NAD+, and build up of pyruvate.
Galactosemia
deficiency in either GALK( makes galactose into galactose 1P),GALT (adds UDP), or GALE (UDP galactose to UDP glucose) leads to lethargy, diarrhea, vomit, jaundice, hepatomegaly, cataracts
Fructose kinase deficiency
Fructosuria or if aldolase B deficiency can lead to fructose intolerance which causes liver damage
Too much glucose and lack of sorbitol dehydrogenase causes:
cataracts, retinopathy, peripheral neuropathy
G6PDH deficiency
X linked recessive disease or too much fava beans. Causes xidative stress and hemolysis
PDH deficiency
increased pyruvate, lactate, alanine leads to chronic lactic acidosis. Treat with lots of carbs and dichloroacetate which inhibits PDH kinase
oligomycin
inhibits Fo portion of ATP synthase causing ETS enhancement until it dies out
DNP
disrupts proton gradient by bringing in H+ to the matrix from intermembrane space
when there’s low ADP/ATP ratio what do you do?
Anabolism and decreased energy production, vice versa when you have high ADP/ATP (catabolism)
where does glycolysis and GNG take place?
glycolysis = cytoplasm GNG = cytoplasm and mitochondria
what do your treat pdh deficiency with
dichloroacetate and lots of carbs
What is B1 a cofactor for
alpha keto dehydrogenase, pyruvate dehydrogenase, transketolase, BCAA dehydrogenase
What inhibits TCA?
NADPH, ATP, and Succinyl Coainhibits citrate synthase and the two dehydrogenases, citrate inhibits the synthase, and calciumactivates alpha keto dehydrogenase
What happens with lack of sorbitol dehydrogenase?
Cataracts, problems with schwann cells, kidney, and lens problems
True or false: outer membrane is permeable of mitochoond
True only inner membrane isn’t
What do complex 1 and 2 donate their enzymes through ?
CoQ which is hydrophobic and they deliver through Fe-S clusters. CoQ gives to Cytochrome C which is hydrophilic and drops to complex 4
What inhibits ETC
Complex 1 - Rotnone, riboflavin deficiency
Complex 2 - Malonate
Complex 3 - Iron deficiency
Complex 4 - cyanide, carbonmonoxide, and Iron/Copper deficiency
How does muscle vs kidney and liver break down glycogen?
Liver and kidney use glucose-6-phosphatase and muscle uses lactate dehydrogenase
two steps of debranching enzyme
removes 1-4 via transferase, and 1,6 via glucosidase
where is glucose 6 phosphatase
in ER, life desaturation (cannot be omega 6 or less, and cannot be past carbon 9). Similar to where fatty acid elongation, and assembly of chylomicron is (in SER)
Where do insulin, epinephrine, and glucagon act?
insulin acts in liver and muscle, epinephrine liver and muscle, and glucagon acts on the liver but NOT muscle, instead Ca2+ and AMP activates
Von Gierke
deficient in glucose 6 phosphatase, caused hypoglycemia and hepatomegaly, large abdomen, hyperlipidemia, hyperuricemia, hyperalaninemia
Pompe
deficient in lysosomal 1-4 glucosidase, cardiomegealy, inclusion bodies
Cori
deficient in glycogen debranching, mild hypoglycemia, hepatomegaly, has short branches and single glucose residue at outer branch
Anderson
deficient in branching enzyme, infantile hypotonia, cirrhosis, very few branches
McArdle
muscle glycogen phosphorylase, muscle cramps and weakness
Hers
Hepatic glycogen phosphorylase, mild fasting, hypoglycemia, cirrhosis
Aminotransaminase (uses B6)
makes alanine and alpha keto into pyruvate and glutamate
Cori cycle
rBC does glycolysis making lactate which can go back to liver and become pyruvate and glucose. Same with alanine, but it does anaerobic glycolysis
Why doesn’t adipose have glycerol kinase
avoiding futile cycle because you want to give that glycerol to liver for GNG which will make it into glycerol 3 phosphate, go through dehydrogenase to make DHAP or glyceraldhyde 3 phosphate to become glucose
What cofactor do you need for propionyl CoA carboxylase and methylmalonyl CoA mutase
you need biotin and B12, you use these enzymes for odd chain fatty acids
What activates GNG?
Adipose catabolism making acetyl CoA, which activates pyruvate carboxylase which uses biotin. This makes pyruvate into OAA which becomes PEP through PEP carboxykinase, and becomes glucose after fructose -1,6 bisphosphatase and glucose 6 phosphatase. PDH and pyruvate kinase inhibits
Short vs long term fasting
Short term: low glucose, insulin, and high glucagon, glycogen degradation for brain and RBC and protein degradation for GNG and urea secretion, fat degradation for glycerol GNG and fatty acids for muscle.
Long term: same shit just glycogen is depleted, protein degradation is reduced, GNG reduces for RBCs, and fats are broken down to glycerol for GNG and fatty acids for acetyl coa> KBs
What are two types of essential linolenic acids?
omega 3 which is alpha and comes from fish, seeds, plants, oils. omega 6 which is gamma comes from eggs, meats, grains, nuts, plants. omega 6 makes yLA>GLA>AA then proinflammatories, and omega 3 makes ALA>EPA>DHA>anti inflammatories
Where are TAGs synthesized?
liver
What are types of enzymes released to break down fatty acids?
fundus of Stomach makes gastric lipase to make fatty acids and DG. Pancreatic triglyceride lipase works with colipase to make MAG.
Functions of cholesterol esterase
in liver helps with asembly of VLDL, produce steroid hormones from CE stores, in small intestine it helps with chylomicron assembly, in macrophages help make foam cells
Abetalipoproteinemia
Malabsorption and deficient transport of fats, cholesterol & fat-soluble vitamins from intestine & liver
Symptoms – fatty stool (steatorrhea), fat-soluble vitamin deficiency
Treatment – restrict LCFA consumption, fat-soluble vit supplements
Biliary atresia
blockage in bile ducts carrying bile from the liver to the gallbladder
Celiac disease
immune disease where people can’t eat gluten because it damages their small intestine (flattened brush border cells, no microvilli)
Gluten is a protein found in wheat, barley & rye
Symptoms – diarrhea, bloating
Treatment – gluten free diet
Cystic fibrosis
. Genetic condition that affects the sweat and mucus glands, as well as various organs in the body. mutation in CFTR that causes thick mucus
Symptoms (digestive) – pancreatic ducts get blocked, problems absorbing fats and fat-soluble vitamins, fatty stool (steatorrhea)
Treatment – no cure, restrict LCFA consumption, fat-soluble vit supplements
Cholestasis
causes a reduction or stop of bile flow from the liver
Symptoms – intense itching, dark urine, light-colored stool
Treatment – diet, medication, or surgery (depends on the underlying cause)
Chronic pancreatitis
an inflammation of the pancreas, reducing digestive enzymes to digest fat, protein, and carbohydrates in the small intestine
Crohn’s disease
chronic inflammatory bowel disease (IBD), can affect any part of digestion (mouth to anus), but usually affects parts of the small & large intestines
Symptoms – diarrhea, abdominal pain, weight loss, fatigue
Treatment – cannot be cured
Lactose intolerance
the inability to digest lactose in dairy products because of lack the enzyme lactase
Whipple disease
a bacterial infection in digestive system that affects how body breaks down fats and carbohydrates
Where does FA synthesis occur?
The cytosol of liver, lactating mammary gland, and adipose by using acetyl CoA and NADPH
What are 3 phases of cholesterol synthesis?
- HMG synthase, then HMGCoa reductase (RL) require acetyl CoA and NAPH like Fa synthesis, and enhanced by insulin 2. make squalene 3. cyclize. Very similar to KB synthesis, but Cholesterol synthesis occurs in cytoplasm and uses HMG-Coa reductase
What regulates cholesterol synthesis?
increased by insulin, thyroxine, protein degradation decreased by glucagon, glucocortoids. HMG CoA is activated by phosphatase and high cholesterol inhibits TF SREBP to cause to prevent TS of Hmg coa reductase.
4 enzymes of Beta oxidation
- dehydrogenation of alpha beta via acyl coa dehydrogenase (uses FAD from succinyl dehydrogease), hydrated by enoyl coA hydratase (from H2O of fumerase), then hydroxyacyl CoA (+malate dehydrogenase for NADH), and finally keto thiolase
What is ABC transporter of peroxisome similar to in mitochondira?
carnitine acyl translocase
Tangier Disease
deficient in ABCA transporter which transports cholesterol from peripheral tissues via HDL to liver. Leads to enlarged tonsils, liver, spleen, increased risk of CVD
PCAT deficiency
fish eye disease due to cholesterol build up in cornea, no hepatomegaly
Hartnup
can’t absorb neutral AA in kidney and intestine so lack of B3 = Pellagra
Kwashiorkor
insufficient dietary protein, causes mental changes unlike hartnup and edema
Deficiency of Carbamoyl Phosphate Synthase
most severe, lethargy and seizure after birth, hyperventilation, increased NH4, treat with arginine to activate NAG
orthinine transcarbamoylase deficiency
most common, increased NH4, respiratory alkalosis, increased orotic acid from leaked carbamoyl phosphate to cytoplasm, treat with lots of carbs and low protein
Deficiency of orthinine citrulline co transporter
translocate orthinine and citruline out mitochondria, without you get HHH, neurological deterioration, treat with orthinine. Also hyper ammonemia can precipitate which causes tremor, slurred speech, and death treat with benzoate
