Clinical Problems Biochemistry Final Exam

Front 1

1. Laboratory examination of your patient shows anemia and the red blood cells have a sickle shape

Back 1

Blood disorder - Sickle cell anemia (HbS);

β-globin 6th residue change Glu -> Val
deoxyHb form fibrous struct, change shape of RBS
Cells become fragile, inflex & plug arterioles & hemolyse

Autos rec, 10% black Am, 25% bl Af
Heterozyg - malaria prot
Det - gel electrophor (HbS moves slower)
Treat - symptomatic, bone marrow transplant

Front 2

2. One of your patients receives long term cumarin derivative therapy and suddenly starts to bleed because of a drug overdose

Back 2

Dicumarol & Warfarin are anticoagulants
Vit K antagonists - inhibit epoxide reductase
Vit K req:
-> for Gla (γ-carboxyglutamate) formation
-> for F. II (prothrombin), VII, IX, X
-> Protein C and S synth (impaired by epoxide red.)
Gla for Ca(2+) binding
Treatment: for anticoag/cumarin deriv OD is quinine form of Vit K, 12-24 hrs to work

Front 3

3. Your patient complains he has diarrhoea after milk consumption.

Back 3

Lactose intolerance
Autosomal recessive
Lactase Enzyme mising. Normally breaks disach.Lactose into monomer subunits galactose and glucose
If not broken down, stays in GI lumen, fermented by bacteria -> water retention and diarrhoea, gasy (CO2) and acidic stool
Treatment: Lactase pills, milk avoidance
Detection: bld [Glu] level after lactose ingest; H(+) levels in breath

Front 4

4. A person cannot make extensive physical effort and suffer painful muscle cramps even after mild exercise.

Back 4

McArdle's Disease, type V glycogen storage disease
Lack enz. Phosphorylase to break down glycogen -> G1P meaning Glycogen stored not avail as energy source
Muscles become alkaline due to breakdown of Creatine Phosphate, no lactic acid formation from glycogen
Cramps from +[ADP]/-[ATP] -> Tetany
Glycogen NOT osmotically activ, usual source for M.

Front 5

5. As a consequence of seemingly harmless drugs (eg antimalarials or sulfa antibiotics) acute hemolytic anemia develops.

Back 5

Glucose-6-phosphate dehydrogenase (G6PD), first step of Pentose Phosphate Pathway
Admin of drugs stim. peroxide formation
Lack of NADPH to reduce glutathione, inabil to deal w/oxidative stress (H2O2)
TypeA G6PD 10% act. retained - sufficient
Antimal. drugs create peroxide intermed accum. which creates strong oxid. stress on RBC -> hemolysis
Affects all cells but in RBC PPP is only way to prod NADPH so most severe here
Other choice ; Glutathione Reductase (red of GSSG -> GSH)

Front 6

6. A relatively healthy adult with much overweight comes t the office and asks the possible reason for being fat.

Back 6

Obesity : Energy intake > Energy output
BMI : Wt/Ht^2 ; N < 25, +Wt 25-30, Obese 30+
Adipocytes release Leptin on fat intake -> inhib Nueropeptide Y in Hypothal -> decrease appetite
Ctrl of Thermogenisis via Thermogenin; T.gnenin (Uncoupling P., UCP) found in brown fat on inr mito memb. Protons flow back thru it only gen heat (not ATP)
Path. Condits leading to OBesity: Social environ, Mental State (depre.-> decr BMR), Genetic Probs (leptin p/way mutations), Tumour in Hunger Centre, Hromonal probs, Thermogen. probs (hypothyroidism, Cushing syndrome, Low amnt of Brown adipose, Defic in UCP

Front 7

7. Unconscious Patient, Acetone breath.

Back 7

Ketone bodies formed (Acetone, Acetoacetate, beta-Hyroxybutyrate).
(1) App in long term starv after Gluc and Glyc stores depleted
Liver synth. KBs (from lipids), N.= 0.1mM. Starv = 3-5mM
(2) Diabetes mellitus (TI or II) up to 30mM KB as cells cant untilise body's Gluc -> incr FA degrad -> FA catabol. to Acety-CoA
Can lead metabolic acidosis, ketosis, and coma (acidosis or dehydration)
(3) Alcoholism leads to +NADH/NAD - shift of redox state
Red. in NAD+ impairs flux of Gluc thru Glycolysis at G3P-DH rxn - limit. energy prod.
Gluc cant be utilised, cant be prod on ihib of Gluconeogen, Final prod of Eth. degrad is Acetone

Front 8

8. Someone takes too much Aspirin to treat high fever for a couple of days and comes to the hospital with gastric bleeding.

Back 8

Aspirin irrev inhibs Cyclooxygenase (COX) -> less prostaglandins
Prostagl. either from Arachidonic Acid or DAG
Prostagl. mediators of pain, fever, inflammation
Thromboxane A2 promotes platelet aggreg & vascon (PGI2 oppo)
Imbalance of protagl leads to bleeding -> Asp red TXA-2 -> anti-thrombic effect
COX-1,-2 exist

Front 9

9. Premature baby is kept in incubator under high oxygen concentration because of respiratory distress

Back 9

Deficiency of Lung Surfactant production
Surfactant is Ca(2+), Prot, Phospholipids (Dipalmitoylphosphatidcholine - DPPC)
Secreted frm T II Pneumocytes
Secretion is signicant in last 2 weeks of pregn. Before that is problematic
Treat : artificial surfactant or Glucocorticoids (stim surf prod)

Front 10

10. Patient with fresh MI; cholesterol level is high and both father and brother dies of MI in mid-40's.

Back 10

MI is obstruction to coronary arteries, usually preceded by Atheriosclerosis. High chol incr. risk for Atherioscler.
Ather : depsoits of Chol. and debris -> hinder bld flow -> higher risk for thrombi & emboli
Familial Hypercholesterolemia : codom; hetero 1:500
Mutations for LDL-R. eg APO-B100 miss./defect -> LDL stays in bld vsl.
APO-E & -B funct mut of CETP
Treat: Diet restric, HDL (anti atherogenic lipoprot), block enterohepatic recyc of bile, inhib of HMG-CoA-reductase

Front 11

11. Unconscious patient with high concentration of ammonia in their blood

Back 11

Hyperammonemia : inability to detoxify or excrete NH(4)+
Amm. can pass BBB
Glutamate + NADP <--> aKG + NH4 + NADPH
Amm. via Glutamate DH can cause aKG depletion
-> Brain dep on TCA cycle for ATP -> aKG an intermed No aKG = No TCA = No ATP => Coma and death
Sypmtoms of decr aKG = Slurred speech, tremors, blurry vision
Acq. Hyperamm. : Liver main site of NH4 detox, any liver damage (cirrhosis alcos) may lead to it. Also renal failure w/fail to extract amm.
Hereditary Hyperamm: def in Enz of urea cycle. Manifests soon after birth -> Hyperamm, Mental retardation eg: N-actyl-Glu synthetase defic, CPS1 def
Ornithine Transcarbamoylase (OTC) def - X linked. Orotic aciduria + Hypamm, MR
Low Prot diet
Amm prod from AA, Purine, Pyrimidine etc

Front 12

12. Blood test of patient demonstrates megaloblastic anemia. What can be the reasons for the development of this disease?

Back 12

Defic of VitB12 or Folic Acid. Both water soluble so result of restricted diet
Rapidly prolif cells, esp hematop. precursors (RBCs) and CNS
Folic Acid req for Purine & Pyrimidine synth. Megal. anem. or Nueral Tube Def when FoA missing frm Mother
B12 important for synth of Mythionine and rel FoA - def is Megalo. Anem
Also for incorp of BrCh FatAcids in Myelin Sheaths (Methyl-malonyl-CoA mutase is dep on B12)

Front 13

13. Mental retardation of a child, compulsory enzyme test not performed after birth.

Back 13

Phenylketonuria: def in deg of Phenylalanine -> Tyr

1. PheAka-hydroxylase def; Classic PKU auto rec. Diet low in PheAla & rest. prot
2. Dihydrobioterin-red def; No 5Ht, DOPA. Give DOPA & 5Ht also
3. Maternal PKU; mat bld too high in PheAla, cause ment ret & heart probs in fetus

Sym
due to lack of Tyr - ment ret, lack of pigment, seizures, hyperactiv, tremors
Testing must wait 48hrs after birth to avoid false read.
Phe 20mg in 100ml is pos.

Front 14

14. Metabolic abnormalities that may lead to development of gout; treatment of gout with allopurine, it's mode of action

Back 14

Lesch-Nyhan syndrome
X-rec, HGPRTase-E which catalizes the salvage p/way of purines (Guanine & Hypoxanthine)
If not utilised by HGPRT uric acid is formed -> neuro probs, self mutil & jerks. Early death (20)
GMP/IMP prod by HGPRT usually inhibs purine base synth. No GMP = no inhib = higher purine level
Treat: block Xanthine oxidase w/ Allopurine (prev form of uric acid)

Front 15

15. Give possible reasons - based on your biochem studies - of immunodeficient states.

Back 15

Congenital or Acquired
Hered def of B/T cells
1. Adenosine Deaminase def (ADA).
Dexoyadenosine accum. In T-cells nucleoside kinase will conv deoxyadenosine to dATP. dATP accum inhibs DNA synth. Rep inf, disfunc of IS, ^[dATP] in RBC. Death bef 2
2. Purine Nucleoside phosphorylase deficiency
deoxyGTP accum, conv -> dADP -> dATP. see above
3. Def of CD45 Tyrosine Phosphatase
Imp for Tyrosine kinase sign transd of Luekocyte. E removes an inhib phosphate
4. Def of CytB558 (x-linked)
Req for prod of superoxide ions in nuetrophils using NADPH oxidase. Malf T-cells cant kill targets. Chron Granulomatosis

Front 16

A malignant tumour could be treated with gene therapy yielding p53 in the malignant cells

Back 16

p53 is a tumour sup gene. TF on Chr17, can lead to cellcycle arrest, apoptosis, DNA dam repair
sev domains: DNA bind, oligom, bind to mismatch DNA, activation domain

Can remain stable in cell (& active) by UV rad, hypoxia, oncog act (via P19ARF). MDM2 subst & accum

Induces P21 -> cell cycle arrest (inhib CDKs)

Induce apoptosis -> upreg of BAX, FAS, induc genes that inr react oxygen accum in malign cell

In malig cell endog P53 didnt work, unclear why exog does

Front 17

VitD deficiency syndrome (Rickets) which cannot be cured with administration of VitD

Back 17

VitD3 is a steroid, binds to nuc rec via a Zn finger motif - aff bones, kindney, GI

Def in VitD res in improper calcification of bones (Rickets, Osteomalacia)

Rickets ind if VitD due to def of gene of hydroxylase the activation of VitD -> 1,25 (OH)2-D3 OR 1,25(OH)2-D3-Rec

Front 18

Opthalmologist finds a retinoblastoma while examing a patient, no family history.

Back 18

Knudson Hypothesis
Tumor seen as grey-white elevations in retina

RB is tum. sup gene act as Neg fb. It binds & inhibs E2F which is a TrF that init S-phase. Loss of RB leads to lack of inhib, no neg fb and tumor

Recessive, (1) Family (2) Sporadic [after birth]

Hetero for it dev tum only after 2nd somatic mutation

Front 19

Nutritional problems of Veggies

Back 19

Veg have less Pr, energy, essentAA, iron & B12

Low caloric => malnut, lack of essAA lead to neg Nitrogen balance, B12 => pernic anemia (it's needed for hemoglobin & oxidative proc)

Growing children, lactating women should avoid (high protenin demand)

Soy contains the essAA [also milk, eggs, nuts, B12 & Fe tabs], Corn + Lys, Peas +Trp (compliment)

Kwashiorkor - energy ok, lack P
Marasmus - energy and P lacking

Front 20

Patient with hyperkeratosis who doesn't see properly at twilight.

Back 20

Vitamin A deficiency
VitA fat soluble, stored in Ito C

(1) Retinoic Acid: dimer for nuc rec. & reg gene expr to maint epithelial tissues and guide different. Inhib Keratins on skin
(2) Cis Retinal: comb w/Opsin to create Rhodopsin ie the visual pigment of the Rods [night vision]

Hyperkerotosis [lack of inhib, epi str keratinise. Rough skin] Night Blindness; Impaired immune sys; Embryo malform

Front 21

A liver biopsy of a chronic alcoholic shows fatty liver and dying hepatocytes.

Back 21

Ethanol deg in liver into Acetoaldehyde, then Acetate. Excess ingest leads to Fatty Liver & necros of perivenous hepatocytes

Patho: Decr oxid of FA (due to incr NADH); Incre TAG synth (also due to incre NADH); alt of mito & plasma memb; microtub alt that inhibit P secr [high Acetald]

Necr of Periv. c: (1) pH decr, E decr due to NADH (2) High o2 util to conv Eth -> Acetate

Hepatitis often middle step btw fatty liver & cirrhosis

Front 22

Major joints are dislocated, skin bruises easily and is hyperextendsible

Back 22

Ehlors-Danlos syndrome - disfunct in form of mature collagens

1. Deficiency Disease: Abs of cof VitC (scurvy) Copper ions (latirism)
2. Inher Dis: Mut of gene of collagen (osteogenesis imperfecta, Alport syn [E-D]); mut in gene of proc E (E-D)

Class of E-D
T1: bioch def in α1 & α2 chains of Collagen TV (fibril form). Hyperexten skin
T4: mut in TIII procollagen. Translusc skin, easily bruise
T5: X linked, Hyperext skin, hypermobile jnts
T6: mut of lysyl hydroxylase. Ocular abnorm eg spont det retina
T7: struct def in procollagen α chain. Hypermob, soft sk

Clinical criteria only, no lab test. Prot clothing

Front 23

Patient with intense abdominal pain. Symptoms stronger since taking pain killers, red urine

Back 23

Acute intermittant porphoryia (dominant)

res of dist in heme synthdue to def of Prophobilinogen Deaminase (PBG) leading to accum of Prophobilinogen. Accompanied by increase in activ of ALA synthesis (usually neg reg by heme synth)

Painkillers act P450 sys in liver for biotransformation. Since P450 is involved in heme snth results in acute increase of Prophobilinogen.
PBG resp for red urine, ALA for neurotoxicity
Treat: infusion of high conc heme

Front 24

Child is very pale, skin is inlamed on those areas which were exposed to sun and urine is red.

Back 24

Erythropoietic porhoryia (recessive)

Def of Urophyrinogene 3 cosynthase. Enz act not lost 100% but heme synth is decr

Uroporphyrin 1 and Coproporphyn 1 accumulate in bones, teeth, urine, skin

Anemia, autofloresc RBCs and teeth, light sens skin, bone & teeth abnorm due to dep of Uroporphyrin and Coproporphyrin in tissues and low heme synth. Liver abnormalities.