CLINICAL CHART -1

A 25 yrs old patient is admitted with a complaint of acute pain

in abdomen and vomiting. He is a known alcoholic and a
smoker.
Following are the biochemical findings:

Parameters Result Reference value

Serum Amylase 1100 SU/dl 80-180 SU/dl

Serum Lipase 800 IU/L 50-75 IU/L

Urinary Amylase 700 SU/dl 375-400 SU/dl

 Questions:

1. What is the probable diagnosis?

• Acute Pancreatitis.
• Acute pain abdomen , alcohol with elevated amylase
and lipase are suggestive of pancreatitis.

2. What are the causes for this condition?

• Alcoholism , Gall stones , Hyperglycemia , Drugs
3.Which parameter is specific for this disease & why?
 Serum Lipase is more specific in diagnosis than serum
amylase because of its t1/2 – 7- 14 days.
The serum amylase values peak between 5-12 hours after the
onset of disease and returns to normal levels within 2-4 days .

 Lipase is secreted only by pancreas, amylase is also secreted

from salivary glands and pancreas.
4. What are secreted by the pancreas?
Exocrine – enzymes – amylase and lipase
Endocrine- hormones – insulin and glucagon.
 5. What is the role of amylase in digestion? What are the causes
of increased amylase?
Amylase acts on α-1,4 glycosidic bonds of starch and helps in
digestion of starch.
Increased amylase – acute / chronic pancreatitis , pancreatic
tumors, obstruction of pancreatic duct, biliary tract disease ,
acute parotitis(mumps) ,salivary duct stones , drugs like
opium.
 CLINICAL CHART -2
A middle aged patient was admitted with chest pain of
24 hrs duration.
Following are the biochemical findings:
Parameter Results Reference value

Total creatine kinase 450 IU/lit 35-175 IU/lit

Creatine kinase (MB) 15% 0-5 %

Total LDH 240 IU/lit 100-225 IU/lit

LDH-1 32% 30%

LDH-2 30% 35%

SGOT 50 IU/lit 8-40 IU/lit

Total Cholesterol 300mg/dl 150-200mg/dl

Questions:
1. What is the diagnosis?
Acute Myocardial Infarction

2. What is the cause for this condition?

Hypercholesterolemia
Smoking, alcohol, stress , Obesity are risk factors.

3. Which isoform is significant and why?

CKMB (isoform of CK) is significant in MI as it rises earliest in
MI than LDH and SGOT.
4. What is flipped pattern?
Normally LDH2 is maximum in serum and
LDH1: LDH2 ratio is <1.
In MI , there is usually a large increase in LDH1 and therefore
reversed pattern – i.e ., LDH1 :LDH2 > 1. This is flipped
pattern.

5. What are markers of myocardial infarction?

CKMB , cardiac Troponin , Myoglobin , LDH , SGOT
 CLINICAL CHART - 3

An elderly patient presents with anemia, bone pain, renal

insufficiency & respiratory infection.
• The following are the biochemical findings:
Parameter Results
Serum proteins 10.2 g/dl

Serum albumin 2.8 g/dl

α -1 globulin 0.2 g/dl

α -2 globulin 0.8 g/dl

β- globulin 1.2 g/dl

γ- globulin 5.2 g/dl

Urinary Bence jones proteins Positive

Serum electrophoresis Abnormal band

 Questions:

1. What is the probable diagnosis?

- Multiple Myeloma – characterized by paraproteinemia ,
anaemia , lytic bone lesions and proteinuria.

2. What is the cause of this disorder?

- Bone marrow tumor – this disorder is due to transformation of
Ig. secreting cells into malignant cells in which one clone
alone is enormously proliferated as M band.
3. What are Bence jones proteins?
- Monoclonal light chain immunoglobulins excreted in urine ,
seen in multiple myeloma.
4. How is Bence jones proteins detected in urine?
- Classical heat test - BJP have special property of precipitation
when heated between 45 – 60 oC . The precipitate dissolves
on heating of urine to 80 - 90 oC . It reappears again on
cooling urine to about 60o C .

5. What abnormal band detected in electrophoresis?

- M band – Myeloma band – with sharp narrow spike.
 CLINICAL CHART -4
A 15 yr old child presented with generalized edema with
facial puffiness in the mornings and decreased urine output
associated with general weakness.
The laboratory findings are as follows:
• Total protein : 4.5 g /dl
• Blood urea : 30 mg/dl
• Serum Creatinine: 1.2 mg/dl
• Urine protein : 6.0 g/day
• Serum cholesterol: 400 mg/dl
• Serum electrophoresis - a sharp and prominent α2 globulin is
seen
 Questions:
1. What is your provisional diagnosis?
- Nephrotic syndrome – characterized by
- Massive Proteinuria(>3 gm/day) , hypoalbuminemia,
hyperlipidemia.
2. What are the biochemical changes in this condition?
- Proteinuria - Albumin is excreted in urine ;
- Serum protein is decreased
- Serum cholesterol is increased
3. What is the cause of edema?
Decreased albumin – due to excretion of albumin in urine
Due to hypoproteinemia, effective colloidal osmotic pressure is
reduced . So, return of water into blood vessels is decreased ,
leading to accumulation of water in tissues .
Oedema occurs if serum albumin < 2 g/dl.
4. Define proteinuria? What are the causes of proteinuria
Excretion of urinary total proteins > 150 mg/day or urinary albumin >
30 mg/day is called as proteinuria.
Causes :-
Physiological – severe exercise, pregnancy , prolonged cold
Pathological – 1) pre-renal – cardiac failure , cerebral haemorrhage ,
hepatic diseases , drugs like barbiturates , opiates
2) Renal – Nephrotic , Polycystic kidney disease, Glomerulonephritis
3) Post- renal – prostate hypertrophy or obstruction , urethral
inflammation , ureteric inflammation , urinary tract diseases.

5. What are the various tests done to detect proteins in urine?

Heat coagulation tests
Dip-stick tests
Estimation of urinary proteins by electrophoresis.
 Clinical chart-5
• A Patient complained of fever, generalized weakness and
passage of dark colored urine since last 15 days.
• He gave history of taking anti-malarial drugs.
• On examination: He was found to have pallor + +, yellowish
discoloration of sclera ++
• Following are the laboratory data:
PARAMETER RESULT REFERENCE VALUE
Total Bilirubin 12.0 mg/dL 0.2-1 mg/dL
Conjugated Bilirubin 1.5 mg/dL 0 – 0.2 mg/dL
UnConjugated Bilirubin 10.5 mg/dL 0.2-0.8 mg/dL
ALT(SGPT) 35 U/L 6-20 U/L
AST(SGOT) 25 U/L 7-20 U/L
ALP 40 U/L 40-125 U/L
Hb 3.5 gm/dL Males:14 – 16 gm/dL
Females:13 – 15 gm/dL
RBC for G6PD 0.6µg/Hb 6-12 µg/Hb
• Urine analysis:
• Bilirubin = Negative Bile salts = Negative
• Benzidine test = positive Urobilinogen = +++

QUESTIONS:
1. What is the probable diagnosis and why?
• Hemolytic / pre-hepatic jaundice
• Increased TOTAL and unconjugated bilirubin in serum and
increased urobilinogen in urine and blood in urine , HISTORY of
anti-malarial drugs are suggestive of hemolytic jaundice.
2. Enumerate the causes?
- Incompatible blood transfusion , sickle cell anaemia , malaria,
G6PD deficiency , congenital Spherocytosis , autoimmune
hemolytic anaemia.
3. What is the role of G6PD?
- Glucose-6-Phosphate dehydrogenase is a key enzyme in HMP
Shunt pathway. It produces NADPH , which is used to maintain
glutathione levels in RBC and protects RBC from free radicals
and damage.
- Deficiency of G6PD leads to premature lysis of RBC –
Hemolysis ( in the presence of presence of simple infection,
ingestion of fava beans, or intake of drugs like antipyretics and
antimalarial drugs like chloroquine, primaquine etc.
4. Name the enzymes of liver function tests?
- Alanine Transaminase (ALT / SGPT) , Aspartate Transaminase (AST/
SGOT ), Alkaline Phosphatase (ALP ) and γ-Gamma Glutamyl
Transaminase (GGT).
5. How Hyperbilirubinemias are classified?
Depending on the cause , it is classified as Congenital and acquired .
Depending on the bilirubin elevated , it is classified as –conjugated
and unconjugated hyperbilirubinemias.
Congenital Hyperbilirubinemias -
a) Unconjugated hyperbilirubinemias : Criggler nazzar syndrome I and
II, Gilberts disease
b) Conjugated hyperbilirubinemias : Rotor syndrome, Dubin Johnson
syndrome
Acquired Hyperbilirubinemias – Physiological Jaundice , Breast milk
Jaundice .
 CLINICAL CHART - 6
A 19 year college student came with complaints of loss of
appetite, fatigue, and low grade fever.
• On examination: His liver was found to be slightly enlarged, no
pallor was seen and yellowish discoloration of sclera was
seen. He was passing pale and clay colored stools but dark
colored urine
• Following are the laboratory data:
PARAMETER RESULT REFERENCE VALUE

Total Bilirubin 10 mg/dL 0.2-1 mg/dL

Conjugated Bilirubin 6 mg/dL 0 – 0.2 mg/dL

UnConjugated Bilirubin 4 mg/dL 0.2-0.8 mg/dL

ALT(SGPT) 130 U/L 6-20 U/L

AST(SGOT) 110 U/L 7-20 U/L

ALP 85 U/L 40-125 U/L

• Urine analysis:
• Appearance - Dark color urine was seen
• Bilirubin = + + Bile salts = -ve urobilinogen = +

• QUESTIONS:
1. What is the probable diagnosis and why?
- Hepatic or Hepatocellular jaundice
- H/O fever , l/o appetite , fatigue – support viral hepatitis as the
cause.
- Increased levels of conjugated and unconjugated bilirubin and
elevation of serum enzymes like AST , ALT with normal ALP
justify the diagnosis.
2. Enumerate the causes.
- Viral hepatitis ( caused by HAV, HBV, HCV,
HDV, HEV) ,
- Toxic hepatitis due to CCL4 ,
chloroform ,white phosphorus etc., and drugs
like isoniazid , pyrazinamide etc .,
- Alcoholic cirrhosis of liver ,
- Hepatocellular carcinoma etc.
 3. What is Vandenbergh reaction and its interpretation?

 Vandenbergh reaction - When serum Bilirubin is treated with diazo-reagent

 {NaNo2 + Sulfanilic acid }, purple color is obtained due to Azo-bilirubin
formation.
 If purple color is obtained immediately, it is called Vandenberg Direct
Positive reaction.
 If purple colour is not developed immediately, but on addition of
methanol ,purple colour develops- it is called Vandenberg Indirect Positive
reaction.
 If purple colour is developed immediately, and on addition of methanol ,
purple colour intensifies- it is called vandenbergh biphasic reaction.
 Interpretation :- Vandenbergh test is used to identify different types of jaundice
-
 Direct positive –increased Conjugated bilirubin as in obstructive Jaundice
 Indirect positive – increased Unconjugated bilirubin as in hemolytic jaundice
 Biphasic reaction - Mixed hyperbilirubinemia as in Hepatic jaundice
4. What are the different types of jaundice?
• Hemolytic jaundice / Pre-hepatic Jaundice
• Hepatic jaundice / Hepato-cellular Jaundice
• Obstructive jaundice / Post-hepatic Jaundice

5. Name the bile salts and bile pigments?

Bile salts - sodium or potassium salts of glycocholic and
taurocholic acids.
Bile pigments are Bilirubin and Biliverdin
 CLINICAL CHART-07
A 40 year old obese female came to medical OPD with
complaining of loss of appetite, vomiting, fever with chills,
and pruritus since 1 month.
• She gave history of pain in right side of the abdomen , with
passing dark colored urine and clay colored stools.
• Following are the laboratory data:
PARAMETER RESULT REFERENCE VALUE

Total Bilirubin 15 mg/dL 0.2-1 mg/dL

Conjugated Bilirubin 14.3 mg/dL 0 –0.2 mg/dL

UnConjugated Bilirubin 0.7 mg/dL 0.2-0.8 mg/dL

ALT(SGPT) 25 U/L 6-20 U/L

AST(SGOT) 95 U/L 7-20 U/L

ALP 1000 U/L 40-125 U/L

• Urine analysis:
• Bilirubin = + + Bile salts = ++ urobilinogen = Negative
• QUESTIONS:
1. What is the probable diagnosis and why?
- Obstructive jaundice
- H/o obesity ,pain abdomen , clay stools , dark urine and
- Increased total and conjugated bilirubin and ALP levels
justify the diagnosis.
2. Enumerate the causes?
- extrahepatic obstruction – due to Gall stones , tumors of head
of pancreas ,
- intrahepatic cholestasis – due to biliary cirrhosis, chronic active
hepatitis , hepatoma etc.
3. Why there is dark colored urine and clay colored stools?
Dark urine is due to increased conjugated bilirubin in urine.
Due to obstruction, bilirubin is not secreted into bile and it is
reabsorbed into circulation and excreted in urine.
Clay stools – due to obstruction in the biliary tract , bilirubin is
not excreted into bile duct and gut , leading to absence of
faecal bilirubin / stercobilin.
4. What is the significance of increased ALP?
ALP – is an enzyme from epithelial cells of biliary
canaliculi (obstruction of bile with consequent
irritation of epithelial cells leads to increased secretion
of ALP into serum) and also from osteoblasts of bone.
Increased levels of ALP is seen in - gallstones, or a
blockage in bile ducts. hepatitis, cirrhosis, liver cancer
etc and bone diseases like osteoblastoma, paget`s
disease, rickets , bone cancer etc.,
5. How are bile salts and bile pigments detected in the
urine?
Bile salts – by Hays` sulphur test
Bile pigments – by Fouchets tests.
 CLINICAL CHART-08

• A 20 yr old man with a family history of Diabetes

(his father suffered from type 2 DM) was advised
Glucose tolerance test by his family physician.
• Following are the lab findings of GTT
Parameter Fasting 1hr 2hr

Blood 75 140 110

glucose
Urine - - -
glucose
• Interpret the above data.

It is a normal GTT,person does not have any symptoms of DM

and the blood glucose levels are with in the normal limits.
• What are the indications & contra indications of GTT?

indications: Diagnosis of diabetes mellitus, Impaired glucose

tolerance, gestational diabetes mellitus, Evaluation of
unexplained neuropathy or retinopathy
contra indications :Confirmed case of DM,Follow-up case of
DM,Acute ill patients.
What are the precautions in preparation of patient?
• Should be on normal carbohydrate diet at least for 3 days
prior to test (approx 150gm CHO/ day)
• Discontinue the drugs that affect blood glucose
(steroids,thiazide diuretics)
• overnight fast for 10 to 12 hrs
• No smoking/caffaine prior to or during test
• During test Complete mental and physical rest
• What is the procedure of GTT?

• Performed in the morning, fasting sample of venous blood

& urine sample collected, 75gm anhydrous glucose in 200

to 250ml of water is given, blood and urine samples

collected at 30min interval for 2hours

• What are the types of GTT?

• Oral GTT

• Intravenous GTT
 CLINICAL CHART-09

• A 48 yrs old obese man complains of general

weakness, increased thirst, frequent urination,
tingling and numbness of toes.
• Following are the lab findings of GTT
Parameter Fasting 1hr 2hr

Blood 150 320 220

glucose
Urine - ++ +
glucose
• What is the probable diagnosis?
• Diabetes mellitus
• What are the causes of hyperglycemia?
• Insulin deficiency, hyper activity of pituitary, thyroid,
adrenal gland, stress
• What are the types of DM?
• Type 1 Diabetes mellitus, Type 2 Diabetes mellitus.
• Gestational Diabetes
• What is glycosuria? Types of glycosuria?
• Excretion of glucose in urine
• Types: Renal glycosuria, Alimentary glycosuria
• What are the diagnostic criteria for DM?
Normal IGT DM
FASTING in mg/dl < 100 111-125 > 126
POST LUNCH in mg/dl < 140 141-199 > 200

• With association of clinical symptoms.

 CLINICAL CHART-10

• A 50 yrs old obese man underwent partial

gastrectomy, complains of dizziness, sweating,
feeling of weakness, nausea, palpitation, 2-3hrs after
taking food.
• Following are the lab findings of GTT
Paramete Fasting ½ hr 1hr 1&½ hr 2hr 2&½ hr
r
Blood 75 220 190 115 80 55
glucose
Urine - + + - - -
glucose
1.What is the probable diagnosis?
• Reactive hypoglycemia
2.What is hypoglycemia?
• Blood glucose level < 40mg/dl
3.What are the causes for reactive hypoglycemia?
• Insulin overdose,β cell tumour,partial gastrectomy,
hyperthyroidism, islet cell tumor.
4.What is Extended GTT?
• Oral GTT extended up to 4 to 5 hours.
5.What is Mini GTT?
• Fasting and 2 hr samples of blood and urine are
collected instead of every 30 min.
 CLINICAL CHART-11

• A boy aged 15 yrs was brought to the casualty in semi-

conscious state. With previous history of complains of
sudden onset of giddiness, thirst, increased urination,
appetite and loss of weight.
• On examination he was dehydrated, had less skin
turgor and dry mouth.
• Deep Respiration with a rate of 32/min.

• Breath was fruity in odour.

• Following are the lab findings:
Parameter Results Reference values

Plasma glucose 420 mg/dl 120-140mg/dl

Serum insulin 5 pico Mol/ L 12 – 150 pico Mol/ L

Serum glucagon 150 pico Mol/ L 20 – 50 pico Mol/ L

Serum sodium 122 meq/L 135-140 meq/L

Serum potassium 5.8 meq/L 3.5-4.5 meq/L

1.What is the probable diagnosis?
• Diabetic keto acidosis
2.What are ketone bodies & how do you detect them in urine
• Acetone,acetoacetate,beta hydroxy butyrate
• Detected by Rothera’s test
3.What are the complications of DM?
• Macro vascular - peripheral vascular,cerebro vascular
disease, ischemic heart disese.
• Micro vascular – retinopathy,nephropathy,neuropathy.
4.Which electrolyte imbalance is commonly seen here?
• NA levels- because ketone bodies excreted in urine as
sodium salts
• K+ - due to decreased uptake of [potassium by the cells
5.What is the significance of Anion Gap?
• Metabolic acidosis. Acetoacetate and betahydroxy
butyrate are acids. When they accumulate, metabolic
acidosis results.
Reduced buffers. The plasma bicarbonate is used up
for buffering of these acids
 CLINICAL CHART -12

A 3 yr old child was brought to the pediatric emergency department in a shock

like state with dizziness, vomiting, sweating and weakness.
The child presented with failure to thrive and hepatic failure.
History of similar episodes after taking food rich in fruits and fruit juice.

Following are the laboratory findings:

Parameter Results
Blood glucose 42 mg/dl
Urine Benedict test positive
1. What is the probable diagnosis?
a. Hereditary Fructose Intolerance

2. What is the metabolic defect in this condition?

a. The defect is in Aldolase-B

3. What is the cause of hypoglycemia and hepatomegaly?

a. Hereditary fructose intolerance causes intracellular
accumulation of fructose 1- phosphate leading to
hepatomegaly. Fructose 1- phosphate allosterically inhibits
glycogen phosphorylase and blocks glycogenolysis leading
to hypoglycemia.
4.What is the confirmatory test?
a. Fructose is excreted in urine , gives positive Benedict's test.
Confirmatory test is by doing enzyme assay
5.How can this case be managed?
a. Withdrawal of fructose from the diet will immediately relieve
the symptoms .
 CLINICAL CHART – 13

A 3 yr old child was admitted with mild mental retardation, poor feeding,
lethargy, tachypnoea, hypotonia and jaundice.
On examination: Eye- cataract present.

Following are the biochemical findings:

Parameter Results
Blood glucose 75 mg/dl
Galactose Increased levels
SGOT 87 IU/lit
SGPT 255 IU/lit
Serum bilurubin 10 mg/dl
Urine for Benedicts test positive
1. What is the probable diagnosis?
a. Galactosemia
2. What is the biochemical defect in this disease?
a. Deficiency of Galactose 1- phosphate uridyltransferase
3. What is the biochemical basis of cataract in this disease?
a. The accumulation of galactose is diverted for the production of
galactitol (dulcitol) by the enzyme aldose reductase. Aldose
reductase is present in lens, nervous tissue, seminal vesicles.
The accumulation of dulcitol in the lens results in cataract
due to its osmotic effect. This is called congenital cataract and is a
very characteristic feature of galactosemia .
4. Why there is enlarged liver and jaundice?
Galactose-1-phosphate accumulates in liver and impairs its
function leading to hepatomegaly .
Bilirubin uptake is less and bilirubin conjugation is reduced , so
unconjugated bilirubin level is increased in blood.
There is enlargement of liver, jaundice and severe mental
retardation.
Galactose-1-phosphate inhibits glycogen phosphorylase
causing hypoglycemia
5.What is the confirmatory test? How u manage the case?
a. Confirmation by showing deficiency of enzyme activity in
erythrocytes.
The therapy includes galactose and Lactose free diet.
Special diet may be withdrawn after 4 years, when
galactose-1-phosphate pyrophosphorylase becomes active
If lactose is withdrawn from the diet, most of the symptoms recede.
But mental retardation, when established, will not improve.
Hence early detection is most important.
 CLINICAL CHART -14

An infant presented with vomiting and diarrheal stools which were

frequent, explosive, acidic and watery.
The mother complained of a persistently unsettled crying infant
On examination:
Pain and distension of Abdomen with excess of gas
Windy baby with loud bowel sounds.
Dehydration and weight loss.
1. What is the probable diagnosis?
a . Lactose Intolerance
2. What is enzyme defect in this condition?
a. Deficiency of Lactase enzyme
3.How many types of Lactose intolerance are present?
a. Inherited / Primary– After birth.

Acquired / Secondary –Adults.

Due to intestinal diseases – Sprue ,Colitis ,Chronic G.E.
4.What is the biochemical test needed for the diagnosis?
a. Confirmatory diagnosis is made by stool acidity test. Undigested
lactose creates lactic acid and other fatty acids that can be detected
in stools
5. What is the plan of management?
a. Lactose free , lactose reduced milk , soy milk and other products
may be beneficial.
Gradual introduction of small amounts of milk/milk products
may help in adaptation in some patients.
 CLINICAL CHART -15

A 12 yrs old girl is brought to hospital with a history of frequent

episodes of weakness, sweating & pallor that disappeared by
consumption of food.
She had a history of delayed milestones.
On examination-she was found to be irritable and lethargic. Gross
hepatomegaly was also seen
Following are the Laboratory findings:

Parameter Result Reference

Glucose 45mg/dl 70-110mg/dl
Serum lactate 25mg/dl 3-8mg/dl
Blood pH 7.25 7.35-7.45
Triglycerides 350mg/dl 75-200mg/dl
Serum uric acid 10mg/dl 4-7mg/dl
1. What is the probable diagnosis?
a. Von Gierke’s disease (GSD type -1)
2. What is the enzyme defect in this condition?
a It is due to the deficiency or absence of glucose-
6-phosphatase in liver, kidney and intestine.
3. What are the clinical features of the disease?
a. Clinical features include enlargement of liver and kidneys ,
doll’s face (rounded cheeks due to fat deposition) , growth
retardation , normal mental development , convulsions
4.What is the cause for hyperuricemia and hyperlipidemia in this
condition?
Glucose 6 phosphate is accumulated , so it is channeled to HMP shunt
pathway , producing more ribose and more nucleotides . Purines are
then catabolized to uric acid , leading to hyperuricemia.
The substrate Glucose 6 phosphate is diverted to lipogenesis pathway
and also increased lipolyusis in adipose tissue due to hypoglycemia
causes hyperlipidemia
5.Which type of acidosis is seen in these patients? What is the reason?
Lactic acidosis is seen in von gierke”s disease due to impairment of
gluconeogenesis. Accumulation of G6P causes inhibition of lactate to
pyruvate conversion , leading to lactic acidosis
 CLINICAL CHART -16
• A 15year old male patient presented with
complains of recurrent abdominal pain,
eruptive xanthomas, and small yellowish
papules on buttocks.
• Following
PARAMETERare the laboratory
RESULT data:
REFERENCE VALUE
Serum cholesterol 400 mg/dL 150- 200 mg/dL
Serum TAG 1000 mg/dL 50 - 200 mg/dL
Serum HDL 20 mg/dL 35 – 75 mg/dL
cholesterol

Serum Electrophoresis: Increased width of chylomicron band at

origin
• QUESTIONS:

• What is the probable diagnosis?

• What is the biochemical defect for this condition?

• Classify Primary Hyperlipoproteinemias?

• What is LDL cholesterol and its significance?

• What are the investigations are done under Lipid

profile?
 1. What is the probable diagnosis?

Type -1 Hyperlipoproteinemia

What is the biochemical defect for this condition?

Deficiency of lipoprotein lipase.

2. Classify Primary Hyperlipoproteinemias?
Frederickson’s classification of hyperliporoteinemias—based on the
electrophoretic patterns of plasma lipoproteins
Type 1 - Deficiency of lipoprotein lipase
Type IIa - Deficiency of LDL receptors
Type IIb –over production of apo -B
Type III –Abnormality in apo-E
Type IV –Overproduction of TG
Type V – Chylomicrons and VLDL elevated
3. What is LDL cholesterol and its significance?
• LDL – Low density lipoprotein

4. Significance – transport cholesterol from liver to other

tissues.

5.What are the investigations are done under Lipid

profile?
• Investigations are done in early morning fasting sample

• Serum total cholesterol,LDL,HDL,serum TG, VLDL

 CLINICAL CHART -17

• A 5 yr old child was referred to an Eye OPD of

teaching hospital from a Primary Health Center.
• O/E; child had posterior dislocation of Lens in
the Left Eye
• With mental and physical retardation, knock
knees, and sparse hair.
Following are the Laboratory findings:
• Routine blood and urine examination were
within normal limits.
• Urine was positive for ninhydrin test & cyanide-
nitropruside test.
• He was treated for 2 weeks with high doses of
pyridoxine, the urine abnormality was reversed.
Questions:

1) What is the probable diagnosis?

homocystenuria

2) Which the enzyme defect in this condition?

Cystathionine beta synthase

3) What is the co-enzyme required for this enzyme?

pyridoxal phosphate (PLP)

4) Why pyridoxine is effective in this case?

The coenzyme required in this case synthesised

from pyridoxine

5) What are the conditions in which urine

ninhydrin test will be positive?

The presence of free alpha amino acids

Ex: alkaptonuria,homocystinuria
 CLINICAL CHART -18
• A male infant of 3 years was brought to the casualty with the
attack of convulsions 2hrs back.
• O/E: child was found to have delayed milestones, unable to
walk & speak properly, dull and blank look with hypo
pigmented skin.
• Mother gave a history of mousy odour in children’s urine.

• Following are the Laboratory findings:

• Plasma phenylalanine level – 30mg/dl (1-2mg/dl)

• Ferric chloride test – positive
• Questions:

• What is the provisional diagnosis?

• What is the basic metabolic defect? Mention the types?

• What are the biochemical changes seen in this condition?

• What is the cause for mousy odour, mental retardation &

skin changes
• What is the screening test?
• Questions:
1.What is the provisional diagnosis?
a. Phenylketonuria
2.What is the basic metabolic defect? Mention the types?
a. Deficiency of phenylalanine hydroxylase
5 types of PKU

Type I is the classical PKU – phenylalanine hydroxylase

Types II and III - dihydrobiopterin reductase.

Type IV and V - deficiency of the enzyme synthesizing

biopterin.
3.What is the biochemical changes seen in this
condition?
• Phenylalanine is diverted to alternate
pathways Resulting in the excessive
production of phenylpyruvate, phenyl acetate,
phenyl lactate and phenyl glutamine.
4. What is the cause for mousy odour, mental
retardation & skin changes
• Phenylacetate gives the urine a mousey odour
• Mental retardation – accumulation of
phenylalanine , low
tyrosine/catacholamines/serotonin, defect in
myelin formation
• skin changes– deficiency of melanin.

5.What is the screening test?

Guthrie tests ( bacterial inhibition assay)

 CLINICAL CHART -19

• A mother brought her child with the complaint

of darkening of his diapers on washing with
soap or exposed to atmosphere.
• O/E: urine when kept in a test tube showed
blackening which started from top layer and
completely blackened in few hours.
• Following are The laboratory findings:

Plasma glucose – 120mg/dl

Ferric chloride test -- positive
Benedicts test -- positive
Silver nitrate test -- positive
1.What is your diagnosis?
• Alkaptonuria

2.What is the primary defect?

• Homogentisate oxidase enzyme deficiency

3.What is the biochemical basis for blackening of urine?

• Homogentisate, on standing, gets oxidized to
benzoquinone, Polymerisation of benzoquinone to
alkaptone gives black or brown colour.
4.Explain the term ochronosis?
• Deposition of Alkapton bodies in connective
tissue, bones , cartilages and various organs
(nose, deposition etc.) intervertebral discs.
5. What is Garrod's tetrad?
• Pentosuria,alkaptonuria,albinism,cystinuria
 Clinical Chart - 20
A 60 yrs old male patient is admitted with recurrent multiple joint
pains with swelling of the joints.
Pain worsened after alcohol consumption.
On examination – Tophi are present on wrist.
Polarising light microscopy of synovial fluid shows Monosodium
urate crystals.
Following are the lab findings:

Parameters Value Reference value

Serum uric acid 12mg/dl 2-7mg/dl

Urinary uric acid 1500mg/24hrs 500-700mg/24hrs

Urinary pH 4.5 5.5-6.5

Questions:
1) What is the diagnosis?
- GOUT- a metabolic disorder in which serum uric acid levels
are increased and deposited in the joints.
2) What is the basic metabolic defect in this disorder?
– increased production of uric acid and deposition of mono
sodium urate crystals in soft tissues.
3) What are the causes of gout?
- Primary – HGPRT ase deficiency , increase in PRPP
Synthetase activity , Glucose-6-Phosphatase deficiency .
- Secondary – Leukemia , lymphomas, polycythemia.
Renal failure, thiazide diuretics and Lactic acidosis .
4) What are tophi? What is the most common site?
Tophi are monosodium urate crystals deposited in joints
and cause swelling , redness and pain of the affected
joints.
Most common site is – 1st metatarsophalangeal joint.
5) What is the drug of choice?
Allopurinol – which competitively inhibits the enzyme
xanthine oxidase and converts itself into alloxanthine-
which is more potential
inhibitor (suicidal inhibition)
 Clinical chart - 21
A 2 ½ year old girl of low income group was brought with
history of loss of appetite, intermittent diarrhoea, recent cough
and fever.
• O/E: she was irritable, has retarded growth, distended
abdomen, enlarged liver, generalized edema with pitting.
• Hair showed alternate pigmented and depigmented areas.
Following are the Laboratory investigations:
• Total protein - 3.8 gm/dl
• Serum Albumin – 1.5 gm/dl
• Hemoglobin - 7 g/dl
• Serum potassium – 3 mEq/l
• Serum Magnesium – 1.1 mg/dl
1. What is the likely diagnosis?
Its a case of Protein energy malnutrition , Kwashiorkor
2. What could be the primary cause for this condition?
Kwashiorkor is due to inadequate protein intake – leads to
protein deficiency (with adequate calorie intake).
Kwashiorkor is seen in children of 1 to 5 yrs age.
Causes are-
1. After weaning ,if child is fed with cereals or starchy food
with no egg /milk (Protein deficient diet)
2. Due to repeated infections like diarrhoea and measles – the
protein requirement is increased.
3. Why there is anemia, oedema, hepatomegaly in this child?
Oedema – is due to decreased albumin (due to deficiency of
protein) and so decreased colloidal osmotic pressure of plasma
Hepatomegaly – is due to decreased VLDL cholesterol synthesis
( due to decreased apoprotein B synthesis)
Anaemia – due to associated decreased iron intake in diet and
infections
4. What are the biochemical abnormalities in this disorder?
• Hypoalbuminemia ( Albumin < 2g/dl) , fatty liver ,
hypokalemia, hypomagnesemia
5. What is PEM?
• Protein- energy Malnutrition – seen in developing countries
due to undernutrition.
• It is of 2 types –
– Marasmus – due to calorie and protein deficiency
– Kwashiorkor – due to protein deficiency
 CLINICAL CHART -22

A patient came with the complaints of loss of appetite, constipation,

weakness, nausea, mental depression, irritability, pins & needle sensation
in the lower limbs.
His dietary history revealed that he was taking polished rice for longer
period.
1. What is the probable diagnosis?
a. Beri-Beri
2.What is the vitamin deficiency in this condition?
a. Thiamine (Vitamin- B1)
3.What are the different types of this disease?
a. Wet Beri-beri – Cardiovascular manifestations are prominent
b. Dry Beri-beri – Central nervous system manifestations are
prominent
c. Infantile Beri–beri – Occurs in infants born to mothers suffering
from thiamine deficiency
4. What are the sources and RDA of this vitamin?
a. The daily requirement of thiamine depends on the intake of
carbohydrate (0.5mg/1000 cal of energy)
Adults – 1-1.5 mg/day
Children – 0.7-1.2 mg/day
Sources : Thiamine is mostly concentrated in outer layer (Bran)
of cereals. Cereals , pulses , oil seeds and yeast are good
sources
5. What is the biochemical role of this vitamin?
a. Acts as Coenzyme (Thiamine pyrophosphate ) for Pyruvate
dehydrogenase , Alpha-ketoglutarate dehydrogenase ,
Transketolase
 CLINICAL CHART -23

A 18yr old college student was admitted with the complaints of weakness and lassitude.
His reflexes were diminished and neuromuscular irritability was seen
He gave a history of 10 – 15 episodes of vomiting after dinner

Following are the laboratory data:

PARAMETER RESULT REFERENCE

VALUE
Blood pH 7.7 7.4-7.6
pCO2 45mmHg 35-45mmHg
Bicarbonate 34.5mEq/L 24-28mEq/L
Carbonic acid 1.35mEq/L 1.2mEq/L
Sodium 145mEq/L 136-145mEq/L
Potassium 3.2 3.5-5 mEq/L
Chloride 95mEq/L 96-105mEq/L
1. What is the probable diagnosis and why?
a. Metabolic Alkalosis , Due to high pH and high bicarbonate along
with history of excessive vomiting
2. Enumerate the causes
a. Prolonged vomiting, Blood transfusion , Intake of Antacids ,
Intravenous administration of bicarbonates
3. Is it compensated? What is the primary compensation?
a. Yes it is compensated
Primary compensation – Respiratory mechanism initiates the
compensation by hypoventilation to retain co2 , thus increasing

H2CO3 . This is slowly taken over by renal mechanism which

excretes more HCO3 and retains H+

4. What is the reason for hypokalemia?
a. In alkalosis there is an attempt to conserve H+ ions by kidneys in
exchange of K+ , so hypokalemia is seen
5.What is Anion gap and what is its normal range?
 Anion gap is defined as the difference between the total
concentration of measured cations (Na+ and K+)and that of
measured anion(Cl- and HCO3-).
 AG= [Na+ + K+ ] – [Cl- + HCO3- ]
 Anion gap in fact represents the unmeasured anions in the
plasma.
 The anion gap in healthy individuals is around 15 mEq/L
(Range 8-18 mEq/L).
 CLINICAL CHART -24

A 45 year old man who is a chain smoker was brought to the hospital in
a drowsy and confused state. He gave history of Chronic cough and
breathlessness
Following are the laboratory data:

PARAMETER RESULT REFERENCE VALUE

pH 7.2 7.4 – 7.6
p CO2 99mm Hg 35-45mm Hg
HCO3- 34 mEq/L 24-28 mEq/L
Carbonic acid 2.6 mEq/L 1.2 mEq/L
Bicarbonate to Carbonic 13:1 20 : 1
acid ratio
1. What is your diagnosis?
2. Is it compensated and what is the compensation?
3. Give few causes for the above condition?
4. What are the different blood buffers present in the body?
5. What is chloride shift?
1. What is your diagnosis?
a. Respiratory acidosis , because of decreased Ph and increased
pco2 and increased H2CO3
2. Is it compensated and what is the compensation?
a. Yes it is compensated
Renal compensation involves excretion of H+ ions and
conserving HCO3- ions.
Respiratory compensation involves hyperventilation which
would result in exhalation of CO2
3. Give few causes for the above condition?

a. Bronchial asthma , Pneumonia , Respiratory muscle paralysis ,

severe sedation , Pneumothorax , Sleep apnea , CNS tumors

4. What are the different blood buffers present in the body?

a. Protein buffer , Bicarbonate buffer and Phosphate buffers are

most important buffer systems present in our body for

regulation of Ph.
 5. What is chloride shift?
• Also know as hamburger effect
• In RBC , due to lack of aerobic metabolic pathway , RBC produce
very little CO2 . The plasma CO2 diffuses into the RBC along the
concentration gradient where it combines with water to form
H2CO3

• In the RBC , H2CO3 dissociated to produce H+ and HCO3- . The

H+ ions are trapped and buffered by hemoglobin. As the
concentration of HCO3- increases in RBC , it diffuses into the
plasma along with the concentration gradient , in exchange for cl-
ions , to maintain electrical neutrality. This phenomenon is referred
 CLINICAL CHART -25

A 35 yr old high strung women was brought with the following complaints:
Hyperventilation, anxiety, paraesthesia, numbness around the mouth and tingling
sensation in the hands and feet. She was going for a job interview.

Following are the laboratory data:

PARAMETER RESULT REFERENCE

VALUE
pH 7.7 7.4-7.6
HCO3- 24mEq/L 24-28mEq/L
Carbonic acid 0.6mEq/L 1.2mEq/L
pCO2 20mmHg 35-45mmHg
Serum Ca++ 8mg/dL 9-11mg/dL
1. What is the probable diagnosis and why?
2. Enumerate the causes
3. What is the compensation
4. What is the cause for tetany?
5. What is isohydric transport of CO2?
1. What is the probable diagnosis and why?
a. Respiratory Alkalosis , as the pH is high and PCO2 is low
2. Enumerate the causes?
a. Hyperventilation, Anemia , High altitude , Salicylate poisoning.
3. What is the compensation ?
• Renal compensation involves involves increased excretion of
HCO3- ions and decreased excretion of H+ ions and increased
absorption of H+ ions.
• Respiratory compensation involves hypoventilation such that CO2
is retained to maintain pH.
4. What is the cause for tetany?
a. Increase in pH favors binding of calcium to proteins , leading to
decreased levels of free ionic Ca2+ , causing tetany.
5. What is isohydric transport of CO2?
a. At the tissue level , hemoglobin binds to H+ ions and helps to
transport CO2 as HCO3- with minimum change in pH which is
referred as Isohydric transport .
 CLINICAL CHART -26
A 35yr old lady with AIDS was brought to the emergency room with a fever of
1010 F and a 3 month history of on and off diarrhea.
O/E: Physical examination is normal, and vitals are stable.
Following are the laboratory data:

PARAMETER RESULT REFERENCE

VALUE
Blood pH 7.25 7.4-7.6
pCO2 27mmHg 35-45mmHg
Bicarbonate 14mEq/L 24-28mEq/L
Sodium 136mEq/L 136-145mEq/L
Potassium 4.0 mEq/L 3.5-5 mEq/L
Chloride 112mEq/L 96-105mEq/L
1. What is the probable diagnosis and why?
2. What is the cause of this acid base disorder?
3. What is likely compensatory response?
4. What is Anion gap and what is its normal range?
5. Mention the causes of Normal Anion gap acidosis ?
1. What is the probable diagnosis and why?

a. It is metabolic acidosis due to low pH and low bicarbonate

2. What is the cause of this acid base disorder?

a. Persistent diarrhea with loss of bicarbonate .

3 What is likely compensatory response?

a. Hyperventilation stimulated by high pco2 is the likely mechanism

and renal mechanism is by more excretion of H+ ions.

4. Mention the causes of Normal Anion gap acidosis ?
• Duodenal fistula with loss of bicarbonate secretions
• Carbonic anhydrase inhibitor drugs used in treatment of
glaucoma ,
• Renal diseases with decreased bicarbonate absorption and
hydrogen ion secretion .
5. Mention the causes of High Anion gap metabolic acidosis ?
Diabetic ketoacidosis , Methanol and ethanol poisoning ,
Uremia (Chronic Renal failure) , Lactic acidosis.
Disorder Primary Compensatory
change mechanism
Met . Acidosis ↓ HCO3- ↓ H2CO3
Hyperventilation

Met . ↑ HCO3- ↑ H2CO3

Alkalosis Hypo ventilation

Resp . ↑ H2CO3 ↑ HCO3-

Acidosis ↑ renal HCO3-
reabsorption
Resp . ↓ H2CO3 ↓ HCO3-
Alkalosis ↓ renal HCO3-
reabsorption
97
 Interpreting ABGs
1. Look at the pH
What is the primary problem ?
– pH < 7.35 ----- acidosis
– pH > 7.45 alkalosis (high)
2. Check the HCO3- (metabolic indicator)
• HCO3- < 22 ----- metabolic acidosis
• > 26 ------ metabolic alkalosis

3. Check the pCO2 (respiratory indicator)

• pCO2 < 35 ---- respiratory alkalosis)
• > 45 ----- respiratory acidosis
• Which is Primary disorder (Resp. or
Metabolic)?
• If the pH is low (acidosis), then look at
pCO2 or HCO3-
– pCO2 - high – Respiratory Acidosis.
– HCO3- - low - Metabolic Acidosis.

• If the pH is high (alkalosis), then look at

pCO2 or HCO3-
– pCO2 - low – Respiratory Alkalosis.
– HCO3- - high - Metabolic Alkalosis.

99
3. For Compensation-
Look at the value that doesn’t correspond
to the observed pH change.
- If it is inside the normal range, there
is no compensation occurring.
- If it is outside the normal range,
the body is partially compensating for the
problem.
• For example:
– In respiratory acidosis (pH<7.35, pCO2>45),
• if the HCO3 is >26, then the kidneys are
compensating by retaining bicarbonate.
• If HCO3 is normal, then not compensating.

100
 CLINICAL CHART - 27

A 50 year old female, attended medical OPD with the complaints of

constipation, weakness , lethargy and cold intolerance for the past
6-8months, getting easily tired and body aches since then.
She gained of 9 kg in the past 6 months.
•O/E - she looked slightly pale, pulse 70/min regular, B.P - 110/80,
chest ,heart and abdomen : Normal
•Thyroid is not palpable.
•All Laboratory tests are unremarkable except a
Thyroid Profile Values Reference Range
Triiodothyronine(T3) 120 ng/dl 110-180 ng/dl

Thyroxine(T4) 3 mg/dl 5-12mg/dl

Thyroid stimulating Hormone(TSH) 7mU/ml 0.5-4mU/ml
Questions:
1) What is the probable diagnosis and why?
2) What are the reasons behind weight gain, cold intolerance, lethargy,
body aches and pain?
3) What are the common causes of hypothyroidism?
4) What are goitrogens?
5) Why should all the newborns screened for hypothyroidism ?
) What is the probable diagnosis?

) The patient is suffering from Hypothyroidism. Low serum T4 levels with

high TSH , along with symptoms like weight gain , lethargy , cold intolerance

are all suggestive of hypothyroidism

) What are the reasons behind weight gain, cold intolerance, lethargy,

body aches and pain?

) The thyroid hormones increase BMR and produce heat . Deficiency would therefore

lead to low energy and heat production due to decreased cellular metabolism like

oxidation of carbohydrates and fats. All this would lead to lethargy , cold intolerance and

slowness of movements .Impaired oxidation of fats and carbohydrates leads to their

increased storage leading to obesity.

3) What are the common causes of hypothyroidism?

 Iodine deficiency

 Surgical Removal of thyroid

 Anti thyroid drugs

 Auto immune thyroid disease

4) What are goitrogens?

Goitrogens are the substances which interfere with the synthesis of thyroid

hormones , such as thiocyanates present in cabbage , cauliflower etc. It

interferes with the iodine uptake by the thyroid.

5) Why should all the newborns screened for hypothyroidism ?

Cretinism, congenital hypothyroidism is associated with severe

neurological deficiency and mental retardation , if left untreated. Since

replacement therapy can easily prevent these complications. It is

advantageous to screen the newborns.

 CLINICAL CHART - 28

A 32 years female, presents with hyperactivity, sweating,

palpitations, weight loss, insomnia, moist skin, fine hair,
irregular menses, diarrhea.

O/E - Tachycardia, Elevated Systolic blood pressure, damp skin,

lid lag, hyper active deep tendon reflexes
Lab findings: Complete Blood Picture within normal limits

Thyroid Profile Values Reference Range

Triiodothyronine 350 ng/dl 110-180 ng/dl
Thyroxine 14 mg/dl 5-12mg/dl
Thyroid stimulating 0.1mU/ml 0.5-4mU/ml
Hormone
Questions:
1) What is the probable diagnosis?
2) What are the causes of Hyperthyroidism ?
3) What tests are included in Thyroid profile ?
4) What is autoimmue thyroid disease?
5) How are T4 and T3 hormones synthesized?
1) What is the probable diagnosis?
The clinical Manifestations of women , along with reduced serum TSH , and
increased T3 and T4 indicate that the women is suffering from Hyperthyroidism
2) What are the causes of Hyperthyroidism ?
Autoimmune / GRAVE`S disease
Thyroiditis
Iatrogenic
Solitary Nodule
Toxic multinodular Goitre
3) What tests are included in Thyroid profile ?
Triiodothyronine (T3)
Thyroxine(T4)
Thyroid stimulating Hormone(TSH)
4) What is autoimmue thyroid disease?
Auto-antibodies are formed against thyroid gland which attack and damages the
thyroid gland , thus causing dysfunction of gland leading to either hypothyroidism or
hyperthyroidism
Mainly two types – Hashimoto’s thyroiditis
- Grave’s disease
5) How are T4 and T3 hormones synthesized?
 Iodine is essential for the synthesis of thyroid hormones. More than half of body’s
total iodine content is found in the thyroid gland
 Thyroglobulin is a glycoprotein and is a precursor for the synthesis of thyroid
hormones
 Tyrosine of thyroglobulin is first iodinated at position 3 to form
monoiodotyrosine(MIT) and then at position 5 to form diiodotyrosine (DIT)
 Two molecules of DIT couple to form Thyroxine (T4) , one molecule of MIT
couples with one molecule of DIT to form Triiodothyronine (T3).
 CLINICAL CHART - 29

A 4 year old boy was brought to the pediatric OPD with the complaints of mild
convulsion about one hour back.. There was no fever or loss of consciousness or
frothing from mouth. He also gave a history of started walking late around 2 years
after birth. His birth was, however normal without any complaints.

•On examination, child’s growth was retarded, and he looked ill and malnourished.
•The limbs had poor muscle tone. His legs bowed and there was knocking of knees
during walking. Abdomen was protruding.
1.What is the likely diagnosis and how it can be confirmed?
2 .What is the biochemical basis of rickets?
3. What is renal rickets?
4. How does sunlight help in rickets?
5. What is the treatment of rickets?
6. What could be the reason of convulsion?
1.What is the likely diagnosis and how it can be confirmed?
a. Rickets. It can be confirmed by
•Low Serum Calcium
•High alkaline phosphatase levels
•X-Ray - ↓ Bone density – Defective mineralization
.
2. What is the biochemical basis of rickets?
a. Due to Vit-D deficiency leading to defective Calcification of bones which
inturn leads to soft bones formation and bony deformities.
3. What is renal rickets?
a. Rickets seen in patients of renal failure is called as Renal Rickets . Activation of
25(OH)-cholecalciferol into 1,25 (OH)2-cholecalciferol occurs in kidney . In renal
damage , this does not occur and hence there is lack of active vitamin D , leading to
renal rickets
 es sunlight help in rickets?
from sunlight are required for the synthesis of cholecalciferol in the skin
ydrocholesterol.
the treatment of rickets?
gh dose of Vit.D –50,000 IU /wk for 8 – 12 weeks , followed by 800 IU /day as
maintenance dose .
cium Supplementation - 1.5 to 2 gm / day .
ould be the reason of convulsion?
ions are due to hypocalcemia
 CLINICAL CHART - 30

An 8 year old girl is brought to OPD with the complaints of dryness of eyes and
difficulty of vision in evening and at night. She also complained of diarrhea and
recurrent infections.
On examination, she looked weak, malnourished and her skin was dry and rough.

Examination of eyes showed dryness of cornea and some brownish spots on the
sclera of the left eye. There was no other finding.
Dietary history revealed that she mainly had cereals, pulses, and processed foods
in diet with very little milk, fruits and vegetables.
Clinician made the probable diagnosis of night blindness with vit-A deficiency.
1.Why was the presumptive diagnosis of night blindness made?
2.Mention the functions of vit-A?
3.Name the sources of Vitamin A and mention its daily requirement?
4.What is the treatment of the night blindness?
5.What do you understand by hypervitaminosis A?
1.Why was the presumptive diagnosis of night blindness made?

a. H/o difficulty in vision in dim light

Dryness of Cornea, Bitot`s spots

Dry , rough skin.

These suggest – Night blindness – due to Vit.A deficiency.

2.Mention the functions of vit-A?

• Vision –11-cis- Retinal

• Reproduction – Retinol

• Growth & Differentiation – Retinoic acid .

• Epithelial integrity

• Anti-oxidant – β-carotene ( Pro-vitamin )

• Immunity.
3.Name the sources of Vitamin A and mention its daily requirement?

a. Sources - Fish oil, Liver, Milk, butter, Green leafy vegetables

Fruits – Papaya, mango.

RDA – 5000IU

4.What is the treatment of the night blindness?

a. Rx – 50,000 IU /day .

5.What do you understand by hypervitaminosis A?

a. Excessive intake can lead to toxicity since vitamin A is stored in the body
Hypervitaminosis can present as Anorexia, Vomiting , Headache, Bony
exostosis (Swelling over long bones), Hepatomegaly.
 Clinical chart - 31

A 38 year old strict vegetarian woman , with a very low consumption of milk products
was found to be anemic (Hemoglobin 7g/dl)
She was lethargic and had the complaints of numbness and tingling of fingers and toes .
Her tongue was beefy red. Her urine had elevated levels of methylmalonate.

Questions:
1.What is the likely diagnosis and how it can be confirmed?
2. What is pernicious anemia ?
3. What is folate trap ?
4. What are the neurological manifestations seen in vitamin B12 deficiency ?
5. How is vitamin b-12 deficiency treated?
1.What is the likely diagnosis ?
A . Based upon history of consumption of strict vegetarian diet along with clinical
symptoms , likely it is a case of vitamin B-12 deficiency .
2. What is pernicious anemia ?
The most important disease associated with B-12 deficiency is pernicious anemia .
It is characterized by low hemoglobin levels , decreased number of erythrocytes
and neurological manifestations.
3.What is folate trap ?
In vitamin B-12 deficiency , increased folate levels are observed in plasma. The
activity of the enzyme homocysteine methyltransferase (methionine synthase) is
low in B-12 deficiency . As a result the only major pathway for the conversion of
N5-Methyl THF to tetrahydrofolate is blocked and body THF pool is reduced . This
is known as folate trap or methyl trap.
4. What are the neurological manifestations seen in vitamin B-12 deficiency ?
a. B-12 deficiency is associated with neuronal degeneration and demyelination of
nervous system .The symptoms include paresthesias (Tingling and numbness of toes
and fingers). In advanced stages , confusion , loss of memory and even psychosis
may be observed.
The neurological manifestations are due to accumulation of methylmalonyl CoA
that interferes with myelin sheath formation.

5. How is vitamin b-12 deficiency treated?

a. Vitamin B-12 is administered in therapeutic doses (100-1000mg) intramuscularly .
Combined supplementation of B-12 and folic acid is employed to treat the patients
with megaloblastic anaemias.
 Clinical chart - 32

A 23 year old female with 3 children had the complaints of weakness and lethargy . She was
was found to be anemic (Hemoglobin 8 g/dl , Normal 12-15 g/dl) .
Her blood was found to contain large abnormal immature erythrocytes .
This women has a highly elevated excretion of formaminoglutamate (FIGLU)
a metabolite of histidine in urine

Questions:
1.What is the likely diagnosis and how it can be confirmed?
2. What is chemistry of folic acid and its daily requirements ?
3. What is the molecular basis for the large erythrocytes in folic acid deficiency?
4 .What are the causes of megaloblastic anemia ?
5. What is relation between folic acid homocysteine ?
1.What is the likely diagnosis and how it can be confirmed?
a. Folate deficiency . Confirmed by assessing serum folate level

2.What is chemistry of folic acid and its sources ?

b. Folic acid consists of pteridine ring , p-amino benzoic acid (PABA)and
glutamic acid . There are multiple forms of folic acid with variable number of
glutamic acid residues.
Daily requirement - 200mg ,
- pregnancy - 400mg
- lactation - 300mg
3.What is the molecular basis for the large erythrocytes in folic acid deficiency?
a. In folic acid deficiency , decreased production of purines and dTMP is observed , which
impairs DNA synthesis . Due to a block in DNA synthesis , the maturation of erythrocytes is
slowed down leading to macrocytic anemia. . The rapidly dividing cells of bone marrow are
seriously affected.
The macrocytic anemia along with macrocytic changes in bone marrow is a characteristic
feature of folate deficiency.

4.What are the causes of megaloblastic anemia ?

a. Megaloblastic anemia could be due to vitamin B-12 deficiency , Folate deficiency ,
genetic defects in utilization of these vitamins or defects in DNA synthesis.
5. What is relation between folic acid and homocysteine ?
a. Elevated plasma levels of homocysteine are associated with increased risk of atherosclerosis ,
thrombosis and coronary artery disease . Hyperhomocysteinemia is mostly due to functional
folate deficiency caused by impairment to form methyltetrahydrofolate by the enzyme
methylene tetrahydrofolate reductase . This results in a failure to convert homocysteine to
methionine . Folic acid supplementation reduces hyperhomocysteinemia and thereby risk for
various health complications.
 Clinical chart - 33

A 3 yr. old boy was admitted with symptoms of Pellagra , accompanied by

Mental retardation. Plasma Tryptophan level is decreased. Urine
Chromatography revealed excess excretion of neutral amino acids .

Q – 1. What is your probable diagnosis ?

2. What is the biochemical basis ?
3. Why does Pellagra occur ?
4. What is the basis of Mental Retardation ?
5. What is the treatment ?
1. What is your probable diagnosis ?

a. Hartnup’s disease.

2. What is the biochemical basis ?

b. Defect in Neutral Amino acid Carrier in Renal tubules and intestine .

3. Why does Pellagra occur ?

a. Tryptophan is not reabsorbed- so, lost in urine and faeces.

Since,50% of NAD is from tryptophan- Niacin deficiency occurs – Pellagra.

4. What is the basis of Mental Retardation ?

a. Since serotonin, Excitatory N.T is not formed

Neurotransmitter imbalance may lead to Mental Retardation.

5. What is the treatment ?

a. Rx- High Protein Diet.

Niacin supplementation in Diet.

 Clinical chart - 34

A 2month old infant was brought to E.D with frequent vomiting and failure to
thrive. On taking history, his mother told that the boy had suffered from
convulsions 3 times since birth.
She noticed that urine of child smells like that of burnt sugar.
Lab Investigations –
pH - 7. 28
Serum Ketoacid - +++
RBS – 120 mg/dl
Q-1. What is your probable diagnosis?
2. What is the biochemical basis?
3. How do you diagnose this disorder?
4. What is the treatment ?
1. What is your probable diagnosis?
a. Maple syrup Urine disease or Branched chain Ketonuria where there is
deficiency of Branched chain α-Keto acid Dehydrogenase Complex.
2. What is the biochemical basis of this disease ?
b. A defect in the enzyme, branched α-Keto acid dehydrogenase which causes
blockade in conversion of the keto acid to the corresponding acyl CoA thio
esters .
3. How do you diagnose this disorder?
Diagnosis done by -
• The Plasma & Urine concentrations of branched amino acids and their α-
ketoacids is increased
• Smell of Urine – Burnt Sugar
• Chromatography of Urine
• Enzyme Analysis
4. What are the biochemical complications of this disease ?

• Accumulation of branched chain amino acids causes impairment in transport

and function of other amino acids .

• Protein biosynthesis is reduced

• Branched chain amino acids competitively inhibit glutamate dehydrogenase

5. What is the treatment ?

• The treatment is to feed a diet with low or no content of branched amino acids .

• Mild variants of MSUD respond to high doses of thiamine .

• In severe cases of MSUD , liver transplantation is required.

 Clinical chart - 35

A full-term infant was observed to have a lack of pigmentation , blue eyes, white
hair .
Q – 1. What is your probable diagnosis?
2. What is the biochemical basis of the disorder ?
3. To which Amino acid metabolism is it related ?
4. What is the risk associated with it ?
A – 1. Albinism .
2.Deficiency of Tyrosinase.
3. Tyrosine – forms Melanin .
Since Tyrosinase is absent , Melanin can`t be formed – So, hypopigmented
skin, white hair and blue eyes.
4. Melanin in skin protects from U.V rays .
Skin Cancer may develop.
 Clinical chart - 36

A 4 year old boy showed signs of learning disability and aggressive behavior ,
besides pain in the joints. It was observed that he had an irresistible urge to bite his
fingers and lips.
The laboratory investigations revealed that the boy had serum uric acid
concentration of 10mg/dl (Normal 4-6mg/dl)

Q – 1. What is your probable diagnosis ?

2. What is the enzyme defect in this disorder ?
3. Why does Hyperuricemia occur in this disorder ?
4. What is the basis of neurological manifestations?
5. What is the treatment ?
1. What is your probable diagnosis ?
a. The clinical manifestations along with elevated serum uric acid levels supports the
diagnosis of Lesch-Nyan syndrome.

2. What is the enzyme defect in this disorder ?

a. This is an inborn error of purine metabolism (Salvage pathway)
• It is a sex- linked disorder
• Lesch Nyan syndrome is characterized by deficiency of enzyme Hypoxanthine-guanine
phosphoribosyl transferase (HGPRT) .

.
3. Why does Hyperuricemia occur in this disorder ?
a. HGPRT deficiency results in increased synthesis of purine nucleotide by two
mechanisms . Firstly decreased utilization of purines (Hypoxanthine and Guanine) by
salvage pathway , resulting in the accumulation and diversion of Phosphoribosyl
pyrophosphate (PRPP) for purine nucleotide. Secondly the defect in salvage pathway
leads to decreased levels of GMP and IMP causing impairment in the tightly
controlled feedback regulation of their production

4. What is the basis of neurological manifestations?

b. This may be related to dependence of brain on the salvage pathway for de novo
synthesis of purine nucleotides.

5. What is the treatment ?

a. Allopurinol for decreasing uric acid.
Neurological manifestations cannot be reversed
 Clinical chart - 37

A 27 year old lady presented in the OPD complaining of nausea ,

weakness and swelling of feet and ankles . She had a history of
recurrent urinary tract infection in the last 2 weeks for which she
was treated with antibiotics , and urine output has also decreased
since last one week .
On examination , she had no fever or pallor but bilateral oedema on
her feet and ankles. Her pulse was 84/Minute , respiratory rate –
20/min , B.P – 145/95

Lab findings are as follows:

 Urine Analysis is as follows
Blood chemistry is as follows

pH 5.0
Volume 460ml/ 24hours Blood sugar 147mg/dl

Specific Gravity 1.005 Blood Urea 106mg/dl

Glucose ++ Serum 3.8mg/dl

Creatinine
Proteins ++

RBC 5-10 / HPF

WBC 5-10 / HPF

Questions
1. Which organ is likely to be affected and responsible for the disease ?
2. What are the indicators of kidney disease ?
3. Define Acute Renal failure ?
4. List common causes of Acute Renal failure ?
5. What is normal GFR and how it is determined ?
1. Which organ is likely to be affected and responsible for the disease ?
a. Kidneys are likely to be involved and responsible for the current illness , because there is
decreased urine output and pedal oedema .

2. What are the indicators of kidney disease ?

a. The probable disease is acute renal failure as indicated by Oliguria , increase in
Serum Creatinine and Blood urea , High B.P and symptoms like nausea and weakness.

3. Define Acute Renal failure ?

a. Acute renal failure is defined as sudden decrease in GFR over a short period of a few
days to weeks , leading to accumulation of excretory waste products , disturbances in
fluid and electrolyte balance and pedal oedema . It is associated with Oliguria , i.e, urinary
volume of less than 500mL /day
4. List common causes of Acute Renal failure ?
• Pre Renal – Decreased blood supply to kidneys due to severe loss of fluid or blood as seen
in severe diarrhea , in cholera , prolonged vomiting in gastritis , Intestinal obstruction ,
severe loss of blood due to trauma .
• Renal – Diseases of the kidneys like diabetic nephropathy , nephrotic syndrome ,
renal stones , ischemia .
• Post Renal – Diseases leading to obstruction to flow of renal filtrate , such as
stones in ureters or bladder , tumor of urinary tract . The accumulated fluid leads to back
pressure and atrophy of the kidneys .

5.What is normal GFR and how it is determined ?

a. GFR or glomerular filtration rate is determined by determining Creatinine clearance .
Its normal range is from 95-140mL/min , average value is 125mL/min .
 Clinical chart - 38

A 48 year old male is admitted with complaints of loss of appetite , nausea , occasional vomiting
and easy fatigability . He is suffering from diabetes mellitus for the last 15 years and has high
blood pressure , for which he is using medication. He gave a history of getting admitted with
similar complaints in the past 8-10 months , when he came to know that he has some
kidney disorder.
On examination , he was anemic , with BP- 160/100mmHg , Pulse 76/min , RR – 24/min

Lab findings are as follows:

 Urine Analysis is as follows Blood chemistry is as follows

pH 5.9 Fasting Blood 175mg/dl

Volume 750ml/ 24hours Glucose
Blood Urea 63mg/dl
Specific Gravity 1.020
Serum 2.6mg/dl
Glucose ++ Creatinine
Proteins ++ Hemoglobin 10.6g/dl

RBC 2-3 / HPF Serum Calcium 8mg/dl

WBC 1-2 / HPF
Questions

1. What is the likely diagnosis?

2. What is likely cause of Renal failure ?
3. What is the reason for his anemia ?
4. Why is hypocalcemia observed ?
5. What is metabolic bone disease ?
1. What is the likely diagnosis?
a. The patient is suffering from chronic renal failure. Lab findings also justify the diagnosis
of kidney disorder.

2. What is likely cause of Renal failure ?

b. This is likely due to long standing diabetes mellitus leading to diabetic nephropathy .
The present renal function tests are deranged and indicate renal failure .
Proteinuria indicate glomerular damage

3. What is the reason for his anemia ?

Due to chronic renal disease , erythropoietin synthesis must be decreased in the kidneys .
This can lead to anemia as erythropoietin is needed for RBC production.
4. Why is hypocalcemia observed ?
a. Hypocalcemia is due to decrease in calcitriol formation , leading to decreased calcium
absorption.

5.What is metabolic bone disease ?

a. Metabolic bone diseases are disorders of bone due to metabolic abnormalities affecting
mineralization and strength. Often these are due to abnormalities of calcium , phosphorus ,
vitamin-D
 Clinical chart - 39

A 52 year old project manager in a IT company came for a routine health check up .
He had no particular complaints except his job involved long sitting hours . He was
a known diabetic and hypertensive for the last 10 years and had regular yearly
check ups in the past .
Physical examination : Height – 170cm , Weight – 95kg
Lab findings are as follows :
•Blood glucose fasting – 146mg/dl , post lunch – 200mg/dl
•Blood urea - 38mg/dl
•Serum Creatinine – 1.3mg/dl
•Triglyceride - 300mg/dl
•Total Cholesterol - 280mg/dl
•HDL-C - 32mg/dl
•LDL-C - 130mg/dl
1.Comment on the findings with the probable diagnosis ?
2. What is Metabolic syndrome or Syndrome X ?
3. What is the cause of Hyperlipidemia ?
4. What is normal HDL-C level ? What is its clinical importance ?
5. What would be the basic principle of management of this patient besides medicines ?
1. Comment on the findings with the probable diagnosis ?
a. The person is showing features of Metabolic syndrome .
Person is obese and BMI is , his diabetes is uncontrolled , and is having
hyperlipidemia

2 . What is Metabolic syndrome or Syndrome X ?

a. Metabolic syndrome is characterized by
• Central obesity
• Glucose intolerance
• Insulin Resistance
• Hypertension
• Dyslipidemia
 Criteria for diagnosis of Metabolic syndrome

1. Elevated waist circumference (For men >90cm , women >80cm)

2. Elevated triglycerides >150mg/dl
3. Reduced HDL cholesterol : For men <40mg/dl , for women <50mg/dl
4. Elevated blood pressure >130/85mmHg
5. Elevated fasting glucose > 100mg/dl
6. Insulin resistance (Hyperinsulinemia)
7. Additional parameters include : Coagulation abnormalities hyperuricemia ,
microalbuminuria , Non alcoholic steatohepatitis (NASH) and increased CRP

Diagnosis is made , if any 3 out of 5 criteria given below

3. What is the cause of Hyperlipidemia ?
a. Due to insulin deficiency , glucose catabolism in peripheral tissues is decreased.
To compensate for energy requirement lipolysis is stimulated because of high glucagon
levels . Increased lipolysis leads to increased fatty acid oxidation , resulting in excessive
acetyl CoA production. This acetyl CoA enters into various pathways , including
cholesterol synthesis and triglyceride synthesis.

4. What is normal HDL-C level ? What is its clinical importance ?

a. A level of HDL-C level of 40mg/dl or above is considered to be normal .
Low HDL-C level is correlated with high risk of atherosclerosis.
5. What would be the basic principle of management of this patient besides
medicines ?
•Control and follow up of diabetes regularly
•Reduction and maintenance of ideal weight
•Regular physical exercises
•Maintenance of blood lipids within normal or target values
•Stress management
 Clinical chart - 40

A 70-year-old man had complaints of increased frequency of urination and pain in

lower abdomen. He had a sensation of obstruction in his urine flow. Physical
examination is normal , except he complained of sudden loss of weight over 6
months . A digital rectal examination revealed that the patient has an enlarged
prostate gland with several palpable discrete nodules.
All lab investigations were normal except - Prostate-specific antigen and Serum
acid phosphatase.
Serum Acid phosphatase : 30 U/L (Normal range: 0.5-5 U/L)

Prostate-specific antigen (PSA) level : 95 ng/mL (Normal range: 0.0–4.0 ng/mL)

1. What is your probable diagnosis ?

2. How it can be confirmed?

3. What do you mean by Tumor markers ?

4. What are the treatment options for cancers?

1. What is your probable diagnosis ?
a. Carcinoma of prostate gland

2. How it can be confirmed?

b. By measuring the serum levels of tumour marker – Prostate specific antigen , and by biopsy
of prostate gland .

3. What do you mean by Tumor markers ?

• The biochemical indicators employed to detect the presence of cancers are collectively
referred as Tumor markers. These are abnormally produced molecules of tumor cells such
as surface antigens , cytoplasmic proteins , enzymes and hormones .
• Tumor markers support the diagnosis of cancers besides being useful for monitoring
the response to therapy and for the early detection of recurrence.
4. What are the treatment options for cancers?

a. Surgical excision, Chemotherapy and Radiotherapy are various treatment options for cancers