Subsection: Liver Function Tests
Case Scenario 1:
A 35-year-old woman presents with complaints of yellowish discoloration of eyes and skin, dark urine, loss of appetite, and fatigue for 1 week. On examination, she has icterus and mild hepatomegaly. Laboratory tests reveal elevated total and direct bilirubin, elevated ALT and AST, and mild elevation of alkaline phosphatase.
- Mention the type of jaundice and its biochemical basis?
- Which liver function tests help in diagnosing this type of jaundice?
- How does the pattern of LFT abnormalities differ in three types of jaundice?
Answer:
- Hepatic jaundice & its biochemical basis:
- Hepatic jaundice is caused by damage to hepatocytes impairing uptake, conjugation, and/or excretion of bilirubin.
- Results in both unconjugated and conjugated hyperbilirubinemia, as hepatocytes fail to process bilirubin properly.
- Causes include viral hepatitis, alcoholic liver disease, toxins, and drugs.
- 2. Liver function tests in hepatic jaundice:
Serum bilirubin: Both indirect (unconjugated) and direct (conjugated) bilirubin are elevated.
Serum enzymes:
- ALT & AST: markedly elevated (more than ALP), indicating hepatocellular injury.
- Mild increase in ALP & GGT.
Other tests: Decreased serum albumin & prolonged PT if liver synthetic function is impaired.
3. LFT pattern in different types of jaundice:
| Feature | Hepatic jaundice | Hemolytic jaundice | Obstructive jaundice |
| Bilirubin type | Both conjugated & unconjugated ↑ | Mostly unconjugated ↑ | Mostly conjugated ↑ |
| ALT & AST | Markedly ↑ | Normal or mild ↑ | Mild ↑ |
| ALP & GGT | Mild ↑ | Normal | Markedly ↑ |
| Urine bilirubin | Present (conjugated) | Absent | Present |
| Urine urobilinogen | ↑ | ↑↑ | ↓ or absent |
Case Scenario 2:
A 25-year-old man presents with complaints of yellowish discoloration of eyes, mild fatigue, and passing high-colored urine for 3 days. He gives a history of fever with chills 1 week ago, and examination reveals pallor and mild splenomegaly. Laboratory investigations show elevated total bilirubin with a predominance of indirect (unconjugated) bilirubin, normal ALT and AST, and normal alkaline phosphatase.
- Mention the type of jaundice and its biochemical basis?
- Which liver function tests help in diagnosing this type of jaundice?
- How does the pattern of LFT abnormalities differ in three types of jaundice?
- Answer: 1. Hemolytic jaundice & its biochemical basis:
- Hemolytic jaundice occurs due to excessive breakdown of RBCs (hemolysis), producing more bilirubin than the liver can conjugate.
- Leads to unconjugated hyperbilirubinemia, as the capacity of conjugation in hepatocytes is overwhelmed.
- Causes include malaria, autoimmune hemolytic anemia, hemoglobinopathies, and G6PD deficiency.
- 2. Liver function tests in hemolytic jaundice:
Serum bilirubin:
- Total bilirubin ↑, mainly unconjugated (indirect).
- Direct (conjugated) bilirubin normal or slightly increased.
Serum enzymes:
- ALT & AST: normal (no hepatocyte injury).
- ALP & GGT: normal (no cholestasis).
Other findings:
- Urine bilirubin: absent (because unconjugated bilirubin is not water-soluble).
- Urine urobilinogen: increased, due to increased bilirubin load to the gut.
- 3. LFT pattern in different types of jaundice:
| Feature | Hemolytic jaundice | Hepatic jaundice | Obstructive jaundice |
| Bilirubin type | Mostly unconjugated ↑ | Both conjugated & unconjugated ↑ | Mostly conjugated ↑ |
| ALT & AST | Normal | Markedly ↑ | Mild ↑ |
| ALP & GGT | Normal | Mild ↑ | Markedly ↑ |
| Urine bilirubin | Absent | Present | Present |
| Urine urobilinogen | Increased | Increased | Decreased or absent |
Case Scenario 3:
A 50-year-old woman presents with complaints of progressive yellowish discoloration of eyes and skin for 2 weeks, pale (clay-colored) stools, dark urine, generalized itching, and mild right upper abdominal pain. On examination, she has icterus and scratch marks on the skin. Laboratory tests reveal elevated total and direct bilirubin, markedly increased alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT), with mild elevation of ALT and AST.
- Mention the type of jaundice and its biochemical basis?
- Which liver function tests help in diagnosing this type of jaundice?
- How does the pattern of LFT abnormalities differ in three types of jaundice?
Answer: a) Obstructive jaundice & its biochemical basis:
- Obstructive jaundice (cholestatic jaundice) occurs due to blockage of bile flow from the liver to the intestine, leading to accumulation of conjugated bilirubin in blood.
- Causes: gallstones, strictures, tumors compressing bile ducts.
- Accumulated conjugated bilirubin (water-soluble) is excreted in urine, while lack of bile pigments in the gut leads to pale stools and itching (due to bile salt deposition in skin).
- b) Liver function tests in obstructive jaundice:
Serum bilirubin: Total bilirubin ↑, predominantly conjugated (direct).
Serum enzymes:
- ALP & GGT: markedly elevated, reflecting bile duct injury & cholestasis.
- ALT & AST: mild to moderate increase.
Other findings:
- Urine bilirubin: present (dark urine).
- Urine urobilinogen: decreased/absent (bile does not reach intestine).
- c) LFT pattern in different types of jaundice:
| Feature | Obstructive jaundice | Hepatic jaundice | Hemolytic jaundice |
| Bilirubin type | Mainly conjugated ↑ | Both conjugated & unconjugated ↑ | Mostly unconjugated ↑ |
| ALT & AST | Mild ↑ | Marked ↑ | Normal |
| ALP & GGT | Markedly ↑ | Mild ↑ | Normal |
| Urine bilirubin | Present | Present | Absent |
| Urine urobilinogen | Decreased/absent | Increased | Increased |
| Stool color | Pale/clay-colored | Normal or pale | Dark-colored (more stercobilin) |
Case Scenario 4:
A 43-year-old male presents to the hospital with yellowish discoloration of sclera and abdominal pain. He is diagnosed with infective hepatitis.
- Which liver function tests (LFTs) should be performed in this patient to reach the diagnosis?
- What are the major functions of the liver?
- Briefly describe the liver function tests and their significance.
Answer
- a) LFTs to be performed in this patient:
In a suspected case of infective hepatitis, the following LFTs help assess liver damage:
- Serum bilirubin (total, direct, indirect) — ↑ (both conjugated & unconjugated) in hepatocellular injury.
- Serum transaminases (ALT & AST) — markedly ↑, indicating hepatocyte injury.
- Alkaline phosphatase (ALP) & GGT — mild to moderate ↑.
- Serum albumin & prothrombin time (PT) — to assess synthetic function; albumin may ↓ & PT may ↑ if severe damage.
- Urine bilirubin & urobilinogen — urine bilirubin ↑ (conjugated), urobilinogen ↑.
- b) Major functions of the liver:
✅ Metabolic functions:
- Carbohydrate metabolism: glycogenesis, glycogenolysis, gluconeogenesis.
- Fat metabolism: synthesis & oxidation of fatty acids, lipoproteins.
- Protein metabolism: synthesis of plasma proteins (albumin, clotting factors), urea cycle.
✅ Excretory & secretory functions:
- Production & secretion of bile.
- Excretion of bilirubin & other waste products.
✅ Storage: Glycogen, vitamins (A, D, B12), iron.
✅ Detoxification: Metabolism of drugs, alcohol, toxins.
✅ Immunological: Kupffer cells help in phagocytosis & immunity.
- c) Liver Function Tests (LFTs):
LFTs assess various liver functions and help differentiate the type of jaundice.
| Test | Purpose & Significance |
| Bilirubin (total, direct, indirect) | Detects hyperbilirubinemia & type of jaundice. |
| ALT & AST | Enzymes released in hepatocyte injury; ALT more specific. |
| ALP & GGT | Elevated in cholestasis & bile duct injury. |
| Serum albumin & PT | Assess synthetic capacity of liver. |
| Urine bilirubin & urobilinogen | Reflects bilirubin metabolism & excretion. |
Subsection: Kidney Function Tests
Case Scenario 5:
A 68 years old male patient suffering from end stage renal disease has decreased glomerular filtration rate (GFR). For the measurement of glomerular filtration rate (GFR), the physician advised clearance test.
- a) What is meant by clearance and how is it calculated?
b) What is the clinical significance of measuring creatinine clearance?
c) Name other substances used for measuring clearance and their importance.
Answer:
- a) Definition and calculation of clearance:
- Clearance of a substance is the volume of plasma completely cleared of that substance by the kidneys per minute.
C=U×V / P
Where:
U = concentration of substance in urine (mg/dL)
V = urine flow rate (mL/min)
P = concentration of substance in plasma (mg/dL)
- b) Clinical significance of creatinine clearance:
- Creatinine clearance approximates Glomerular Filtration Rate (GFR) because creatinine is freely filtered and minimally secreted.
- Normal creatinine clearance: ~95–120 mL/min in adults.
- Decreased clearance indicates reduced GFR and impaired kidney function, seen in acute or chronic renal disease.
- It helps in:
- Staging chronic kidney disease (CKD).
- Monitoring progression of renal failure.
- Adjusting drug dosages in renal impairment.
- c) Other substances used to measure clearance:
| Substance | Significance |
| Inulin | Gold standard for measuring GFR (not secreted or reabsorbed). |
| Urea | Urea clearance is less accurate than creatinine for GFR. |
| Para-aminohippuric acid (PAH) | Used to measure renal plasma flow (RPF) as it is completely cleared from plasma in one pass. |
Case Scenario 5:
A 55-year-old man comes to the hospital with complaints of swelling of legs, decreased urine output, fatigue, and loss of appetite for 2 weeks. On examination, he has pitting edema and mild hypertension. Laboratory investigations reveal elevated blood urea and serum creatinine.
- What are the major functions of the kidney?
- Enumerate the kidney function tests that should be performed in this patient.
- Briefly describe the tests to assess glomerular and tubular function.
Answer
- a) Major functions of the kidney:
Excretory function: Elimination of nitrogenous wastes (urea, creatinine, uric acid).
Homeostasis: Regulation of water, electrolytes, and acid-base balance.
Endocrine function: Secretion of erythropoietin, renin, activation of vitamin D.
Metabolic function: Gluconeogenesis, metabolism of hormones.
- b) Kidney function tests (KFTs) to perform:
- Tests for glomerular function:
- Blood urea, serum creatinine.
- Clearance tests (creatinine, inulin).
- Estimation of glomerular filtration rate (GFR).
- Urinalysis: proteinuria, hematuria.
- Tests for tubular function:
- Urine concentrating and diluting ability.
- Specific gravity & osmolality of urine.
- Acidification tests (e.g., ammonium chloride loading test).
- Other tests:
- Electrolytes (Na⁺, K⁺, HCO₃⁻).
- Imaging studies (if needed).
- c) Tests for glomerular & tubular function:
| Function | Test | Significance |
| Glomerular function | Serum creatinine & urea | ↑ in decreased GFR. |
| Creatinine clearance | Estimates GFR (~95–120 mL/min). | |
| Inulin clearance | Gold standard for GFR (~125 mL/min). | |
| Tubular function | Urine specific gravity & osmolality | Assess concentrating ability. |
| Water deprivation test | Detects diabetes insipidus or tubular defect. | |
| Acid load test | Tests acidification of urine (distal tubule). |
Subsection: Thyroid Function Tests
Case Scenario 6:
A 35-year-old woman presents with complaints of weight loss despite increased appetite, heat intolerance, palpitations, and tremors for the past 2 months. On examination, she has tachycardia, moist warm skin, and a diffuse goiter. The doctor orders thyroid function tests (TFTs) to confirm the diagnosis.
- What are the major functions of the thyroid gland and the hormones it secretes?
- Which thyroid function tests should be performed in this patient?
- How do the TFT results help differentiate between hypothyroidism and hyperthyroidism?
Answer
- a) Major functions of the thyroid gland & hormones:
The thyroid gland secretes:
- Thyroxine (T₄) and Triiodothyronine (T₃):
- Increase basal metabolic rate (BMR).
- Stimulate protein synthesis & growth.
- Enhance carbohydrate & fat metabolism.
- Increase heat production (calorigenic effect).
- Essential for normal CNS development.
- Calcitonin (from parafollicular C-cells):
- Lowers blood calcium by inhibiting bone resorption.
- b) Thyroid function tests (TFTs) to perform:
✅ Serum T₃ & T₄:
- Total & free T₄ and T₃ levels reflect hormone production.
- Elevated in hyperthyroidism, decreased in hypothyroidism.
✅ Thyroid-stimulating hormone (TSH):
- Most sensitive test.
- Decreased in primary hyperthyroidism (due to negative feedback).
- Increased in primary hypothyroidism.
✅ Free T₄ index (FTI) & Free T₄:
- More accurate in assessing thyroid hormone status when binding protein abnormalities are suspected.
✅ Other tests (if needed):
- Anti-thyroid antibodies (e.g., TPO antibodies in Hashimoto’s).
- Radioactive iodine uptake (RAIU) — increased in hyperthyroidism.
- c) TFT findings in hyperthyroidism vs. hypothyroidism:
| Parameter | Hyperthyroidism | Hypothyroidism |
| Serum T₄ & T₃ | ↑ | ↓ |
| Free T₄ & T₃ | ↑ | ↓ |
| TSH | ↓ (primary) | ↑ (primary) |
| RAIU (if done) | ↑ | ↓ |
Likely findings in this patient (hyperthyroidism):
- ↑ T₄ & T₃
- ↓ TSH
- ↑ RAIU (if tested)
- Positive anti-TSH receptor antibodies (if Graves’ disease).
Case Scenario 7:
A 40-year-old woman presents with complaints of weight gain, fatigue, constipation, dry skin, and cold intolerance for the past 3 months. On examination, she has bradycardia, coarse skin, periorbital puffiness, and a small goiter. The doctor suspects hypothyroidism and orders thyroid function tests.
- What is hypothyroidism and what are its clinical features?
- Which thyroid function tests are useful in diagnosing hypothyroidism?
Answer
- a) Hypothyroidism & its clinical features:
- Hypothyroidism is a clinical condition resulting from deficiency of thyroid hormones (T₃ & T₄) leading to reduced metabolic activity.
- Causes:
- Primary: Hashimoto’s thyroiditis, iodine deficiency, post-thyroidectomy.
- Secondary: pituitary or hypothalamic failure.
- Clinical features:
- Weight gain, fatigue, lethargy, bradycardia.
- Cold intolerance, dry/coarse skin, hair loss.
- Constipation, hoarseness of voice, periorbital puffiness.
- In children: cretinism (if congenital).
- b) Thyroid function tests in hypothyroidism:
✅ TSH (Thyroid Stimulating Hormone):
- Best initial test.
- ↑ in primary hypothyroidism due to loss of negative feedback.
- ↓ or normal in secondary hypothyroidism.
✅ Serum T₄ & T₃:
- Free T₄ ↓ (more reliable than total T₄).
- T₃ may also be ↓, but less sensitive.
✅ Other tests (if needed):
- Anti-thyroid peroxidase (TPO) antibodies: positive in autoimmune thyroiditis (Hashimoto’s).
- Radioactive iodine uptake (RAIU): ↓ in hypothyroidism.