Early Clinical Exposure: A Case Based Approach in Clinical Physiology Manjinder Kaur, Naren Kurmi, Sangita Chauhan
INDEX
ABCDEFGHIJKLMNOPRSTUVWX
Page numbers followed by f refer to figure and t refer to table.
A
Abdominal examination 14
Aberrant conducting tissue 40f
Acetone breath 80
Achalasia cardia, pathophysiology of 32f
Acid neutralizing drugs 28
Acid peptic disease 26
etiology of 27f
Acidosis 76
Acne 71
Acromegaly 71
clinical features of 72f
Activated partial thromboplastin time 13
Acute mountain sickness 56
pathophysiology of 56f
Air conduction 105, 106
Aluminium salts 28
Alzheimer's brain 103f
Alzheimer's disease 102
Amenorrhea 88
primary 114
Anemia 5
classification of 2
clinical classification of 3t
etiological classification of 2t
grades of 3
hemolytic 8
morphological classification of 2, 2t
Anorexia 80
Antacids 28
Anticholinesterase drugs 17
Antihypertensive medication 75
Antisecretory drugs 28
mechanism of action of 28f
Apathy 1
Aphasia 100
types of 101t
Apoferritin 3
Appetite, loss of 1, 82
Atrioventricular
conduction block 38
nodal blocks 38
node 38
Autoimmune 76
thyroiditis 64
Azoospermia 115
B
Barium swallow 32f
Basal ganglia 95f
Beta-amyloid plaques cause 103
Bicarbonate therapy 81
Bird beak appearance 32f
Bleeding time 13
Blood
loss 2, 73
pressure 61
urea nitrogen 61
Blurred vision 24
Body
ache 54
fluids, loss of 45
Bone conduction 105, 106
Botulism, pathophysiology of 24f
Breast enlargement 90
Breath 54
severe shortness of 41
shortness of 41
Breathlessness 1, 41, 50
Brown tumor, physiological basis of 83f
Brown-Sequard syndrome 92
clinical features of 93f
Brushfield spots 112
C
Caisson's disease 54
pathophysiology of 54f
Carbohydrate metabolism 77
Cardiac failure 41
Cardiac muscle 38f
Cardiovascular system 23
Carpopedal spasm, physiological basis of 85f
Caudate nuclei 95
Central nervous system 23, 102
examination 58
Cerebellar ataxia 96
Cerebellar function test 100
Cerebellum, functional division of 97f
Cerebrocerebellum 96
Chest
heaviness 47
muscles 24
Cholesterol, serum 73
Chromosomal aberrations, physiology of 112
Chronic obstructive pulmonary disease 50, 52, 53
clinical features of 53f
pathophysiology of 52, 52f
Chronic renal failure 61, 61t, 62
pathophysiology of 62f
Clostridium botulinum 24
Cochlear implants 106
Cold
intolerance 63
weather 99, 99t
Color vision 107, 109
Concave lens, use of 107f
Concussion, severe 96
Conductive deafness 105
Confrontation test 107, 109, 110
Congestive cardiac failure
management of 44, 44f
pathophysiology of 42, 43f
Consciousness, loss of 100
Constipation 35, 63, 82
Convulsions 54
Cornea 108
Cortical sensations 94
Cortisol 73
Cranial nerve examination 100
Creatinine, serum 61
Crude touch, sensation of 92
Cry, excessive 10
Cushing's syndrome 73
clinical features of 74f
D
Deaf ear 105t
Death 23
Deep vein thrombosis 89
Dehydration, signs of 80
Dehydroepiandrosterone 73
Diabetes mellitus 75
juvenile 79
pathophysiology of 78f
primary 76
secondary 76
Diabetic ketoacidosis 79
clinical features of 80f
pathophysiology of 80
Diarrhea 5
Digestive tract 26
Diplopia 16
Distant vision 110
Divalent metal transporter 3
Dizziness 37, 56, 98
Double vision 16
Down's syndrome 112
pathophysiology of 113f
Dry skin 63
Duchenne muscular dystrophy 21
clinical features of 21f
pathophysiology of 21f
Duodenal ulcer 27, 27t
Dysarthria 101
Dyspnea, mild 47
E
Ear 105, 105t, 106
Echocardiography 42f
Edema, lower extremity 61
Electrodiagnostic repetitive nerve stimulation 17
Elevated fasting blood sugar, basis of 71
Embolism, pulmonary 89
Emesis 61
Endocrinal functions 90
Endocrine physiology 63
Enteric nervous system 35f
Enterochromaffin 28
Epigastrium 26
Erectile dysfunction 86
Erythroblastosis 11
fetalis 10
Erythroblasts 11
Extracorpuscular defects 8
Extreme tiredness 24
Eye 107f
F
Facial expressions 94
Facial hair 73
Far vision 107, 109
Fasting blood
glucose 75
sugar 73
Fat metabolism 77
Fatigability 16
Fatigue 56, 63
Ferro protein transporter 3
Fever 100
Fluent aphasia 101
Fluid replacement 81
Follicle stimulating hormone 89
Foodborne botulism 24
sources of 24
Fracture 96
G
G-6-PD deficiency 8
pathophysiology of 8, 9f
Gait, shuffling 94
Gastric 7
ulcer 27, 27t
Gastroesophageal reflux disease 30
pathophysiology of 31f
Gastrointestinal system 23, 26
Gastrointestinal tract 3, 3f, 5, 6f
organization of 35f
Giddiness 22
Global aphasia 101
Globus pallidus 95
Glomerular filtration rate 89
Glucosuria 76, 89
H
Hair cells, loss of 106
Hashimoto's thyroiditis 64
HCL, mechanism of secretion of 28f
Headache 56, 71, 107
Healthy neuromuscular junction 18f
Hearing
aids 106
loss 104, 106
conductive 104
test 105
Heart 38f
block 37
classification of 39f
first degree 38
second degree 38
third degree 38
types of 38
rate 1, 89
Heat
balance, methods of 98f
gain 99
loss 99
stroke 98
Helicobacter pylori infection 27
Hematology 1
Hemoglobin 1
beta-globin chain of 14
concentration of 3
electrophoresis 14
Hemolytic anemia 8
causes of 8t
Hemolytic disease, pathophysiology of 10, 11f
Hemophilia 12
A 13f
pathophysiology of 12f
Hemorrhage 45
intracranial 103
Hepatobiliary system 90
High performance liquid chromatography 14
Hirschsprung's disease 35
pathophysiology of 36f
Hirsutism 71
Hormone assay 87
Hot weather 99, 99t
Human chorionic somatomammotropin 90
Hydrops fetalis 10
Hyperglycemia 76, 77
Hyperkalemia 76
Hyperkinetic features, causes of 95
Hyperparathyroidism 83f
primary 82, 83
secondary 83
Hypertension 61
Hyperthyroidism 67
clinical features of 68f, 69f
pathophysiology of 67f
Hypertonia 94
Hypocalcemia 85f
Hypoparathyroidism, secondary 84
Hypothyroidism 63
Hypovolemic shock 45
causes of 45, 45t
management of 46f
pathophysiology of 46f
I
Icterus 14
gravis neonatorum 10
Immunity, passive 10
Immunological test 88f
Impulse, transmission of 18f, 38f
Indigestion 5
Infertility
male 86
primary 86
Insulin
deficiency of 77t
infusion of 80
lack of 79
physiological actions of 77f
Interstitial fluid 28
Intracorpuscular defects 8
Iodine deficiency 64
Iron
absorption of 3, 3f
deficiency anemia 1, 2
clinical features of 4f
pathophysiology of 4
Ishihara's color plates 107, 109
J
Jaeger's chart 107, 109
Jargon speech 101
Jaundice 10
obstructive 33
Joint pains 14
K
Kent bundle 40f
Ketosis 76
Kidneys 45
Klinefelter's syndrome 115
pathophysiology of 115f
Knee, hematoma of 12
Koilonychia 1
Kussmaul breathing 80
L
Lambert-Eaton syndrome, pathophysiology of 20f
Legs 24
Lens, curvature of 108
Lesions, effects of 111f
Lethargy 61
Libido, loss of 86
Lightheadedness 37
Limbs 100
Lipid profile 75
Lipoprotein lipase 77
Lithium 64
Logorrhea 101
Lower esophageal sphincter 89
Lower motor neuron 92
Lung disease, restrictive 53
Luteinizing hormone 89
M
Magnesium 28
Malaise 98
Mean corpuscular
hemoglobin concentration 1
volume 1
Menstrual cycles 67, 71
Mental retardation, mild degree of 112
Metabolism 77f
Micturition 58, 75
frequency of 75
Mini-mental state examination test 102
Mood swings 67
Motor
aphasia 101
examination 100
functions 94
loss 92
vehicle accident 96
Mountain sickness, acute 56
Murmur, systolic 1
Musculoskeletal physiology 16
Myasthenia gravis 16, 20f
pathophysiology of 19f
Myocardial infarction 47
Myopia 107
Myopic eye 107f
N
Nausea 47, 56, 61, 98
Near vision 107, 109
Neologism 101
Neostigmine 17
Nerve deafness 105
Nervousness 67
Neurogenic bladder 58
dysfunction, pathophysiology of 59f
Neuropathy, peripheral 5
Non-fluent aphasia 101
Nonsteroidal anti-inflammatory drugs 27
O
Obstructive jaundice 33
features of 34f
pathophysiology of 34
Obstructive lung disease 53
Oily skin 71
Orthodontics 112
P
Packed cell volume 1
Pain 8f, 26, 104
abdominal 80
retrosternal 30
Pallor 1, 14
Palpitations 40
Paraphasia 101
Parkinson disease 94
pathophysiology of 95
Peripheral blood film 1, 14
Phalanges, subperiosteal bone resorption of 82f
Phospholipid 12
Plasma
glucose level 77
volume, loss of 45
Poikilocytosis 8
Polychromasia 8
Polydipsia, physiological basis of 78f
Polyphagia, physiological basis of 78f
Polyuria 80
physiological basis of 78f
Post-thyroidectomy
hypoparathyroidism 84
hypothyroidism 85f
Potassium replacement 81
Pregnancy 88, 89f
normal 88
Presbycusis 106
Presbyopia 109
pathophysiology of 109f
Primary hyperparathyroidism 82, 83
clinical features of 83f
Primary hyperthyroidism 70
Prophylaxis 10
Proprioception 92
Prostaglandin analogs 29
Protein metabolism 77
Prothrombin time 13
Proton pump inhibitors 29
Proximal muscle weakness 16
Pruritus 61
Ptosis 16
Puffer fish 22f
Punctum proximum 109
Putamen 95
R
Rapid breathing 80
Reflexes, pupillary 107, 109
Refractive error, correction of 107f
Renal blood flow 89
Renal failure 61
acute 61, 61t, 62
chronic 61, 61t, 62
Renal function tests 75
Renal transplant, indications of 58
Repetitive speech, sudden onset of 100, 100f
Reproductive physiology 86
Respiratory physiology 50
Respiratory system 23, 89
examination of 50
Restlessness 100
Retina 107f
Rinne's test 105, 106
Road traffic accident 58
Romberg sign 97
S
Salt and pepper sign 82f
Schwabach test 105, 106
Semen analysis 87
normal 87t
Sensory
aphasia 101
ataxia 97
function 94
loss 92
Shock
hypovolemic 45
management of 46
stages of 45, 45t
Short stature 114
webbed neck 114
Sickle cell anemia 14
pathophysiology of 15f
Sickling test 14
Slight memory loss 63
Snare proteins, types of 25
Snellen's chart 107, 109
Snore 71
Sore throat 104
Special senses, physiology of 104
Speech 100, 101f
agrammatic 101
slow 63
Sperm
count 87
morphology 87
Spinal cord 58f
Spinocerebellum 96
Spirometer, parameter of 53
Spirometry 51, 51f
Stiffness 92
Stimulates hormone sensitive lipase 77
Stokes-Adams syndrome 38
Stress management 28
Striatum 95
Substantia nigra 95
Subthalamic nucleus 95
Supraventricular tachycardia 40
Sweating 99
excessive 71
Swollen knee 12
Synaptobrevin 25
Syncope 37, 40
Syntaxin 25
T
Tachycardia 50
Tachypnea 50
Tactile discrimination 92
Tanner stage 114
Tau proteins 103
Testosterone 73
levels 71
Tetrodotoxin poisoning 22
pathophysiology of 23f
Thyroid
Gland
abnormal 64
removal of 84
hormone secretion, regulation of 66f
nodule 84
synthesis, inborn errors of 64
Thyroidectomy 84
Total iron binding capacity 1
Touch sensation, loss of 92
Trans ferritin 3
Tremors 94
Tuning fork test 105t, 106t
Turner's syndrome 114
pathophysiology of 114f
U
Ulcer 29
Upper motor neuron 92
Urinary bladder 58
Urinary tract infection 89
V
Vasoactive crisis 15
Vestibulocerebellum 96
Vibration 92
Vision, field of 107, 109
Visual acuity 107, 109, 110
Visual disturbance 71
Visual pathway 110, 111f
Vitamin B12
absorption of 5, 6f
deficiency 5
causes of 7t
Vomiting 45, 98
W
Water loss 34
Weakness 16
signs of 100
Webbed neck 114
Weber test 105, 106
Weight
gain 63, 90
loss 30
Wolff-Parkinson-White syndrome 40, 40f
X
X chromosome 114, 115
X-ray
chest 51f
hand 82f
skull 82f
×
Chapter Notes

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HematologyCHAPTER 1

PY2.5 Describe anemias and jaundice. Discuss their physiological principles of management.
PY2.9 Describe hemostasis, coagulation pathways, mechanism of action of anticoagulants and briefly discuss pathophysiological aspects of bleeding and clotting disorders (e.g., hemophilia, purpura).
After finishing this module, you should be able to:

Learning objectives

  • Analyze the clinical problem on the basis of its signs and symptoms, laboratory findings, to reach a differential diagnosis for that problem.
  • Describe the pathophysiology of the given clinical condition based on the clinical and laboratory findings.
  • Discuss the rationale of management, based on the derangement of physiological parameters in a case scenario.
 
Case 1.1 Iron deficiency anemia
A 35-year-old female complains of breathlessness, loss of appetite, apathy and easy fatigability. Examination of the patient revealed pallor, koilonychia, increased heart rate and systolic murmur.
Laboratory investigations of this patient were obtained as under:
  • Hemoglobin: 6.0 g% (Reference value: 12–14 g% in females; 14–16 g% in males)
  • Packed cell volume (PCV): 30% (Reference value: 42–45%)
  • RBC count: 3.0 million/cu.mm (Reference value: 4.5–5.5 million/cu.mm)
  • S. ferritin: 9 nanogram/mL (Reference value: 12–300 ng/mL)
  • Mean corpuscular volume (MCV): 70 fL (Reference value: 80–100 fL)
  • Total iron binding capacity (TIBC): 500 microgram/dL (Reference value: 240–450 microgram/dL)
  • Mean corpuscular hemoglobin concentration (MCHC): 28% (Reference value: 32–36%)
  • Peripheral blood film (PBF): RBC are microcytic and hypochromic2
Based on the above case, answer the following questions:
  1. What do you think this patient is suffering from?
  2. How would you grade the anemia of this patient based on clinical classification?
  3. What do you understand about microcytic and hypochromic RBCs in this patient?
  4. How is the deficient nutrient absorbed and utilized in our body?
  5. Define anemia.
  6. Classify anemia according to the etiology (cause).
  7. Classify anemia according to the morphology of RBCs.
  8. Describe the physiological basis of clinical features/symptoms of this disease.
Provisional diagnosis: Iron deficiency anemia (IDA).
Definition: Decreased oxygen carrying capacity of blood with or without decreased hemoglobin content or RBC count or both.
 
Classification of Anemia
 
 
Etiological Classification
Table 1.1   Etiological classification of anemia.
Main etiology
Increased blood loss
Increased breakdown of rbc
Decreased production of rbc
Various causes
Acute blood loss
Chronic blood loss
Red cell membrane defects
Enzyme defects
Abnormal hemoglobin
Immune mediated hemolysis
Deficiency of nutrients
Bone marrow disorders
Examples
Acute hemorrhage due to road traffic accident, major surgeries, etc.
Hemorrhoids (piles), hookworm infestation, dysfunctional uterine bleeding in women, etc.
Hereditary spherocytosis, ovalocytosis
Glucose-6- phosphate dehydrogenase (G6PD) deficiency
Sickle cell anemia
Incompatible ABO blood transfusion
Iron deficiency, folic acid/vitamin B12 deficiency, protein deficiency
Aplastic anemia, etc.
 
Morphological Classification
Table 1.2   Morphological classification of anemia.
Hypochromic (MCHC <31 g/dL)
Normochromic (MCHC = 31–33 g/dL)
Size of RBC <7 μm (microcytic; MCV <80 fL)
Iron deficiency anemia thalassemia lead poisoning
Chronic infection
Size of RBC = 7 μm (normocytic, MCV = 80–100 fL)
Chronic hemorrhage
  • Acute blood loss hemolytic anemia
  • Aplastic anemia
Size of RBC >7 μm (macrocytic; MCV >100 fL)
Liver disease
  • Vitamin B12 deficiency
  • Folic acid deficiency3
 
Clinical Classification
Table 1.3   Clinical classification of anemia.
Concentration of Hb
Grades of anemia
>10 g/dL
No anemia
8–10 g/dL
Mild anemia
5–8 g/dL
Moderate anemia
<5 g/dL
Severe anemia
 
Absorption of Iron from GIT
Refer Figure 1.1.
zoom view
Fig. 1.1: Absorption of iron from GIT.[DMT: divalent metal transporter; FP: ferro protein transporter; TF: trans ferritin (synthesized in the liver); AF: apoferritin]
4
zoom view
Fig. 1.2: Physiological basis of clinical features of iron deficiency anemia.
 
Pathophysiology of IDA and Physiology of Clinical Symptoms (Fig. 1.2)
 
Laboratory Diagnosis
  • Decreased RBC count (<4.5 million/cc in females and 5 million/cc in males) and hemoglobin content (<10 g/dL)
  • Peripheral blood film shows microcytic hypochromic RBCs
  • Red cell indices: MCV <80 fl, MCHC <31 g/dL
  • Decreased S. ferritin levels (<10 ng/mL in adult females and <20 ng/mL in adult males)
  • Increased total iron binding capacity (TIBC) (>450 μg/mL)5
 
Case 1.2 anemia due to vitamin B12 deficiency
A 45-year-old male complains of indigestion, diarrhea, soreness in angles of mouth, loss of appetite and tingling sensation in the hands and feet. Examination of the patient revealed angular stomatitis, red beefy tongue and peripheral neuropathy.
Laboratory investigations of these patients were obtained as under:
  • Hemoglobin: 9.0 g%
  • RBC count: 1 million/cu.mm.
  • S. Iron: 170 microgram/dL (Reference value: 60–170 mg/dL)
  • MCV: 100 fL
  • MCH: 50 pg
  • Reticulocyte count: 6% (Reference value: 1–2%)
Based on the above case, answer the following questions:
  1. What do you think this patient is suffering from?
  2. What is the cause of peripheral neuropathy in this type of anemia?
  3. Why do you see large nucleated RBC (megaloblasts) in PBF, in this condition?
  4. How is the deficient nutrient absorbed and utilized in our body?
  5. Why is this type of anemia seen in patients with gastric atrophy?
  6. What are the other conditions with a similar blood picture? What are the causes for the same?
  7. What will happen if you give only folic acid supplementation in pernicious anemia?
PBF: RBC are macrocytic and normochromic with some large nucleated RBC, neutropenia with hypersegmented neutrophils and decreased platelets per high power field.
Provisional diagnosis: Megaloblastic anemia (vitamin B12 deficiency).
Note: Deficiency of intrinsic factor due to autoimmune causes is termed as pernicious anemia.
 
Absorption of Vitamin B12 from GIT (Refer Fig. 1.3)
Both vitamin B12 and folic acid, act as methyl carriers and are responsible for the nuclear maturation of the cells, hence present with macrocytic, normochromic and megaloblastic anemia. The cytoplasmic maturation of the cells is normal.
Supplementation of only folic acid, in a patient with vitamin B12 deficiency, may result in improvement of blood picture but worsening of peripheral neuropathy. Hence, the patient should be properly evaluated before starting the supplementation.
PBF: The RBCs in peripheral blood film of megaloblastic anemia (both in vitamin B12 and folic acid deficiency) are macrocytic and normochromic. The red cells are larger in size but the hemoglobin concentration is normal (increased MCV, normal MCHC). Some of the RBCs are nucleated (seive like nucleus); called as megaloblasts, hence the name ‘megaloblastic anemia’. The other cells (WBCs and platelets) are also affected showing neutropenia and shift to right on Cooke-Arneth along with thrombocytopenia.
Various causes of vitamin B12 deficiency are given in Table 1.4.6
zoom view
Fig. 1.3: Absorption of vitamin B12 from GIT.
7
Table 1.4   Various causes of vitamin B12 deficiency.
Gastric
Intestinal
Cause
Deficiency of intrinsic factor (IF)
Decrease absorption of vitamin B12
Examples
  • Autoimmune causes of failure of secretion of IF (pernicious anemia)
  • Gastrectomy
  • Congenital lack of IF
  • Tropical sprue
  • Crohn's disease
  • Fish tapeworm infestation
  • Intestinal blind loop syndrome8
 
Case 1.3 G-6-PD Deficiency: Hemolytic anemia
A 20-year-old male complains of pain in loin and passage of dark urine after eating fava beans. Examination of the patient revealed nothing significant.
Laboratory investigations of this patient were obtained as under:
  • Hemoglobin: 10 g%
  • RBC count: 3 million/cu.mm.
(Note: Plasma hemoglobin and methemoglobin levels are raised)
PBF: RBC are normocytic and normochromic with polychromasia, basophilic stipplings and marked poikilocytosis.
Based on the above case, answer the following questions:
  1. What do you think this patient is suffering from?
  2. What are the causes of this type of anemia?
  3. What is the mechanism of action of the deficient enzyme in this condition?
  4. How can you prevent this condition?
  5. What are the other types of hemolytic anemia and what is the cause in each one of them?
  6. What are target cells? In which condition, they are seen?
Provisional diagnosis: Hemolytic anemia (G-6-PD deficiency).
Hemolytic anemia could occur due to many causes, as given in Table 1.5.
 
Pathophysiology of G-6-PD Deficiency and Physiology of Clinical Symptoms
See Figure 1.4.
Table 1.5   Causes of hemolytic anemia.
Due to defects within the RBCs (intracorpuscular defects)
Due to various pathologies outside the RBCs (extracorpuscular defects)
Defects in red cell membrane:
  • Hereditary spherocytosis
  • Hereditary ovalocytosis
Mechanical trauma to RBCs:
  • Thrombi within circulation
  • Exotoxins
Defective hemoglobin chains (hemoglobinopathies):
  • Thalassemia
  • Sickle cell anemia
Antigen antibody mediated hemolysis:
  • ABO incompatibility
  • Rh incompatibility
  • Drug induced
Enzyme defects:
  • G-6-PD deficiency
  • Pyruvate kinase and hexokinase deficiency9
zoom view
Fig. 1.4: Pathophysiology of G-6-PD deficiency anemia.
10
 
Case 1.4 Erythroblastosis fetalis
A 4-day-old home delivered male baby was brought to the pediatrician with complaints of excessive cry and jaundice. The mother of the baby is from a village and did not avail any antenatal check-up during the pregnancy. She has a 2-year-old male child who was a full term normal home delivered baby.
Mother has no history of abortion and no history of jaundice in the first baby after birth. Details of the blood group of the family are not available.
On examination: Baby is lethargic with poor muscle tone, poor feeding and jaundice.
Investigations:
  • Mother: Blood group is B negative.
  • Baby:
    • Blood group: AB positive
    • Hb: 10 g%
    • Erythroblasts: Abundant (erythroblastemia)
    • S. bilirubin: 18 mg/dL (Reference value: 0.2–0.8 mg/dL)
Based on the above case, answer the following questions:
  1. What is the probable diagnosis?
  2. What is the pathophysiology behind the clinical condition presented?
  3. How can this condition be prevented in subsequent pregnancies?
  4. What is the physiological basis of prophylaxis given?
Provisional diagnosis: Hemolytic disease of newborn due to Rh incompatibility (erythroblastosis fetalis).
 
Pathophysiology of Hemolytic Disease of Newborn (HDN) (Fig. 1.5)
The first pregnancy can also be affected by Rh incompatibility, in case of previous exposure to D-antigen (as in case of transfusion of Rh positive blood to Rh negative lady).
The concentration of anti-D antibodies formed in the mother will depend upon the antigen load entering the maternal circulation.
Based on the severity of HDN, it is classified as:
  1. Hydrops fetalis: Most severe. Baby is swollen and baby dies in utero or few hours after birth.
  2. Icterus gravis neonatorum: Characterized by hemolytic jaundice, anemia, erythroblastemia, kernicterus (deposition of bilirubin in basal ganglia, if more than 18 g%) and liver damage.
Prophylaxis: Injection anti-D (RhoGam) within 72 hours of delivery. It is a type of passive immunity.
Treatment:
  1. Intrauterine fetal blood transfusion
  2. Exchange transfusion: Transfusing Rh negative blood of same ABO type to stop hemolysis, till the antibodies persist in neonatal blood.
  3. Phototherapy
  4. Immunoglobulin therapy11
zoom view
Fig. 1.5: Pathophysiology of hemolytic disease of newborn.Note: Erythroblastosis means the increased number of circulating erythroblasts.
12
 
Case 1.5 Hemophilia
A young boy of 8-year-old complained of a swollen knee after he fell from the bicycle. He also complained of some bluish discoloration of the skin of right arm. His past history is suggestive of prolonged bleeding even after minor injury. On examination, he was found to have a hematoma of the knee. His laboratory investigations show prolonged CT, APTT with normal BT and PT. His hemoglobin is 9.0 g%.
Based on the above case, answer the following questions:
  1. What is the probable diagnosis?
  2. Why is the bleeding time normal in this patient despite a prolonged CT and APTT?
  3. What is the physiological basis of the clinical symptoms?
Provisional diagnosis: Hemophilia A
Hemophilia is a bleeding disorder and is of two types:
  1. Hemophilia A: Due to deficiency of factor VIII (more common)
  2. Hemophilia B: Due to deficiency of factor IX
Hemophilia A is a clinical condition that arises due to deficiency of factor VIII resulting in bleeding tendencies.
zoom view
Fig. 1.6: Pathophysiology of hemophilia A.(PL: phospholipid)
13
zoom view
Fig. 1.7: Inheritance in hemophilia A patients.
Factor VIII is present on the X- chromosome and hence it is inherited as a X-linked recessive genetic disorder.
Diagnosis of hemophilia begins with a good clinical history and physical examination supported by the following laboratory investigations:
  1. Bleeding time (BT): Normal (as platelet count is normal, temporary hemostasis is not affected).
  2. Clotting time (CT): Prolonged (due to derangement in the intrinsic pathway of coagulation).
  3. Prothrombin time (PT): Normal
    • PT is a test used for extrinsic pathway and common pathway of coagulation (factors involved are VII, X, V, II, I)
  4. Activated partial thromboplastin time (APTT): Prolonged.
    • Test is used for intrinsic and common pathway of coagulation (factors involved are XII, XI, IX, VIII, X, V, II, I)
    • Factor VIII and IX are a part of intrinsic pathway, so APTT is increased in hemophilia A and hemophilia B).14
 
Case 1.6 Sickle cell ANEMIA
A three-and-a-half-year-old male child was brought to the OPD with complaints of refusal to eat and off and on pain in the abdomen. He also complained of off and on joint pains.
On examination: The child was cooperative but irritable, well oriented to time, place and person.
Vitals: Normal.
Pallor and icterus: Present
Abdominal examination: Splenomegaly
CVS and respiratory system: NAD
Laboratory investigations:
  • Hb: 8 g%
  • RBC: 3 million/cmm
  • PCV: 30%
  • MCV: 86 fL
  • MCHC: 32%
  • Peripheral blood film: Normocytic normochromic RBCs
  • S. bilirubin: 2.8 mg/dL
  • Hb electrophoresis: SS pattern
  • Solubility test also known as sickling test: Showed sickle cells
  • High performance liquid chromatography (HPLC): technique: Presence of HbS
Based on the above case, answer the following questions:
  1. What is the probable diagnosis?
  2. What is the pathophysiology of the given disease?
  3. What is sickle cell crisis?
  4. How does it differ from thalassemia?
Provisional diagnosis: Sickle cell anemia
Definition: It is a genetic disorder characterized by the presence of HbS instead of Hb A.
Pathophysiology:
Normal person
Person with sickle cell anemia
DNA
CTC
CAC
mRNA
GAG
GUG
It is a type of point mutation in the gene that encodes for the beta-globin chain of hemoglobin. It leads to formation of an abnormal Hb, known as HbS. In HbS, at the 6th position of the β-chain, glutamate (which is normally present in HbA) is replaced by valine.
Clinical presentation
  • Occlusion of the microvasculature
    ↓
    Ischemic pain and necrosis of tissue distal to the occlusion
  • Features of hemolytic anemia
  • Features of hemolytic jaundice15
  • Hepatosplenomegaly
  • Vasoactive crisis:
    • Stroke
    • Ischemic necrosis
    • Acute chest syndrome
zoom view
Fig. 1.8: Pathophysiology of sickle cell anemia.