Degradation of Purine Nucleotides
Uric acid is formed in humans in
A |
Liver |
|
B |
Kidney |
|
C |
GIT mucosa |
|
D |
Joints |
Uric acid is formed in humans in
A |
Liver |
|
B |
Kidney |
|
C |
GIT mucosa |
|
D |
Joints |
GIT mucosa
Most of the dietary purines are converted to uric acid in lhe intestinal’mucosal cell only. Intestinal bacterialJlora is intolved in degradation of the rest of dietary purines that remain unabsorbed.
A patient with increased Hypoxanthine and Xanthine in blood with hypouricemia which enzyme is deficient?
A |
HGPRTase |
|
B |
Xanthine oxidase |
|
C |
Adenosine deaminase |
|
D |
APRtase |
A patient with increased Hypoxanthine and Xanthine in blood with hypouricemia which enzyme is deficient?
A |
HGPRTase |
|
B |
Xanthine oxidase |
|
C |
Adenosine deaminase |
|
D |
APRtase |
- Hypouricemia- Hypouricemia and increased excretion of hypoxanthine and xanthine are associated with xanthine oxidase deficiency.
- Lesch-Nyhan Syndrome- The Lesch-Nyhan syndrome, an overproduction hyperuricemia characterized by frequent episodes of uric acid lithiasis and a bizarre syndrome of selfmutilation reflects a defect in hypoxanthine-guanine phosphoribosyltransferase, an enzyme of purine salvage.
- Adenosine Deaminase Deficiency- Adenosine deaminase deficiency is associated with an immunodeficiency disease in which both thymus-derived lymphocytes (T cells) and bone marrow-derived lymphocytes (B cells) are sparse and dysfunctional. Patients suffer from severe immunodeficiency.
- Purine Nucleoside Phosphorylase Deficiency- Purine nucleoside phosphorylase deficiency is associated with a severe deficiency of T cells but apparently normal B cell function
Degradation of Pyrimidine Nucleotides
What is the end product of catabolism of pyrimidine?
A |
NH3 |
|
B |
CO2 & H2O |
|
C |
Both |
|
D |
None |
What is the end product of catabolism of pyrimidine?
A |
NH3 |
|
B |
CO2 & H2O |
|
C |
Both |
|
D |
None |
The end products of pyrimidine catabolism is CO2 and H2O.
Which is the product excreted unchanged in catabolism of pyrimidine?
A |
Uric acid |
|
B |
NH3 |
|
C |
Pseudouridine |
|
D |
Beta alanine |
Which is the product excreted unchanged in catabolism of pyrimidine?
A |
Uric acid |
|
B |
NH3 |
|
C |
Pseudouridine |
|
D |
Beta alanine |
Pseudouridine is excreted unchanged as it cannot be catabolized in human.
Steps Of Protein Synthesis (Translation)
A | Ribosomal RNA | |
B | Messenger RNA | |
C | Signal recognition particle | |
D | Peptidyl transferase |
A | Ribosomal RNA | |
B | Messenger RNA | |
C | Signal recognition particle | |
D | Peptidyl transferase |
Signal recognition particles (SRPs) recognize the signal sequence on the N-terminal end of proteins destined for the lumen of the endoplasmic reticulum (ER). SRP binding arrests translation and an SRP receptor facilitates import of the SRP, ribosome, and nascent protein into the ER lumen. A signal peptidase removes the signal sequence from the protein, which may remain in the membrane or be routed for secretion.
Common to both eukaryotic and prokaryotic protein synthesis is the requirement for ATP to activate amino acids. The activated aminoacyltRNAs then interact with ribosomes carrying mRNA. Peptidyl transferase catalyzes the formation of peptide bonds between the free amino group of activated aminoacyl-tRNA on the A site of the ribosome and the esterified carboxyl group of the peptidyl-rRNA on the P site; the liberated rRNA remains on the P site.
GTP is required by which of the following steps in protein synthesis?
A |
Aminoacyl—tRNA synthetase activation of amino acids |
|
B |
Attachment of mRNA to ribosomes |
|
C |
Attachment of ribosomes to endoplasmic reticulum |
|
D |
Translocation of tRNA—nascent protein complex from A toP sites |
GTP is required by which of the following steps in protein synthesis?
A |
Aminoacyl—tRNA synthetase activation of amino acids |
|
B |
Attachment of mRNA to ribosomes |
|
C |
Attachment of ribosomes to endoplasmic reticulum |
|
D |
Translocation of tRNA—nascent protein complex from A toP sites |
he entry of the aminoacyl-tRNA into the A site results in the hydrolysis of one GTP to GDP.
Translocation of the newly formed peptidyl-tRNA in the A site into the P site by EF 2 similarly results in hydrolysis of GTP to GDP and phosphate.
Thus, the energy requirements for the formation of one peptide bond include the equivalent of the hydrolysis of two ATP molecules to ADP and of two GTP molecules to GDP, or the hydrolysis of four high-energy phosphate bonds.
Protein synthesis in eukaryotes is different from prokaryotes. Which of the following is NOT TRUE about steps in initiation of eukaryotic protein synthesis?
A |
Dissociation of the ribosome into its 40S and 60S subunits |
|
B |
Binding of a ternary complex to the 40S ribosome |
|
C |
Binding of mRNA to the 60S preinitiation complex to form the 43S initiation complex |
|
D |
Combination of the 48S initiation complex with the 60S ribosomal subunit |
Protein synthesis in eukaryotes is different from prokaryotes. Which of the following is NOT TRUE about steps in initiation of eukaryotic protein synthesis?
A |
Dissociation of the ribosome into its 40S and 60S subunits |
|
B |
Binding of a ternary complex to the 40S ribosome |
|
C |
Binding of mRNA to the 60S preinitiation complex to form the 43S initiation complex |
|
D |
Combination of the 48S initiation complex with the 60S ribosomal subunit |
Initiation of protein synthesis can be divided into four steps:
- Dissociation of the ribosome into its 40S and 60S subunits;
- Binding of a ternary complex consisting of the initiator methionyl-tRNA, (met-tRNAi), GTP, and eIF-2 to the 40S ribosome to form the 43S preinitiation complex;
- Binding of mRNA to the 40S preinitiation complex to form the 48S initiation complex; and
- Combination of the 48S initiation complex with the 60S ribosomal subunit to form the 80S initiation complex.
Chain initiation in protein synthesis is by‑
A |
AUG |
|
B |
GLA |
|
C |
UGA |
|
D |
UAG |
Chain initiation in protein synthesis is by‑
A |
AUG |
|
B |
GLA |
|
C |
UGA |
|
D |
UAG |
A i.e. AUG
The cellular component for protein synthesis is :
A |
Smooth endoplasmic reticulum |
|
B |
Rough endoplasmic reticulum |
|
C |
Ribosomes |
|
D |
Mitochondria |
The cellular component for protein synthesis is :
A |
Smooth endoplasmic reticulum |
|
B |
Rough endoplasmic reticulum |
|
C |
Ribosomes |
|
D |
Mitochondria |
C i.e. Ribosomes
Termination process of protein synthesis is performed by:
A |
Releasing factor |
|
B |
Stop codon |
|
C |
UAA codon |
|
D |
All |
Termination process of protein synthesis is performed by:
A |
Releasing factor |
|
B |
Stop codon |
|
C |
UAA codon |
|
D |
All |
A, B, C i.e. Releasing factor, Stop codon, UAA codon
Which of the following is not required for protein synthesis of eukaryotes:
A |
RNA polymerase |
|
B |
Ribosomes |
|
C |
Peptidyl transferase |
|
D |
Amino acyl tRNA synthetase |
Which of the following is not required for protein synthesis of eukaryotes:
A |
RNA polymerase |
|
B |
Ribosomes |
|
C |
Peptidyl transferase |
|
D |
Amino acyl tRNA synthetase |
Ans. a. RNA polymerase (Ref Harper 28/e p362) RNA polymerase enzyme is involved in transcription process, not in translation.
The a-amino group of the new aminoacyl-tRNA in the A site carries out a nucleophilic attach on the esterified carboxyl group of the peptidyl-tRNA occupying the P site (peptidyl or polypeptide site).
Peptidyl transferase: Catalyses two reactions, peptide bond formation between amino acids and together with release factor, peptide release.
False about eukaryotic protein synthesis is:
A |
N formyl Met is the first-RNA to come into action |
|
B |
mRNA read from 5′ to 3′ |
|
C |
Eft shift between GDP to GTP |
|
D |
Capping helps in attachment of mRNA to 40 S ribosome |
False about eukaryotic protein synthesis is:
A |
N formyl Met is the first-RNA to come into action |
|
B |
mRNA read from 5′ to 3′ |
|
C |
Eft shift between GDP to GTP |
|
D |
Capping helps in attachment of mRNA to 40 S ribosome |
A i.e. N formyl Met is the first – RNA to come into action
Protein synthesis occurs in:
September 2012
A |
Smooth endoplasmic reticulum |
|
B |
Rough endoplasmic reticulum |
|
C |
Golgi bodies |
|
D |
Nucleus |
Protein synthesis occurs in:
September 2012
A |
Smooth endoplasmic reticulum |
|
B |
Rough endoplasmic reticulum |
|
C |
Golgi bodies |
|
D |
Nucleus |
Ans. B i.e. Rough endoplasmic reticulum
Rough ER
- The surface of the rough endoplasmic reticulum (often abbreviated RER) is studded with protein-manufacturing ribosomes giving it a “rough” appearance (hence its name).
Acute myeloid leukemia (AML)
Non-specific esterase is positive in all the categories of Acute Myeloid Leukemia, EXCEPT:
A |
M3 |
|
B |
M4 |
|
C |
M5 |
|
D |
M6 |
Non-specific esterase is positive in all the categories of Acute Myeloid Leukemia, EXCEPT:
A |
M3 |
|
B |
M4 |
|
C |
M5 |
|
D |
M6 |
Non specific esterase is negative in M3 type of Acute myeloid leukemia (AML).
Alpha naphthyl acetate esterase (ANAE), Alpha naphthyl butyrate esterase (ANBE) and Alpha naphthyl AS esterase (NASA) are the non specific esterase reactions that are positive in M4 (acute myelomonocytic leukemia) and M5 (acute monocytic/monoblastic leukemia) type of AML.
Their presence is variable in M6 (acute erythroid leukemia).
Ref: Wintrobe’s Clinical Hematology, 10th Ed, Page 2221; Textbook of pathology, B N Datta, 2nd Edition, Page 1118 & 1119.
A 32 year old male is diagnosed of having acute myeloid leukemia. His total WBC count was less than normal initially. Which of the following factor has a bad prognosis in AML?
A |
Monosomies of chromosomes |
|
B |
Young age |
|
C |
Patients with t(15;17) |
|
D |
Low WBC count |
A 32 year old male is diagnosed of having acute myeloid leukemia. His total WBC count was less than normal initially. Which of the following factor has a bad prognosis in AML?
A |
Monosomies of chromosomes |
|
B |
Young age |
|
C |
Patients with t(15;17) |
|
D |
Low WBC count |
Prognostic factors of acute myeloid leukemia (AML):
- Advancing age is associated with a poorer prognosis, in part because of its influence on the patient’s ability to survive induction therapy.
- The leukemic cells in elderly patients more commonly express the multidrug resistance 1 (MDR1) efflux pump that conveys resistance to natural product–derived agents such as the anthracyclines.
- Patients with t(15;17) have a very good prognosis, and those with t(8;21) and inv(16) a good prognosis, while those with no cytogenetic abnormality have a moderately favorable outcome.
- Patients with a complex karyotype, t(6;9), inv(3), or -7 have a very poor prognosis.
- Among patients with hyperleukocytosis (>100,000/L), early central nervous system bleeding and pulmonary leukostasis contribute to poor outcome with initial therapy.
- Karyotypes include monosomy chromosome 5 or chromosome 7 have 78% of relapse rate.
All of the following genetic syndromes are associated with Acute Myeloid Leukemia, except:
A |
Down’s Syndrome |
|
B |
Klinefelter’s Syndrome |
|
C |
Patau Syndrome |
|
D |
Turner’s Syndrome |
All of the following genetic syndromes are associated with Acute Myeloid Leukemia, except:
A |
Down’s Syndrome |
|
B |
Klinefelter’s Syndrome |
|
C |
Patau Syndrome |
|
D |
Turner’s Syndrome |
Of all the options given Turner’s syndrome is not found to be associated with increased incidence of acute myeloid leukemia (AML). Down’s syndrome, Klinefelter’s Syndrome, Patau Syndrome are associated with AML.
Ref: Harrison’s Principles of Internal Medicine16th Edition, Page 631; Excellent Care for Cancer Survivors: A Guide to Fully Meet Their Needs By Kenneth Miller – Pg 327; Childhood Leukemia: A Practical Handbook, By Gregory H. Reaman – Pg 11
All of the following are poor prognostic factors in a case of acute myeloid leukemias, except:
A |
Age more than 60 years |
|
B |
Presence of t(8:21) |
|
C |
Secondary leukemias |
|
D |
Leucocyte count more than 1,00,000/microl |
All of the following are poor prognostic factors in a case of acute myeloid leukemias, except:
A |
Age more than 60 years |
|
B |
Presence of t(8:21) |
|
C |
Secondary leukemias |
|
D |
Leucocyte count more than 1,00,000/microl |
Patients t(8;21) and inv(16) has a good prognosis, approximately 55% of these patients are cured. t(15:17) is associated with a very good prognosis, while those without any cytogenetic abnormality have a moderately favorable outcome.
Which of the following is a poor prognostic factor in Acute Myeloid Leukemia (AML)
A |
Monosomy |
|
B |
Deletion of X or Y chromosome |
|
C |
t (8; 21) translocation |
|
D |
Nucleophosphin mutation |
Which of the following is a poor prognostic factor in Acute Myeloid Leukemia (AML)
A |
Monosomy |
|
B |
Deletion of X or Y chromosome |
|
C |
t (8; 21) translocation |
|
D |
Nucleophosphin mutation |
Answer is A (Monosomy)
Monosomy is consistently associated with an unfavorable or poor prognosis.
Monosomy is associated with a poor prognosis
Monosomy especially those involving chromosome 7 (monosomy 7) and chromosome 5 (monosomy 5) are consistently associated with poor prognosis in both adults and children with AML
Deletion of X or Y chromosome is associated with a favorable / intermediate prognosis
‘Monosomy of the X chromosome in a female patient (loss of the Y chromosome) is the most common whole chromosome loss identified in pediatric patients with AML. This numeric abnormality is usually associated with t(8; 21) translocation and AML M2 which carry a good prognosis’ – ‘Childhood Leukemias’ by Puri 2″d/253
`Loss of Y and X chromosomes are most frequently observed in patients with t(8; 21) which carries a favourable prognosis’ – ‘Blood: Principles and Practice of Hematology’ 2″d/108
Nucleophosphin mutation is associated with a favorable prognosis |
||
|
||
Factor |
Favourable |
Unfavourable |
Nucleophosphin mutation |
Present |
Absent |
t (8; 21) translocation is associated with a favorable prognosis |
Factor |
Favourable |
Unfavourable |
Cytogenetics |
t(15;17), 1(8;21), inv(16) |
-7, del(7q), -5, del(5q), 3q21 and 3q26 abnormalities, complex karyotypes |
Prognostic Feature in Acute Myeloid Leukemia:
Factor Favourable Unfavourable |
||
Clinical |
||
Age |
<45 yr |
<2yr, >60yr |
ECOG performance status |
0-1 |
> I |
Leukemia |
De novo |
Antecedent hematologic disorder, myelodysplasia, myeloproliferative disorder |
Infection |
Absent |
Present |
Prior chemotherapy |
No |
Yes |
Leukocytosis |
<25,000/mm3 |
> 100,000/mm2 |
Serum LDH |
Normal |
Elevated |
Extramedullary disease |
Absent |
Present |
CNS disease |
Absent |
Present |
Cytoreduction |
Rapid |
Delayed |
Morphology |
||
Auer rods |
Present |
Absent |
Eosinophils |
Present |
Absent |
Megaloblastic erythroids |
Absent |
Present |
Dysplastic megakaryocytes |
Absent |
Present |
FAB type |
M2, M3, M4 |
MO, M6, M7 |
Surface/enzyme markers |
||
Myeloid |
CD34-, CDI4-, CD13- |
CD34+ |
HLA-DR |
Negative |
Positive |
TdT |
Absent |
Present |
Lymphoid |
Cd2+ |
CD7+, CD56+ Biphenotypic (2 or more lymphoid markers) Present |
MDR-1 |
Absent |
|
Cytogenetics |
||
Cytogenetics |
1(15;17), 1(8;21), inv(16) |
-7, del(7q), -5, del(5q), 3q21 and 3q26 abnormalities, complex karyotypes |
Molecular markers |
||
Fms-related tyrosine kinase-3 mutation |
Absent |
Present |
Ecotropic viral integration site 1 expression |
Absent |
Present |
Mixed-lineage leukemia partial tandem duplication |
Absent |
Present |
Nucleophosphin mutation |
Present |
Absent |
CCAAT/enhancer-binding protein- a mutation |
Present |
Absent |
Brain and acute leukemia cytoplasmic gene expression |
Absent |
Present |
Vascular endothelial growth factor expression |
Absent |
Present |
In acute myeloid leukemia, Auer rods are numerous in:
September 2009
A |
M2 |
|
B |
M3 |
|
C |
M4 |
|
D |
M5 |
In acute myeloid leukemia, Auer rods are numerous in:
September 2009
A |
M2 |
|
B |
M3 |
|
C |
M4 |
|
D |
M5 |
Ans. B: M3
The diagnosis of AML is based on the presence of at least 20% myeloid blasts in the bone marrow. Myeloblast have delicate nuclear chromatin, two to four nucleoli, and more voluminous cytoplasm than lymphoblasts.
The cytoplasm often contains fine, peroxidase-positive azurophilic granules.
Auer rods, distinctive needle like azurophilic granules, are present in many cases; they are particularly numerous in AML with the t(15;17) (acute promyelocytic leukaemia-M3).
Sjogren syndrome
Biopsy of the parotid gland in a patient with Sjogren’s syndrome shows –
A |
Neutrophils |
|
B |
Lymphocytes |
|
C |
Eosinophi Is |
|
D |
Basophils |
Biopsy of the parotid gland in a patient with Sjogren’s syndrome shows –
A |
Neutrophils |
|
B |
Lymphocytes |
|
C |
Eosinophi Is |
|
D |
Basophils |
Ans. is ‘b’ i.e., Lymphocytes
o The earliest histological finding in both the major and minor salivary glands is periductal and perivascular lymphocytic infilteration which eventually becomes extensive
Sjogren’s syndrome refers to disease of ‑
A |
Parotid glands |
|
B |
Thyroid disease |
|
C |
Parathyroid glands |
|
D |
Multiple endocrine neoplasia |
Sjogren’s syndrome refers to disease of ‑
A |
Parotid glands |
|
B |
Thyroid disease |
|
C |
Parathyroid glands |
|
D |
Multiple endocrine neoplasia |
Ans. is ‘a’ i.e., Parotid glands
All of the following are true about Primary Sjogren’s syndrome, except:
A |
May be seen in children |
|
B |
Sensation of sand or gravel in eyes |
|
C |
Associated with rheumatoid arthritis |
|
D |
Salivary gland enlargement |
All of the following are true about Primary Sjogren’s syndrome, except:
A |
May be seen in children |
|
B |
Sensation of sand or gravel in eyes |
|
C |
Associated with rheumatoid arthritis |
|
D |
Salivary gland enlargement |
Answer is C (Associated with Rheumatoid Arthritis):
Kelly’s Rheumatoid arthritis is associated with Secondary Sjogren’s Syndrome and not Primary Sjogren’s Syndrome.
Primary Sjogren’s Syndrome |
No Connective Tissue /Chronic inflammatory disorder |
Secondary Sjogren’s Syndrome |
Underlying Connective Tissue / Chronic inflammatory disorder |
Keratoconjunctivitis Sicca (Sensation of sand or gravel in eyes) and salivary gland enlargement are typical symptoms of Sjogren’s syndrome (Both Primary and Secondary). Primary Sjogren’s syndrome typically affects women in their middle age (Female to male ratio = 9:1) but it may occur at any age including childhood. Primary Sjogren’s syndrome
has been reported infrequently in children with onset as early as 5 years of age. The presence of symptoms and signs of Sjogren’s ‘s syndrome (Dry eyes; Dry mouth; Salivary Gland Enlargement) in the setting of another connective tissue disease or chronic inflammatory pathology like Rheumatoid Arthritis, SLE, Systemic Sclerosis by definition is termed as Secondary Sjogren’s Syndrome.
All of the following are features of Sjogren’s syndrome except:
A |
It is an autoimmune chronic inflammatory disease |
|
B |
Typically occurs in women after the menopause |
|
C |
In primary Sjogren’s syndrome, keratoconjunctivitis sicca is associated with rheumatoid arthritis |
|
D |
In secondary Sjogren’s syndrome, dry eye and/ or xerostomia (dry mouth) is associated with rheumatoid arthritis |
All of the following are features of Sjogren’s syndrome except:
A |
It is an autoimmune chronic inflammatory disease |
|
B |
Typically occurs in women after the menopause |
|
C |
In primary Sjogren’s syndrome, keratoconjunctivitis sicca is associated with rheumatoid arthritis |
|
D |
In secondary Sjogren’s syndrome, dry eye and/ or xerostomia (dry mouth) is associated with rheumatoid arthritis |
Ans. In primary Sjogren’s syndrome, keratoconjunctivitis sicca is associated with rheumatoid arthritis
Regarding Sjogren’s syndrome, all are true except:
September 2010
A |
Keratoconjuctivitis sicca |
|
B |
Rheumatoid arthritis |
|
C |
Epiphora |
|
D |
Autoimmune in nature |
Regarding Sjogren’s syndrome, all are true except:
September 2010
A |
Keratoconjuctivitis sicca |
|
B |
Rheumatoid arthritis |
|
C |
Epiphora |
|
D |
Autoimmune in nature |
Ans. C: Epiphora
SjOgren’s syndrome (also known as “Mikulicz disease” and “Sicca syndrome”, is a systemic autoimmune disease in which immune cells attack and destroy the exocrine glands that produce tears and saliva
SjOgren’s syndrome can exist as a disorder in its own right (Primary Sjogren’s syndrome) or it may develop years after the onset of an associated rheumatic disorder such as rheumatoid arthritis, systemic lupus erythematosus, scleroderma, primary biliary cirrhosis etc. (Secondary SjOgren’s syndrome)
True regarding Sjogren’s syndrome are all of the following except:
September 2009
A |
Autoimmune condition |
|
B |
Males are commonly affected |
|
C |
Progressive destruction of lacrimal and salivary gland |
|
D |
No single laboratory investigation is pathognomic |
True regarding Sjogren’s syndrome are all of the following except:
September 2009
A |
Autoimmune condition |
|
B |
Males are commonly affected |
|
C |
Progressive destruction of lacrimal and salivary gland |
|
D |
No single laboratory investigation is pathognomic |
Ans. B: Males are commonly affected
SjOgren’s Syndrome (SS) is a systemic autoimmune disease characterised by lymphocytic infiltration, acinar cell destruction and proliferation of duct epithelium in all salivary and larimal gland tissue.
Extra glandular involvement of muscles, blood vessels, lungs, kidneys may also occur.
Females are affected more than the males
It may be primary and secondary (when associated with other connective tissue diseases). There is a risk of progression to lymphoid malignancy.
Dry mouth, dry eyes and arthritis/arthralgia are the 3 common presenting features.
Of the extraarticular manifestations, Raynaud’s phenomena is the most common skin manifestation seen in 35% of patients. Vasculitis has been reported in 5% of patients with Sjogren’s syndrome. This includes small vessel leucocytoclastic vasculitis and medium vessel necrotising vasculitis.
Distal RTA may be silent or lead to renal stones, nephrocalcinosis and compromised renal function. Hypergammaglobulinemia may be due to polyclonal activation of B cells.
The diagnosis is base on the history as no single laboratory investigation is pathognomic of either primary or secondary Sjogren’s syndrome
Development of Lymphoma in Sjogren’s syndrome is suggested by all of the following except
A |
Persistent parotid gland enlargement |
|
B |
Cyoglobilinemia |
|
C |
Leukopenia |
|
D |
High C4 compement levels |
Development of Lymphoma in Sjogren’s syndrome is suggested by all of the following except
A |
Persistent parotid gland enlargement |
|
B |
Cyoglobilinemia |
|
C |
Leukopenia |
|
D |
High C4 compement levels |
Ans. is ‘d’ i.e., High C4 complement levels
- Lymphoa is a well-known complication of Sjogren’s syndrome Most lymphomas are extra-nodal, low grade marginal B cell lymphomas.
- Development of Lymphoma in Sjogren’s syndrome is suggested by low C4 complement levels.
Lymphoma in Sjogren’s syndrome
The development ofLymphomas in patients with Sjogren syndrome is suggested by : –
- Persistent parotid gland enlargement
- Purpura
- Leukopenia
- Cryoglobulinemia
- Low C4 complement levels
Glucose-6 -phosphate dehydrogenase deficiency (G6PD)
Acute hemolytic anemia in G6PD deficiency is triggered by all, EXCEPT:
A |
Fava beans |
|
B |
Infections |
|
C |
Drugs |
|
D |
Anemia |
Acute hemolytic anemia in G6PD deficiency is triggered by all, EXCEPT:
A |
Fava beans |
|
B |
Infections |
|
C |
Drugs |
|
D |
Anemia |
Acute hemolytic anemia in G6PD deficiency is triggered by fava beans, infections, and drugs. The onset can be extremely abrupt especially with favism in children.
Ref: Harrison, 18th edition, Page 878.
The most serious complication of acute hemolytic anemia in G6PD deficiency is:
A |
Acute renal failure |
|
B |
Congestive cardiac failure |
|
C |
Cerebral infarction |
|
D |
Acute liver failure |
The most serious complication of acute hemolytic anemia in G6PD deficiency is:
A |
Acute renal failure |
|
B |
Congestive cardiac failure |
|
C |
Cerebral infarction |
|
D |
Acute liver failure |
The most serious threat from acute hemolytic anemia is the development of ARF. Ref: Harrison’s principles of internal medicine, 18th edition ; Page :879
All of the following are true regarding G6PD deficiency except:
March 2010
A |
A recessive X-linked trait |
|
B |
Females are commonly affected |
|
C |
Oxidative stress causes hemolysis |
|
D |
Protective against plasmodium falciparum malaria |
All of the following are true regarding G6PD deficiency except:
March 2010
A |
A recessive X-linked trait |
|
B |
Females are commonly affected |
|
C |
Oxidative stress causes hemolysis |
|
D |
Protective against plasmodium falciparum malaria |
Ans. B: Females are commonly affected
G6PD deficiency is a recessive X-linked trait, placing males at higher risk for symptomatic disease.
It is most common in Black patients or African descent (Class III). It has a protective effect against plasmodium falciparum malaria.
Pathophysiology
- Glucose-6-phosphate dehydrogenase (G6PD)
– Catalyzes NADP to NADPH (pentose phosphate path)
– NADPH prevents oxidative damage to cells
– RBCs depend on G6PD for sole pathway to NADPH
– RBCs are most susceptible to insufficient G6PD
- Oxidative stress results in acute Hemolytic Anemia
- Drug-induced Hemolysis affects older cells -Younger cells have adequate enzyme levels to survive
- G6PD mutations occur on distal long arm of C chromosome
Causes
- Medications in G6PD Deficiency-Onset within 72 hours of intake
– Chloroquine and primaquine
– Sulfonamides
– Nitrofurantoins
- Infection (most common cause)
– Salmonella
– Eschirichia coli
– Beta-hemolytic Streptococcus
With regards to G6PD deficiency, which of the following in false
A |
Affects the pentose phosphate pathway |
|
B |
Associated with neonatal jaundice |
|
C |
Acute haemolysis can be precipitated by broad beans |
|
D |
X-linked recessive disorder that does not affect heterozygous famales |
With regards to G6PD deficiency, which of the following in false
A |
Affects the pentose phosphate pathway |
|
B |
Associated with neonatal jaundice |
|
C |
Acute haemolysis can be precipitated by broad beans |
|
D |
X-linked recessive disorder that does not affect heterozygous famales |
Ans. is ‘d’ i.e., X-linked recessive disorder that does not affect heterozygous famales
- Glucose 6-phosphate dehydrogenase (G6PD) deficiency, an X-linked disorder, is the most common enzymatic disorder of red blood cells in humans, affecting 400 million people worldwide.
Clinical spectrum
- The clinical expression of G6PD variants encompasses a spectrum of hemolytic syndromes
The four forms of symptomatic G6PD deficiency :
- Acute hemolytic anemia
- Favism
- Congenital nonspherocytic hemolytic anemia
- Neonatal hyperbilirubinemia
- G6PD deficiency is expressed in males carrying a variant gene that results in sufficient enzyme deficiency to lead to symptoms.
Acute hemolytic anemia
- Almost all individuals with the most prevalent G6PD variants, G6PD A- and G6PD Mediterranean, are asymptomatic in the steady state.
- They have neither anemia, evidence of increased red cell destruction, nor an alteration in blood morphology,. o However sudden destruction of enzyme deficient erythrocytes can be triggered by certain drugs or chemicals, by selected infections, and rarely by metabolic abnormalities (eg, diabetic ketoacidosis).
Clinical course
- At two to four days after drug ingestion, there is the sudden onset of jaundice, pallor, and dark urine, with or without abdominal and back pain.
- This is associated with an abrupt fall in the hemoglobin concentration of 3 to 4 g/dL, during which time the
- peripheral blood smear reveals red cell fragments, microspherocytes, and eccentrocytes or “bite” cells.
- The anemia induces an appropriate stimulation of erythropoiesis, characterized by an increase in reticulocytes that is apparent within five days and is maximal at 7 to 10 days after the onset of hemolysis.
- Even with continued drug exposure, the acute hemolytic process ends after about one week, with ultimate reversal of the anemia.
Inciting events
- Patients with class II or III variants develop intermittent hemolysis only after one or more of the following inciting events.
- Infection
- Oxidant drugs
- Chemical agents (eg, moth balls, aniline dyes, henna compounds)
- Diabetic ketoacidosis
- Ingestion of fava beans
Drugs and chemicals
- Primaquine, dapsone, and a number of other drugs can precipitate hemolysis in G6PD deficient subjects.
Foods: fava beans and bitter melon
- G6PD deficiency can also be precipitated by the the ingestion of fresh fava beans (favism).
- Manifestation offavism begins 5-24 hrs after fava bean ingestion and include headache, nausea, back pain.
Congenital nonspherocytic hemolytic anemia
- Patients with class I G6PD variants have such severe G6PD deficiency that lifelong hemolysis occurs in the absence of infection or drug exposure.
- Such patients fall under the category of having congenital nonspherocytic hemolytic anemia.
- These G6PD variants have low in vitro activity and/or marked instability of the molecule, and most have DNA mutations at the glucose-6-phosphate or NADP binding sites.
- These sites are central to the function of G6PD, which oxidizes glucose-6-phosphate and reduces NADP to NADPH. It is presumed that the functional defect is so severe that the red cells cannot withstand even the normal oxidative stresses encountered in the circulation.
- Anemia and jaundice are often first noted in the newborn period, and the degree of hyperbilirubinemia is frequently of sufficient severity to require exchange transfusion.
- After infancy, hemolytic manifestations are subtle and inconstant. Most individuals have mild to moderate anemia (hemoglobin 8 to 10 g/dL) with a reticulocyte count of 10 to 15 percent. Pallor is uncommon, scleral icterus is intermittent, splenomegaly is rare, and splenectomy generally is of little benefit.
- Hemolysis can be exaggerated by exposure to drugs or chemicals with oxidant potential or exposure to fava beans.
- Some drugs with relatively mild oxidant potential that are safe in patients with class II or class III G6PD variants may increase hemolysis in patients with class I variants.
Neonatal hyperbilirubineinia
- The clinical picture of neonatal jaundice due to G6PD deficiency differs from neonatal jaundice seen in hemolytic disease of the fetus and newborn (HDFN) associated with Rh(D) incompatibility in two main respects.
- G6PD deficiency-related neonatal jaundice is rarely present at birth; the peak incidence of clinical onset is between days two and three.
- a There is more jaundice than anemia, and the anemia is rarely severe. The severity ofjaundice varies widely, from being subclinical to imposing the threat of kernicterus if not treated
Healing of specialised tissue (fracture healing)
Following a fracture of the humerus, an adult patient has a biopsy of the healing area. Which of the following types of bone will the biopsy most likely show?
A |
Cancellous |
|
B |
Compact |
|
C |
Spongy |
|
D |
Woven |
Following a fracture of the humerus, an adult patient has a biopsy of the healing area. Which of the following types of bone will the biopsy most likely show?
A |
Cancellous |
|
B |
Compact |
|
C |
Spongy |
|
D |
Woven |
Last step in fracture healing is:
A |
Haematoma |
|
B |
Callus formation |
|
C |
Remodeling |
|
D |
Consolidation |
Last step in fracture healing is:
A |
Haematoma |
|
B |
Callus formation |
|
C |
Remodeling |
|
D |
Consolidation |
C i.e. Remodeling
The time necessary for healing of fracture depends on the following factors:
A |
Age of the patient |
|
B |
Location of the fracture |
|
C |
Type of the fracture |
|
D |
All of the above |
The time necessary for healing of fracture depends on the following factors:
A |
Age of the patient |
|
B |
Location of the fracture |
|
C |
Type of the fracture |
|
D |
All of the above |
D i.e. All
The most important factor in fracture healing is:
A |
Good alignment |
|
B |
Organization of blood clot |
|
C |
Accurate reduction and 100% apposition of fractured fragments |
|
D |
Immobilisation |
The most important factor in fracture healing is:
A |
Good alignment |
|
B |
Organization of blood clot |
|
C |
Accurate reduction and 100% apposition of fractured fragments |
|
D |
Immobilisation |
D i.e. Immobilization
Healing of # of bone is affected by:
A |
Micromovement |
|
B |
Muscle interposition |
|
C |
Hypoxia |
|
D |
All |
Healing of # of bone is affected by:
A |
Micromovement |
|
B |
Muscle interposition |
|
C |
Hypoxia |
|
D |
All |
A i.e. Micromovement; B i.e. Muscle interposition; C i.e. Hypoxia
Delayed wound healing is seen in all except‑
A |
Malignancy |
|
B |
Hypertension |
|
C |
Diabetes |
|
D |
Infection |
Delayed wound healing is seen in all except‑
A |
Malignancy |
|
B |
Hypertension |
|
C |
Diabetes |
|
D |
Infection |
Ans. is ‘b’ i.e., Hypertension
Callus formation is seen between what duration of fracture healing ‑
A |
0 – 2 weeks |
|
B |
2 – 4 weeks |
|
C |
4 – 12 weeks |
|
D |
12 – 16 weeks |
Callus formation is seen between what duration of fracture healing ‑
A |
0 – 2 weeks |
|
B |
2 – 4 weeks |
|
C |
4 – 12 weeks |
|
D |
12 – 16 weeks |
Ans. is ‘c’ i.e., 4 – 12 weeks
Healing of a fracture
The process of fracture healing varies according to the type of bone involved and the amount of movement at the fracture site. Following healing processes are there :‑
Indirect fracture healing (healing by callus)
This is the ‘natural’ form of healing in tubular bones and in the absence of rigid fixation when there is micromovement at fracture site. There is formation of internal and external callus. This stage is divided in three phases which are further subdivided into five stages :
Stem cells
Stem cells are located in which region of hair follicle:
A |
Bulb |
|
B |
Root |
|
C |
Bulge |
|
D |
Papilla |
Stem cells are located in which region of hair follicle:
A |
Bulb |
|
B |
Root |
|
C |
Bulge |
|
D |
Papilla |
Bulge
Stem cells are thought to reside mainly in the troughs of rete pegs, and in the outer root sheath bulge of the hair follicle
Stem Cell Niches
Stem cell |
Organ |
Niche |
Epidermal stem cell |
Hair follicle, Epidermis |
Hair follicle bulge |
Intestinal stem cell |
Intestine |
Base of colonic crypt above paneth cell |
Oval cell (liver stem cell) |
Liver |
Canal of herring |
Corneal stem cell |
Cornea |
Limbus |
Neural stem cell |
Brain |
Olfactory bulb, Dentate gyrus of hippocampus |
Satellite cells |
Skeletal/Cardiac muscles |
Beneath the myocyte basal lamina |
Progenitor hematopoetic stem cells originate in’-
A |
Bone Marrow |
|
B |
Thymus |
|
C |
Lymph node |
|
D |
Spleen |
Progenitor hematopoetic stem cells originate in’-
A |
Bone Marrow |
|
B |
Thymus |
|
C |
Lymph node |
|
D |
Spleen |
Ans. is ‘a’ i.e., Bone marrow
- Blood cells first appear during the third week of fetal embryonic development in the yolk sac, but these cells are generated from a primitive stem cell population restricted to the production of myeloid cells.
o Most studies suggest definitive hematopoietic stem cells arise in the mesoderm of the intraembryonic aorta/ gonad/mesonephros region, but evidence also exists for an origin within a small subset of yolk sac-derived cells.
- By the third month of embryogenesis, stem cells derived from the AGM and/or yolk sac migrate to the liver, which is the chief site of blood cell formation until shortly before birth.
- Beginning in the fourth month, stem cells migrate to the bone marrow to commence hematopoiesis at this site. o By birth, marrow throughout the skeleton is hematopoietically active and virtually the sole source of blood cells. o Up to the age of puberty, marrow throughout the skeleton remains red and hematopoietically active. o By age 18 only the vertebrae, ribs, sternum, skull, pelvis, and proximal epiphyseal regions of the humerus and femur retain red marrow, the remaining marrow becoming yellow, fatty, and inactive.
OVAL cells seen in stem cells of –
A |
Skin |
|
B |
Cornea |
|
C |
Liver |
|
D |
Bone |
OVAL cells seen in stem cells of –
A |
Skin |
|
B |
Cornea |
|
C |
Liver |
|
D |
Bone |
Ans. is ‘c’ i.e., Liver
o Stem cells are located in sites called niches. These include :
Epidermal stem cells located in the bulge area of the hair follicle serve as a stem cells for the hair follicle and the epidermis.
Intestinal stem cells are located at the base of a colon crypt, above Paneth cells.
Liver stem cells (commonly known as OVAL cells) are located in the canals of Hering , structures that connect bile ductules with parenchymal hepatocytes.
Corneal stem cells are located in the limbus region, between the conjunctiva and the cornea
The bone marrow contains hematopoietic stem cells as well as stromal cells capable of differentiation into various lineages.
Stem cells are taken from all except –
A |
Liver |
|
B |
Bone marrow |
|
C |
Blood |
|
D |
Adipose tissue |
Stem cells are taken from all except –
A |
Liver |
|
B |
Bone marrow |
|
C |
Blood |
|
D |
Adipose tissue |
o There are three accessible sources of adult stem cells in humans :
- Bone marrow, which requires extraction by harvesting, that is, drilling into bone (typically the femur or iliac crest),
- Adipose tissue, which requires extraction by liposuction, and
- Blood, which requires extraction through pheresis, wherein blood is drawn from the donor (similar to a blood donation), passed through a machine that extracts the stem cells and returns other portions of the blood to the donor.
- Stem cells can also be taken from umbilical cord blood just after birth
When stem cells transforms to form cells characteristic of other tissues, the process is called as –
A |
De-differentiation |
|
B |
Re-differentiation |
|
C |
Trans-differentiation |
|
D |
Sub-differentiation |
When stem cells transforms to form cells characteristic of other tissues, the process is called as –
A |
De-differentiation |
|
B |
Re-differentiation |
|
C |
Trans-differentiation |
|
D |
Sub-differentiation |
Ans. is ‘c’ i.e., Trans-differentiation
Transdifferentiation
o Transdifferentiation takes place when a non-stem cell transform into a different type of cell, or when an already differentiated stem cell creates cells outside its already estabilished differentiation.
o Remember very important fact that it is the non-stem cell or already differentiated stem cell (i.e. mature cell) that is transformed into other type of cell. It is not stem cell that is transforming.
o Transdifferentiation is a type of metaplasia.
o Then, what is the difference between transdifferentiation and metaplasia.
In Transdifferentiation only differentiated stem cell is transformed into other cell type, while in metaplasia any of the two, either stem cell or differentiated cell can transform into other cell type.
So, all transdifferentiation processes are metaplasia, but not all metaplasia are transdifferentiation. o Most likely question has been wrongly framed here, there should be non-stem cell instead of stem cell in the question. Anyways answer remains the same, as no other option is related to this type of transformation.
Stem cells are located in which of the following location in the body?
A |
Retina |
|
B |
Endometrium |
|
C |
Intestine |
|
D |
Choana |
Stem cells are located in which of the following location in the body?
A |
Retina |
|
B |
Endometrium |
|
C |
Intestine |
|
D |
Choana |
Ans. is ‘c’ i.e., Intestine
Stem cells are located in sites called niches. These include :
Epidermal stem cells located in the bulge area of the hair follicle serve as a stem cells for the hair follicle and the epidermis.
Intestinal stem cells are located at the base of a colon crypt, above Paneth cells.
Liver stem cells (commonly known as OVAL cells) are located in the canals of Hering , structures that connect bile ductules with parenchymal hepatocytes.
Corneal stem cells are located in the limbus region, between the conjunctiva and the cornea
The bone marrow contains hematopoietic stem cells as well as stromal cells capable of differentiation into various lineages.
Stem cells are present where in cornea?
A |
Limbus |
|
B |
Stroma |
|
C |
Epithelium |
|
D |
Descmet’s membrane |
Stem cells are present where in cornea?
A |
Limbus |
|
B |
Stroma |
|
C |
Epithelium |
|
D |
Descmet’s membrane |
Limbal stem cells (also c/d corneal epithelial stem cells) are stem cells located in the basal epithelial layer of the corneal limbus.
urolithiasis
Which one of the following gastrointestinal disorders predisposes to urolithiasis –
A |
Peutz – Jegher’s syndrome |
|
B |
Short bowel syndrome |
|
C |
Familial polyposis coli |
|
D |
Ulcerative colitis |
Which one of the following gastrointestinal disorders predisposes to urolithiasis –
A |
Peutz – Jegher’s syndrome |
|
B |
Short bowel syndrome |
|
C |
Familial polyposis coli |
|
D |
Ulcerative colitis |
Ans. is ‘b’ i.e., Short bowel syndrome
Gallstones and kidney stones are known complications of IBD
Granulocyte Colony Stimulating Factor(G-CSF)
Drug of choice for Neutropenia due to cancer chemotherapy is
A | Vitamin B-12 | |
B |
IL 11 |
|
C | Filgrastim | |
D |
Erythropoietin |
Drug of choice for Neutropenia due to cancer chemotherapy is
A | Vitamin B-12 | |
B |
IL 11 |
|
C | Filgrastim | |
D |
Erythropoietin |
Filgrastim REF: KDT 6TH edition, page 833, internet resources
See APPENDIX 37 “ANTICANCER DRUGS TOXIC AMELIORATION”
A | Has greater oral bioavailability | |
B | Is more likely to cause thrombocytopenia | |
C | Is more likely to elicit an allergic reaction | |
D | Stimulates production of a wider variety of hematopoietic stem cells |
A | Has greater oral bioavailability | |
B | Is more likely to cause thrombocytopenia | |
C | Is more likely to elicit an allergic reaction | |
D | Stimulates production of a wider variety of hematopoietic stem cells |
Stimulates production of a wider variety of hematopoietic stem cells
GM-CSF has wider biologic activity than G-CSF; it stimulates early myeloid stem cells in addition to cells destined become neutrophils.
Kostmann’s syndrome-treatment is
A |
Anti-thymocyte globulin + cyclosporin |
|
B |
Anti-thymocyte globulin + cyclosporin + GMCSF |
|
C |
G-CSF |
|
D |
GM-CSF |
Kostmann’s syndrome-treatment is
A |
Anti-thymocyte globulin + cyclosporin |
|
B |
Anti-thymocyte globulin + cyclosporin + GMCSF |
|
C |
G-CSF |
|
D |
GM-CSF |
G-CSF [Ref : Nelson Ighle p. 913]
- Kostmann’s syndrome is an inherited disorder of the bone marrow.
- It is also known as severe congenital neutropenia.
- It is inherited in an autosomal recessive manner.
- Congenital neutropenia is usually very severe and neutrophils are often completely absent in the blood of these patients at the time of diagnosis.
- These patients usually show arrest of maturation of neutrophils at the promyelocyte stage.
– This means that their neutrophils rarely. fully mature into the cells that are capable of fighting infections. – As a result these patients usually suffer from severe infections ?
– Omphalitis (infection of the navel)
– Pneumonia
– Skin abscesses
– Otitis media during their first few years of life.
Pathogenesis
- Kostmann’s syndrome or severe congenital neutropenia is believed to he caused by defect in a gene on chromosome (in p35-p34.3) that codes for granulocyte colony stimulating factor (GCSF).
- This disease is believed to be caused due to defect in receptor in granulocyte colony stimulator factor.
– This receptor is located on granulocytes or neutrophils. The purpose of this receptor is the binding of the granulocyte to the cytokine (GCSF) in order to give signal to the cell to mature, to multiply, and enhance .function.
GCSF is a natural cytokine produced by the human body.
– Patients with congenital neutropenia also produce GCSF hut because of the defect in GCSF receptor the response of their neutrophils to the normal amounts of GCSF in the blood is reduced.
– These patients will respond to higher dose of GCSF (This is the basis of tit of disease).
- In some patients the GCSF receptor develops changes that could also indicate progression towards leukemia. Treatment
- Patients with congenital neutropenia respond to administration of GCSF.
– As soon as congenital neutropenia is diagnosed, patients should start treatment with GCSF. – This treatment usually stabilizes the neutrophil count of the patient.
– The response of these patients to GCSF treatment is different. There is a big variation in the dose of GCSF that different people receive.
– A small group of patient does not respond to even very high doses of GCSF.
- In patients who do not respond to GCSF doses of 100 mcg/kg within fourteen days, a search for bone marrow donor should be started immediately and bone marrow transplantation should be performed as soon as matching donor is identified.
A | Vitamin B-12 | |
B | IL 11 | |
C | Filgrastim | |
D | Erythopoie tin |
A | Vitamin B-12 | |
B | IL 11 | |
C | Filgrastim | |
D | Erythopoie tin |
Filgrastim
Filgrastim is used in treatment of:
A |
Anemia |
|
B |
Neutropenia |
|
C |
Malaria |
|
D |
Filarial |
Filgrastim is used in treatment of:
A |
Anemia |
|
B |
Neutropenia |
|
C |
Malaria |
|
D |
Filarial |
Filgrastim is a recombinant human granulocyte colony stimulating factor (G-CSF) which is a 175 – aminoacid glyco-protein.
It differs from the natural granulocyte stimulating factor due to its lack in glycosylation and the presence of an extra N-terminal methionine. It has proved to be effective in the treatment of severe neutropenia.
Ref: Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 11th Edition, Pages 1429-32; Immunopharmacology By Manzoor M. Khan, Pages 49-50
A child with recurrent severe bacterial infections is diagnosed of having Kostmann’s syndrome. Treatment is:
A |
Antithymocyte globulin + cyclosporine |
|
B |
Antithymocyte globulin + cyclosporine – C31-CSF |
|
C |
G-CSF |
|
D |
GM-CSF |
A child with recurrent severe bacterial infections is diagnosed of having Kostmann’s syndrome. Treatment is:
A |
Antithymocyte globulin + cyclosporine |
|
B |
Antithymocyte globulin + cyclosporine – C31-CSF |
|
C |
G-CSF |
|
D |
GM-CSF |
Filgrastim is used in the treatment of –
A |
Anemia |
|
B |
Neutropenia |
|
C |
Malaria |
|
D |
Filaria |
Filgrastim is used in the treatment of –
A |
Anemia |
|
B |
Neutropenia |
|
C |
Malaria |
|
D |
Filaria |
Ans. is ‘b’ i.e., Neutropenia
o Filgrastim is a recombinant human granulocyte colony stimulating factor (G-CSF) effective in the treatment of severe neutropenia.
Drug of choice for Neutropenia due to cancer chemotherapy is –
A |
Vitamin B-12 |
|
B |
IL 11 |
|
C |
Filgrastim |
|
D |
Erythropoietin |
Drug of choice for Neutropenia due to cancer chemotherapy is –
A |
Vitamin B-12 |
|
B |
IL 11 |
|
C |
Filgrastim |
|
D |
Erythropoietin |
Ans. is ‘c’ i.e., Filgrastin
o Filgrastim is a recombinant human granulocyte colony stimulating factor (G-CSF) effective in the treatment of severe neutropenia.
Kostmann’s syndrome-treatment is –
A |
Anti-thymocyte globulin + cyclosporin |
|
B |
Anti- thy mocyte globulin + cyclosporin + GM-CSF |
|
C |
G-CSF |
|
D |
GM-CSF |
Kostmann’s syndrome-treatment is –
A |
Anti-thymocyte globulin + cyclosporin |
|
B |
Anti- thy mocyte globulin + cyclosporin + GM-CSF |
|
C |
G-CSF |
|
D |
GM-CSF |
Ans. is ‘c’ i.e., G-CSF
Kostmann’s syndrome (severe congenital neutropenia)
- Kostmann’s syndrome,an autosomal recessive disorder, is an inherited disorder of the bone marrow in which there is arrest of maturation of neutrophils at promyelocyte stage.
o There is congenital neutropenia and neutrophils are often completely absent in the blood at time of diagnosis. o Because of neutropenia, these patients suffer from severe infections e.g., omphalitis (infection of navel), Pneumonia, Skin abscesses, otitis media.
o Kostmann’s syndrome is believed to be caused due to defect in receptor of granulocyte colony stimulating factor (GCSF) on neutrophils (granulocytes). The purpose of this receptor is binding of the granulocyte to the cytokine (GCSF) in order to give signal to the cell to mature and multiply.
Patients with Kostamann’s syndrome produce GCSF but because of the defet in GCSF receptor the response of neutrophils to normal amounts of GCSF in the blood is reduced. However, they can respond if the amount of GCSF is increased –> These patients will respond to higher dose of GCSE