1. Q No 1
 A 22-year-old woman nursing her newborn develops a
tender erythematous area around the nipple of her left
breast. A thick, yellow fluid is observed to drain from
an open fissure. Examination of this breast fluid under
the light microscope will most likely reveal an
abundance of which of the following inflammatory
cells?
 (A) B lymphocytes
 (B) Eosinophils
 (C) Mast cells
 (D) Neutrophils
 (E) Plasma cells

2.  Acute mastitis

3. Q No:2/5
 A 5-year-old boy punctures his thumb with a rusty
nail. Four hours later, the thumb appears red and
swollen. Initial swelling of the boy’s thumb is
primarily due to which of the following mechanisms?
 (A) Decreased intravascular hydrostatic pressure
 (B) Decreased intravascular oncotic pressure
 (C) Increased capillary permeability
 (D) Increased intravascular oncotic pressure
 (E) Vasoconstriction of arterioles

4.  Infl edema

5. Q No 3/9
 A 36-year-old woman with pneumococcal pneumonia
develops a right pleural effusion. The pleural fl uid
displays a high specific gravity and contains large
numbers of polymorphonuclear(PMN) leukocytes. Which
of the following best characterizes this pleural effusion?
 (A) Fibrinous exudate
 (B) Lymphedema
 (C) Purulent exudate
 (D) Serosanguineous exudate
 (E) Transudate

6.  Diagnosis: Bacterial pneumonia, pleural effusion

7. Q No 4/11
 A 10-year-old boy with a history of recurrent bacterial
infections presents with fever and a productive cough.
Biochemical analysis of his neutrophils demonstrates that
he has an impaired ability to generate reactive oxygen
species. This patient most likely has inherited mutations
in the gene that encodes which of the following
proteins?
 (A) Catalase
 (B) Cytochrome P450
 (C) Myeloperoxidase
 (D) NADPH oxidase
 (E) Superoxide dismutase

8. Ans: D
 Diagnosis: Chronic granulomatous disease

9. Q No 5/14
 A 41-year-old woman complains of excessive menstrual
bleeding and pelvic pain of 4 months. She uses an
intrauterine device for contraception. Endometrial biopsy
reveals an excess of plasma cells and macrophages within
the stroma. The presence of these cells and scattered
lymphoid follicles within the endometrial stroma is evidence
of which of the following conditions?
 (A) Acute inflammation
 (B) Chronic inflammation
 (C) Granulation tissue
 (D) Granulomatous inflammation
 (E) Menstruation

10.  Diagnosis: Chronic endometritis

11. Q No. 6

12. Regeneration, repair and
wound healing

13.  Regeneration:When healing takes place by
proliferation of parenchymal cells of same type.
 Repair:When healing takes place by proliferation of
connective tissue elements resulting in FIBROSIS or
SCARRING.

18. Regeneration
 requires intact extracellular matrix framework
 In mammals : compensatory growth (hypertrophy and
hyperplasia) rather than true regeneration (eg. growth
after partial hepatectomy and nephrectomy)
 Continuously cycling cells ( bone marrow, epithelium of
skin and GI mucosal epithelium) regenerate if stem
cells are intact

19. Cell types ( based on their proliferative
capacity) 1.
 Labile cells ( continuously dividing cells)
Surface epithelia: skin, oral cavity, vagina, cervix
Excretory duct epithelia: saliv.glands, pancreas, biliary tract
Columnar epithelia: GI, uterus
Transitional epith: urinary tract
Bone marrow cells and hematopoietic cells
Derived from pleuripotent stem cells….

20. Cell types ( based on their proliferative
capacity) 2.
 Stable cells ( quiescent cells)
 They don’t but can enter G1
 Liver, kidney, pancreas ( acini)
 Fibroblasts, smooth muscle, endothelium,
lymphocytes etc.

21. Cell types ( based on their proliferative
capacity) 3.
 Permanent cells ( nondividing cells)
 Can’t enter the cell cycle
 Neurons(?) ( neural precursor cells!)
 Skeletal muscle(?) ( satellite cells!)
 Myocardium

22. Stem cells
 Prolonged self-renewal capacity and asymmetric
replication
 Embryonic stem cells, adult stem cells (bone marrow
SC, tissue SC)
 REGENERATIVE MEDICINE ( therapeutic cloning !)
 New observations:
 Stem cells in the brain
 Bone marrow stem cells – multiple developmental option
(developmental plasticity)
 Some tissue stem cells – similar to embryonic stem cells
 Niches
 Eg. Base of colon crypts, hair follicle bulges, oval cells (liver
stem cells) in canals of Hering

24. Stem cells
 self-renewal properties
 capacity to generate differentiated cell lineages.
 stem cells need to be maintained during the life of
the organism.
 achieved by two mechanisms:
(a) obligatory asymmetric replication: one of the
daughter cells retains its self-renewing capacity…
(b) stochastic differentiation: 50- 50.. Depending on
luck factor…

26. Embryonic Stem Cells: uses
• To study the specific signals and differentiation
steps required for the development of many
tissues.
• To study various disease models with help of
knockout mice or “knock-in” mice.
• ES cells may in the future be used to repopulate
damaged organs.

27. Reprogramming of Differentiated Cells: iPS Cells
 Differentiated cells of adult tissues can be reprogrammed
to become pluripotent by transferring their nucleus to an
enucleated oocyte.
 oocytes implanted into a surrogate mother
 Develop embryo and ultimately cloned animal
 This technique is K/A reproductive cloning(dolly).
 Similar is therepeutic cloning… but ethical issues…

29. Bone marrow stem cells
 Hematopoietic stem cells
 Stromal cells: have potentially important therapeutic
applications.
 Multipotent adult progenitor cells
( adult counterpart of embryonic stem cells)

30. Tissue stem cells 1.
 Liver - Oval cells
 Niche: canals of Hering
 Bipotential progenitors (→ hepatocytes and biliary cells)
 Activated when hepatocyte proliferation is blocked (eg.
carcinogenesis, cirrhosis, fulminant hepatic failure)
 Brain- Neural stem ( precursor) cells
 Niche: the subventricular zone (SVZ) & dentate gyrus of
hyppocampus
 Neurogenesis ?
 Being studied for degenerative neural disorder…

31. Tissue stem cells
 Skin:
located in the hair follicle bulge, interfollicular areas of the
surface epidermis, and sebaceous glands.
 Skeletal muscle- satellite cells
 Niche: beneath basal lamina
 Diff. toward myocytes, adipocytes, osteocytes
 Intestinal epithelium:
located immediately above Paneth cells in the small intestine,
or at the base of the crypt, as is the case in the colon
Cornea: limbal scleral cells…

33. Growth factors
 Bind to specific receptors
 Initiate cell proliferation
 Act on contractility, differentiation, locomotion,
angiogenesis etc.

34. Growth factors
 EGF, TGFα
 Mitogenicfor epithelial cells, fibroblasts, hepatocytes
 Bind EGFR→therapeutic target ( ERB B1 and ERB B2 or HER-
2/neu)
 Hepatocyte Growth Factor (HGF)
 Vascular Endothelial Growth Factor (VEGF)
 Vasculogenesis, angiogenesis
 Platelet-Derived Growth Factor (PDGF)
 Migration and proliferation of fibroblasts, smooth muscle cells
 Activation of oval cells

35. Growth factors 3.
 Fibroblast Growth Factor (FGF)
 Angiogenesis, wound healing, hematopoiesis, development of
skeletal muscle etc.
 TGF-β
 Growth inhibitor for epithelial cells and leukocytes ( blocks the
cell cycle)
 Stimulates the proliferation of fibroblasts and smooth muscle
cells, fibroblast chemotaxis, production of collagen, fibronectin
etc.→ FIBROSIS
 Anti-inflammatory effect

36. SIGNALING MECHANISMS IN CELL GROWTH

39. Signal Transduction Pathways

40. Signaling from tyrosine kinase receptors

41. ECM
 Networks of macromolecules outside the cell
 Networks: Interstitial matrix and BM
 Macromolecules:
1. Fibrous structural proteins ( collagens, elastin, fibrillin,
elastic fibres)
2. Proteoglycans and hyaluronic acid
3. Cell adhesion molecules ( integrins, selectins, cadherins,
osteonectin, tenascin etc.)

42. Extracellular matrix

43. Mechanisms by which ECM components and growth factors interact and activate
signaling pathways.

44. REPAIR
 Replacemnt of injured tissue by fibrous tissue
includes the following basic features:
• inflammation
• angiogenesis,
• migration and proliferation of fibroblasts,
• scar formation
• connective tissue remodeling.
 TWO PROCESS:
(A) GRANULATION TISSUE FORMATION
(B) CONTRACTION OF WOUND

46.  The relative contributions of repair
and regeneration are influenced by:
(1) the proliferative capacity of the cells of
the tissue;
(2) the integrity of the extracellular matrix;
and
(3) the resolution or chronicity of the injury
and inflammation.

47. Granulation tissue
 Hallmark of healing
 ~ term from macroscopy ( granular, pinkish)
 Microscopy: angiogenesis ( new vessels leaky→ edema),
fibroblasts, macrophages, (ly, mast cells, eosinophils)

48. GRANULATION TISSUE
FORMATION
 THREE PHASES
(A) phase of inflammation
(B) phase of clearance
(C) phase of ingrowth of granulation

49. PHASE OF INFLAMMATION
 FOLLOWING TRAUMA BLOOD CLOT AT SITE OF
INJURY
 ACUTE INFLAMMATORY RESPONSE WITH
 EXUDATION OF PLASMA
 INFILTRATION OF NEUTROPHIL AND SOME
MONOCYTE WITH 24 HOURS

50. PHASE OF CLEARANCE
 PROTEOLYTIC ENZYME FROM NEUTROPHIL
 AUTOLYTIC ENZYMES FROM DEAD TISSUE CELLS
 PHAGOCYTIC ACTIVITY OF MACROPHASE
 CLEAR OFF NECROTIC TISSUE DEBRIS & RBC.

51. PHASE OF INGROWTH OF
GRANULATION
 TWO PROCESSES
(1.) Neovascularisation
(2.) Fibrogenesis

52. GRANULATION
TISSUE

53. Granulation tissue

54. GRANULATION TISSUE

55. BLOOD
VESSELS
FIBROBLAST
NUCLEI

56. NEOVASCULARISATION
 Formation Of New Blood Vesseles
 Proliferaton Of Endothelial Cells From Margins Of
Severed Blood Vesseles
 Under Influences Of
VEGF
PDGF
TGF – β
B FGF

57. Angiogenesis from Preexisting Vessels
• Vasodilation: in response to nitric oxide, and VEGF
• Proteolytic degradation of the basement
membrane:by MMPs
• Migration of endothelial cells toward the angiogenic
stimulus
• Proliferation of endothelial cells, just behind the
leading front of migrating cells
• Maturation of endothelial cells,
• Recruitment of periendothelial cells (pericytes and
vascular smooth muscle cells) to form the mature
vessel

58. ANGIOGENESIS

59. FIBROGENESIS
 COLLGEN FIBRILS BEGINS TO APEAR BY 6TH DAYS
 AS MATURATION PROCEEDS MORE AND MORE
COLLAGEN FORMED WHILE THE NO. OF
FIBROBLAST & NEW BLOOD VESSELES DECREASE.
 THIS RESULT FORMATION OF INACTIVE LOOKING
SCAR CALLED AS CICATRISATION.

60. FIBROBLAST NUCLEI
SCAR

61. CONTRACTION OF WOUND
 START AFTER -2-3 DAY
 COMPLETED UP TO 14TH DAY
 MECHANISM INVOLVES
 (1.) DEHYDRATION – REMOVAL OF FLUID BY DRYING OF
WOUND
 (2.) CONTRACTION OF COLLAGEN
 (3.) DISCOVERY OF MYOFIBROBLAST

62. CONTRACTION

63. W
O
U
N
D
H
E
A
L
I
N
G

64. Healing by first intention
Healing by second intention

65. FACTORS INFLUENCING WOUND HEALING
•LOCAL
Type, size, location surgical, blunt trauma
Blood supply face, leg
Infection delay, deforming scars
Irradiation inhibition of cell division

66. FACTORS INFLUENCING WOUND HEALING
SYSTEMIC
Age cardiovascular status
Metabolic diabetes infections, blood supply
status scurvy inhibition of collagen synthesis
Hormones cortisons, steroid,
inhibition of collagen synthesis
thyroid
estrogens indirect actions
androgens

67. Complications of wound healing
1. Deficient scar formation ( wound dehiscence,
ulceration)
2. Excessive formation of repair components (
hypertrophic scar, keloid, exuberant granulation,
desmoid or aggressive fibromatosis)
3. Contracture

68. Keloid

69. Healing of bone
fractures