Wa0007.

APOPTOSIS
- Activation of enzymes called Caspases

- Initiator Caspases of extrinsic pathway – caspase 8,10
- Initiator Caspase of mitochondrial pathway – caspase 9
- Executioner Caspases are 3, 6,7
- Nuclear changes are due to enzyme endonucleases
- Anti-apoptotic genes – BCL.2, BCL-XL, MCL-1
- Pro apoptotic genes BAK & BAX
Coagulative Liguefactive Caseous Fatty Fibrinoid
Most common Seen in ischemic Caseous means Saponification is Seen in
cause – ischemia damage to brain cheese like seen immunologically
mediated
vasculitis
syndrome
Most common Seen in Seen in pancreas Seen in

organ affected – tuberculosis Rheumatic fever
heart
Localized area
called infarct
Metastatic calcification – due to hypercalcemia, deposition of calcium in normal tissue
Causes
Increased PTH Resorption of Bone Vitamin D related disorders
Primary hyperparathyroidism Primary tumours of bone marrow Vitamin D intoxication

– multiple myeloma
Secondary hyperparathyroidism Metastatic tumour Sarcoidosis

(chronic renal failure)
Ectopic secretion of PTHrP Accelerated bone turnover – Idiopathic hypercalcemia of

Paget’s disease infancy
Summary of mediators of inflammation (very important)
Vasodilation
Vasoconstriction Increased vascular permeability
Histamine
Thromboxane A2 Histamine
Brady kinin
Leukotrienes A4, Leukotrienes
Nitric oxide
C4, D4, E4 Bradykinin
Prostacyclin I2
Prostaglandin D2
Examples:
•Tuberculosis
•Leprosy
•Syphilis
•Sarcoidosis
•Crohn disease
Hypersensitivity Reactions
Type I Type II Type III Type IV
Activation of TH2 cell and Antibody mediated due to IgG, IgM Immune complex Mediated by TH1, TH17
production of IgE antibody mediated & CD8 + T cell
Example Example Example Example
• Anaphylaxis • Autoimmune hemolytic anemia • SLE • Rheumatoid
• Bronchial asthma • Autoimmune • PSGN arthritis
• Allergic rhinitis, sinusitis thrombocytopenic purpura • Polyarteritis Nodosa • Type 1 diabetes
• Vasculitis caused by ANCA • Reactive arthritis • Inflammatory
• Good pasture syndrome bowel disease
• Graves disease • Contact dermatitis
• Acute rheumatic fever
TUMOR SUPPRESSOR GENE
Gene Chromosome No Carcinoma

1 TP53 17 Lifraumeni syndrome
2 RB (Retinoblastoma) 13 Retinoblastoma Osteosarcoma
3 APC 5 Carcinoma colon, stomach, pancreas
Adenomatous polyposis coli
4 STK 11/LKB1 19 Peutz Jeghers syndrome
5 BRCA1 BRAC2 17 Familial breast ovarian carcinoma
13
6 WT1 11 Wilms tumours
7 NF1 17 Neurofibromatosis type 1 Neuroblastoma
Juvenile myeloid leukemia
8 NF2 22 Neurofibromatosis type 2
(Acoustic schwannoma& meningioma)
9 PTEN 10 Follicular carcinoma of thyroid Endometrial
carcinoma
Breast cancer
10 VHL 3 Renal cell carcinoma Cerebellar hemangioblastoma
Retinal angioma
Tumour markers
Hormone Enzymes Oncofetal antigens
Calcitonin – Medullary carcinoma Neuron specific enolase Carcinoma embryonic
of thyroid - Neuroblastoma Antigen – Carcinoma colon,
Human chorionic gonadotrophin - Small cell carcinoma of lung pancreas, lung, breast,
- Gestational trophoblastic Prostatitic acid phosphatase ovarian cancer
tumours - Prostate carcinoma Alpha fetoprotein
- Choriocarcinoma Placental alkaline phosphatase - Hepatocellular carcinoma
- Non seminomatous germ cell - Seminoma
- Non seminomatous germ
tumour’ - Dysgerminoma
cell tumor
Vanillylmandelic acid –
Neuroblastoma,
pheochromocytoma
Paraneoplastic syndromes
Endocrine paraneoplastic syndromes
Hypercalcemia – due to production of PTH – rP (parathormone – related peptide)
- Most commonly seen in breast cancer
- Also seen in squamous cell carcinoma of lung
Syndrome of inappropriate antidiuretic hormone (SIADH) – Small cell carcinoma of lung
Cushing syndrome – Increased ACTH
- Small cell carcinoma of lung
** In small cell carcinoma of lung SIADH > Cushing syndrome
Heart and blood vessel
Migratory thrombophlebitis (Trousseau syndrome)
- Seen in adenocarcinoma – mainly pancreatic adenocarcinoma
Non bacterialthrombotic endocarditis
- Adenocarcinoma
APPEARNCE
AL AMYLOIDOSIS / PRIMARY AA amyloidosis / Reactive systemic amyloidosis
AMYLOIDOSIS It is seen in association with:
− Amyloidosis associated with plasma cell (a)Rheumatoid arthritis (most common)
disorder. (b)Inflammatory bowel disease – Crohn’s
− Amyloid deposists can be seen in interstitium
disease and ulcerative colitis.
of any organ outside of the central nervous
(c)Heroin abusers
system.
Solid tumors – Renal cell carcinoma; Hodgkin
− Kidneys are the most frequently affected
lymphoma.
organ.
− Heart is the second most commonly affected Chronic Infections – Tuberculosis; Subacute
organ and heart failure is the most common endocarditis

cause of death.
− Macroglossia is pathognomonic
AA amyloidosis / Reactive systemic amyloidosis
It is seen in association with:
(a)Rheumatoid arthritis (most common)
(b)Inflammatory bowel disease – Crohn’s disease and ulcerative colitis.
(c)Heroin abusers
Solid tumors – Renal cell carcinoma; Hodgkin lymphoma.
Chronic Infections – Tuberculosis; Subacute endocarditis
PLATELET FUNCTIONAL DISORDERS
Bernard – Soulier Syndrome Glanzmann Thromboasthenia

Defect in GpIb – IX Defect in GpIIb/IIIa
Giant platelets Normal size platelets
Absent ristocetin induced platelet Normal ristocetin induced platelet
aggregation aggregation
Autosomal recessive Autosomal recessive
Mucocutaneous & GI bleeding Mucocutaneous and GI bleeding
present present
VON WILLEBRAND DISORDERS
• Autosomal Dominant
• Present with mucosal bleeding – epistaxis, easy bruising and menorrhagia
• Type 1 VWD – Most common type, mild VWD
• Type 2 – abnormal form of VWF present
• Type 3 – most severe form
• PTT – may be normal
• VWF – Ag – Total amount of VWF protein present is decreased in all 3 types
• Treatment type 1 – desmopressin
• Type 2 & 3 – VWF concentrates
CLOTTING DISORDERS
Hemophilia A Hemophilia B Hemophilia C Parahemophilia
Factor VIII deficiency Factor IX deficiency Factor XI deficiency Factor V deficiency
X linked recessive X linked recessive Autosomal recessive Autosomal recessive
Hallmark Feature is Hallmark Feature is Oral cavity bleeding Mucocutaneous bleeding
Hemarthrosis Hemarthrosis
PTT increased PTT Increased PTT Increased PT & PTT increased
Mild – Desmopressin Recombinant factor IX In dental extraction FFP
fibrinolytic inhibitor along
Recombinant factor VIII FFP
with plasma replacement
Emicizumab therapy
FFP
Cryoprecipitate
Differences IDA Anemia of chronic
inflammation
Iron deficiency anemia
and anemia of chronic
Ferritin Reduced Normal to increased
inflammation
• Similarities
• PBF – microcytic Total iron binding Increased Normal / decreased
hypochromic picture capacity
• Serum iron levels are
decreased Soluble transferrin Increased Normal
receptor
Cytokine level Normal Increased

Autosomal Dominant Autosomal Recessive
• Mainly affects structural protein • Mainly affects enzymatic proteins
• Usually one parent is affected • Both parents are unaffected
• No carrier status • Carries are present
• Normally no skipping of generation seen • Skipping of generation present
• Variable expression is seen • Uniform expression is seen
• Recurrence risk – 50% • Recurrence risk – 25%
X Linked Dominant X Linked Recessive
• Both males and females are affected • Mainly males are affected
• Affected sons must have an affected • Affected sons are usually born to
mother unaffected mother
• Affected father will have affected • Affected father will have carrier
daughter daughter

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APOPTOSIS

- Activation of enzymes called Caspases

Most common Seen in Seen in pancreas Seen in

Primary hyperparathyroidism Primary tumours of bone marrow Vitamin D intoxication

Secondary hyperparathyroidism Metastatic tumour Sarcoidosis

Ectopic secretion of PTHrP Accelerated bone turnover – Idiopathic hypercalcemia of

Gene Chromosome No Carcinoma

organ and heart failure is the most common endocarditis

Bernard – Soulier Syndrome Glanzmann Thromboasthenia

Cytokine level Normal Increased

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