medical school pathology lectures. Year end review of pathology. Term 2 - Haematology and gastrointestinal systems.

1. As is our Pathology,
so is our Practice.
-- Sir William Osler, M.D.
(Father of Modern Medicine & Founding professor of John Hopkins,
developed first residency program for physicians.)
Pathology: The science of medicine !

2. CPC21: Week Overview
2013 Term 2 CPC 1 Title: Haematopoetic 1/2 Anaemia
System: Haematopoietic system
Aim: To train students in:
Clinical, pathological & population studies of patients with
anemia (RBC disorders)
Objectives: 1. History taking & clinical examination of patients with
anaemia
2. Physical examination for anaemia and related illnesses.
3. Pathophysiology of common and important rare causes of
anaemia, particularly in the tropics and Indigenous
populations.
4. Review of Basic sciences relating to bone marrow, red blood
cell production and turnover of iron, routine blood test
parameters, measurement of iron stores, and precursors
important for red cell production.
5. Pathophysiology of acute anaemic processes.
6. Complications of anaemia.
7. Anaemia as a presentation for other pathologies and as an
illness in itself.

3. Core Learning Issues:
• Basic Science Review:
–RBC life cycle, structure, functions.
–Iron, B12 & Folate, Hemoglobin/bilirubin metabolism.
• Major Learning:
–CBC – Principles & Interpretation (reticulocytes).
–Microcytic, Macrocytic & Normocytic anemia.
–Overview & Classification of Anemias
–Common An: IDA, MA, Hemolytic & ACD
•Minor Learning:
–Congenital anemia– sickle, thalassaemia, G6PD, HS.
–Aplastic and hypoplastic anemia.
–Disorders of excess RBC – Polycythemia.
–Myelodysplastic syndromes (refractory anemia).
3

4. Haemopoiesis:
4
Leukemia

5. 5

6. Blood Smear - Normal
6
Lymphocyte
RBC
crenated RBC

7. Blood count - C.B.C / F.B.C
• Haemoglobin - 15±2.5, 14 ±2.5 - gms/dl.
• PCV/HCT - 0.47 ±0.07, 0.42 ±0.05 - lit/lit (%)
– RBC vol – better than Hb for anemia diagnosis.
• RBC count - 5.5 ±1, 4.8 ± 1 x1012/lit
• MCHC - Hb/PCV - 30-36 – grams/deci lit.
– Hb synthesis within RBC
• MCH - Hb/RBC - 29.5 ± 2.5 pg picogram (wt)
– Average Hb in RBC
• MCV - PCV/RBC 85 ± 8 – fl femto litres (vol)
7
30
33
85

8. Reticulocyte: Immature RBC
Reticular RNA - Methylene blue stain.
Reticulocyte
RBC
Reticulocytes (Immature RBC)  Increased RBC production
Reticulocytosis  Hemolytic anemia/bleeding 5-7 days
(Bluish, Large (high MCV)

9. MCV
Microcytic Normocytic Macrocytic
Measure Ferritin
Low Normal/high
Iron def
Anemia
Anemia of
chronic disease/
Congenital Hb dis.
Reticulocyte count
high low Anemia of chronic disease
Renal failure
Marrow failure
Hemolytic anemia
or blood loss
Measure B12 + folate
Megaloblastic
anemia
Normal Low
Anemia clinical
Types & Diagnosis

10. Haemopoiesis in Def. anemias
10
Iron Def. Anem Normal Megaloblastic
Normal DNA, Low Hb
More cell division
Micro-Normoblasts
Low DNA, Normal Hb
Less Cell division
Megaloblasts
Normal DNA & Hb
Normal cell division
Normoblasts
Macropoly, pancytopenia

11. IDA – Clinical Features
11
Bald Fissured - Glossitis
Angular chelitis
Pale creases
…Why?

12. Stages of Iron Deficiency:
12

13. Hypochromic Microcytic RBC
13

14. Megaloblastic Anaemia:
14
Marrow Hyperplasia Erythroblasts - Megaloblasts
Giant metamyelocyte - Macropolycyte Megaloblastic marrow

15. 15
ANEMIA OF CHRONIC
DISEASE:
• Defective iron transfer.
• By Inflammatory
mediators.
•  erythropoietin
production.
•  Iron transfer.
• IDA with normal or
increased iron stores.
• Does not respond to
hematenic therapy.
• Responds to
erythropoietin or
resolution of
inflammation.

16. “The future belongs to those
who believe in the beauty of
their dreams.”
–Eleanor Roosevelt

17. Self-pity is an opiate!
--Napoleon Hill

18. Hemolytic anemia: Morphology
• Abnormal shapes
(here a spherocyte)
• Polychromatophil
(large, bluish, no central palor)
• Nucleated RBC
(small, pyknotic)
18
Thalassemia

19. Hemolytic Anemia - Types:
• Acquired/External causes:
– Immune Hemolytic Anemia
• Warm Antibody HA (WAHA) & Cold Ab (CAHA)
• Allo immune hemolytic anemia.
– Mechanical Damage
• Valve, Microangiopathy (DIC), prosthesis, march
– Infection induced
• Clostridia, malaria, septicemia
• Congenital/Internal Defects
• Membrane (Hereditary Spherocytosis)
• Enzyme defect (G6PD deficiency)
• Hb defects (Qual: Sickle cell dis, Quant: Thalassemias)
19
1
2
3
Commonest

20. Autoimmune Hemolytic An: AIHA
• Auto antibody binding to red
cell surface antigens / Drug
complex.
• RBC phagocytosis in spleen
or complement fixation and
intravascular hemolysis.
• Warm (IgG) & Cold (IgM)
types.
• Warm: Drugs, Ideopathic.
• Cold: Infections, Lymphoma
• Lab diagnosis: Coombs
Test, Direct / Indirect.
20
Warm / IgG
Cold / IgM

21. AIHA: Lab diagnosis – Coombs test.
21
Direct Coombs Test:
(for antigen on patient RBC)
Indirect Coombs Test:
(for antibodies in the serum.)
Pos
Neg

22. Sickle Cell Anemia - Pathology

23. Sickle Cell Anemia
• Commonest congenital hemolytic anemia.
• Hemoglobinopathy – β chain 6(ValGlu)  HbS
• Deoxigenation  cryst. Hb  rigid sickle  obstruction, hemolysis.
• BS - Sickle cells, anisocytosis, poikilocytosis, and target cells.
• Hemolytic anemia, Multiple Infarcts, autosplenectomy(adult),
pigment gall stones, hemosiderosis.

24. Thalassemia:
24
• Quantitative Hb defect.
• Defective protein chain
synthesis.
• α, β, , , … types.
• α thal  α  Hb   β (β
β or β tetramers)
• Decreased normal Hb.
• Abnormal Hb (α/β tetramers).
• Like IDA (minor) Destruction
 hemolytic anemia (major)
• Minor: micro hypo, target cells
• Major: severe with hemolysis.
Minor / Trait
Major / Disease

25. “The only person who never
makes a mistake is a person who
never does anything”
- Theodore Roosevelt
25

26. 2013 Term 2 CPC 2 Title: Haematology 2/2
System: Haematopoetic System
Aim: To train students in:
Clinical and pathological presentation of haematological
malignancy
Objectives: 1. History taking & clinical examination of patients with
haematological malignancy
2. Physical examination of haematopoeitic system and related
systems in malignancy.
3. Pathophysiology of haematological malignancies.
4. Review of basic sciences relating to bone marrow, red blood
cell production and turnover of iron, routine blood test
parameters, measurement of iron stores, and precursors
important for red cell production.
5. Pathophysiology
6. Complications of haematological malignancies.
CPC22: Week Overview

27. 27
Normal Blood Cells:
Neutrophil
Basophil
Eosinophil
Lymphocyte
Non granular, Mononuclears
Specific Immunity
Granulocytes, Polymorphs
Non-Specific Immunity

28. WBC Absolute counts in disease:
Penia Philia
Neutro
Penia Philia
Eosino
Penia cytosis
Mono
Penia cytosis
Lympho

29. Granulopoiesis – Leukocytosis – Shift to left

30. Leukemia Classification
• Acute Leukemias:
– Acute Myeloid Leukemia - AML
• AML M0, M1, M2, M3, M4, M5, M6 & M7
– Acute Lymphoid Leukemia - ALL
• ALL - L1, L2 & L3 - maturity
• Chronic Leukemias:
– Chronic Myeloid Leukemia- CML
• Eosinophilic, neutrophilic, myelomonocytic etc.
– Chronic Lymphoid Leukemia - CLL
• Myeloma, Hairy cell, prolymph, Sezary sy. etc.

31. ALL - AML

32. Leukemia - Clinical Features
Decreased Hemopoiesis:
• Anemia (low RBC)
• Fever - Infections (low WBC)
• Bleeding tendency (low PLT)
Organ Infiltration:
• Bone pain / back pain.
• Lymphadenopathy.
• Hepato-spleenomegaly.

33. ALL - AML
• Dense chromatin
• Few nucleoli
• Scanty cytoplasm.
• No cytoplasmic granules.
• Fine lacy chromatin
• Many nucleoli
• More cytoplasm
• Cytoplasmic granules

34. CML CLL
• Middle age 40-60y
• Philadelphia chrom. t(9:22)
• Anemia, Fever & Bleeding
• Marked leucocytosis –
>50,000 (abnormal)
• Marked splenomegaly,
Hepatomegaly.
• Elderly age
• Anemia, fever & bleeding
– slow over years.
• Lymphocytosis &
Lymphadenopathy
• Marked Spleenomegaly
• Common B cell (CD5 +ve)
Chronic phase Accelerated crisis
Clinical course 

35. Lymphoma
• Definition: Neoplasms of lymphoid tissue
• Etiology: Idiopathic, Genetic, Infective.
• Pathogenesis:
– overexpression of antiapoptotic gene
– t(14-18)  bcl-2+IgM.  B Lymph. neoplasia *
• Clinical: Lymphadenopathy, weight loss, Fever,
Anemia.
• Hodgkins lymphoma (HL) – RS cells.
• Non-Hodgkins lymphoma (NHL) – no RS.
– B, T & Histiocytic “B commonest”

36. Hodgkins Lymphoma:
• Only Reed-Sternberg cells are malignant ‘B’
cells. Others cells are reactive.
• Types:
• Nodular sclerosis HL
• Lymphocyte-rich classical HL
• Mixed cellularity HL
• Lymphocyte depletion HL
• More RS cells = poor prognosis.
• Progresses by continuity – nearby LN first.
• Staging is important for prognosis. (x NHL)

37. Hodgkins Lymphoma:
• B cell lymphoma with special RS cells.
• Only Reed-Sternberg cells are malignant
‘B’ lymphocytes. Others cells are mixed
inflammatory cells with eosinophils.
• Many sub types: based on % of RS cells.
• More RS cells = poor prognosis.
1. Lymphocyte-rich classical HL
2. Nodular sclerosis HL – commonest.
3. Mixed cellularity HL
4. Lymphocyte depletion HL
• Spread to nearby LN not distant.
• Good prognosis, cure likely*
RS
RS
RS

38. Non-Hodgkins Lymphoma:
• Large group of lymphatic malignancies.
• types B, T & Histiocytic. “B common”
• Clinical Features:
– Fever, anemia, infections,
– Lymphadenopathy. Spleen+/-.
– low, intermediate & high grade.
• Pathology
– Lymphnode tumour – no RS cells, all one type.
– Follicular / Diffuse, Small / Large / mix Cells.
• Special types:
– Burkitts lymphoma – lymphoblastic.
– Multiple Myeloma – plasma cell.

39. NHL types- Diffuse & Nodular types

40. Lymphoma: Hodgkins Non Hodgkins
Age Average age is 27.7 with
two peaks, 15-24y , >55.
Average age is about 67.
Occurrence ~ 15% of all lymphomas ~ 85% of all lymphomas
Location above the collar bone 85%
(the mediastinum),
Extranodal in 4%
Chest in 40%, more abdomen
(exception lymphoblastic
lymphoma)
Extranodal in ~23% & BM
Affected
Lymph
Cells
B-Lymphocytes
characterized by the
Reed-Sternberg Cell
B, T, Histiocytes, NK Cells
depending on the subtype
Symptoms More likely to have
systemic ("B") Symptoms
Less likely to have "B“
symptoms.(27%)
Progression Early diagnosis,
Predictable, continuous
involvement. Better prog.
Late stages, less predictable
more spread.
Good to Worse prognosis.

41. Burkitt’s lymphoma: B cell.
• Young children, EBV virus.
• Endemic in Africa
• High grade, fast growing,
• Tumour in jaw bones.
• Lymphoblastic lymphoma
• Many macrophages – “starry sky”
appearance.

42. Multiple Myeloma:
• Malignancy of Plasma cells (Mature
B lymphocytes with Ab production)
• Hyper gammaglobulinemia
• Monoclonal antibody – neoplastic.
• Thick viscous blood – infarctions,
visual difficulties & even blindness.
• Old age, males common.
• Multiple, punched out Lytic bone
lesions (Osteolysis) & fractures.
• Immunodeficiency – infections.

43. "Creativity is inventing,
experimenting, growing,
taking risks, breaking
rules, making mistakes,
and having fun."
-- Mary Lou Cook

44. MyeloProliferative Syndromes:
• Neoplastic, Proliferation, Slow, chronic, & Mature cells.
• JAK2 gene mutation on 9p*  Erythropoietin
hypersensitivity.
• Increased number (Functionally abnormal)
• Extramedullary spread – Hepatosplenomegaly.
• May transform to Acute Leukemia (AML).
• Classification:
– RBC - Polycythemia vera (PV)
– WBC
• Chronic Myeloid Leukemia (CML)
• Chronic neutrophilic leukemia
• Chronic eosinophilic leukemia/HE syndrome.
– PLT - Essential Thrombocythemia (ET)
– Fibroblasts - Myelofibrosis (MF)

45. ET - Blood Film & clinical.
Plenty of
Platelets
Megakaryocyte

46. Polycythemia Rubra Vera (PV)
Hypercellular Marrow,
Red skin & Hepatosplenomegaly

47. MPS : MF. Hepatosplenomegaly
Massive hepato-splenomegaly secondary to
Extramedullary hematopoiesis due to Myelofibrosis.

48. Myelodysplastic Syndromes:
• Excess proliferation & destruction of dysplastic cells in
BM  Peripheral pancytopenia.
• Also known as Refractory Anemia’s
FAB classification
RA : Refractory Anemia (BM Blasts <1%)
RARS : RA with Ring Sideroblasts (<1%)
RAEB : RA with excess blasts (<5%)
RAEB in T : RAEB in transformation (5-30%)
(>30% blasts in BM  Leukemia)
Abnormal cells &
Recurrent infections in MDS

49. Worrying is like a rocking
chair, it gives you
something to do, but
doesn't get you anywhere.
-- Anonymous.
….Instead.. join winners club….!

50. The goal of mankind is knowledge,
which is is inherent in man. No
knowledge comes from outside: it is all
inside. What man 'learns' is really what
he “discovers” by taking the cover off
his own soul.
Swami Vivekananda
Education… from Eduse (latin) to bring out..

51. 2013 Term 2 CPC 3 Title: Hepatobiliary 1/2
System: Hepatobiliary System
Aim: To train students in:
Clinical Diagnosis & Understanding of patients with liver
disease.
Objectives:
(breakdown of
Aim)
1. History taking & clinical examination in patients with
liver disease.
2. Pathophysiology of acute & chronic hepatitis.
3. Pathophysiology of cirrhosis.
4. Review of basic sciences of hepatobiliary system.
5. Professional, ethical & legal issues in alcohol & drug
abuse.
6. Epidemiology of addiction, public health strategies.
CPC23: Week Overview
Note to tutors: There are two cases this week. Either case illustrates the learning issues.
Please feel free to use either case (or both).

52. 52
Liver Function Tests: Interpretation
• Synthesis / Function.
– Total protein & albumin low,
PT?Hepatocyte Injury.
– ALT, AST, LDH - high. ??
– Alk Phos – mild increase??
• Bile Duct Damage:
– Alk Phos – increased ??
• Other:
– GGT – alcohol use. – why?
– Viral serology -
– Auto-Antibody panel.
GGT ↑ Alcohol (centrilobular)
IgG ↑ Autoimmune hepatitis
IgM ↑ Primary biliary cirrhosis
IgA ↑ Alcoholic cirrhosis
AFP +ve Hep. Cell. Carcinoma
Anti-
mitochondrial
antibody
+ve Primary biliary cirrhosis
Anti-smooth
muscle, & ANA
+ve Autoimmune hepatitis

53. 53
• 1.5 kg, wedge shape
• 4 lobes, Right, left,
(Caudate, Quadrate)
• Double blood supply
• Hepatic arteries
• Portal – Venous blood
Normal

54. CPC 4.2.3 – 2013 – “yellow eyes”
• Fatigue / Anorexia..?
• Nausea, Vomiting..?
• Haematemesis… ?
• Itching..?
• Fever..?
• Abdominal distension slow..?
• Bleeding / Bruising..?
• 10 stubbies/day /more..?
• Many Tattoos..?
• BMI – if low / High..?
54
Mr. T.D. 50 year old, presents to his GP. ‘My stomach appears big
and my wife has noticed a yellow tinge in my eyes’.
CASE STUDY 1
Abd distension, fatigue, yellow discoloration of eyes for 1 week
Presenting Symptoms:
• Liver failure…
• Liver failure…
• Portal Hypertension
• Obstructive jaundice.
• Hepatitis.
• Cirrhosis.
• Vit-K deficiency.
• Alcoholic hepatitis.
• Viral Hepatitis (B/C)
• Anorexia / Obesity –
steatosis.
• Differential Diagnosis:
• Hepatitis: Alcoholic/Infective/Malignant/Drug/Toxins
• Acute / Chronic? Primary/Secondary?
• “HBV / HCV, CMV, Lepto, Dengue, Melioidosis.

55. 55
Viral Hepatitis A: Serology

56. 56
Viral Hepatitis B: Serology
Sequence of serologic markers for hepatitis B viral hepatitis demonstrating (A)
acute infection with resolution and (B) progression to chronic infection.

57. 57
Pathogenesis of Hepatitis A & B:

58. 58
Acute Hepatitis:
• Portal & Diffuse Inflammation.
• No clear border between inflammation & normal tissue
• Because of active necrosis & apoptosis at margins.
• Abnormal enzymes.

59. 59
Liver Biopsy – Chronic
Inflammation
• Portal Inflammation.
• No Necrosis
• Liver enzymes normal

60. 60
Acute viral Hepatitis: Swelling & Apoptotic cells.
• Diffuse Inflammation.
• Necrosis & Apoptosis.
• Liver enzymes raised.

61. 61
Fulminant Hepatitis:
• Rapid Hepatic failure with in 2-3 weeks.
• Massive necrosis, shrinkage, wrinkled
• Only portal tracts visible
• Little or massive inflammation – time
• Complete recovery – or - cirrhosis.

62. 62
Clinical Spectrum of HBV inf:
Acute
Chronic

63. 63
Cirrhosis – Portal hypertension
1. Cirrhosis-obstruction
2. Portal hypertension
3. Splenomegaly
4. transudation - Ascites

64. 64
Liver Biopsy – Cirrhosis
Reg. nodule
Fibrous septa

65. Primary Biliary Cirrhosis
• Autoimmune.
• Females 6:1.
• Pruritis, jaundice,
hepatosplenomegaly (initial).
• Intrahepatic Bile duct inflammation
• Cholestasis (bile stained liver)
65

66. "The past, the present and the
future are really one: they are
today!"
-Harriet Beecher Stowe
The past has gone and future you cannot see. The present, when you can do something, that is the Gift
(Present) with which you can make your future & past memorable.
- Sai Baba

67. 67
Chronic Alcoholism:
Acetaldehyde

68. 68
Alcoholic Liver Damage

69. 69
Alcoholic Hepatits - Mallory's hyalin

70. 70
Alcoholic Fatty Liver

71. 71
Alcoholic Fatty liver:

72. 72
High Risk
Intermediate
Low Risk
Safe drinking…

73. 73
Learn from the mistakes
of others. You can't live
long enough to make
them all yourself…!
61% of 5th year students exceeded ‘sensible’ limits
Drugs and alcohol were taken mainly for pleasure and were
perceived as a normal part of life for many students…
Capability of advising patients…?
http://www.lycaeum.org/research/researchpdfs/1996_webb_1.pdf

74. CPC24: Week Overview
2013 Term 2 CPC 4 Title: Hepatobiliary 2/2
System: Hepatobiliary & Pancreas
Aim: To train students in:
Understanding of & clinical approach to diagnosis of
patients with obstructive jaundice & gall bladder disease.
Objectives: 1. History taking & clinical examination
2. Physical examination for liver, gall bladder, jaundice.
3. Pathophysiology of obstructive jaundice.
4. Review of Basic sciences: Bile synthesis and
metabolism.
5. Professional, ethical & legal issues.
6. Epidemiology, Public Health.

75. 75
HBS:
Common
Clinical Presentations.
Why!

76. Biliary Obstructions:
• Extrahepatic Obstruction:
– Dislodged gallstones
– Ca. CBD, Ca. Head of pancreas.
– inflammatory stricture of CBD
– accidental surgical ligation of CBD.
• Intrahepatic Obstruction:
– Biliary atresia – Congenital.
– Primary Biliary Cirrhosis
– Primary Sclerosing Cholangitis.
– Cystic fibrosis.
Common Disorders:
• Cholecystitis
• Cholelithiasis
• Choledocholithiasis.
(Adeno Carcinoma)
95% - Cholelithiasis (+cystitis)

77. Cholelithiasis:
• Morphology & Types:
– Mixed Chol (Ca+Bile salt)* Multiple,
faceted, yellow-grey - commonest.
– Rarely Pure cholesterol: Round spiky.
– Bile Pigment stones (black/brown).
Infection / Jaundice. % Calcium = radio
opaque.

78. Complications of Cholelithiasis:
• Obstruction
• Sec biliary cirrhosis*
• Cholecystitis
• Cholangitis
• Biliary colic
• Jaundice
• Empyema
• Liver abscess
• Mucocele
• Pancreatitis.
• Peritonitis
• Carcinoma
• Fistula formation
• Gall stone ileus.
Gallstone ileus

79. Acute Cholecystitis:
• 90% Cholelithiasis. 10% non-calculous
• Females common.
• Outflow obstruction by a small gallstone.
• Infection – E.coli.  Empyema.
• Risk of perforation, peritonitis, fistula
 Gall stone ileus when stone enters GIT.
• Serum amylase normal (high with pancreatitis).
• Mild jaundice in 20% - obstructive.
• Acute inflammation, hemorrhage, edema, neutrophils.
• Gangrenous cholecystitis: when obstruction is severe
compromising blood supply. Green-black necrotic.

80. Chronic Cholecystitis:
• Females.
• Recurrent / Chronic.
• Thick fibrotic wall.
• Thick bile – biliary gravel.
• Aschoff-Rokitansky sinuses –
diverticula - Due to increased
luminal pressure (obstruction)
• Diffuse infiltration by chronic
inflammatory cells.

81. Acute Hemorrahagic Pancreatitis - Clinical
Severe
Mild
Grey Turner Sign - Cullen’s Sign

82. SUMMARY:
Trypsin  Kallikrein  Thrombosis - Necrosis
Protease  Blood Vessel injury – Bleeding.
Lipase  Fat necrosis  Inflammation.

83. Chronic fibrosing Pancreatitis:
Acute Hemorrhagic
Acute Hemorrhagic
Chronic fibrosing
Carcinoma

84. Acute Hemorrhagic Pancreatitis:
Fat Necrosis
Acini Necrosis
Hemorrhage
Normal Acini

85. Pancreatic Ca with fibrosis (Chronic pancreatitis)
Note: dysplastic glands infiltrating into fibro (spindle cells) myxoid (pale blue) stroma.
Malignant gl.
Ca. Infiltration
Islet (normal)
Fibrous stroma

86. Ca Pancreas
Clinical Features
Tumour marker:
CEA & CA19–9 antigen
Trousseau syndrome

87. Give someone a fish and you
feed him for a day.
Teach someone to fish and you
feed him for a lifetime!
Lao Tzu

88. CPC25: Week Overview
2013 Term 2 CPC 5 Title: GIT 1/3
System: Gastrointestinal
Aim: To train students in:
Understanding pathology & Clinical diagnosis of patients with
upper GIT disorders.
Clinical diagnosis of Acute Abdomen
Objectives: 1. History taking & clinical examination of patients with upper
GIT symptoms.
2. Physical examination of Abdomen. Recognition of an Acute
abdomen.
3. Pathophysiology of peptic ulcer disease.
4. Pathophysiology of gastric cancer.
5. Review of Basic sciences – Anatomy & functions of upper GIT
6. Professional, Ethical & Legal issues in chronic diseases.
7. Epidemiology & Public Health issues of Helicobacter pylori.
(Australian Nobel Laureate).
8. Presentation, epidemiology & Public Health issues of acute
appendicitis. Risk factors and counseling.

89. Esophagus & Stomach Normal
Glandular – Gastric  Normal  Squamous Oesophagus

90. Dysphagia
• Dysphagia: Difficulty in swallowing.
– Odynophagia: painful swallowing – inflam, ulcer,
Carcinoma.
• Sites:
– oropharyngeal, esophageal, esophagogastric, and
paraesophageal .
• Symptoms:
– Solids – Mechanical Obstruction – tumors/strictures.
– Solids & Liquids – Motility disorders – Achalasia.
– Liquids – Pharyngeal disorders.
• Causes:
– Local, Systemic, central.
– Mechanical, neural, functional.
– ulcers, tears, webs, rings, tumors, strictures,
paralysis abnormal peristalsis. (stroke),

91. Esophageal Disorders:
• Reflux Oesophagitis.
• Barrett’s
• Stricture – Inflam.
• Mallory-Weiss.
• Varices
• Hernia
• Zenker diverticulum
• T-E Fistula.
• Web – IDA – P-V Sy.
Herniations

92. Oesophagus motility Disorders:
Hernia: 30% incidence over 50years. (mostly asymptomatic)
Achalasia: Lack of relaxation of lower sphincter.
95% 5%
Achalasia Hernia-Sliding Hernia-Rolling

93. Oesophagitis:
• Acute: errosive, alcohol, infection.
• Chronic: Acid reflux (GERD),
chemical, alcohol, smoking,
candida, radiation, idiopathic
(eosinophilic).
• Endoscopic view 
Microscopy:
• Acute inflammation.
• Eosinophils: Few (reflux) more in
Eosinophilic.
Candida

94. GORD: Clinical Classification
GORD
Heartburn
Oesophagitis
24%
Barrett’s
1%
Non-Erosive
Reflex Disease (NERD)
(normal endoscopy)
75%
Endoscopy
24-hr pH Study
AET +ve
SI +ve
AET -ve
SI +ve
AET -ve
SI –ve
? MERD
AET: Acid Exposure Index
SI: Symptom Index.
MERD: minimal change.. RD
Etiology: (LES)
• Alcohol, Tobacco,
• Obesity,
• CNS depressants,
• Pregnancy,
• Hiatal hernia
• Delayed gastric emptying
• increased gastric volume

95. GERD: Pathogenesis.
Normal  Hyperplasia  Dysplasia  Carcinoma
Normal
Sq. Ep.
Metaplastic
Col. Ep.
Inflammed
Sq. Ep.
Basal cell hyperplasia

96. Squamous Carcinoma - Adenocarcinoma.
• Less common
• Upper end
• Tobacco, diet, toxins.
• More common
• Lower end
• Reflux disease (Barretts)
Tumour
Normal
Tumour
Normal

97. • Acute Gastritis:
– Drugs, toxins, alcohol, Ischemia.
– Infections (H.pylori transient)
• Chronic Gastritis:
– Autoimmune: Pernicious an.
(autoantibody)
– Chem: NSAIDs, Bile reflux,
Alcohol.
– Bacterial: Helicobacter pylori.
Gastritis:
Normal ↑
← Acute
Chronic ↓

98. H. Pylori Gastritis - Silver stain
Bacteria over
epithelial cells

99. Peptic Ulcer Morphology:
• Common in duodenum than stomach (4:1)
• > 80% single ulcer
• Round small, clean,
• punched out, <2cm*.
• Radiating folds.
• Microscopy:
– Superficial necrotic layer.
– Inflammatory cells zone.
– Granulation tissue zone - B
– Collagenous scar zone - C.
Note: Radiating mucosal folds from the ulcer.. Why?

100. Gastric Peptic ulcer: Scar
Note: Radiating mucosal folds from the ulcer.. Why?

101. Barry J Marshal, 2005 Nobel Prize….!
There were a lot of people who
didn't believe what we said but
they couldn't keep us quiet…!
A.A.Press.. 4 Oct 2005.
Barry J. Marshall & J. Robin Warren
was a trainee at that time…..!

102. Gastric Adeno Carcinoma:
Intestinal Type
• H.pylori Metaplasia
• C. gastritis / atrophy
• HER-2/NEU mutation
• Well differentiated
• No Signet ring cells.
• Gland formation.
• Better Prognosis
Diffuse Type
• Idiopathic/familial.
• No precursor lesion
• E-Cadherin mutations
• Poorly differentitated
• Signet ring cells
• No gland formation,
• Poor Prognosis

103. Fungating Carconoma

104. Diffuse Ca - Fibrotic
Linitis Plastica / Leather bottle stomach.
Malignant cells between fibrous stroma 
Endoscopy

105. Gastric Carcinoma
Malignant
Normal Gland

106. To attain knowledge, add
things every day.
To attain wisdom, remove
things every day.
Lao Tzu

107. CPC26: Week Overview
2013 Term 2 CPC 6 Title: GIT3/3
System: GIT.
Aim: To train students in:
Understanding pathology & Clinical diagnosis of patients
with lower GIT Conditions including Bowel Cancer &
Inflammatory bowel disorders.
Objectives:
(breakdown of Aim)
1. Physical examination of abdomen.
2. Review of basic sciences – Lower GIT structure &
function.
3. Pathology & Epidemiology of inflammatory bowel
disease.
4. History taking & clinical examination of patients with
Lower GIT Malignancy.
5. Genetic basis of colonic neoplasms.
6. Review of Basic sciences – Carcinogenesis, Knudson
theory, hereditary syndromes of colon cancer.
7. Professional, Ethical & Legal issues in malignancies.
8. Epidemiology & Public Health issues of lower GIT
malignancies (Global & Australian)

108. Etiology: Exact etiology not known…
“Unregulated and exaggerated
local immune response to Gut
flora in genetically susceptible
individuals”
• Etiology theory:
– 1. Genetic susceptibility
– 2. Environmental Factor:
Gut flora.
– 3. Immune
dysfunction/Autoimmunity.
• 15% family history, 30-59%
concordance in twins.
• HLA: DR1B1 (UC), DR7, DQ4
(CD) - 27%
• Hygiene hypothesis *
NOD2
Caspase
TNF, IL1, IL6,
IL23 R

109. Whole of GIT
Only Colon

110. Crohn’s - vs - U. Colitis:
• Chronic granulomatous.
• Transmural – full thickness.
• Ulcers deep, narrow.
• Firm thick, narrow lumen.
• Fibrosis - significant.
• Skip Lesions & fistula
• Rectal bleeding 100%
• No significant perianal sores.
• Malabsorption - Fat (ileum)
• HLA-DR7, DQ4. IL17 - TH1 cells.
• Acute infl – edema.
• Superficial - mucosal
inflammation.
• Ulcers shallow, broader.
• Normal/Thin wall, dilated lumen.
• Fibrosis - no/little.
• Continuous, no fistula.
• Rectal bleeding 75-85%
• perianal sores in 25-35%
• Malabsorption – no
• HLA – DRB1, - TH2 cells.
NOD2* IL-23R*

111. Crohn’s Disease: microscopy
Lymphocytes
Granuloma
Giant cells
No caseation.

112. UC - inflammation limited to mucosa,
atrophy of colonic glands, normal muscle layer.
Normal submucosa.

113. Diverticulosis:
• Later age. (>30y)
• Constipation alternating with
diarrhoea.
• Two types:
– Acquired / False common, no
muscular layer.
– True rare, congenital, all layers
present. E.g. Meckles.

114. Intestinal Obstructions:
• Mechanical Obstruction: (commonest)
– Adhesions, Hernias, Intussusception, Volvulus.
• Others:
– Tumors, gallstones, fecaliths, foreign bodies, Congenital stricture, atresias,
Meconium in cystic fibrosis.

115. Pseudomembranous Colitis:
Clostridium difficile: Controlled by normal flora. Antibiotic
therapy may result in over growth of cytotoxin producing
strains causing fibrinopurulent debris and mucus tightly
adherent to ulcerated mucosa (pseudomembran).

116. Polyps of Colon:
Villous
Adenoma
Tubular
Adenoma
Hyperplastic
Polyp Adeno-
Carcinoma

117. Polyps of Colon:
Hyperplastic - 90% - no/low malignant potential Tubular Adenoma 9% - malignant potential
Villous Adenoma 1% high malignant potential Tubulovillous Adenoma - mixed

118. Hereditary Colon Cancer Sy. *Rare
• HNPCC (Lynch Syndrome) (10%).
– AD, Mutation in DNA mismatch repair genes MMR
– increased risk of GI and non-GI cancers
– Few adenomatous polyps.
• Familial Adenomatous Polyposis (1%).
– AD, mutation in APC gene on 5q21
– >100 - 2500 polyps throughout GIT duodenum*
– virtually 100% risk of carcinoma by 50years.

119. Pathogenesis 1. – Adenoma Ca Path
More common – 70%

120. Pathogenesis 2. – Mismatch pathway
(also in sporadic Right type).
Less common – 10-15%

121. Left sided Ca Colon –
Constricting –
Napkin ring (Gross)
Apple core (Xray)

122. Adeno Carcinoma / Normal

123. Ca Colon – Dukes Staging - Prognosis.

124. “When we accept without
questioning, we forfeit the power to
control our own lives"
Bryce Courtenay
knowledge is power and ignorance is enslavement.
To question is the key to learning…!

125. CPC27: Week Overview
2013 Term 2 CPC 7 Title: Head and Neck 1/1
System: Respiratory Tract
Aim: To train students in clinical approach & diagnosis of
patients with symptoms of Upper Respiratory Tract
Infection (URTI).
Objectives: 1. History taking & clinical examination in Patients with
URTI.
2. Physical examination of head & neck.
3. Pathophysiology and Microbiology of URT & URTIs
4. Review of Basic sciences – Anatomy of Head &
Neck.
5. Professional, Ethical & Legal issues.
6. Epidemiology, Public Health.

126. Leukoplakia - Erythroplakia
Leuko+Erythroplakia
Erythroplakia
Leukoplakia

127. Progression of oral neoplasia
C
Cigarette, Alcohol & Tobacco.

128. Dental Pathology:
• Caries:
– Tooth decay, Mineral dissolution acid, carbs,
bacteria.
– Role of fluoride and oral hygiene
• Gingivitis:
– Junctional mucosa, hygiene.
Plaque/calculus.
– Inflammation of soft tissue around the teeth
• Periodontitis:
– Inflam. of supp. structures.
– Important in IE, pulmonary and brain
abscess

129. Oral Pathology:
• Irritation Fibroma:
– Fibrous scar, Rx excision
– Along bite line or a gingivo-dental
margin
• Pyogenic granuloma:
– Chronic ginvitis. Children,
pregnancy.
• Aphthous ulcers:
– Common, painful, shallow ulcers,
cause obscure.
• Glossitis:
– Trauma, dentures,
– Infections – herpes, candida,
syphilis
– Anemia – IDA, Meg.

130. Nasal Polyp (inflammatory):
• Chronic/recurrent URTI
• Allergy, hypersensitivity
• Mucosal inflam. Polyp
• Eosinophils.

131. Laryngeal Neoplasms:
• Vocal cord nodules:
singers/smokers nodules. Irritation,
Fibrous, may bleed, no malignancy.
• Recurrent (Juvenile) Papillomatosis:
children, multiple HPV (6,11).
• Single papillomas in adults.
• Laryngeal Carcinoma: Persistent
hoarseness of voice. Smokers (less
with alcohol, radiation). Vocal cords,
SCC usu. (95%)

132. Nasopharyngeal Carcinoma
• Africa (children) & China
(adults)...!
• EBV, Diet, likely
environment important.
• Undifferentiated
carcinoma with plenty of
reactive lymphocytes.
• Can be keratinising SCC,
non keratinising SCC and
undiff Ca
• Locally invasive, spread.
• 50% 3y survival.

133. Sialadenitis:
• Acute / chronic, Traumatic, viral, bacterial, autoimmune,
• xerostomia  infections.
• Parotid most common.
• Complications – calculus (sialolithiasis) or fibrosis 
duct obstruction  Recurrent sialadenitis.
• Mumps, Sjogren’s (autoimmune), S aureus, S viridans.

134. Pleomorphic Adenoma
• Mixed tumor, Most common (60%)
• Adults, Slow growing, Asymptomatic.
• Single, Irregular, nodular, Well defined
borders, less mobile.
• Mature Epithelial & connective tissue.
• Recurrence common.
Other tumours:
• Warthin’s tumour (lymphoepithelioma)
• Mucoepidermoid Ca.
• Adenoid cystic carcinoma
• Adeno / Squamous Cell Ca.

135. Education must award
character & self-confidence,
the courage to depend on
one’s own strength.
- Sai Baba