Chapter 1 - Introduction to Pathology

Introduction to Pathology, definitions and common terms used.

additional resource: power-point lecture self-assessments

Introduction: Pathology is "Scientific study of disease" Study of structural and functional changes in disease. You need to have a basic knowledge of normal Anatomy (structure) and Physiology(function) to understand Pathology. Pathologists assist medical management of patient by providing diagnosis by examination of specimens taken from patients. Commonly pathology is equated to laboratory testing, but actually pathology is more than that. "Pathology deals with knowledge of what causes disease, how disease starts, progresses & it explains the reason for signs and symptoms of patient" knowing pathology provides a sound foundation for rational clinical care and therapy. Branches of Pathology: Histopathology / Anatomic Pathology : Pathologists specialising in anatomical changes in disease. Usually using a tissue biopsy. Cytopathology: Pathologists specialising in study of body fluids & Cells. Haematology: Study of blood and blood forming organs. Morbid Anatomy: Autopsy or Post mortem study for legal or educational purpose. Knowledge of pathology helps in better understanding of patient and his disease. Diseases is expression of "discomfort" due to structural or functional abnormality. This abnormality can be caused by various agents Eg. Bacteria, virus, heat, radiation etc. collectively called 'etiology'. Factors causing disease are mainly two types. Environmental or external factors and Genetic or Internal factors. Diseases which present since birth are called Congenital diseases and all other diseases are known as Acquired diseases. Diseases which occur in families are known as Familial diseases. Pathology of a disease is formally studied under four subdivisions. Etiology - Study of cause / causative agent of disease Pathogenesis- Study of disease progression or evolution. Morphology - Study of structural changes in disease (Gross & microscopic) Clinical Significance - Study of how clinical features are related to changes. Major groups of diseases are Inflammatory, Degenerative & Neoplastic. Inflammatory disorders are due to damage to tissues by various injuries (physical, chemical, infections etc.) Degenerative disorders are due to lack of growth or ageing. Neoplastic disorders are due to excess cell division forming tumours.

Biopsy is a sample of tissue or fluid taken for the purpose of diagnosis. Two major types 1. Tissue biopsy 2. Cytological biopsy - fluids.

Chapter 2 - cell injury & adaptations

Diseases, Cell injury, Adaptations, Necrosis & Ageing.
additional resource: power-point lecture self-assessments
Introduction: (Overview of chapter) What is disease (dis+ease)? "Discomfort due to Structural or functional abnormality" Diseases occur when there is variation in normal structure or function due to external or internal factors(Etiology) eg. Bacteria, stress. Familiarise yourself to the following: (important points in the topic) Disease presents with many 'problems' known as symptoms eg. Pain. And abnormalities noticed by physician known as Signs eg. Abnormal heart sounds. Finding the nature of disease is known as diagnosis. Predicting the future course of disease is known as Prognosis, and taking precautions to prevent disease is known as Prophylaxis. All diseases can be classified into three Major groups. Inflammatory - Disease due to destruction of tissue. (most common type) Degenerative - Due to lack of growth eg. Ageing Neoplastic - Due to excess growth - Eg. Cancers. Diseases can be Congenital (present from birth) or Acquired (develop after birth). Diseases occurring in families are known as Familial disorders (usually genetic). Factors which can cause injury: " Environmental or external factors - Physical, Chemical, Biologic, Nutritional. " Genetic or Internal factors. Mild injury causes stress on the cell but not cell death, such injury is known as reversible injury, such cells develop structural or functional changes to overcome injury known as adaptation. When injury is severe enough it causes death of cell termed irreversible injury. Changes occurring in dead cells is known as necrosis. For example when blood supply to heart is reduced heart muscle suffer damage called "Ischemia" and presents as severe pain and it recoveres when blood supply is restored. But when blood is blocked for more than 10 min, then cells in that part of heart die.

When we start physical exercise our muscles sense the excess workload and increase their size to avoid trauma this is called "hypertrophy". When we stop using a muscle (eg. After fracture) the muscle cells become thin (atrophy). Read different examples. "Term Necrosis is used to describe structural changes occurring in dead cells within living tissue". Understand different types of necrosis with. What is Caseous necrosis, what is Coagulative necrosis, what is a gangrene? Read some examples. What happens after necrosis? Ageing: Ageing is time related gradual loss of structural and functional capacity of cells. Certain factors like 'stress' accelerate ageing. Read about other factors which can affect your ageing..!

Chapter 3 - inflammation
What happens when tissues are injured? An overview of tissue injury and inflammation
additional resource: power-point lecture self-assessments Introduction: (over view of the topic) We studied cellular response to injury. But tissues differ in their response to injury due to cellular mechanisms of defence, blood supply, antibodies etc. Review the following: (Background knowledge needed to understand) Study general structure of tissues types of tissues such as epithelial, connective etc., Understand blood circulation, how blood transports nutrition and removes wastes. Also you need to know the blood cells the Red (RBC) and white (WBC) blood cells their function. What is an antibody? How body defends against disease? Etc. Familiarise yourself to the following: (important points in the topic) Inflammation is "dynamic response of vascularized tissues to injury". It is a complex multi step process of tissue response to injury. The purpose of Inflammation is to defend against injurious agent and start healing & repair of injured tissue. Inflammation is an important part of body's defence mechanisms. Inflammation brings together defence forces such as WBC, antibodies and other chemicals apart from bringing more nutrients and healing factors to the site of injury. Study Clinical signs of inflammation. Understand Lewis triple response: Flush(redline), Flare(red zone) & weal(edema), and classic five signs - Rubor(redness), tumor(swelling), Calor(Heat), Dolor (pain) and Loss of function of inflammation. Mechanism of Inflammation: It starts with dilatation of blood vessels(vasodilatation) to bring more blood (Hyperemia) and along with it the mediators of defence & healing. Blood vessels become leaky allowing escape of fluids(transudation), proteins & cells (exudation) into tissue space causing edema. The WBC crawl of capillary(emigration) towards site of injury attracted by chemicals(Chemotaxis) and engulf debris (phagocytosis). Antibodies and other chemical mediators of inflammation serve to

neutralise the injurious agents such as microbes. These events are caused or regulated by chemical mediators of inflammation such as histamine, seratonin, bradykinin & prostaglandins. Many painkiller or anti-inflammatory drugs act by blocking synthesis of these chemical mediators. For example common drug aspirin inhibits synthesis of prostaglandins. Inflammation can be of different types. Most common form which is for short duration followed by healing is known as acute inflammation. When inflammation remains for long time then healing with fibrosis also occur side by side such inflammation is called chronic inflammation. When excess fluid and WBC leak out they form "pus" and such inflammation is known as pyogenic or suppurative. Collection of this fluid in tissue space is an Abscess. When an abscess enlarges it may open onto surface causing "sinus" or when it opens into another organ it is known as fistula. Understand that although inflammation is a protective defence mechanism, inflammation causes pain and distress to the patient and is the main reason our drugstores are loaded with anti-inflammatory drugs, and these drugs should be used with caution.Excess inflammation or inflammation due to abnormal immune reaction such as allergy can be very destructive. Example Asthma is inflammation of respiratory mucosa due to hypersensitivity reaction.

What happens after inflammation? Overview of healing and repair.

chapter 4 - healing & regeneration

additional resource: power-point lecture self-assessments

Introduction: (over view of the topic) We studied inflammation as a response of tissues to injury. What happens after? Yes, removal of dead tissue and replacement by new tissue to regain the structure and function, this process is called Healing. Inflammation also sets in process of healing. Review the following: (Background knowledge needed to understand) Understand inflammation, various stages and types. Understand cell division. Familiarise yourself to the following: (important points in the topic) Healing is replacement of dead and injured tissue by healthy tissue. This occurs by two process 1. Proliferation or Cell division and 2. Differentiation (functional maturity). During healing, dead tissue is removed by macrophages, and surrounding viable tissue divide to produce more cells which move into the area of wound and start dividing to replace dead tissue, these cells synthesise matrix and other non cellular elements of tissue. Newly formed Fibrous tissue in the process of healing is called scar tissue. It contains tough fibrous protein Collagen which gives the strength to the scar. Healing of skin wounds: Two types 1. Primary Union - when clean cut wound healing within weeks. 2. Secondary Union - When large open wounds heal with large scars such as ulcers and burn wounds. Stages of healing: 1. Immediate - Blood clot fills the wound 2. Within 24 hours - Inflammation, WBC move to site of injury.

3. 3-7 days - Macrophage activity & granulation tissue, epithelial regeneration. 4. Weeks - Fibrous vascular union with intact epithelium, mild inflammation. 5. Months - No inflammation, Remodelling, avascular thin scar, minimal contraction. In Secondary union the stages of healing are prolonged, with more scab and scar formation, more wound contraction. Healing in special tissues: Muscles: All striated muscles cannot regenerate, so healing by fibrosis. Nerves: Axon only damage repairs by regrowth. Damage to nerve cells is healed by fibrosis, as nerve cells cannot regenerate like striated muscle. Bone Healing: Fracture heals by 1. 2. 3. 4. 5. Immediate - Blood clot Hours - inflammation, neutrophils & macrophages. Days - Granulation tissue with osteoblasts and matrix (soft callus) Weeks - Deposition of Calcium (calcification) to form hard callus Months - Remodelling - removal of excess irregular bone

Factors affecting healing: Healing is a complex process and can be affected by several factors. A. Systemic Factors which affect healing are 1. Age 2. Malnutrition, vitamin deficiency 3. Other diseases such as diabetes. B. Local factors such as 1. Infection 2. presence of dead or foreign tissue 3. Blood supply 4.Mobility as in fractures.

Chapter 5 - circulatory disorders

Disorders of Circulation - Obstruction, infarction, edema, & 'Shock'
additional resource: power-point lecture self-assessments Introduction: (over view of the topic) Blood is fluid as long it is flowing...! Any stagnation initiates coagulation leading to clot formation. When this happens the tissues supplied suffer anoxia (ischemia) and die (infarction) of (activation of enzymes in plasma leading to formation of solid fibrin clot). Review the following: (Background knowledge needed to understand) Revise physiology of blood circulation & coagulation. Study structure and function of blood vessels (anatomy). Familiarise yourself to the following: (important points in the topic) Formation of blood clot within blood vessel is known as Thrombosis. Factors leading to thrombosis are 1. Alterations of blood flow ex. Aneurysm, Obstruction, turbulence. 2. Damage to blood vessel ex. Atherosclerosis.

3. Altered composition of blood ex. Septicaemia. Abnormal dilatation of blood vessels is known as aneurysm. Two major types are 1. Fusiform (uniform) 2. Saccular (one sided). Aneurisms change axial flow to turbulent blood flow favouring coagulation and thrombus formation. When thrombus is formed in slow flowing blood as in a vein, more cells gets into the clot forming a soft red clot(red thrombus). When clot forms in fast flowing blood as in artery, it consists mainly fibrin and platelets and is hard(White thrombus). When alternating layers of red and white thrombus is formed it is known as mixed thrombus. When a thrombus detaches and gets carried in the blood stream it is known as Thrombo-embolism. Abnormal Solid matter carried in blood stream and cause obstruction at distant location is known as embolism. Types of emboli are, 1. Solid - such as clot, tumour cells, bacterial clumps, parasites etc. 2. Gaseous - air in chest injury& fractures, nitrogen in decompression sickness. 3. Liquid - Fat embolism, amniotic fluid embolism during parturition(labour) When a blood vessel is slowly obstructed, the organ does not suffer ischemia, as normally closed excess blood vessels (collateral & anastomotic vessels) open up. This is called collateral circulation. "ischemia" is decreased blood supply affecting tissue or organ function. Death of tissue due to lack of blood supply is known as "Infarction" Edema is accumulation of excess fluid in intercellular spaces. Edema can be localised as in venous obstruction, or it can be generalised(anasarca) as in systemic inflammation, or hypoprteinemia. Excess fluid in body cavities is called effusion ex. Pleural effusion. Shock is sudden depression of vital functions due to decreased circulating blood volume. This may be due to actual decrease in blood volume as in bleeding, or dehydration. It can also result from excess vasodilatation due to parasympathetic nerve stimulation as in neurogenic or cardiogenic shock. Common types of shock are 1. Hypovolaemic 2. Cardiogenic & 3. Septic or toxic. During shock there is decreased cadiac output, reduced blood pressure, sympathetic nerve stimulation, and dilatation of vessels of vital organs and less blood to peripheral organs. This results in cold clammy skin & loss of conscious ness. This results in fall of shocked person, this is a protective mechanism by bringing blood to brain by horizontal position. Shock progresses in two stages. 1. Early Stage - Reactive changes to maintain blood pressure. 2. Advanced stage of low blood pressure due to failing compensatory mechanisms.

Chapter 6 - growth disorders 1 - non neoplastic

Disorders of Growth - Neoplastic and non-neoplastic growth
additional resource: power-point lecture self-assessments
Introduction: Cell division and growth are essential for development and repair of organs and tissues.

However excess or uncontrolled growth are important causes of disease such as cancer. Review the following: (Necessary Background knowledge) 1. Revise your knowledge of ell division 2. Types of cell division Mitotic & Meiotic, their stages. 3. Control of normal cell division. 4. Types of cells according to capacity of regeneration(Labile, stable & permanent) Familiarise yourself to the following: (important points in the topic). When excess growth occurs due to a purpose or necessity it is known as Non-Neoplastic growth. Such as increase in muscle size with exercise. Characters of non neoplastic growth are they are controlled, reversible and have a purpose. Examples of Non-Neoplastic growths - Hyperplasia, Hypertrophy, Metaplasia, Dysplasia Excess cell division leading to increased cells is known as Hyperplasia Ex. Enlargement of breast in puberty, uterus in pregnancy, thyroid in iodine deficiency, Prostate in old age. When a cell cannot divide, it increases in size known as Hypertrophy, Ex. Skeletal muscle after exercise, Heart enlargement in hypertension (high blood pressure). When increase in growth also causes change in cell type it is known as Metaplasia. Example change of respiratory epithelium to squamous epithelium in chronic smokers. When excess growth occurs for long time, the resulting cells may be disorganized and is known as Dysplasia. Example Respiratory mucosa in smokers, chronic cervicitis. Dysplasia if persists for long time leads to cancer. When growth occurs due to loss of control over cell division it is known as Neoplasm. Neoplasia literally means new growth, commonly known as tumor. It is defined as Progressive Purposeless Proliferation of cells which is irreversible. Simply put neoplasia is "cells dividing without control". Neoplasms can be two types Benign and Malignant on clinical basis. Benign tumors are usually localized, capsulated and do not spread. Malignant tumors do not have a capsule and spread by infiltration and/or metastasis. Cancer is the common term for malignant neoplasm. Characters of a neoplasm are 1. Differentiation (Resemblance to normal cell - functional maturity), Anaplasia (cellular and nuclear abnormality), Invasiveness (destruction of surrounding tissue) and metastasis (ability to spread to distant organs). Metastasis can occur by direct spread, blood vessels or lymphatic vessels. Nomenclature of neoplasms: Neoplasms are named according to their cell of origin (epithelial or connective tissue) with a suffix to describe type of neoplasm. All Benign tumors have suffix "oma" epithelial malignancies have "carcinoma" and connective tissue malignancies have "sarcoma" Example: Cell or origin Benign tumor Fibrous tissue Fibroma Fat tissue Lipoma Bone Osteoma Squamous epithelium Papilloma Glands Adenoma Cartilage Chondroma Smooth muscle Leiomyoma Some exceptions: Lymphoma, leukaemia, papilloma (tumor with a stalk). malignant tumor Fibrosarcoma Liposarcoma Osteosarcoma Squamous carcinoma Adenocarcinoma Chondrosarcoma Leiomyosarcoma

Chapter 7 - growth disorders 2 - neoplastic

Disorders of Immune system: Introduction, Allergy, Autoimmune disorders
additional resource: power-point lecture self-assessments
Introduction: (over view of the topic) Immune system is body's defence system. Immunity is ability to defend against foreign tissues and organisms. During embryonic stage body learns what is self, later it differentiates and responds to foreign substance(antigen) by producing appropriate immune response. Familiarise yourself to the following: (important points in the topic). Foreign substances which produce a immune response is known as "Antigen" and the resulting in development of Immunity, this is known as active immunity such as infection or vaccine. (Vaccine is dead or deactivated pathogen in suspension, toxoid is a suspension of inactivated toxins). Immunity can also be artificially induced by injecting prepared antibodies (antisera) known as passive immunity. E.g. Tetanus antisera. Depending on type of antigen, developed immunity can be two types. 1. Humoral immunity - by stimulation of B lymphocytes which secrete antibody Depending on the structure, antibodies are of five types IgG, IgA, IgM, IgE & IgD. Most common is IgG (longterm) and IgM (shortterm). IgE is typically seen in allergic reactions. Two types of immune response can result depending on the type of antigen. 2. Cell-mediated immunity - Stimulation of T lymphocytes which activate macrophages to engulf parasites and cancer cells. On first exposure to antigen body tries to learn and then slowly produces appropriate antibody, this is known as primary response, and this information is stored in memory lymphocytes. When body is attacked by same pathogen second time, the immune response is fast and strong due to stored memory, this is known as secondary response. When a antigen combines with antibody the resulting product is called 'immune comlex' which activates 'complements', highly toxic enzymes which kills the antigen and surrounding cells.

Disorders of Immune system: abnormality in recognising self antigens leads to development of Autoimmune disorders such as Rheumatoid arthritis, Systemic Lupus Erythematoses where auto-antibodies are produced against own connective tissue proteins and cause chronic inflammatory damage to collagen tissue in joints, heart & Blood vessels. These patients are managed by drugs which inhibit immune system such a steroids, and anti-inflammatory drugs. Hypersensitivity is a condition of excess immune response to certain antigens causing damage, commonly known as "Allergy" and such antigens are known as "Allergens" Four major types of hypersensitivity reactions Types I, II & III are of humoral type, type IV is cell mediated. Type I is common mediated by IgE, e.g. Anaphylaxis, atopy & allergy such as Asthma. Asthma is a disorder of airways of lungs Bronchial asthma. 'Allergens' in air initiate immune reaction causing inflammation and damage to mucosa with excess mucous production which block the airways causing difficulty in breathing "wheezing". These patients are managed by drugs which dilate bronchi (Broncho-dilators) and immuno suppressive drugs such as steroids.

Disorders of Immune system: Introduction, Allergy, Autoimmune disorders

additional resource: power-point lecture self-assessments

chapter 8 - immune disorders 1- Autoimmune

Introduction: (over view of the topic) Immune system is body's defence system. Immunity is ability to defend against foreign tissues and organisms. During embryonic stage body learns what is self, later it differentiates and responds to foreign substance(antigen) by producing appropriate immune response. Familiarise yourself to the following: (important points in the topic). Foreign substances which produce a immune response is known as "Antigen" and the resulting in development of Immunity, this is known as active immunity such as infection or vaccine. (Vaccine is dead or deactivated pathogen in suspension, toxoid is a suspension of inactivated toxins). Immunity can also be artificially induced by injecting prepared antibodies (antisera) known as passive immunity. E.g.

Tetanus antisera. Depending on type of antigen, developed immunity can be two types. 1. Humoral immunity - by stimulation of B lymphocytes which secrete antibody Depending on the structure, antibodies are of five types IgG, IgA, IgM, IgE & IgD. Most common is IgG (longterm) and IgM (shortterm). IgE is typically seen in allergic reactions. Two types of immune response can result depending on the type of antigen. 2. Cell-mediated immunity - Stimulation of T lymphocytes which activate macrophages to engulf parasites and cancer cells. On first exposure to antigen body tries to learn and then slowly produces appropriate antibody, this is known as primary response, and this information is stored in memory lymphocytes. When body is attacked by same pathogen second time, the immune response is fast and strong due to stored memory, this is known as secondary response. When a antigen combines with antibody the resulting product is called 'immune comlex' which activates 'complements', highly toxic enzymes which kills the antigen and surrounding cells.

Disorders of Immune system: abnormality in recognising self antigens leads to development of Autoimmune disorders such as Rheumatoid arthritis, Systemic Lupus Erythematoses where auto-antibodies are produced against own connective tissue proteins and cause chronic inflammatory damage to collagen tissue in joints, heart & Blood vessels. These patients are managed by drugs which inhibit immune system such a steroids, and anti-inflammatory drugs. Hypersensitivity is a condition of excess immune response to certain antigens causing damage, commonly known as "Allergy" and such antigens are known as "Allergens" Four major types of hypersensitivity reactions Types I, II & III are of humoral type, type IV is cell mediated. Type I is common mediated by IgE, e.g. Anaphylaxis, atopy & allergy such as Asthma. Asthma is a disorder of airways of lungs Bronchial asthma. 'Allergens' in air initiate immune reaction causing inflammation and damage to mucosa with excess mucous production which block the airways causing difficulty in breathing "wheezing". These patients are managed by drugs which dilate bronchi (Broncho-dilators) and immuno suppressive drugs such as steroids.

Chapter 9 - immune disorders 2 - Immunodef.

Autoimmune disorders & Immunodeficiency disorders AIDS

additional resource: power-point lecture self-assessments
Autoimmune disorders: Disease due to immune reaction against own tissues. Mechanisms resulting in Autoimmune disorders: 1. Breakdown of self recognition mechanism - loss of self tolerance 2. Molecular mimicry - Antigen resemblance - Rheumatic heart disease. 3. Genetic factors: Immune dysregulation. Eg. ankylosing spondylitis(HLAB27). AUTOIMMUNE DISORDERS: Examples - Hemolytic anemia, Type I diabetes, Rheumatoid arthritis, SLE,Thyroiditis. Systemic Lupus Erythematosus (SLE) Classic prototype of autoimmune disorder. Unknown aetiology. Immune dysfunction. 1. Several autoantibodies to cellular components and blood group antigens. Most significantly Antinuclear antibodies (ANA). 2. Pathogenesis - Immune reaction against self - skins, joints, BV, heart, kidney. 3. Skin & joint inflammation(Arthritis & Dermatitis), Anemia(RBC) 4. Kidney - autoimmune Nephritis- Renal failure. Laboratory diagnosis: Indirect Immunofluorescence for ANA. (Patient serum + tissue) High titres suggest disease progression. Used for follow up. Management: suppression of immune system (eg. Steroids) Rheumatoid Arthritis: Microbial infection in genetically susceptible persons(1%) develop autoantibody against connective tissue and IgG. Multisystem, but arthritis is prominent. Pathogenesis:. Autoantibody, Synovial inflammation, destruction, fibrosis, scarring and later ankylosis. Symmetrical involvement. Rhemuatic skin nodules, vasculitis & neuritis. Rheumatic Heart Disease: Post streptococcal autoimmune disorder due to antigenic similarity between streptococci and connective tissue in genetically susceptible individuals. Mitral valve inflammation, fibrosis & scarring leading to mitral stenosis. IMMUNODEFICIENCY DISORDERS: Deficiency of one or more components of immune system. Specific System: Humoral or Cell mediated. Non-Specific: Phagocytes & Complement. Two major types of immunodeficiency: 1. Primary - Inherited, Genetic

Agammaglobulinemia - Absent B cells, no immunoglobulins. IgA deficiency - Common, infections, allegry.

Combined immunodeficiency - Tcell & B cell defect - viral and fungal infections.

2. Secondary - Infections, drugs, Malnutrition & radiation etc. also produce immunodeficiency. Particularly in those strict dieting, junk food, children with parasitic infestations etc. Frequent infections. Vit-C*

AIDS - Retrovirus Human Immunodeficiency Virus (HIV) types I & II. Pandemic form of immunodeficiency disorder. Incidence from 0.01% in australasia to 67% in sub Saharan Africa. Increasing incidence, 33 million in 1999. Virus attacks and kills Helper T lymphocytes (T4) necessary for immune response.

Sexual promiscuity, IV drug users, Blood product recipients, sexual contacts. HIV 1 & 2 , Several antigens, p24 is the most readily tested (ELISA). Pathogenesis: two targets T4 lymphocytes & neurons. Immunodeficiency, opportunistic infections, pneumocystis, candida & TB Brain degeration, brain tumors, skin tumours - Kaposi sarcoma. Stages: latent (no symptoms), Aids Related Syndrome (ARS), Clinical AIDS.

Heredity, Genes & Disease

chapter 10 - genetic disorders

additional resource: power-point lecture self-assessments

Introduction: (over view of the topic) DNA is a long chain of neucleic acids. Chromosomes are condensed DNA formed only during cell division. Segment of DNA responsible for producing a protein or character is known as Gene. Every human body cell has two pairs of similar chromosomes (diploid) where as sperm and ovum has single pair (haploid). Allele is a single gene of the gene pair. When both alleles are same they are known as homozygous and when different - heterozygous. Every cell of our body has complete set of genes but only few are functionally active. Genetic damage can result from various modes eg. chemicals, radiation & viruses. Disorders due to abnormality of genetic material - DNA are known as genetic disorders. More common than we think! (670/1000 including cancers and cardiovascular diseases) Familiarise yourself to the following: (important points in the topic). Diseases which are present since birth are known as Congenital diseases. Familial disorders are any disorders occurring in families. Congenital disorders are classified into following types, 1. Genetic disorders - Altered/abnormal genetic material. 2. Developmental defects - Malformations- Agenesis, Atresia, ectopia etc. 3. Multifactorial disorders. Mutation is permanent change in DNA sequence resulting in functional or structural abnormality. DNA damage is more common during stage of cell division, such as embryogenesis. Agents which bring about DNA damage during embryogenesis are known as mutagens. Genetic abnormalities may be inherited or acquired during embryogenesis or acquired after birth. Neoplasms (tumors) are the most important disorders due to genetic abnormalities acquired after birth. Mutations are classified as below: 1. Genomic: Loss of gain of whole chromosome. eg. Trisomy 21 - 'Down's syndrome 2. chromosomal: visible abnormality of a single chromosome. eg. 5q deletion - or 3. Gene: Affecting one or more genes (Micro change) and Point (affecting single base substitution). Single Gene or Mendelian disorders - eg. Hemophilia Medelian disorders are further classified into two types autosomal or sex linked and a gene disorder can also be Dominant or recessive. Autosomal Dominant: 50% children abnormal, Marfans, familial hypercholesterolemia Autosomal Recessive: 25% normal, 50% carriers, 25% affected. Eg. Cystic fibrosis, Sickle cell anemia. Sexlinked: Usually recessive, males affected, females carry - Hemophilia A - F8 deficiency. Down's Syndrome: Trisomy 21. Due to non dysjunction (separation) one of gamete has more double chromosome. Common 1:700 births, common in aged mothers. Mental deficiency, flat face, mongolism, simian crese, heart defects etc.

Chapter 11 - hematology 1
Introduction to Haemopoietic system & RBC disorders Anemias
additional resource: power-point lecture self-assessments
Haemopoietic system constitutes blood and organs which produce and maintain blood i.e. Bone marrow the site of blood production(Haemopoiesis) & spleen, the site of destruction of aged and damaged blood cells. During fetal life, blood is primarily produced in Liver. Blood production is stimulated by hormone erythropoietin in response to tissue hypoxia. Most blood disorders are manifested by basically three mechanisms. Decreased number of blood cells: such as Anemia(low RBC) , Leucopenia(low WBC), Thrombocytopenia(low PLT). Which can be due to two causes 1. Decreased production - Aplastic anaemias & deficiency anemias. 2. Increased destruction - Haemolytic anaemia. Increased number of cells: Such as Polycythemia (excess RBC) or due to neoplasms of blood cells such as Leukemias & lymphomas. (Myeloid cells and lymphocytes) Dysfunciton of cells: Due to abnormal structure or function of blood cells such as thalassemias, sickle cell disease.etc. Review the following: Haemopoietic system. Production of blood, Structure and function of RBC. Familiarise yourself to the following: Understand causes and types of anaemia. How anemia occurs. Anemias result due to two main reasons Decreased production - Deficiency anemias, Aplastic anemia Increased loss - Blood loss and Hemolytic anemias. Read about deficiency anaemias ( Iron def. & Megaloblastic) How they occur & differ? How to diagnose them by laboratory tests. Mineral Iron & vitamins B12 & folates are important for normal development of RBC & WBC. Deficiency of Iron causes decreased Hb in RBC making the RBC small and with less Hb content. Vitamin B12 & folates are necessary for DNA synthesis. Deficiency of these vitamins cause delay in maturations resulting in megaloblastic anemia few abnormally big RBC.

Laboratory tests: Hb - Haemoglobin, MCV-Mean cell volume, PCV or Hematocrit - Packed cell volume RBC count . WBC count, PLT count, Morphology: (shape & size) Normocytic normochromic - Normal size & color (hb content) Microcytic hypochromic - small and pale - Iron deficiency, Macrocytic normochromic - large and normal color - Megaloblastic anemia. anisocytosis-varying size, poikilocytosis - varying shape - haemolytic anemia. Anemia can also result from excess blood loss by bleeding due to worm infestations (pacific), ulcers, cancer etc. RBC may be damaged by immune reactions, genetic abnormality or due to infections and results in haemolytic anemia. It is characterized by jaundice due to excess Bilirubin formation by Hb breakdown. Two types of Hemolytic anemias 1. Extrinsic due to immunity, toxins or infections, malaria, autoimmune haemolytic anemia etc. 2. Intrinsic due to genetic abnormality. Examples sickle cell anemia, thalassemia.

Pathology of Cardiovascular system (CVS) Overview

additional resource: power-point lecture self-assessments
Introduction: Heart attack or Myocardial infarction is infarction of part of heart due to blockage of blood supply. Common cause is atherosclerosis of coronary arteries.

Systemic Pathology Chapter 11 - CVS part 1

Review the following: Heart itself is supplied by two branches of aorta, the left and right coronary arteries. Study the blood supply of heart. Study Structure and function of blood vessels. Familiarise yourself to the following: Inflammation of heart is known as Carditis. Inflammation of outer lining of heart, pericardium, cardiac muscle tissue & inner endothelium are known as pericarditis. Myocarditis & endocarditis respectively. Understand the terms Heart attack and Heart failure. Ischaemic heart disease - Diseases of heart due to reduced blood supply. Two major types. Angina pectoris is condition of attacks of chest pain caused by myocardial ischemia that falls short of inducing infarction. And Myocardial infarction. Most common cause is Atherosclerosis of coronary arteries. Following obstruction to blood supply there is necrosis of muscle tissue followed by inflammation then gradual healing to form fibrous scar. Stages of development of Myocardial infarction: 1. Hours : edema, pale muscle - no microscopic changes, mild edema 2. 3-4 days: yellow rubbery center with red border - Inflammation, necrosis. 3. 1-3 weeks: Pale and thin - Granulation tissue 4. 3-6 weeks: silvery white hard scar - Dense fibrosis.

Complications usually occur before scar formation due to weak area. Common complications are: sudden death, arrhythmias, Cardiac failure, embolism, Cardiac rupture and ventricular aneurysm. Understand term valvular heart disease,.Common types. What are common infectious diseases of heart what are they known as? Understand common Congenital heart diseases., ASD, VSD & PDA Diseases of arteries present also as aneurisms or abnormal dilatation of blood vessels. Aneurisms can be fusiform, saccular or Dissecting. Pathogenesis of atherosclerosis understand the term aneurysm, varicose veins and arteriosclerosis. Understand Hypertension and its effects on blood vessels and Heart.

chapter 12 - hematology 2

HEMATOLOGY 2

Disorders of White Blood Cells Leukaemia, Lymphoma

additional resource: power-point lecture self-assessments
Introduction: White blood cells are the non-colour cells in blood and function as body's defence system. They vary greatly in number due to constant exposure to antigens and sub-clinical infections. Increase in WBC suggests active defence system. Familiarise yourself to the following: They are composed of two groups of cells Granulocytes (neutrophils, eosinophils & basophils) because of their granular cytoplasm. These granulocytes take part in non-specific immune reactions against bacteria and parasites. Non granulocytes include lymphocytes & monocytes. Unlike granulocytes, non-granulocytes take part in specific immunological mechanisms (antibody & cell mediated). Common disorders of WBC are 1. Reactive increase in number - "philias" due to active defence mechanisms.

Neutophils - Neutophilia - Acute inflammation & Bacterial infections. Lymphocytes - Lymphocytosis - viral infections Eosinophils - Eosinophilia - Allergy & Parasitic infestation

2. Decreased production causing low numbers - "penias"

Neutropenia, Lymphopenia & Eosinopenia - Usually due to drugs reactions, Aplastic anemia, Bone marrow diseases, Leukemias.

3. Neoplastic disorders of Marrow.

Malignancy of hemopoietic cells - Leukemia. (Abnormal leukemic cells in blood-Blast) Malignancy of lymphoid tissue forming tumor Lymphoma. (two types Hodgkins lymphoma & Non-Hodgkins lymphoma (NHL) - with many subtypes) Non malignant proliferations - Myeloproliferative and Myelodysplastic disorders.

Leukemias: What is leukemia? Understand types and common clinical features. Understand difference between Acute and Chronic leukemias. What type of leukemia occurs in children. What leukemia is common in old age. Leukemias are mainly of two types Rapidly progressing Acute leukemia and slowly progressing chronic Leukemia. Depending on cell of origin, leukemias are of two types Myeloid (all WBC except lymphocytes) and lymphoid (of lymphocytes). So there are 4 major types of leukemias. ALL & AML, CLL & CML. Treatment is different for each type. Clinical Features: Anemia, Infections and Bleeding due to decreased normal RBC, WBC & PLT. Also bone pains due to destruction of bones by cancer cells. Clinical features of leukemia are due to lack of normal cells than presence of malignant cells. Main features are Anemia(low RBC), Infections (low WBC), Bleeding (low PLT) & Bone pains, and hepato-spleenomegaly (Infiltration by leukemic cells). Lymphoma is malignancy of lymphocytes occurring in lymphatic tissues & nodes. Two major subttypes are Hodgkins lymphoma (better prognosis) and non-hodgkins lymphoma (variable progrnosis), with several sub types. Lymphoma patients present with chronic fever, infections and Lymphnode enlargements. Myeloma is a special type of malignancy of Plasma cells (B-lymphocytes) in bone marrow. Common in old age and presents with lytic bone lesions seen on X-Ray. Myelodysplastic Syndromes Dysplasia destruction in marrow pancytopenia. Myeloproliferative Syndromes (hyperplasia resulting in functionally abnormal cells) syndromes are Premalignant disorders present with marrow failure, or results in functionally abnormal cells. In long term they usually transform to leukemia.

Chapter 13 - CVS part 2 CVS 2

Pathology of Cardiovascular system (CVS) Part2
additional resource: power-point lecture self-assessments

HYPERTENSION: Hypertension is sustained increase in blood pressure. Usually above 140/95mm of Hg. blood pressure. Hypertension is the common cause of cardiac failure and a major risk factor for Aherosclesosis. Increased blood pressure could be due to four important factors. Hormones controlling blood pressure, Nervous control of blood vessels (sympathetic and parasympathetic system), blood volume & contraction of heart. Hypertension can result from diseases of kidney known as renal hypertension or over secretion of hormones. Such type of hypertension due to a known cause is classified as secondary hypertension. But in majority (95%) of hypertension cases no cause is known and are grouped as Essential or Primary hypertension. Etiology is multifactorial including genetic and familial factors similar to diabetes. Clinically essential hypertension develops slowly over years resulting in thickening of small blood vessels (arterioles) known as Hyperplastic arterioloslcerosis, leading to ischemic damage to vital organs. As prolonged blood pressure affects endothelium, atherosclerosis occurs more commonly than in non hypertensive patients. When Hypertension develops rapidly within weeks it is known as Malignant hypertension. Results in necrosis of BV. Common complications of Hypertension include Myocardial ischemia, infarction, atherosclerosis, renal failure, Cerebral Hemorrhage, arterial aneurysms and rupture all due to microvascular thickening due to hypertrophic DIABETES: Diabetes Mellitus is a group of related disorders of metabolism due to lack of insulin function resulting in hyperglycaemia (increased blood sugar) Normal fasting (8 hour) blood sugar levels are 2.2-6.7 mmol. Classification:

Primary Diabetes: - Unknown etiology o Type-I - Insulin dependent DM (IDDM), common in Children, Autoimmune disease. o Type-II -Non-Insulin dependent (NIDDM), Adult onset, Multifactorial etiology. Secondary Diabetes: Known destruction of pancreas such as TB, malignancy etc.

Complications: Complications in diabetes are two types. Acute attacks of hyper or hypoglycaemia and acidosis due to metabolic derangements, may rarely cause coma or death. Chronic complications are mainly due to glyucosylation (combination of glucose) of blood vessel wall proteins resulting in thickening of walls of small blood vessels known as "Hyaline arterolosclerosis" leading to ischemic damage to vital organs. (compare with Hypertension) Acute metabolic complications - Hypoglycemic coma, Ketoacidosis Chronic Vascular complications - Thickening of small blood vessels.

chapter 14 - respiratory system 1

RESPIRATORY DISORDERS
Rhinitis, Bronchitis, Pneumonia, Asthma
additional resource: power-point lecture self-assessments
Introduction: (over view of the topic) Respiratory tract infections are the most common reasons for medical visits. Review the following: (Necessary Background knowledge) Anatomy and physiology of Respiratory system. How oxygen exchange takes place. How breathing occurs. You need to revise chapter inflammation, why & what happens in inflammation. Points to remember: Inflammation of an organ is named with suffix 'itis' to organ name. For example inflammation of bronchus is 'bronchitis'. Common cold or inflammation of nasal mucosa is known as Rhinitis. Inflammations of respiratory system are commonly caused by viral infections. Coryza is common name for viral Rhinitis, occurs in two phases. 1. Viral infection phase: There are all the features of inflammation with some loss of surface epithelium but without cellular exudates. This destruction weakens mucosa. 2. Bacterial secondary infection phase. Invasion of weak mucosa by many normal throat bacteria to produce cellular exudates or pus. E.g. streptococci & Haemophillus. Common viruses are Rhinoviruses. As the immunity is only for short duration, and viruses are of many types and ubiquitous in nature, repeated infections are common. Inflammation of paranasal air sinuses is known as Sinusitis. Common types of sinusitis are maxillary, mastoid, frontal sinusitis etc. Sinusitis can be acute or chronic. Usually

sinusitis results from extension of infection from nasal or pharyngeal regions. Chronic sinusitis results from Repeated acute inflammations causing destruction of mucosa and bacterial or fungal infections. Frequent inflammation and swelling of mucosa produce tumour like growth called polyps, which blocks opening of sinuses causing obstruction to flow of mucus resulting in bacterial infection producing pus. Otitis media referes to middle ear inflammation. Allergic Rhinitis & Bronchitis or Hay fever: Due to allergens like pollen grains, dust mite etc. Usually seasonal with repeated attacks. Initial antigen antibody reaction producing severe inflammation and increased mucous production producing typical secretions. It may be followed by secondary infection producing mucopurulent exudates (pus). A double membrane called pleura encases the lungs. Outer Parietal pleura lines the chest cavity and inner Visceral pleura covers the lung. The space in between is called pleural space which contains small amount of lubricating pleural fluid secreted by cells of pleura. Inflammation of pleura produces more fluid to collect in this space and is called pleural effusion.

chapter 15 - respiratory system 2

RESPIRATORY DISORDERS 2
Tuberculosis & Lung Cancer
Tuberculosis: (over view of the topic)

additional resource: power-point lecture self-assessments

Mycobacterial infection caused by Mycobacterium tuberculosis. Affect every organ in the body, but Lungs are most commonly involved. Affects immunosuppressed or malnourished individuals living in crowded condition. In endemic areas first infection occurs early in life (Primary TB) and usually heals with no complications. Secondary tuberculosis occurs later in age due to breakdown of body resistance. Secondary TB is a Chronic slowly progressive disease, causing much tissue damage & complications. Damage & Necrosis are due to cytolytic enzymes of the macrophages and not due to bacteria. Tubercle is the microscopic lesion of TB. Central caseous necrosis surrounded by macrophages, giant cells & lymphocytes with fibrosis around. Macrophages are large with more organelles called epitheloid cells. Highly resistant to treatment, requiring prolonged treatment.

Mycobacteria have mycolic acid (wax) coat which protects against cytolytic enzymes and antibiotics. M.tuberculosis BCG vaccine confers immunity against complications of primary TB only.

Bronchogenic Carcinoma:

Most common cancer arises from epithelium of large bronchus hence the name. Common site is near the bifurcation of the trachea. Strong relation to smoking. Incidence is directly related to quantity of inhaled smoke. Humidity with pollution/smoke increases incidence as toxins concentrate in the water particles and gets deposited in the lungs. Pathogenesis: Smoking - mucosal irritation - metaplasia - dysplasia - Carcinoma (neoplasia) - spread. Three major types. Squamous carcinoma, Adenocarcinoma & small cell or oat cell carcinoma. Bronchogenic carcinoma spreads through four routes. Lymphatic vessels(lymph nodes, liver & brain), Through Bronchi (to other parts of lung and to opposite lung), Blood vessels (systemic spread) & direct (heart, ribs and chest wall). Syndrome: Syndrome is set of signs and symptoms occurring together. Such as Cushings syndrome. Central obesity, osteoporosis, Hypertension due to ACTH excess. Syndromes occurring in a patient with malignancy, but not directly due to tumour are known as paraneoplastic syndromes, usually due to release of certain substances. Many Lung cancers are known to produce several hormones causing endocrine diseases. Oat cell carcinoma of lung is known to produce several hormones such as ACTH (adreno-cartico-trophic hormone) which causes adrenal gland hyperplasia causing disease "Cushings syndrome". Production of Parathormone causes Hypercalcemia.

chapter 18 - alimentary system 1

ALIMENTARY DISORDERS
Pharyngitis, Peptic ulcer, Enterocolitis, Appendicitis
additional resource: power-point lecture self-assessments

Introduction: (over view of the topic) 1. Disorders of Mouth and Pharynx o Pharyngitis, Tonsilitis, Apthus ulcers. 2. Disorders of Oesophagus & Stomach. o Oesophagitis, Gastritis, Peptic Ulcer, Gastric cancer. 3. Disorders of Intestine. o Enterocolitis, Typhoid, Hemorrhoids, Hernia.Cancer of Colon, Disorders of Mouth & Pharynx: Canker sores or Aphthous ulcers are very painful ulcers of mouth of unknown etiology. Usually heal in a week, may recur. Oral thrush is a severe candida (fungus) infection of mouth usually seen in debilitated or immunosuppressed patients. Glossitis is inflammation of tongue, usually due to infections or irritants but also common in Vitamin B group deficiencies & Iron deficiency. Cancers of mouth are seen in people abusing alcohol and tobacco, and prolonged exposure to sunlight. They are mostly Squamous cell carcinomas. Pharyngitis/Tonsilitis is inflammation of Pharynx/Tonsils. Usually due to Streptococcal or viral infection.

Disorders of Oesophagus & Stomach: Common cause of Oesophagitis is reflux of acid contents from stomach called peptic or reflux Oesophagitis. This occurs in patient on prolonged bed rest, abnormalities of oesophageal sphincter or Herniation & Diverticula. If chronic, leads to formation of gastric mucosa (Gastric metaplasia, also known as Barrett's oesophagus) which may lead to oesophageal cancer. Hernia is abnormal protrusion of a viscera through an aperture. Leads to obstruction or necrosis of the organ. Diverticula is a sac or pouch extending from a hollow organ. Congenital oesophageal diverticula occur rarely. Varices is abnormal dilatation of veins, usually due to obstruction to venou return. Oesophageal varices occurs due to increased portal blood pressure in liver cirrhosis (diffuse scarring of liver). This may bleed producing severe hematemesis (blood vomiting) or rupture of oesophagus.

Peptic Ulcer: Ulceration due to peptic digestion by gastric juice. Common cause of gastritis and peptic ulcer has been proved to be infection by bacteria Helicobacter pylori. Which breaks down mucosal defence by producing ammonia. Presents as punched out shallow ulcers in the mucosa. Complications include erosion to produce perforation, bleeding and development of carcinoma. Common sites are duodenum & stomach. Treatment is by antibiotics. Gastric Carcinoma: Relatively common form of cancer. Common Etiology is chronic gastritis due to H. pylori infection, atrophic gastritis & unknown. Common site is at pylorus(85%). Three morphologic types 1. Fungating - elevated tumor. 2. Schirrous type - infiltrating with marked fibrosis, diffuse form known as Linitis plastica 3. Ulcerating type - large ulcer. Histologically they are usually adenocarcinomas (cancer of glands). Gastric carcinoma spread to local lymphnodes, direct spread to peritoneum, pancreas, & colon.Through blood to liver, lung & brain. H.pylori- Spirochete, gram negative, spiral flagellate bacteria. Colonize mucous, release ammonia by splitting urea to neutralise the acid. Diagnosis by gastric biopsy, microscopy, special stains (toludine blue), culture, and tests for urease production. Also clinical breath test using radiolabelled urea.

chapter 19 - alimentary system 2

Malabsorption, Enterocolitis, Cholera, Typhoid...
additional resource: power-point lecture self-assessments
Introduction: (over view of the topic) Disorders of Intestines 1. Obstruction 2. Mal-absorption 3. Inflammations - Infections 4. Neoplasms. Obstructions are usually caused by scarring and adhesions, Neoplasms, Volvulus & Intussusceptions. It is a surgical emergency presents with severe dehydration & colicky pain.

ALIMENTARY DISORDERS 2

Malabsorption: surgical resection, blind loop syndrome, lymphatic obstruction, Coeliac disease and Tropical Sprue. Coeliac disease - Hypersensitivity to wheat protein gluten (gluten enteropathy). Inflammation, mucosal destruction, atrophy of villi. Gluten free diet improves the condition. Tropical Sprue: Similar pathology but due to bacterial infection, chronic diarrhoea, anemia. Dysentery: Acute bacterial infection, painful bloody diarrhoea. Usually by shigella group. Cholera: Enterotoxigenic diarrhoea by Vibrio cholerae. Exotoxins cause inflammation and severe fluid loss, and death due to hypovolemia. Salmonella food poisoning: Caused by Salmonella typhimurium infection - Food poisoning by contaminated Poultry and meat, acute gastroenteritis only. Typhoid Fever: Systemic infection by Salmonella typhi, causes ulceration of Peyers patches in intestine. Three clinical phases 1. Invasion of intestinal lymphoid tissue - asymptomatic. 2. Invasion of blood - toxemia, fever 3. Localisation of bacteria in organs - ulceration, necrosis Immunological test for antibodies to bacteria is known as Widal test. Less severe form caused by S.paratyphi is known as Paratyphoid fever. Pseudomembranous enterocolitis - Clostridium difficile - Due to broad spectrum antibiotics altering normal bacterial flora. Large ulcers, necrosis, inflammation, acute bloody diarrhoea. Staphylococcal enterocolitis is also similar condition due to antibiotic abuse. Tuberculosis of Intestine: Classic and Bovine both cause. Chronic ulceration, fibrosis, stricture with obstruction & perforation. Parasitic Diseases: Helminths (round & flat worms) - Unhygenic conditions predispose to infection. Fecooral route, skin penetration - bare foot. Cause malnutrition, diarrhoea, obstruction or anemia due to blood loss. Rarely systemic spread. Giardiasis: Protozoa Giardia lamblia. Traveller's diarrhoea, malabsorption, mild inflammation, diarrhoea. Amoebiasis: Colitis, mucosal inflammation and ulceration caused by Entamoeba histolytica. Ulceration, bloody painful diarrhoea. Feco-oral transmission, unhygienic conditions.

Chronic Inflammatory disorders of Unknown Etiology: Crohns & Ulcerative Colitis. Crohns Disease: Chronic transmural granulomatous inflammation of predominantly small intestine. Thickened intestinal wall, obstruction, ulceration, perforation. Ulcerative Colitis: Chronic diffuse superficial inflammation of predominantly colon. Mucosal inflammation, Diarrhoea & dehydration. Common complications are toxic dilatation, perforation & haemorrhage.

chapter 18 - hepatobiliary system

Jaundice, Hepatitis, Alcoholic, Viral, Cirrhosis
additional resource: power-point lecture self-assessments
Introduction: (over view of the topic) Liver is the major organ of metabolism of carbohydrates, fats & proteins, Detoxificaton of several toxins and toxic endproducts. It synthesises digestive bile juice, albumin & coagulation factors. Liver disease presents clinically as Jaundice, associated with weakness, indigestion, bleeding & hypoproteinemia. Common Disorders of Liver & gall bladder are : 1. Acute / Chronic Hepatitis - inflammation - eg. Alcohol, Virus, drugs & chemicals. presents as "Jaundice" 2. Cirhosis - Diffuse scarring of liver with liver failure. 3. Hepatoma or Hepatocellular Carcinoma - Malignant tumor of liver 4. Cholecystitis - Inflammation of Gall bladder 5. Cholelithiasis - stone formation in gall bladder. Bilirubin metabolism: Bilirubin is the toxic end product of hemoglobin ketabolism from dead RBC. Bilirubin is normally insoluble and liver converts insoluble toxic Bilirubin (un-conjugated) to soluble bilirubin (conjugated) which gets excreted in the bile, via GIT to stools & part of it gets absorbed and gets excreted in urine. Normally majority of serum Bilirubin is unconjugated.

DISORDERS OF THE LIVER

Jaundice: yellow discoloration of skin & sclera due to hyperbilirubinemia (increased serum Bilirubin). Two major types Conjugated or Obstructive & unconjugated or nonObstructive jaundice. Urine contains only soluble conjugated form so high colored urine is seen only in obstructive or conjugated form only. Jaundice due to excess RBC breakdown is known as haemolytic jaundice which is a unconjugated type of jaundice. Jaundice due to biliary obstruction (stone, tumors) is usually conjugated type. Jaundice in hepatitis is combined type with both conjugated & unconjugated forms due to cell necrosis and obstruction due to inflammation. Viral Hepatitis: Common cause of Hepatitis. Type A, B, C, D, E and non ABC. Type A & E are epidemic verity, self limited, water borne disease and results in life long immunity. Type B, C & D spread by serum (body fluids, injections, sexual contact) hence they are also known as serum hepatitis. They cause both acute & chronic recurrent hepatitis, may complicate with chronic liver failure, necrosis, cirrhosis, and hepatocellular carcinoma (also known as hepatoma). Vaccine is now available for Hepatitis A, B & C viruses. Alcoholic Hepatitis: Alcohol blocks the metabolic enzymes and its end product acetaldehyde causes destruction of cellular proteins. Resulting in inflammation, fat accumulation (fatty change) and cell necrosis due to rupture. later stage leads to diffuse scarring (Cirrhosis). Morphologically liver is inflamed, with varying grades of hepatocyte necrosis fatty change and fibrosis. Cirrhosis is diffuse fibrous scarring of liver due to hepatitis. Both alcoholic and viral hepatitis may end in Cirrhosis. Due to loss of architecture and necrosis there is liver

failure, Tumors of Liver: Common tumor of livers are metastatic tumors from abdominal malignancies. Primary Malignant tumour is hepatocellular carcinoma (or hepatoma. Usually arises over a post hepatitis cirrhosis. Very aggressive tumor spreads all over body and has poor prognosis. Benign tumors are rare. Cholecystitis: Inflammation of gall bladder. Usually with gall stones or infection. May be acute or chronic. Leads to formation of pus - empyema. Cholelithiasis: Inspissations of bile leading to formation of stone. "Fatty, Female of forty". Contain mainly cholesterol. Stones of Bile pigment is seen in haemolytic anemia. Carcinoma of Gall bladder & bile ducts: Associated with stones, present with jaundice due to obstruction of bile duct. Liver function tests: Bilirubin, Albumin, Prothrombin time - measure metabolic function. Enzymes AST & ALT measure hepatocyte necrosis. Alkaline phosphatase measure biliary damage.

chapter 19 - urinary system

Glomerulonephritis, kidney Failure, nephrolithiasis
additional resource: power-point lecture self-assessments
Introduction: Daily Kidneys filter over 1700 litres of blood to produce a litre of urine. In doing so they excrete waste products, regulates water, salt and pH and blood pressure balance. Kidney is also an endocrine gland producing Renin (controls blood pressure) and Erythropoietin (RBC production) hormones. Initially blood is filtered off water and all small molecules to produce about 180 liters of glomerular filtrate/day, then complex mechanisms of absorption and secretion in the tubules produce 1.5L of concentrated urine. Disorders affecting these mechanisms cause either excess or decreased production of urine, affecting balance in the body. Review the following: Revise Anatomy and physiology of Urinary system. Review the Structure of glomerulus and its function. How kidney filters out urine. What is pH balance, water and salt balance in body how is it regulated.

URINARY SYSTEM

Familiarise yourself to the following: Renal disorders present with disturbances in Urine formation, water and salt & pH balance, and affect blood pressure. Renal disorders can be classified into four major groups. 1. Glomerulonephritis Glomerular diseases -- Destruction of glomeruli by immune or infections. 2. Acute tubular necrosis Tubular diseases -- Necrosis of tubules by toxins or infections. 3. Pyelonephritis Interstitial diseases -- Infections 4. Nephrosclerosis Vascular diseases -- thickening of blood vessels Hypertension leading to micro infarctions.

Most renal disorders produce one of four clinical syndromes. Nephritic syndrome. Oliguria, Haematuria, Proteinuria, Oedema. 1. Nephrotic syndrome. Gross proteinuria, hyperlipidemia, 2. Acute renal failure. Loss of Kidney function - within weeks - Uremia. Chronic renal failure. Over months and years - Uremia Kidney Failure: Or end stage kidney disease is terminal stage of destruction of kidney to totally affect kidney function. Patient presents with uremia (excess urea in blood), high blood pressure, and anuria (no urine) or oliguria (little urine). Fatal disease, and requires continuous dialysis (artificial filtering of blood) What is dialysis? Hemodialysis and peritoneal dialysis. What is kidney transplantation, when is it done, how is it done. Nephrolithiasis: Formation of stone in kidney, Urolithiasis (formation of stone in urinary tract) results in obstruction to flow, and dilatation of urinary tract called hydronephrosis. Laboratory investigations (routine) for the diagnosis of renal disorders: 1. Urine chemistry: Sugar, Bilirubin, Ketones.

2. Microscopy - Cells, Casts & Crystals 3. Serum electrolytes - Sodium & Potassium 4. Blood urea Nitrogen (BUN) & creatinine.

chapter 20 - hematology 3
Haemostasis, Coagulation & Platelets. Bleeding disorders
additional resource: power-point lecture self-assessments
Introduction: Haemmostastasis is mechanism of prevention of blood loss following injury. Every cell in our body is supplied with a blood vessel. Literally, we are bag of blood vessels. In the absence of haemostatic mechanisms, any minor injury potentially leads to death by bleeding. Familiarise yourself to the following:Understand that Blood clotting is just one of three components of haemostasis. 1. Blood vessel constriction - temporary constriction of BV soon after injury. 2. Platelet clumping - Platelets glue together to the site of injury. 3. Coagulation to produce fibrin clot o Also there are Thrombolytic and Anticoagulant mechanisms to stop the process and lyse the clot. Coagulation: Activation of several inactive enzymes (clotting factors) occurs at the site of injury which finally activate prothrombin to powerful enzyme thrombin, which converts soluble fibrinogen protein to insoluble fibrin fibres which forms a net of hard fibres and blood cells get trapped in this net for form blood clot. Activation of cascade of enzymes occur in two pathways. Short pathway which produces thrombin faster is known as Extrinsic pathway. Then a long and sustained pathway known as Intrinsic pathway.

Platelets and Haemostasis: Platelets are the non-nucleated cells in blood produced in the marrow. When activated They agglutinate (clump) and attach to injured areas like bricks forming a plug called Primary Haemostatic plug, which forms soon after injury to prevent bleeding. Then coagulation occurs forming secondary or stable plug of blood clot. Bleeding due to platelet abnormality: Bleeding disorders: (Congenital & Acquired) Presents as excess bleeding following injury or spontaneous bleeding. Common sites of bleeding are intestinal bleeding, nose, gums, in the urinary tract. Haematoma formation common in coagulation defects. Skin bleeding is common in platelet deficiency and can be small (Petechiae) or large (Ecchymoses). Disorders of coagulation: Congenital or acquired deficiency of C. factors.

Congenital: Haemophilia- Deficiency of Factor 8 or 9 (genetic sex linked) Acquired: Liver diseases (liver is the site of synthesis of many factors) Overuse: In septicemia, due to Disseminated Intravascular Coagulation(DIC) Results in deficiency of many factors & PLT.

Disorders of Platelets: Congenital or acquired. Two types Thrombocytopenia or low platelets and or functionally abnormal platelets e.g., in patients on certain drugs such as "aspirin".

Laboratory Tests: Screening tests are Bleeding time, Clotting time (BT,CT), PLT. Prothrombin time(PT) is to measure the extrinsic pathway, Partial thromboplastin time(PTT) measures Intrinsic pathway.

Trauma, Stroke, meningitis, Tumors

Chapter 21 - CNS disorders

additional resource: power-point lecture self-assessments

Introduction: Nerves are highly complex cells, incapable of regeneration. They need continuous and maximum energy & oxygen supply. Brain is a very delicate & soft (fluid) tissue closely packed in hard bony shell (skull), and cushioned by Cerebrospinal fluid (CSF). Brain is first to get damaged in hypoxia or decreased blood flow. As Neurons are incapable of cell division, injury is permanent. Also space is limited within skull and any injury, inflammation or growth results in marked and generalised brain damage due to increased pressure. Familiarise yourself to the following: Disorders of brain are mainly Vascular, Infections, Degenerative & Neoplastic. Clinical features of CNS diseases are either lack of nerve impulse(paralysis) or excess stimulation resulting in sudden movements (fits or seizures). When seizures occur repeatedly then the condition is known as 'epilepsy' Trauma: Common in road traffic accidents. Any sudden movement can damage brain tissue. Types: Direct injury & indirect injury, blunt or sharp injury & Contra coup injury (Injury on the opposite side of impact). Hemorrhage may occur below (subdural) or over the duramater (extradural) causes death due to increased intracranial pressure. Concussion: Is transient loss of consciousness due to nerve dysfunction by impact.

Cerebral edema is a serious complication of several brain disorders. Edema increases intracranial pressure leading to brain damage by pressure & herniation of brain through the opertures in the skull causing destruction called coning. Vascular disorders such as Ischemia or Infarction results in "sudden neurological deficit called Stroke. Stroke results from embolism, rupture or thrombosis of blood vessels commonly due to Atherosclerosis. Diabetes, hypertension. Hyper lipidemia, smoking life style, age, male sex are its risk factors.

Infection of brain is known as encephalitis. Inflammation of coverings of the brain (meninges) is known as meningitis. Inflammation of both is meningoencephalitis. Two types of meningitis. Diagnosis is done by examining CSF. Septic meningitis: Neutrophils, high protein, low sugar - Bacterial Aseptic meningitis: Lymphocytes, low protein, normal sugar - Viral Clinical features are severe headache, neck stiffness, altered consciousness. Neoplasms: Both benign and malignant Tumors of brain are dangerous due to limited space and damage to vital structures. are Mature neurons cannot divide and hence they cannot produce tumours. Brain tumors can be primary arising from supporting glial cells(Glioma) or from meninges (Meningioma) or secondary due to spread from other organs such as lungs or breast. Degenerative disorders are dementia due to progressive loss of neurons Two common disorders are Parkinson's disease: Basal ganglia degeneration leading to Tremors & dyskinesia. 1% Alzheimers disease: Cerebral Cortical degeneration, dementia. Hydrocephalus: Blockage to CSF flow resulting in occumulation of CSF leading to pressure atrophy of brain tissue. Presents are markedly dilated ventricles of brain.

GLOSSARY
X A
Xenograft Transplantation from one species to another