General Veterinary Pathology VPP-211 2016 PDF

General Veterinary Pathology VPP-211  General Veterinary Pathology 2016 VPP-211 COURSE OVERVIEW VPP - 211: GENERAL VETERINARY PATHOL...

General Veterinary Pathology VPP-211  General Veterinary Pathology 2016 VPP-211 COURSE OVERVIEW VPP - 211: GENERAL VETERINARY PATHOLOGY Credit Hours: 1+1=2 The subject of Veterinary Pathology provides a link between the basic subjects of anatomy, physiology and biochemistry of livestock and poultry and the applied clinical subjects of medicine, surgery and gynaecology and obstetrics and enhances the understanding of diseases, aids in diagnosis and helps in deciding suitable treatment. To achieve this object, the fundamentals of disease processes have to be understood before proceeding to the proper subject of systemic and specific pathology. This is the aim of this course. The course begins with an introduction to the subject with their basics involved and the causes of diseases. Then the course deals with how these causes induce various forms of injuries to the structural and functional unit of the organism, the cell, even leading to the death of the cell(s) or the organism. During the course, you will be taught how the animal responds to such injuries (inflammation, chemical mediators, systemic effects, clinical manifestations) and recovers from the same (Healing, growth factors, cell cycle, HSP) and different haemodynamic changes occurring during disease processes. The consequences of local death of cells (Necrosis) viz. gangrene, calcification and even death of the animal are also taught. When the death occurs (Somatic death) and what happens to the dead animal following death (Post-mortem changes) is brought out during the study. Yet another important area is the disturbances in growth where in no growth (Aplasia) to proliferation (Hyperplasia) to increase (Hypertrophy) or decrease in size of organs after development (Atrophy) or development of different tissue (Metaplasia) and precancerous condition (Dysplasia) are dealt and causes for the same. Though immunity is to provide protection to the body, at times the same may be detrimental to health. This is dealt under inflammation and autoimmune diseases (Antibodies against its own tissue components). Nithin.B. Page 2  General Veterinary Pathology 2016 VPP-211 In the concluding session, the most dreaded disease neoplasia is taught with their classification, characteristics (Benign, malignant), causative factors, pathogenetic mechanism, mode of spread, clinical effects, immunity, diagnosis and staging and grading. The above exposure will make you easily understand the diseases of different systems of the body and specific diseases affecting livestock and poultry when they are taught in the subsequent courses without repetition of the fundamental mechanisms involved in such processes. Nithin.B. Page 3  General Veterinary Pathology 2016 VPP-211 MODULE-1: INTRODUCTION AND SCOPE OF VETERINARY PATHOLOGY Learning objectives  In this module, the viewer will learn on the fundamental things involved in disease processes (Pathology), diagnosis, prognosis, branches of pathology and scope of veterinary pathology in diagnosis and treatment of ailing animals. INTRODUCTION AND SCOPE OF VETERINARY PATHOLOGY The aim of study of veterinary and animal sciences is to produce a competent veterinarian. The veterinarian is involved in the diagnosis of diseases of livestock and poultry. The study of diseases is essential component of pathology.  Pathology (Gr. Path(o) - Disease; logos: science, treatise, sum of knowledge in a particular subject)  Pathology is the subject linking basic subjects of anatomy, histology, embryology, physiology and biochemistry to clinical subjects of medicine, surgery and obstetrics and gynaecology.  Pathology is subject of terminology.  It is important to learn different terminologies used in describing disease conditions. The definition of each terminology is the gateway to understanding the particular disease process. VETERINARY PATHOLOGY - DEFINITIONS  Pathology literally means study of disease or discourse of disease  Pathology is that branch of medicine treating of the essential nature of disease especially of the changes in body tissues and organs which cause or caused by disease (Dorland).  Pathology is study of the molecular, biochemical, functional and morphological aspects of diseases in the fluids, cells, tissues and organs of the body. Summary: Pathology is study of the functional and morphological alterations in tissues and fluids of the body during the disease (Thomson, 1984) Health  Normal condition of the body and mind i.e. with all the parts functioning normally. Disease (Dis – Negative ease)  Any deviation from or interruption of normal structure or function of any body part, organ, or system that is manifested by a characteristic set of symptoms and signs whose aetiology, pathology, and prognosis may be known or unknown.  Disease is any departure from healthy state.  The following are the essential components in the study of diseases : Nithin.B. Page 4  General Veterinary Pathology 2016 VPP-211 Aetiology  The science dealing with causes of disease  Study of causation of disease Incubation period  Incubation period is the time that lapses between the action of a cause and manifestation of disease. Pathogenesis  Pathogenesis is development of morbid conditions or of disease or mechanism by which the causes produce diseases. e.g. In traumatic reticuloperitonitis in cattle sharp objects like nails ingested are usually trapped in the reticulum.  Movement of reticulum and pressure from pregnant uterus in cows favours the piercing of foreign body through the wall of the reticulum, setting up reticulitis and then into peritoneal cavity causing injury causing peritonitis.  If the foreign body is carrying pyogenic organisms purulent inflammation is found. Clinical signs  Clinical signs are outward manifestations of the patient’s suffering from diseases while alive. Lesions  Lesions are macroscopical (visible to naked eye) or microscopical changes in tissue structure. Pathognomonic lesion(s)  Pathognomonic lesion(s) is/are characteristic for a particular disease e.g. Blue tongue in sheep- Haemorrhages in the base of the pulmonary artery and base of the aorta. Course of the disease  Course of the disease is the duration of time through which the series of changes characteristic of disease pass through to their ultimate end. Nithin.B. Page 5  General Veterinary Pathology 2016 VPP-211 Termination of disease  Termination of disease is recovery or death or may prolong for a considerable length of time as in chronic disease. Diagnosis  Diagnosis is the art of determination of the nature of disease, its causes, symptoms, lesions etc. Morphological diagnosis  Where diagnosis is based on the alterations observed in a tissue or organ. i.e. naming the lesion e.g. Pneumonia (Inflammation of lungs), enteritis (Inflammation of intestine). This provides information to clinician on the extent, duration, distribution and type of lesion. Aetiological diagnosis  Where specific cause of the disease can be identified i.e. naming the cause. e.g. Cause of pneumonia-Bacteria, virus, fungus, foreign body Specific or definitive diagnosis  Where the pathognomonic lesions are characteristic of the disease can be observed. i.e. naming the specific entity involved e.g. Corrugated appearance of intestine in Johne’s disease in cattle, haemorrhages in the base of the aorta and pulmonary artery in blue tongue in sheep Differential diagnosis  Differential diagnosis is aimed at diagnosing a disease by differentiating from different diseases based on clinical and pathological findings. This is the first step in diagnosis. Prognosis  Prognosis is pronouncing probable/expected outcome of the disease  Prognosis of a disease is the estimate by a clinician of probable severity and outcome of the disease. Sequelae  Final end result of the disease Nithin.B. Page 6  General Veterinary Pathology 2016 VPP-211 Morbidity  Morbidity is the percentage of affected animals that get exposed  Number of animals exposed is 100  Number of animals affected is 50  Morbidity 50% Mortality rate  Mortality rate of a disease is the percentage of deaths among animals affected by that disease.  Number of animals exposed is 100  Number of animals affected is 60  Morbidity 60%  Number of deaths among affected animals 30  Mortality rate 50% Autopsy  Autopsy is seeing with one’s own eyes (Used in human medicine)  The pathologist cuts open a corpse to see the lesions in diseases. Necropsy  Necropsy is seeing a carcass (Used in veterinary medicine) Biopsy  Biopsy is examination of biological samples like fluid, tissue, etc., collected from living animals. Scope of Pathology  Pathology is aiding in the diagnosis of diseases.  Helps in understanding the disease process.  Hence, prognosis, control and rationale treatment and prevention are possible. Nithin.B. Page 7  General Veterinary Pathology 2016 VPP-211 BRANCHES OF PATHOLOGY  General pathology deals with fundamental processes that are common to more than one tissue or organ  Systemic pathology is study of diseases peculiar to certain systems or organs  Special pathology is study of diseases caused by specific microbial pathogens  Clinical pathology is that branch of pathology used in the diagnosis of the diseases in the hospital at the patient’s bedside. Pathology applied to find the solution to clinical problems especially the use of laboratory methods in clinical diagnosis.  Comparative pathology is the study of diseases of animals and comparing them to those occurring in man.  Nutritional pathology is the study of disease processes resulting from deficiency or excess of essential foods  Experimental pathology means the study of disease artificially produced in animals  Chemical pathology deals with alterations in biochemical processes in diseases  Toxicopathology means the study of diseases caused by toxic substances  Oncology (Gk. Onco-Tumour) is study of tumours. The purpose of study of pathology is to diagnose, treat, control and prevent the diseases from the knowledge gained through the cause, pathogenesis and effects. These are achieved through examination of tissues from living animals (Biopsy) and dead animals/carcass (Necropsy) or by experimentation. Thus pathology deals with disease processes involving aetiology, pathogenesis and clinical effects of diseases in animals and tries to explain what went wrong. It is linking the basic knowledge gained in anatomy, histology, physiology and biochemistry and clinical subjects in making diagnosis of diseases and helps in treatment, prevention and control of diseases. Nithin.B. Page 8  General Veterinary Pathology 2016 VPP-211 MODULE-2: AETIOLOGY Learning objectives  Through this module, the viewer will learn the causes of diseases, their classification and developmental defects (Anomalies and monsters). AETIOLOGY DEFINITION AND CLASSIFICATION Definition  Aetiology is defined as study of causation of disease. Classification There are several agents or factors that can produce disease in animals and which originate from within the body or outside the body. Thus, the causes are broadly classified into two categories.  Predisposing causes (Intrinsic factors)  Definitive causes (Extrinsic factors) o Predisposing causes make the animal susceptible to definitive causes. These include o Heredity-Inherited-Glycogen storage diseases e.g. Pompe’s disease (Lysosmal acid maltase deficiency) in cattle, dog o Species-Rinderpest is found in cattle not in other animals. o Breed-Certain breeds are more susceptible to some diseases than others. Heavier breeds of dogs suffer from bone diseases o Age-Young animals are comparatively more prone for disease than adults. o Sex-Diseases of reproductive organs in respective sex. Colour (Pigmentation)-Sunburns in melanin deficiency, eye cancer in Hereford cattle DEFINITIVE CAUSES Definitive causes are actual agents that produce diseases. These are Physical causes  Trauma-Mechanical, Accidents  Excess heat-Burns  Excess cold-Frost bite, cold shock  Radiation-UV irradiation, x-radiation Nithin.B. Page 9  General Veterinary Pathology 2016 VPP-211 Chemical causes  Acids-HCl, H 2 SO 4  Alkalis-NaOH  Inorganic chemicals-HgCl 2 is nephrotoxic  Organic chemicals-CCl 4 -Hepatotoxic Viable/biological causes  Bacteria-Anthrax bacilli  Viruses-Foot and mouth disease virus (Picorna virus)  Mycoplasma-Respiratory disease in chicken  Rickettsia-Ehrlichiosis  Fungus-Dermatomycosis, aspergillosis (e.g. Brooder pneumonia in chicks)  Parasites-Haemonchosis in ruminants, ascaridiasis (Pups, buffalo calves) Nutritional causes  Excess-Hypervitaminosis A, D  Deficiency-Hypoproteinaemia, hypovitamonosis (e.g. Xerophthalmia in vitamin A deficiency, star gazing in chicken in vitamin B 1 deficiency), Hypocalcaemia (Milk fever in high yielding cows) Immunological diseases-Hypersensitivities-Anaphylaxis Toxins-Phytotoxins, Zootoxins (Snake venom), Pesticides (Organochlorines, organophosphorus compounds) Physical causes-Traumatic injuries  Perforation is a wound caused by a bullet or nail.  Laceration is a wound in which there is tearing of tissues. e.g: Automobile accidents.  Concussion is a violent shock caused by an injury and is usually applied to injuries of the head. There may or may not be loss of consciousness.  Sprain is an injury of joint in which there may be stretching or rupture of ligaments, muscles or tendons. In this anatomical relationship of the structures is maintained.  Luxation or dislocation is deviation from its original position in which the anatomical relationship are not maintained and the ligaments may be torn.  Fracture is discontinuity of a bone. Miscellaneous causes  Atrogenic disease is a condition produced by the physician by over or needless medication.  Idiosyncrasy is different reaction of animals to drugs. Nithin.B. Page 10  General Veterinary Pathology 2016 VPP-211 DISTURBANCES IN DEVEOPMENT (ANOMALIES & MONSTER)  Anomaly is developmental defect affecting an organ or part of the body.  Anomaly is the disturbance of development that involves an organ or a portion of an organ.  Monster is an animal in which extensive abnormal developments are present.  A Congenital disease is one in which the patient is born with the disease whereas an inherited disease is one which is due to factors in the genetic materials received from the parents. CLASSIFICATION OF ANOMALIES A. Arrest of Development 1. Agenesia is an incomplete and imperfect development of an organ or part and aplasia is absence of an organ or part.  Acrania is absence of most or all of the bones of the cranium.  Amelia is absence of one or more limbs.  Anencephalia is absence of the brain.  Hypocephalia is incomplete development of the brain.  Hemicrania is absence of half of the head.  Exencephalia is defective skull with brain exposed or extruded. If the protruding brain contains a ventricle which is filled with excessive amount of fluid, the malformation is a hydrencephalocele.  Arhinencephalia is absence or rudimentary development of the olfactory lobe with corresponding lack of development of the external olfactory organs.  Agnathia is absence of the lower jaw.  Anophthalmia is absence of one or both eyes.  Abrachia is absence of the forelimbs.  Abrachiocephalia is absence of forelimbs and head.  Adactylia is absence of digits. 2. Fissures on the median line of the head, thorax, and abdomen.  Craniooschisis (skull)  Cheiloschisis (lip), often referred to as harelip.  Palatoschisis (oral) cavity, often called cleft palate. Harelip and cleft palate result from faulty development of the maxillary process derived from the first visceral arch.  Rachischisis (spinal column).  Schistorrachis or spina bifida (spinal column)  Schistothorax (thoraz or sternum).  Schistosomus (abdomen).  Schistocormus (thorax, neck or abdominal wall). Results from arrested development of the amnion. Nithin.B. Page 11  General Veterinary Pathology 2016 VPP-211 Palatoschisis 3. Fusion of paired organs  Cyclopia (eyes)  Ren arcuatus (kidneys), often referred to as horseshoe kidney. B. Excess of Development 1. Congenital hypertrophy  Hemi hypertrophy (partial) 2. Increase in the number of a part  Polyotia (ears)  Polyodontia(teeth)  Polymelia (limbs)  Polydactylia(digits)  Polymastia (mammary gland)  Polythelia(teats) DISPLACEMENTS DURING DEVEOPMENT A. Displacements of organs  Dextrocardia is transposition of the heart to the right side.  Ectopia cordis cervicalis is displacement of the heart into the neck. Nithin.B. Page 12  General Veterinary Pathology 2016 VPP-211 B. Displacements of tissues  Teratoma is inclusion of multiple displaced and also neoplastic tissue within an individual.  Dermoid is inclusion within an individual of a mass containing skin, hair, feathers, or teeth depending on the species and often arranged as an epidermal cyst (Dermoid cyst).  Odontoid cyst is inclusion within an individual of a mass of dental enamel and cement.  Dentigerous cyst is inclusion within an individual of one or more imperfectly formed teeth.  Fusion of Sexual Characters  Hermaphrodite is an individual having both testicular and ovarian tissue. Pseudohermaphrodite is an animal having unisexual development of the sex glands (either testicular or ovarian tissue), but having also either a unisexual or bisexual development of the other parts of the genitalia.  Freemartin is a female calf having arrested development of the sex organs and being the twin of perfect male. MONSTERS A monster or monstrosity is a disturbance of development that involves several organs and causes great distortion of the individual. For the most part monsters possess a duplication of all or most of the organs and other parts of the body. They develop from a single ovum. They are therefore the product of incomplete twinning. Classification of the Monsters  Twins Entirely Separate o Although separate, these twins are in a single chorion. One twin as a rule is well developed; the other is malformed (acardius). In the malformed foetus there is arrested development of the heart, lungs, and trunk. Such monsters may lack a head (acephalus), limbs and other recognizable features (amorphous), or the trunk (acormus).  Twins United o These twins are more or less completely united and are of symmetrical development. TWINS UNITED A. Anterior Twinning: The anterior part of the individual is double, the posterior single.  Pygopagus – united in the pelvic region with the bodies side by side.  Ischiopagus – united in the pelvic region with the bodies at an obtuse (not pointed) angle.  Dicephalus – two separate heads; doubling may also affect the neck, thorax and trunk.  Diproosopus – doubling in the cephalic region without complete separation of heads; only the face doubled. Nithin.B. Page 13  General Veterinary Pathology 2016 VPP-211 B. Posterior Twinning: The posterior part is double, the anterior single.  Craniopagus – brains usually separated; bodies as a rule at an acute angle.  Cephalothoracopagus – union of head and thorax.  Dipygus – doubling of posterior extremities and posterior part of body. C. Twinning Almost Complete: Duplication of the whole trunk or the anterior or posterior extremities with parallel, ventral arrangement of the foetuses. The pair is joined in the region of the thorax, and also often in the abdominal region.  Thoracopagus – united only by the thorax.  Prosopothoracopagus – besides the union the thorax the abdomen, the head and neck are united.  Rachipagus – thorax and lumbar portion of the spinal column united. Nithin.B. Page 14  General Veterinary Pathology 2016 VPP-211 MODULE-3: HAEMODYNAMIC DERANGEMENTS-1 Learning objectives  In the first part of this module, the viewer will be taught on changes in cardiovascular system in disease processes like various conditions leading to congestion, bleeding (haemorrhage) and leakage of fluids from blood vessels and its accumulation in various sites of the body (Oedema). HYPERAEMIA AND CONGESTION Definition  Hyperaemia is increased volume of blood in affected tissue or part. Hyperaemia (Active hyperaemia)  Occurs in arterioles or arteries  Increased blood flow in capillaries Congestion (Passive hyperaemia)  Occurs due to impaired venous drainage  Stasis of blood in veins CLASSIFICATION OF HYPERAEMIA Nithin.B. Page 15  General Veterinary Pathology 2016 VPP-211 ACTIVE HYPERAEMIA  Increased blood in arterial side  Usually due to inflammation  All active hyperaemia are acute  Chronic active hyperaemia does not occur  Occurs when there is a demand for oxygen and nutrients - increase metabolism  It is beneficial. ACUTE GENERAL ACTIVE HYPERAEMIA Increased blood throughout the body Causes  Various systemic diseases. E.g. Pasteurellosis, erysipelas o Rapidly beating heart → increased blood supply  Renal diseases - due to retention of fluids Macroscopically  Bright red color or organs Microscopically  Arteries and capillaries dilated with blood Result  Disappears if cause is removed ACUTE LOCAL ACTIVE HYPERAEMIA  Increased amount of blood in arterial system within a local area (leg, Stomach, lung)  Most common type of hyperaemia Causes  Physiological o Occurs in stomach and intestine following a meal o Lactating mammary gland o Muscles during exercise o Genital tract during oestrus Nithin.B. Page 16  General Veterinary Pathology 2016 VPP-211 Blushing  Acute inflammation Macroscopically  Enlarged, swollen, heary  ↑ warmth in Skin Microscopically  In live animals, arteries, arterioles and capillaries are distended with blood  Difficult to detect in dead animals PASSIVE HYPERAEMIA OR CONGESTION  Increased blood in the venous end due to improper drainage.  GRNERAL - if interference is central (i.e.) lungs, heart  LOCAL - if vein of an organ or body  It can be acute or chronic Brain congestion  Chonic venous congestion is more common Nithin.B. Page 17  General Veterinary Pathology 2016 VPP-211 ACUTE GENERAL PASSIVE HYPERAEMIA  Increase in the amount of blood on the venous side of circulatory system  Due to sudden obstruction to the flow of blood in heart and lungs. Causes  Heart failure o Degeneration and necrosis of myocardium o Myocardial infarction  Pneumonia  Pulmonary thrombosis or embolism  Hydropericardium, Haemopericadium, etc.  Hydrothorax, Haemothorax, etc. Macroscopically  Organs are blue in color (Unoxygenated blood)  Veins distended with blood  Organs enlarged, heavy  Upon incision, blood oozes out Result  Causes are mild → Recovery  Causes are severe → Death CHRONIC GENERAL PASSIVE HYPERAEMIA Increased blood on venous end persisting for long period of time causes Permanent changes (fibrosis, atrophy). Causes due to central lesions in heart and lungs  Heart lesions o Stenosis of valvular openings  Valvular insufficiency o Failure of cusps of valves to close property o Inflammatory tissue o Thrombus  Myocardial failure o Degeneration and necrosis of muscles o Degeneration and necrosis of muscles Nithin.B. Page 18  General Veterinary Pathology 2016 VPP-211 Contraction of muscles ↓ Blood pushed in arteries ↓ But accumulates in venous side  Anomalies of heart o Persistent foramen orale o Interventricular septal defects Blood moves from one chamber to another ↓ Arterial blood pressure maintained ↓ Blood accumulates in venous end.  Constrictive lesons in pericardium o Traumatic pericarditis in cattle  Lesions of lungs o Obliteration of capillary bed in lungs o Prevents free flow of blood through the lungs o Retards flow through right side of heart o Blood back flows into Liver o Causes  Chronic alveolar pulmonary emphysema in horses (BROKEN WIND)  Pneumonia  Hydrothorax, haemothorax o Compression of major pulmonary vessels  Tumours  Cysts  Abscesses  Nithin.B. Page 19  General Veterinary Pathology 2016 VPP-211 Lesions in CVC Liver  Lesions in Rt A-V valve or lungs  Increase in size and weight on section,  “Nutmeg pattern” Liver - CVC  Central veins are prominent  Area surrounding central vein is congested  Congested area is surrounded by hypoxic areas Morphologic features of CVC  Veins all over the body engorged with blood  Blood is bluish red in color  Oedema of tissues  Atrophy of organs  Degeneration and Necrosis or organs Nithin.B. Page 20  General Veterinary Pathology 2016 VPP-211 Microscopically Mitral valve diseases ↓ Affected in Left – sided heart failure ↓ Alveolar capillaries distended with blood ↓ Rupture of capillaries ↓ Minute intra – alveolar haemorrhages ↓ Haemosiderin release from RBCs ↓ Phagocytosed by macrophages ↓ Heart failure cells (Macrophages) ↓ Fibrosis (induration) of alveolar septa ↓ Nithin.B. Page 21  General Veterinary Pathology 2016 VPP-211 Brown induration of lungs ↓ (due to haemosiderin) Spleen  Enlarged and cyanotic  Due to congestion of Liver  Occurs in vegetative endocarditis (swine) and  Traumatic pericarditis (cattle)  Hard and indurated - Cyanotic induration Kidneys  Pressure on renal veins by o Tumours of adrenals o Abscesses  Grossly, enlarged and dark purple  Cortico-medullary junction – dark red in color ACUTE LOCAL PASSIVE HYPERAEMIA Increase in blood in the veins of a portion (foot, tail, kidney etc) Due to sudden obstruction to blood flow Causes  Malposition of viscera o Volvulus, intussusception, torsion  External pressure o Ligatures, tourniquets, bandages Nithin.B. Page 22  General Veterinary Pathology 2016 VPP-211 Pathogenesis HYPOSTATIC CONGESTION Accumulation of blood in ventral portions of the body due to gravity. Causes  Occurs in heart diseases  Recumbency  Inactive animals  Large animals  Heart failure - Agonal congestion Nithin.B. Page 23  General Veterinary Pathology 2016 VPP-211 Appearances  Veins in ventral portion or organs distended with blood  Lungs - increase capillary bed  Intestine & kidneys – necrosis and gangrene  Causes pneumonia and gangrene of intestine Significance  Indicates o the side of animals which was ventral at the time of death o Heart was not able to pump properly o Location of body in medico–legal cases Grossly and microscopically Veins are engorged with blood ↓ Necrosis of endothelial cells ↓ Haemorrhage CHRONIC LOCAL PASSIVE HYPERAEMIA  Increase in amount of blood for a long time in veins  Permanent tissue changes (atrophy, fibrosis) Causes  External pressure o Tumors, abscesses  Obstruction from within o Thrombus (blood clot) Nithin.B. Page 24  General Veterinary Pathology 2016 VPP-211 Gross and microscopic appearance  Enlarged initially later undergoes atrophy  Veins - bluish blood  Oedema due to increase permeability of capillaries  Fibrosis HAEMORRHAGE Definition  It is the escape of blood from a vessel. Two types  Haemorrhage by rhexis : When there is rupture of a blood vessel  Haemorrhage by diapedesis : When blood leaves through intact blood vessels Site of haemorrhage Epistaxis Bleeding from nose Haematemesis Blood in vomit Haemoptysis Blood in sputum Metrorrhagia Bleeding from uterus Enterrohagia Bleeding from intestine Melena Blood in stools Haematuria Blood in urine Haemothorax Blood in thoracic cavity Haematocoel Bleeding into tunica vaginalis Apoplexy Hemosalphinx Bleeding in oviducts Hematoma Tumour-like accumulation of blood Apoplexy Haemorrhage into brain Nithin.B. Page 25  General Veterinary Pathology 2016 VPP-211 Size of haemorrhage  Petechiae: minute; pinpoint  Purpura: approximately 1cm in size  Ecchymoses: 1 – 2 cm in size  Extravasation: Larger area Petechiae-Intestine Purpura - Spleen Ecchymoses - Spleen Extravasation Internal haemorrhages-Abdominal cavity Source of haemorrhage  Cardiac  Arterial  Venous  Capillary Causes  Conditions affecting the blood vessels  Conditions affecting the blood Nithin.B. Page 26  General Veterinary Pathology 2016 VPP-211 Conditions affecting blood vessels  Trauma: Lacerations, incisions, contusions  Clumps of bacteria, swine erysipelas, anthrax, haemorrhagic septicaemia  Necrosis of vessel wall o Ulcers in gastric mucosa o Neoplasms  Diseass of vessel walls o Aneurysm - e.g. Strongylus vulgaris infection in horses o Atheroma  Toxic injury to capillary endothelium o Bacterial : Anthrax, haemorrhagic septicaemia, black quarter o Viral : Hog cholera o Chemicals : Arsenic, phosphorus, chloroform, cyanide o Enterotoxins : Sheep & calves – Clostridium welchii - ASPHYXIA  Increased blood pressure o Excessive exercise → increased blood pressure → Rupture of blood vessel - Seen in race horses  Hypoxia and lack of nutrition o Passive venous congestion → damage to endothelium - Haemorrhage Conditions affecting blood constituents  Haemophillia: Hereditary sex linked disease; Delayed clotting  Thrombocytopenic purpura: Decrease in platelets seen in toxaemias  Nutition o Deficiency of vitamin K  Vitamin K which is required for prothrombin formation and in its absence clotting will not take place.  Increased use of sulpha drugs may not permit intestinal microflara to synthesis vitamin K o Deficiency of vitamin C  Vitamin C is required for formation of ground substance. Invitamin C defeciency capillary endothelium becomes more fragile leading to haemorrhage  Heparinoid state o In anaphylactic shock and irradiation, excess of heparin is found which impairs clotting.  Plant toxins o Brakern fern and sweet clover poisoning prevent prothrombin formation Microscopical appearance  Presence of erythrocytes outside blood vessels  Recent haemorrhage stains deeply Nithin.B. Page 27  General Veterinary Pathology 2016 VPP-211 Haemorrhage disintegrates due to action of tissue enzymes ↓ Haemoglobin Haemosiderin (Iron) and hamatoidin (Non iron) ↓ Bilirubin ↓ Phagocytosed by macrophages  Prussian blue reaction reaction to demonstrate iron Significance and result  Depends on volume, rate, site. Sudden loss of about 30% of blood volume or slow losses of large volume of blood will have no clinical significance. e.g. Stomach worm infection  Site of haemorrhage is very important. Small haemorrhage in brain is fatal whereas small haemorrhage in skeletal muscle or subcutaneous tissue is NOT FATAL. Haemorrhage in pericardial sac (CARDIAC TAMPONADE) is fatal.  Iron deiciency anaemia is due to repeated and chronic loss of blood from external surface  When erythrocytes are retained in body cavities, joints, tissues, iron is recaptured and haemoglobin is synthesized. Fate of haemorrhage  In small haemorrhage fluid portion is reabsorbed, WBCs move into blood vessels and RBCs are phagocytosed  In larg haemorrhage, RBCs are haemolysed and haemoglobin is split into haeme (Haemosiderin which is iron containing portion of haeme and haematoidin is iron free portion) and globin. Nithin.B. Page 28  General Veterinary Pathology 2016 VPP-211 Arrest of haemorrhage Vascular contraction Small blood vessels Platelet aggregation White clot Clot formation Red clot → When blood flow is slow Tissue pressure  Increased perivasular pressure in tissue  Decreased intra vascular pressure Decreased blood pressure Large harmorrhage ↓ Decreased BP ↓ No bleeding OEDEMA Definition  Abnormal accumulation of fluid in the intercellular tissue spaces or body cavities o Localized : Due to obstruction of venous outflow – leg o Generalized : Chronic venous Congestion or heart failure Terms used to describe oedema  Anasarca: Generalized subcutaneous oedema  Ascites: Fluid in peritoneal cavity  Hydrothorax; Edematous fluid in thorax  Hydropericardium: Edematous fluid in pericardium Oedema is of two types 1. Inflammatory oedema 2. Non-inflammatory odema Nithin.B. Page 29  General Veterinary Pathology 2016 VPP-211 Mechanism of oedema formation Two forces called “STARLING’S FORCES “  Filtration force: Expels fluid from the vessel  Absorption force: Draws fluid into the vessel Physiology of fluid balance  At the arterial end of capillary hydrostatic pressure is 45mm of Hg and osmotic pressure of blood is 30mm of Hg (due to albumin / globulin). Therefore, fluid expelled into the intercellular space (filtration force) is 15mm Hg.  At te venous end, hydrostatic pressure of blood falls to 15mm of Hg and osmotic pressure of blood is 30mm of Hg. Therefore, absorption force is 15mm of Hg CAUSES OF OEDEMA  Decreased plasma osmotic pressure  Increased hydrostatic pressure  Increased permeability of vascular endothelium  Lymphatic obstruction  Sodium retention Decreased plasma osmotic pressure - Hypoproteinemia (Albuminemia)  Decreased protein synthesis  Excessive loss from blood - Low osmotic pressure in the blood - More fluid flows into intercellular space Hydrostatic pressure at arterial end is 45mm Hg and osmotic pressure at arterial end is 20mm Hg. So, the rate of fluid flow into tissues is 25mm Hg. Osmotic pressure at venous end is 20mm Hg and hydrostatic pressure is 15mm Hg. Thereby, the rate of fluid flow in to vein is 5mm Hg. Because of the pressure diffeences ( Hydrostatic and osmotic pressure) at the arterial and venous end, the rate of fluid accumulation in tissues is 20mm Hg Decreased plasma osmotic pressure mostly results in generalised and severe oedema  Malnutrition  In advanced hepatic disease (Cirrhosis), protein synthesis will be affected leading to nutritional or cachetic oedema  Loss of protein through intestine and stomach - stomach worms → Parasitic oedema  Kidney or renal amyloidosis – blood lost in urine - Renal odema Nithin.B. Page 30  General Veterinary Pathology 2016 VPP-211 Increased hydrostatic pressure  General or passive hyperaemia → venous stasis  Central lesion in heart or lungs or local obstruction in a vein Hydrostatic pressure at arterial end is 45mm Hg, whereas osmotic pressure is 30mm Hg. So the rate of fluid flow into tissues is 15mm Hg. At the venous end, osmotic pressure is 30mm Hg and hydrostatic pressure is 25mm Hg. The rate of fluid flow into vein is 10mm Hg. So the rate of fluid accumulating in tissues is 5mm Hg.  This type of oedema is mild. Mainly the cause is in the heart. Hence called cardiac oedema. Increased permeability of capillary endothelium  Due to venous stasis → increased hydrostatic pressure  Inflammation Lymphatic obstruction Causes  Tumours, cyst, abscess, bandages, thrombi  Parasites (Demodex canis, mites)  Filariasis – Wucheria bancrofti - humans  Inflammatory conditions – farcy; ulcerative lymphangitis In lymphatic obstruction, fluid and protein in intercellular space will not be drained leading to oedema (LYMPHOEDEMA) Sodium retention Causes  Congestive heart failure  Nephrosis/Nephritis  Acute renal failure Due to failure of excretion sodium in urine, water will be retained leading to generalized oedema Nithin.B. Page 31  General Veterinary Pathology 2016 VPP-211 Differences between transudate and exudate S. No. Characters Transudate Exudate 1 Colour Clear, water like pale yellow Cloudy, white, yellow-red 2 Consistency Thin, watery no tissue fragments Thick, creamy, contains tissue fragments 3 Odour None Have odour 4 Ph Alkaline Acidic 5 Specific gravity 1.015 or less 1.018 or higher 6 Protein Low, < 3% High > 4% 7 Cell count Low High, RBCs, WBCs 8 Enzyme count Low High 9 Bacteria None Present 10 Inflammation None Present Macroscopical appearance  Swollen, increase in weight  Cold due to decrease blood, flow and increase heat dissipation  Less color  No pain  Incision results in flow of fluid from cut surface  Pits on pressure  Fibrosis Microscopical appearance  Space between adjacent cells widened  During life space filled with fluid  H&E stain - fine granular material - stains faintly pink - ↑ pink if ↑ protein  Atrophy of parenchymatous cells  Fibrosis - chronic cases Significance and result  Disappears if cause is removed  Oedema in lung & brain are fatal  Subcutaneous oedema impairs wound healing Nithin.B. Page 32  General Veterinary Pathology 2016 VPP-211 TYPES OF OEDEMA 1. Inflammatory oedema 2. Cardiac oedema 3. Renal oedema 4. Hunger/Famine/War oedema 5. Pulmonary oedema 6. Cachetic oedema 7. Myxoedema 8. Parasitic oedema 9. Angioneurotic oedema 10. Brisket disease 1. Inflammtory oedma  Toxins damage blood vessels - Increased permeability of endothelium - Fluid rich in protein pass out - “INFLAMMATORY EXUDATE” 2. Cardiac oedema  Congestive heart failure leads to CVC which results in insufficient renal circulation ischaemia leading to oliguria with diminished chloride excetion. This results in sodium retention which raises tissue osmotic pressure aggrevating oedema Oedema - Abdominal cavity - Ascites  Causes for cardiac oedema o Increased hydrostatic pressure of blood o Increased vascular permeability o Sodium retention  Symptoms o Oedema of dependant parts o Traumatic pericarditis in bovines Cardiac oedema may develop in horses with chronic vesicular emphysema. Nithin.B. Page 33  General Veterinary Pathology 2016 VPP-211 3. Renal oedema  In acute glomerulonephritis (in man), oedema in face and eyelids are usually seen. o Causes of acute glomerulonephritis are  Decreased osmotic pressure of blood  Toxins damage glomerular capillaries resulting in albuminuria and hypoproteinaemia.  Increased osmotic pressure of ECF  In acute nephritis, oliguria / Anuria results in sodium retention  Increased capillary permeability  Increased hydrostatic pressure in capillaries in venous side  Toxins damage kidney and heart causing cardiac failure and its outcome is CVC  Subacue nephritis and nephrosis o Decreased colloidal osmotic pressure of blood o Increased sodium retention o Hypoalbuminaemia stimulates adrenal cortex to secrete increased amount of aldosterone which helps in reabsorption of sodium chloride. This retained salt increases osmotic pressure and cause oedema.  Chronic glomerulonephrtis o Hypertension for long period throws great strain on heart resulting in heart failure and thereby causing CVC which increases blood pressure in capillaries. As a resut of this, oedema occurs. 4. Hunger / Famine / war oedema  Hypoproteinaemia → Decreased plasma osmotic pressure  War / famine → Decreased protein availability 5. Pulmonary oedema  Causes o Cardiac failure - hypertension; valvular disease - pericarditis o Renal lesions o Pressure on pulmonary veins by neoplasm o Injury to brain o Rapid removal of effusion from pleural / peritoneal cavity o Poisons o Infections Nithin.B. Page 34  General Veterinary Pathology 2016 VPP-211 Oedema - Lung - Rib markings 6. Cachetic oedema  Anaemia  Wasting diseases  Malnutrition  Cardiac illness 7. Myxoedma  This occurs in chronic thyroid deficiency. In this condition there will be increased protein accumulation in tissue fluid which raises pressure of fluid locally and water is drawn into the site. 8. Parasitic oedema  This type of oedema is most commonly seen in animals suffering with stomach worms, liver flukes, amphistomes. During migratory life of cercaria, haemorrhage & necrosis occurs in liver. Adult flukes inhabitats bileduct causing chronic irritation of lining mucosa of the duct resulting in cirrhosis. Affected liver cannot synthesis protein leading to oedema formation.  Due to hypoproteinemia, there will be an accumulation of fluid in lower jaw called as “BOTTLE JAW” which is a characteristic feature of parasitic oedema. 9. Angioneurotic oedema  In man, allergens like snake venom produces hypersensitivity reaction which increases capillary permeability resulting in oedema in lips, glottis, thorax  In animals (cattle, horses), endogenous / exogenous allergens (plant, protein; fish meal) cause release of histamine which damage blood vessels and oedema results. Nithin.B. Page 35  General Veterinary Pathology 2016 VPP-211 10. Brisket disease  Cattle moved to high altitude 9000ft above sea level develop oedema in abdomen, brisket, neck and jowl.  At high altitudes, partial pressure of oxygen is decreased. The resulting hypoxia develops polycythemia (Increased viscosity of blood) and polypnoea (Increased heart beat). Cardiac muscle becomes degenerated as it works in hypoxic condition and hence hypertrophied heart slowly dilates and which draws valves downwards resulting in valvuar incompetency and gives rise to chronic venous congestion.  Reason for development of oedema in high altitude o Hypoxia o Chronic venous congestion - Develops due to increased capillary blood pressure and hypoxia Nithin.B. Page 36  General Veterinary Pathology 2016 VPP-211 MODULE-4: HAEMODYNAMIC DERANGEMENTS-2 Learning objectives  In this part of this module, the viewer will learn about other changes occurring in cardiovascular system in diseases viz. formation of blood clots within the CV system (Thrombosis), circulation of foreign bodies (Emboli), blockage of vessels leading to death of tissues (Infarction) for want of oxygen and nutrition and shock. THROMBOSIS  Formation of clotted mass of blood within the cardiovascular system  Clotted mass – Thrombus (singular) and thrombi (plural) Differences between thrombus and blood clot Thrombus Blood clot Formation Blood vessels Blood clotting system Platelets Blood clotting system Composition Platelets Only fibrin Fibrin Prognosis Life threatening Life saving Causes for  Injury to endothelium o Trauma : lacerations, contusion, rupture, i/r injection o Toxins : Streptococci, erysipelothrix (vegetations) o Degenerations : Atherosclerosis (damage to intima) o Viruses : Hog cholera virus o Parasites : Strongylus vulgaris in anterior mesenteric artery in horses o Tumours : Invading tumours Nithin.B. Page 37  General Veterinary Pathology 2016 VPP-211 Mechanism of thrombus formation  Active o Antithrombotic factors and prothrombotic factors are seen on surface of endothelium  Passive o Endothelium is thromboresistant wheras subendothelial connective tissue is highly thrombogenic. o Subendothelial onnective tissue consists of collagen, elastic, fibrinonectin, laminin glycosoaminoglycans andthrombosporin. o Damage to endothelium exposes the subendothelial connective tissue and activates intrinsic blood clotting pathway and platelet adhesion. Antithrombotic factors (present on endothelial cells) - Inhibit thrombosis  Anticoagulant properties o Thrombo modulin - Protect against action of heparin and thrombin which converts fibrinogen to fibrin  Anti platelet properties - Inhibit platelet aggregation o Prostacyclin (PGI2) o Nitric oxide (NO2)  Fibrinolytic properties o Tissue plasminogen activator (tPAs) - Promotes fibrinolytic activity in blood and reacts against blood clots Thrombotic factors  Tissue factor (Thromboplastin) o Present on endothelium in small amounts o Activate extrinsic clotting pathway o Stimulated by  Endotoxins  Cytokines (IL – 1)  Tumour necrosis factor (TNF)  von Willebrand factor (vWF) o Protein helps in platelet adherence thrombus  Platelet Activating Factor (PAF) o Helps in platelet aggregation thrombus  Inhibitor of Plasminogen Activator o Prevents fibrinolysis thrombus Normal homeostasis: There will be a balance between antithrombotic and prothrombotic factors in normal endothelium. Nithin.B. Page 38  General Veterinary Pathology 2016 VPP-211 Thrombus formation  Increase prothrombotic factors  Decrease antithrombotic factors Alterations in constituents of blood  Increase in number of platelets o Parturition o surgery  Increase in adhesiveness of platelets o Parturition o Surgery  Decrease in heparin (anticoagulant) in diseases  Increased plasma fibrinogen and prothrombin o Trauma  Increased viscosity of blood o Dehydration o Polycythemia  Sludging of blood o Clumping of cells  Increased fragility of RBCs  Increased cortisone therapy – Rheumatoid arthritis - Increase blood lipids - Increase platelet aggregation - Coronary thrombosis Alterations in normal blood flow  Slowing of blood flow results in platelet aggregation  Turbulence damage endothelium Types of thrombus  Arterial thrombus  Venous thrombus  Cardiac thrombus Causes for slowing of blood  Chronic venous congestion venous stasis  Old and debilitated animals  Varicose veins Nithin.B. Page 39  General Veterinary Pathology 2016 VPP-211 Comon sites for thrombosis  Animals o Scrotal plexus - horses o Vascular sinuses – horse and cows (Nasal passage) o Large veins of Broad ligament of uterus – cow o Anterior mesenteric artery - horses  Humans o Leg veins – Congestive heart failure, bed ridden patients CLASSIFICATION OF THROMBI I. Based on location within blood vascular system 1.Cardiac thrombi  Mural thrombus: Seen on the wall of left auricle o Bovines - black quarter o Caused by Clostridium chauvoei  Valvular thrombus o Pigs – Streptococcus pyogenes, Erysipelothrix rhusiopathiae o Cattle– Cornybacterium pyogenes o Horses– Streptococcus equi  Ball thrombus: Seen in auricle - Unattached. If it is large,it causes valvular obstruction 2. Arterial thrombi  Located within arteries  Common in domestic animals o Horses : Strongylus vulgaris larvae in anterior mesenteric artery o Dogs : Spirocerca lupi in aorta o Cattle: Onchocerca armillata in aorta 3. Venous thrombi  Phlebothrombosis  Common in bed ridden patients  Rare in animals  Seen in recumbent calves Leg veins collapse and press against hard surface. Endothelium gets damaged and thromboplastin is released resulting in thrombus formation. In general passive hyperaemia, veins will be distended and leads to slowing of blood which favours thrombus formation. Nithin.B. Page 40  General Veterinary Pathology 2016 VPP-211 Locations  Human - Femoral, popliteal, iliac veins  Animals  Nasal vascular sinuses – Cow, horses  Veins of broad ligament – Cow o Scrotal plexus – Horses 4. Capillary thrombi  Seen in inflammation  Injury to endothelium 5. Lymphatic thrombi  Seen in lymphatics draining inflammation area  Beneficial II. Classification based on location within heart or bood vessels  Mural thrombi - Attached to wall of heart / blood vessel  Valuvlar thrombi - Valves  Lateral thrombi - Attached to one side of blood vessel  Occlusive thrombi - Attached to entire circumference of vessel  Saddle thrombi -Site of bifurcation of blood vessel  Canalised thrombi - New blood channel is formed through clot III. Classification based on infectious agent  Septic thrombi - Bacteria  Aseptic thrombi - Without bacteria / parasites  Parasitic thrombi - Strongylus vulgaris (Horses) and Dirofilaria immitis (Dogs) IV. Classification based on colour of thrombi  Pale / White Thrombi - composed of platelets and are seen in heart / aorta  Red Thrombi – composed of platelets / fibrin, RBCs and WBCs and are seen in veins ( Commonly seen)  Mixed Thrombi –Mixture of White and red thrombi (White - Formed during fast flow of blood; Red - Formed during sluggish flow)  Laminated thrombi o Type of mixed thrombi  Excessive exercise - increase blood flow to legs – White Thrombus  Rest - increase blood flow to legs - Red Thrombus Nithin.B. Page 41  General Veterinary Pathology 2016 VPP-211 Fate of thrombus  Propagation : Enlargement - obstruction of vessel  Contraction : Shrinkage of thrombus may occur due to contraction of fibrin  Embolus : Carried to other sites; and cause dangerous infarction o Enzymes from WBCs / platelets digest thrombi and emboli are formed  Abscessation : Pyogenic bacteria in thrombus may gives rise to bacterial emboli  Resolution : Fibrinolysis o Fresh thrombus – Complete digestion o Old thrombus – incomplete digestion  Organization & Canalisation Significance and results  Negligible effects - Jugular vein; carotid arteries  Beneficial effects - Control of haemorrhages  Harmful effects - Vessel without collateral circulation o Infarction o Embolism o Passive hyperemia o Lymphoedema o Aneurysm – Strongylus vulgaris o Gangrene – intestinal thrombus o Colic, lameness o Septicaemia / Death Character Thrombus Postmortem clot Size Fills vessels Small Consistency Dry & friable Smooth / glistening Color White, red, mixed Red / yellow Attachment Yes No Endothelium Damaged Undamaged Composition Platelets Fibrin Rapidity of blood flow Formed in flowing stream Stagnant stream Animal Living Dead Organization Yes No Structure Laminated (Line of Zahn) Homogenous Nithin.B. Page 42  General Veterinary Pathology 2016 VPP-211 EMBOLISM  An embolus is any foreign body floating in blood. The process is called embolism. Location of embolism  Artery / venous / capillaries / lymphatics  In domestic animals emboli always occurs in arteries  In human, venous embolism is common  Thrombus in leg vein may form emboli to reach large blood vessel, right side heart and pulmonary artery embolism Types / Causes of emboli  Thrombotic emboli : Thrombo embolism – arteries (Thrombi detach to form emboli) o Heart – vegetations o Parasitic; atherosclerotic; bacteria  Bacterial emboli : Septicaemia  Parasitic emboli : Dirofilaria immitis - Pulmonary artery – dog o Schistosomes – Portal; mesenteric; Nasal blood vessels o Trypanasomes – If tartar emetic is given rapidly, it kills large number of organism and forms emboli on coronary vessels which is fatal. o Filarial - Lymphatics emboli in brain  Neoplastic emboli : Clumps of tumour cells in circulation producing metastatic tumours.  Fibrin - In blood transfusion, when blood is improperly defibrinated / inadequate anticoagulants  Fat emboli - In fracture of long bones, fat in the marrow cavity gets dislodged and forms emboli. These are lodged in lungs and leads to death. o “Fat embolism syndrome“ (Acute respiratory symptoms, tachycardia neurological symptoms)  Air or gas emboli o Incision of large neck veins (surgery / suicide) o Air sucked into veins Embolism o In criminal abortion Pumping air into uterus o Air in large uterine vein o Emboli o Enters circulation o Heart o Foamy blood o Acute heart failure – Sudden death  Caission's disease o Humans o Sudden change in atmospheric pressure o Under water construction workers o Deep sea / scuba divers o Unpressurised aircrafts ascends rapidly o Under water construction workers o Increase air pressure within under water compartment to compensate water pressure o Breathing o Increase air dissolve in blood, tissue fluid and fat o If the worker surfaces suddenly i.e decompresses Nithin.B. Page 43  General Veterinary Pathology 2016 VPP-211 o Dissolved gases come out as bubbles (O2, CO2, N2) o O2 and CO2 are soluble and cause no harm; N2 which is insoluble form emboli o AIR embolism (Brain, heart etc) o “Caission” means - water tight chamber used underwater o Also called “BENDS” – severe cramping pain  Clumps of normal of normal body cells o Occurs when tissue / organ is damaged  Amniotic fluid embolism o Complication of labour o Infusion of amniotic fluid (Epithelial cells, fat, mucin, meconium) o Maternal circulation o Due to tear in placental membrane or rupture of uterine veins o Maternal mortality (Respiratory distress; cyanosis, shock, convulsions, coma, death) o Rare in domestic animals - due to anatomical differences in placental / uterine structures Pradoxical emboli  Emboli that pass directly from the right auricle into the left auricle through patent foramen ovale thereby emboli originating from vein will be lodged in systemic vessels instead of being in pulmonary vessels. Significance / Result of embolism  Character of emboli o size - large emboli → large blood vessel blocked o septic / aseptic – new foci of infection o neoplasms – metastasis  Number of emboli o Increased sites of obstruction  Organs involved o Liver / Lung / muscle - Large blood supply o Very little effect o Heart / Kidney / Spleen - no collateral circulation - Infarction INFARCTION  An infarct is an area of coagulative necrosis results due to sudden blockage of an end artery which has no collateral circulation. Causes Thrombus / embolus  Pressure on the vessel wall causing ischaemia o Ligatures o Decubitus ulcers o Torniquets o Tumours Nithin.B. Page 44  General Veterinary Pathology 2016 VPP-211 o Cysts / abscess o Volvulus / intussusception of intestine  Contraction of vessel wall Ergot poisoning  Smooth muscle contraction  Narrowing of blood vessel  Ischaemia  Seen in extremities (legs, ears, tail, wattles)  Hypotension Shock Ischaemia Brain infarction Pathogenesis Thrombus (blocking of end artery)  Ischaemia capillaries dilate to increase blood supply  Hypoxia Area red color [Red infarct] Nithin.B. Page 45  General Veterinary Pathology 2016 VPP-211  Damage to endothelium  Haemorrhage  >2 hours - Fusion of RBCs into homogenous mass  Degeneration of cells  24hours - Coagulation necrosis of cells  72hours - Lysis of RBCs  Release of haemoglobin  Loss red color [Pale infarct]  Inflammation Nithin.B. Page 46  General Veterinary Pathology 2016 VPP-211  Scar (yellow / brown due to haemosiderin Macroscopical appearances  Red or pale in color  Cone shaped – apex of cone is at the point of obstruction of vessel - base towards periphery Infarcts of kidneys  Common in cows and pigs  Yellow or pale  Wedge shaped – seen in cortex  Apex at arcuate arteries  Base at capsular end of cortex  No capsular necrosis  Appears as healed, depressed areas  Causes o Cardiac vegetations – Corynebacterium pyogenes, streptococci o Cows – very common – emboli of uterine vein after parturition Infarcts of spleen  Pale or red color  Seen in borders  But in dogs, it is band like  Due to cardiac thrombi Infarction of intestines  Common in horses – anterior mesenteric artery (Strongyle worms)  Whole surface of bowel is affected  Red in color  Causes Nithin.B. Page 47  General Veterinary Pathology 2016 VPP-211 Volvulus, intussuception, strangulation  CVC  Necrosis  Gangrene  Sequelae o Fatal o Toxaemia o Shock o Peritonitis Infartion of brain  Common in man  Due to arteriosclerosis  Animals – Dogs – automobile accidents  Cerebral infarction  Softening → Myelin engulfed by microglia – “ Compound granular corpuscles”  Organization or cyst formation (neuroglial cells)  Cyst with yellow fluid “Apoplectic cysts” Infarcts of heart  Common in man due to arteriosclerosis  Not seen in animals  Red or pale  Healed infarcts – Scar  Sequelae of cardiac infarcts – Myomalacia cardis Nithin.B. Page 48  General Veterinary Pathology 2016 VPP-211 Infarcts of liver  Causes o Tumours o Thrombus due to Clostridium hemolyticum in bovines o Red in colour Infarcts of lungs  Common  Cone shaped  Red color  Causes o Emboli from o Cows – Uterine veins & posterior vena cava (Abscess) o Horses – Mesenteric veins o Pigs – Pulmonary veins (Hog cholera) o Hypostatic congestion o Chronic venous congestion o Cattle and sheep – Pasteurella infection → Pulmonary infarction (Haemorrhagic septicaemia) Sequelae of infarcts  Organization and scar formation  Gangrene  Death (Brain, heart, intestine) – SHOCK/ Toxaemia/ Septicaemia SHOCK  A common grave medical emergency characterized by a reduction in effective circulating blood volume and in the blood pressure. Definition  Shock (cardiovascular collapse) is a circulatory dishomeostasis associated with loss of circulating blood volume and reduced output and or inappropriate peripheral vascular resistance.  Although causes of shock can be diverse the underlying cause of shock are relatively stereotyped i.e. hypoperfusion. Causes of shock  Trauma / burns  Profuse haemorrhage  Bacterial septicaemia Nithin.B. Page 49  General Veterinary Pathology 2016 VPP-211  Myocardial infarction (man)  Pulmonary embolism (man)  Psychic stimuli (man)  Crushing injuries (automobile accidents) in dogs  Cold, exhaustion, depression animals  General anaesthesia Classification of shock  Primary shock  Secondary shock Primary shock (Syncope, fainting)  Appears immediately after extensive injury  Nervous stimuli in which widespread paralysis of capillaries occurs  Animals o Rough handling of animals o Undue manipulation of intestine in abdominal surgery  Humans o In psychic state like fear, excitement and apprehension, neurogenic impulses causes vasodilation and blood pressure decreases which leads to cerebral ischaemia and results in loss of consciousness (Pallid face, slow breathing, feeble pulse) o Transient / Patient recovers with rest. Secondary shock It is fatal Nithin.B. Page 50  General Veterinary Pathology 2016 VPP-211 Causes of shock 1. Reduction in blood volume o Loss of blood from injuries (Haemorrhages) o Loss of fluid into injured tissues  Severe burns  Crushing injuries Oedema  Vomition  Diarrhoea Dehydration  Na deficiency  Addison’s disease Dehydration  Diabetic coma  Poisons (Phosgene, mustard gas, ANTU) 2. Capillary bed dilation o Decreased cardiac output → decreased blood volume  Neurogenic Stimuli  Anxiety, fear, pain, bleeding wounds  Bacterial toxins  Burns, crushing injuries  Anoxia Nithin.B. Page 51  General Veterinary Pathology 2016 VPP-211 3. Acute circulatory failure o Infarction, cardiac tamponade o Pulmonary embolism → No circulation → Shock Classification based on fundamental underlying problem  Cardiogenic shock  Hypovolumic shock  Blood maldistribution shock o Septic shock o Anaphylactic shock o Neurogenic shock Cardiogenic shock results from failure of heart to adequately pump blood.  This occurs due to o Myocardial infarction o Ventricular tachycardia o Fibrillation or other arrhythmia o Dilating and cardiac myopathy o Obstruction of blood flow from the heart  e.g. Pulmonary embolism and pulmonary or aortic stenosis o Other cardiac dysfunction  Unsuccessful compensation leads to stagnation of blood and progressive tissue hypoperfusion. Hypovolumic shock arises from reduced circulatory blood volume due to blood loss caused by haemorrhage of fluid loss secondary to vomiting, diarrhoea or burns. This leads to decreased vascular permeability and tissue hypoperfusion.  Immediate compensatory mechanisms to increase vascular pressure o Vasoconstriction and fluid movement into plasma.  Loss of about 10% blood volume can occurs without consequence, but when blood loss approaches 35-45% blood pressue and cardiac output can fall dramatically. Blood maldistribution shock is characterised by decrease peripheral vascular resistance and pooling of blood in peripheral tissue. The systemic vascular dilatation results may dramtically increase microvascular area and although the blood volume is normal. The effective circulating blood volume is decreased. Nithin.B. Page 52  General Veterinary Pathology 2016 VPP-211  Anaphylactic shock is generalised type I hypersensitivity. o Causes  Exposure to insect or plant allergen.  Drugs  Vaccine Interaction of an inciting substance with Ig E and mast cell results in mast cell degranulation, release of histamine and systemic vascular dilatation, increased vascular permeability and tissue hypoperfusion.  Neurogenic shock o Causes  Trauma (particularly nervous system)  Electrocution (Lightening stroke)  Fear  Emotional stress Here autonomic discharge that results in peripheral dilatation followed by venous pooling of blood and tissue hypoperfusion. When compared to anaphylactic and endotoxic shock wherein cytotoxic plays a major role in intial peripheral vascular dilatation.  Septic shock o Common type of shock associated with blood maldistribution. o Here components of bacteria or fungi (endotoxin, a lipopolysaccharide within the cell wall of gram negative bacteria) which are released from degenerating bacteria is potent stimulus and causes for septic shock. Pathogenesis of shock  Ischaemic shock Nithin.B. Page 53  General Veterinary Pathology 2016 VPP-211 Septic shock Nithin.B. Page 54  General Veterinary Pathology 2016 VPP-211 Vasoactive principles Symptoms of shock  Lethargy; recumbent; weak pulse rate  Cold extremities  Anxiousness  Shallow breathing Microscopical appearance  Venules and capillaries engorged with blood  Fat embolism in lungs – traumatic shock  Fatty degeneration and necrosis in liver / heart  Renal tubular necrosis – casts in tubules  Adrenal cortex is foamy, due to depletion of cholesterol Nithin.B. Page 55  General Veterinary Pathology 2016 VPP-211 Significance and results  Recovery – on blood transfusion / supportive treatment  Death – irreversible shock  Renal insufficiency o Oliguria, anuria, uraemia o Pigment casts in tubules o Inflammatory oedema compresses renal parenchyma o Ischaemia – due to vascular collapse o Tubular degeneration and necrosis  Cardiac failure  Cerebral ischaemia - decreased BP → Anoxia → Neuronal degeneration ↓ Encephalomalacia ↓ Death  Pulmonary infection – Pulmonary oedema → Bacterial growth Morphology of shock  Hypoxic cell injury  Brain – Neurons – reversible cell injury o Irreversible cell injury (ischaemic encephalopathy)  Heart – Subpericardial / Subendocardial haemorrhages and necrosis  Kidneys - Acute tubular necrosis  Lungs o Resistant to hypoxic cell injury o Not affected in hypo volumic shock o But changes seen in endotoxic or neurogenic shock  GIT – patchy mucosal haemorrhages “Haemorrhagic enteropathy”  Liver – Fatty changes / central necrosis Nithin.B. Page 56  General Veterinary Pathology 2016 VPP-211 Macroscopical appearance  Haemorrhages – Pale tissues  Increased vascular permaeability – Oedematous tissues  Passive congestion of liver, kidneys, lungs, intestines  Petechiae on serous surfaces  Fatty changes ← necrosis in liver, kidney, heart  Pulmonary oedema and congestion  Kidneys enlarged, pale cortex, red – blue pyramids  Adrenal cortex – brilliant yellow – early stage reduced size / Pale – Later stage Nithin.B. Page 57  General Veterinary Pathology 2016 VPP-211 MODULE-5: CELL SWELLINGS, GLYCOGENOSIS, FATTY CHANGES, HSP, LSD Learning objective  This module deals on cellular accumulations like fluid, glycogen and fat caused by different aetiological agents besides lysosomal storage disease. The role of heat shock proteins in cell injury (HSP) is also discussed. ACUTE CELL SWELLING This occurs whenever the cells are incapable of maintaining ionic and fluid homeostasis. It is difficult to appreciate the change with light microscopy. It is the first change to all forms of injury to the cell. The organ is swollen. Causes  As discussed in the reversible cell injury Grossly,organs appears pallor, increase in turgor, increase in weight when involves all cells in the organ. Acute cell swelling - Swollen kidneys - Chicken Microscopically, enlargement of cells is mostly observed in liver, convoluted tubules of the kidney,or in skeletal and cardiac muscle. Cytoplasm stains slightly more eosinophilic and more granular than normal. Nithin.B. Page 58  General Veterinary Pathology 2016 VPP-211 It is discernible by compression of microvaculature of organs. e.g. hepatic sinusoids and capillary network inrenal cortex. Hydropic degeneration A variant of cell swelling with excessive accumulation of fluid leading to even bursting of cells. It is caused by more severe irritant. Causes  Physical causes o Rubbing o Friction injury o Axe handling o Ill fitting shoes  Thermal injuries o Fire accident o Hot substances – water and oil o Blisters are seen.  Chemicals o Application of croton oil, rediodide of mercury  Infectious agents o FMD in cattle – vesicles o Pox – blisters in stratified squamous epithelium  Neoplasm o Cervical cancer Grossly, blisters are seen onskin. Fluid escapes on incision and blister collapses consequent. Microscopically, cells are swollen. Cytoplasm shows vacuoles which represent distended and sequestrated segments of endoplasmic reticulum. Cells may enlarge with coalition of fluid and may burst showing blisters and vesicles. Prickle cell layer is affected. Eosin stains pink depending on protein content. Using negative method of staining i.e. staining of fat or glycogen, vacuoles with water are identified. Sequelae  Healing occurs rapidly in uncomplicated cases without scar formation. Invasion of pyogenic bacteria like Streptococci and Staphylococci may cause abscesses or septicaemia. Nithin.B. Page 59  General Veterinary Pathology 2016 VPP-211 Mucinous or mucous degeneration Mucinous or mucous degeneration is the excessive accumulation of mucin in degenerating epithelium cell. Mucin is glassy, viscid, stringy, slimy glycoprotein normally produced by epithelium cell lining mucous membranes. Mucus is mucin mixed with water. Causes  It is caused by mild irritant.  Mechanical or chemical injury (Disinfectant or soap).  Thermal injury by heat or cold.  Infectious diseases – Canine distemper, bovine viral diarrhoea Grossly, mucous covering is seen as clear transparent material on mucous membrane which is stringy and slimy inconsistency. e.g. common cold. Mucosa is hyperaemic. In oestrus, large amount of mucous is normally produced which may be hanging from vulva of cattle. Microscopically, cytoplasm shows small droplets of mucous which may coalesce forming large droplets displacing nucleus to side and compressing the nuclei. As the mucin accumulation continues the cell ruptures and desquamated. Haematoxylin stains the mucin blue. Mucicarmine and PAS stains the mucin red. Sequelae  On removal of the causative agent, epithelium lost is repaired by regeneration following stoppage of overproduction of mucin. Mucoid or myxomatous degeneration Mucoid is a glycoprotein similar to mucin in connective tissue found in foetus but not in adult tissue. Causes  Neoplasm of connective tissue e.g.Myxoma and myxosarcoma  Thyroid deficiency in human –myxoedema  Cachexia, starvation, parasitism or chronic disease Nithin.B. Page 60  General Veterinary Pathology 2016 VPP-211 Grossly, adipose tissue shows the change. Affected tissue is shrunken, flabby, flaccid in consistency and has translucent jelly-like appearance. Microscopically, degenerated tissue stains intensely blue with haematoxylin, nuclei are hyperchromatic and intercellular fluid takes slight bluish tinge. Sequelae  In cachexia, the fat becomes normal on correction of condition. Tumours indicate embryonal nature and it isunfavourable. Pseudomucin which resembles mucin degeneration is secreted by ovarian cystadenomas and parovarian cysts. Pseudomucin is not precipitated by acetic acid and stains pink with eosin whereas mucin is precipitated by aceticacid and stains blue with haematoxylin. Pseudomucin is not harmful and secretion of a normal cell. Hyaline degeneration (Hyaline change) (L.hyaline – glassy) It is the descriptive terminology of microscopical appearance. Affected tissue appears homogenous glassy and pink in H & E staining. It may be found in different conditions.  Keratohyaline  Cellular hyaline  Connective tissue hyaline Keratohyaline  It is normally found in stratum corneum. Pathological amounts of keratohyaline o Mechanical injury - e.g. saddles andharness o Papillomas in dogs and cats o Chlorinated naphthalene poisoning in cattle causes hyperkeratosis o Hypovitaminosis A –keratinisation of epithelium of digestive and upper respiratory tract  May be protective but the condition like corns may be very painful.  Removal of the cause results in desquamation of excessive keratohyaline and epithelium becomes normal. Cellular hyaline  The dead cells are kneaded together forming homogenous mass resembling sand; since it stains with iodine it is called corpora amylacea (Starch-like). They are commonly seen in prostate.They are observed in lungs in pneumonia, pulmonary infarction, mammary glands of cows which are dried off quickly, in brain as brain sand, in islets of Langerhans in diabetes and in renal nephritis as the renal tubular epithelium gets desquamated and forms hyaline cast with albumin. Nithin.B. Page 61  General Veterinary Pathology 2016 VPP-211 Connective tissue hyaline  This is found in old scars, degenerating stroma of tumours, lymph nodes in chronic inflammation and arteriosclerosis. This is permanent change persisting for life. Gout  This is mainly observed in birds in which the end product of protein metabolism is uric acid (insoluble inwater) and is produced in liver. Mammals are ureotelic organisms i.e. urea is the end product of protein metabolism which is water soluble.  The gout is defined as increase in the amount of deposition of uric acid and urates in tissue (viscera and joints).  There are two types of gouts o Visceral gout o Articular gout Causes It is mainly due to  Failure of urinary excretion of urates o Obstruction of ureters o Renal damage o Dehydration (common with water deprivation)  Hypovitaminosis A  Oosporin (mycotoxicosis)  Sodium bicarbonate treatment Hyperuricaemia is the result insodium bicarbonate toxicity. It is the sequel of alkalosis with protein breakdown. It is found only at necropsy. Visceral gout  The deposits of urates are found in kidney, serous surfaces of heart, mesentery, air sacs and peritoneum and in severe cases deposition are found in the synovial sheath, tendons, joints and muscular surfaces. It appears as white chalky coat.  Microscopically, urate crystals found in clusters which are pale elongated and needle shaped. It is surrounded by inflammatory cells like neutrophils, lymphocytes and foreign body giant cells and fibroblasts. On H & E section, it appears as clefts. Articular gout  It is a sporadic problem. Nithin.B. Page 62  General Veterinary Pathology 2016 VPP-211 Clinical signs  Leg shifting, lameness and inability to bend the toes are observed. Tophi are characteristics of articular gout which are deposition of urates around joints particularly of the feet. The joints are enlarged with deformed feet. Deposits are seen as white semifluid substance. GLYCOGEN STORAGE DISEASES (GLYCOGENOSES)  The cells may accumulate abnormal amount of glycogen in the cytoplasm. The cells are swollen with foamy cytoplasm. The condition is not common in animals. It may be associated with prolonged hyperglycaemia and there may be lack of enzymes that metabolize carbohydrates. It is a group of disease in which two forms are recognized in animals.  Type II or Pompe’s disease: There is deficiency of lysosomal α-glucosidase with accumulation of glycogen in the lysosome of brain, muscle and liver. This condition is seen in cattle, dogs, cats and sheep.  Type III or Cori-Forbes' disease: There is deficiency of amylo-1,6-glucosidase which converts glycogen to glucose. Hence, glycogen is stored in the cytoplasm of liver, heart, skeletal and smooth muscle and nerve cells. This condition is reported in dogs and cats.  Type Ia (von Gierke disease in humans): There is deficiency of glucose-6-phosphatase that catalyses hydrolysis of glucose-6-phosphate to glucose and phosphate. Affected pups show tremors, weakness and neurological signs due to hypoglycaemia and growth retardation and progressive hepatomegaly is found as they develop. Massively enlarged hepatocytes show vacuolations with aggregation of glycogen rosettes. GLYCOGEN OVERLOAD  It is excessive intracellular accumulation of glycogen with derangement in glucose or glycogen metabolism. The condition is not a significant entity in animals as compared to humans. Glycogen overload may be encountered in: o Neutrophils in inflammation o Fast growing neoplastic cells o Necrotic areas o Diabetes mellitus o Liver of young and growing animals o Well-fed animals  Grossly, changes are not usually detected, but pale enlarged liver is observed in steroid induced hepatopathy.  Microscopically, clear cytoplasmic vacuoles in the hepatocyte represent the glycogen. To demonstrate glycogen, sample should be collected immediately after death and tissue must be fixed in non-aqueous solution like alcohol to avoid loss of glycogen since the glycogen is water soluble and glycogen is converted to glucose after death. Glycogen stains red with PAS and Best’s carmine staining. MECHANISM OF HEPATIC LIPIDOSIS It is the accumulation of triglycerides or true fats and cholesterol in the cytoplasm of parenchymatous cells. Lipidosis is more common than other conditions.  Mobilization of free fatty acids from the gut (Chylomicrons) or adipose tissue Nithin.B. Page 63  General Veterinary Pathology 2016 VPP-211  Mitochondrial injury leading to decreases in β-oxidation of fatty acids to ketones etc. (Hypoxia, toxins)  Decreased apolipoprotein synthesis e.g. CCl4 poisoning and aflatoxicosis  Failure to form lipoproteins  Failure to release lipoproteins from hepatocytes o The last two conditions are uncommon.  Hepatic lipidosis can occur from one or more mechanisms. Fatty acid mobilisation from adipose tissue is common in animals following higher energy demand. Starvation increases triglyceride mobilisation. Protein malnutrition affects apolipoprotein synthesis. Chemicals like CCl 4 and yellow phosphorous can also induce hepatic steatosis.  Grossly , enlarged, pale to yellow, soft and friable liver is found in moderate to higher grade fatty changes. Enlarged with rounded borders. Upon incision, fat droplets are seen on the blades of knife. Tissue may float in the fixatives. Fatty liver - Chicken - Yellow  Microscopically, hepatocytes show vacuolations which may be small, clear to variable sized and may also form a single large vacuole, pushing the nucleus to a side. During the processing of fat tissue with xylol clearing, the fat will be dissolved by the xylol and gives vacuolated appearance in the Haematoxylin and eosin stained sections. To differentiate from hepatic degeneration, fluid and glycogen accumulation, cryostat sections are used to stain fat. Special stans for fats are sudan III, sudan black, scarlech red and Oil Red O. Oil Red O stains fat red and while it is PAS negative, sudan III and sudan black im