Transcript Shashi Mar-03 - lgh

Cellular Injury & Ageing
Disease
• Dis + Ease = Disease.
• “Discomfort due to Structural or functional
abnormality”
• Disease is caused by an agent.
• Causes (etiology) can be
– External / Environmental. E.g.. Heat, Bacteria.
– Internal E.g. stress, genes, ageing.
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Cellular Injury & Adaptation:
• Normal cell is in a steady state
“Homeostasis”
• Change in Homeostasis due to stimuli Injury
• Injury - Reversible / Irreversible
• Adaptation / cell death
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Response to Injury:
•
Adaptations (reversible)
–
–
–
–
–
•
Hydropic degeneration
Hypertrophy
Hyperplasia
Atrophy
Accumulations - hyaline, fat, etc.
Necrosis (irreversible) – cell death.
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Terminology:
• Necrosis: Morphologic changes seen in
dead cells within living tissue.
• Autolysis: Dissolution of dead cells by the
cells own digestive enzymes. (not seen)
• Apoptosis: Programmed cell death.
Physiological, for cell regulation.
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Types of Necrosis:
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•
•
•
Coagulative – Eg. Infarction
Liquifactive - Brain, abscess
Caseous - Bacterial / Tuberculosis
Gangrene - With infection
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Sequels of Necrosis:
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Cell Death
Necrosis
Autolysis
Phagocytosis
Organization & fibrous repair.
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Ageing:
“Progressive time related loss of structural
and functional capacity of cells leading to
death”
• Senescence, Senility, Senile changes.
• Ageing of a person is intimately related to
cellular ageing.
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Factors affecting Ageing:
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Genetic – Clock genes, (fibroblasts)
Diet – malnutrition, obesity etc.
Social conditions Diseases – Atherosclerosis, diabetes etc.
Werner’s syndrome.
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Cellular mechanisms of ageing
• Cross linking proteins &
DNA.
• Accumulation of toxic byproducts.
• Ageing genes.
• Loss of repair
mechanism.
• Free radicle injury
• Telomerase shortening.
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Telomerase in ageing:
Germ
Cells
Somatic
Cells
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Ageing –changes:
•
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Gradual atrophy of tissues and organs.
Dementia
Loss of skin elasticity
Greying and Loss of hair
BV damage – atherosclerosis/bruising.
Loss of Lens elasticity  opacity  vision
Lipofuscin pigment deposition – Brown
atrophy in vital organs.
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Pathology
of elderly
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Factors affecting ageing:
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Stress
Infections
Diseases
Malnutrition
Accidents
• Diminished stress
response.
• Diminished immune
response.
• Good health.
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Conclusions:
•
•
Cellular Injury - Various causes
Reversible Injury  Adaptations
– Hypertrophy, Hyperplasia, Atrophy
– Accumulations - Hydropic, hyaline, fat..
•
Irreversible Injury - Necrosis
– Coagulative, Liquifactive, Caseous
•
Ageing - Causes, Changes, Factors
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Inflammation
• “Inflame” – to set fire.
• Inflammation is “dynamic response of
vascularised tissue to injury.”
• Is a protective response.
• Serves to bring defense & healing
mechanisms to the site of injury.
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Lewis Triple Response:
• Flush: capillary dilatation.
• Flare: arteriolar dilatation.
• Weal: exudation, edema.
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Red, Warm & Swollen
(Flare, Flush & Weal – Lewis)
Triple response
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Cardinal Signs of Inflammation
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Rubor : Redness – Hyperaemia.
Calor : Warm – Hyperaemia.
Dolor : Pain – Nerve, Chemical med.
Tumor: Swelling – Exudation
Loss of Function:
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Inflammation - Mechanism
1. Vaso dilatation
2. Exudation - Edema
3. Emigration of cells
4. Chemotaxis
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Mechanism of Inflammation:
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Chemical Mediators:
• Chemical substances synthesised or
released which mediate the changes in
inflammation.
• Histamine by mast cells - vasodilatation.
• Prostaglandins – Cause pain & fever.
• Bradykinin - Causes pain.
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Morphologic types
• Acute:
– Exudative Inflammation: excess fluid. TB lung.
– Suppuration/Purulent – Bacterial - neutrophils
– Fibrinous – pneumonia – fibrin
– Serous – excess clear fluid – Heart, lung
– Haemorrhagic – b.v.damage - anthrax.
• Chronic inflammation: with healing.
– Grannulomatous – clusters of epitheloid* cells
eg. TB, Fungus, Foreign body.
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Inflammation Outcome
Fibrosis/Scar
Resolution
Injury
Acute
Inflammation
Chronic
Inflammation
Abscess
Fungus
Virus
Cancers
T.B. etc.
Ulcer
Fistula
Sinus
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Acute Vs Chronic
• Flush, Flare &
Weal
• Acute inflammatory
cells - Neutrophils
• Vascular damage
• More exudation
• Little or no fibrosis
• Little signs Fibrosis,
• Chronic
inflammatory cells
– Lymphocytes
• Neovascularisation
• No/less exudation
• Prominent fibrosis
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Stages of Healing:
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Hemorrhage
Inflammation
Granulation tissue (soft callus)
Scar – Fibrosis (hard callus)
Remodeling & Wound strength
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Repair
• Regeneration of injured tissue by
parenchymal cells of the same type
• Replacement by connective tissue
• In other words
– Regeneration
– Scar
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Proliferative Potential
• Labile cells - continuously dividing
– Epidermis, mucosal epithelium, GI tract
epithelium etc
• Stable cells - low level of replication
– Hepatocytes, renal tubular epithelium,
pancreatic acini
• Permanent cells - never divide
– Nerve cells, cardiac myocytes, skeletal mm
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Polypeptide growth factors
• Most Important Mediators affecting Cell
Growth
• Present in serum or produced locally
• Exert pleiotropic effects; proliferation, cell
migration, differentiation, tissue
remodeling
• Regulate growth of cells by controlling
expression of genes that regulate cell
proliferation
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Repair by connective tissue
• Occurs when repair by parenchymal
regeneration alone cannot be
accomplished
• Involves production of Granulation Tissue
• replacement of parenchymal cells with
proliferating fibroblasts and vascular
endothelial cells
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Components of the process
of fibrosis
• Angiogenesis - New vessels budding from
old
• Fibrosis, consisting of emigration and
proliferation of fibroblasts and deposition
of ECM
• Scar remodeling, tightly regulated by
proteases and protease inhibitors
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Wound healing
• Induction of acute inflammatory response
by an initial injury
• Parenchymal cell regeneration
• Migration and proliferation of parenchymal
and connective tissue cells
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Wound healing (cont’d)
• Synthesis of ECM proteins
• Remodeling of parenchymal elements to
restore tissue function
• Remodeling of connective tissue to
achieve wound strength
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Healing by
First Intention
Focal Disruption of
Basement Membrane
and loss of only a few
epithelial cells
e.g. Surgical Incision
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Healing by
Second Intention
Larger injury, abscess,
infarction
Process is similar but
Results in much larger
Scar and then
CONTRACTION
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Wound Strength
• After sutures are removed at one week,
wound strength is only 10% of unwounded
skin (Walker’ Law)
• By 3-4 months, wound strength is about
80% of unwounded skin (Walker’s Law)
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Factors affecting Healing:
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Systemic
Age
Nutrition
Vitamin def.
Immune status
Other diseases
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Local
Infection
Size or extent.
apposition
Blood supply
Mobility
Foreign body
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Summary:
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Healing – Proliferation & Differentiation.
Labile, Stabe & Permanent cells
Stages of Healing: 1-2-3-4….
Healing by First or Second intention.
Skin wound healing - bone healing.
Factors affecting healing – Local /
Systemic
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Circulatory disorders:
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BV - Narrowing, rupture, aneurism.
Thrombosis
Embolism
Venous congestion
Edema
Shock
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Thrombosis:
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Intravascular coagulation
Vessel damage - atheroma, toxins
Blood changes - stasis, *coagulation factors
Types: White, Red & Mixed.
Sites:
– Arterial: Brain, Heart, limbs, eys.
– Venous: Leg
– Capillary: DIC in septicemia
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Embolism:
• Abnormal solid mass carried in blood.
• Source – destination
• Types.
– Thromboembolism - atherosclerosis
– Fat - Fractures
– Tumor - cancers
– Gas – ‘Caisson disease’
– Liquid – Amniotic fluid in new born.
• Rapid onset of infarction –vs. Thrombosis
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Sequels of Block
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•
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Collateral circulation:
Ischemia,
Infarction, Gangrene
Haemorrhage
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Common Sites of B.V block:
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Edema & Shock….!
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Normal Microcirculation
Capillary
Arterial
Hydrostatic Pressure + 36
Oncotic Pressure
- 26
Net filtration Pressure + 10 mmHg
(leak-out)
Venous
+ 16
- 26
- 9 mm Hg
(Reabsorb)
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Edema:
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•
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•
Increased interstitial fluid volume
Two major types
Local - inflammation
Generalised - anasarca - Systemic
causes.
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Edema mechanism:
• Leaky vessels – inflammation.
• Increased capillary hydrostatic
pressure
– Venous obstructions
– Cardiac failure
• Decreased Osmotic pressure
– Hypoproteinemia – liver disease, anemia.
• Lymphatic obstruction
– Elephantiasis
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Shock:
• “Depressed vital functions due to
decreased circulating blood volume”
• Types:
– Hypovolaemic - true/vasovagal
– Cardiogenic – Heart failure, MI.
– Obstructive – Pulm embolism.
– Anaphylactic – vasodilation due to allergy.
– Septic – capillary damage by infection.
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Shock Featurs:
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Hypotension
Tachycardia
Cold clammy skin
Rapid shallow respiration.
Drowsiness, confusion, irritability
Multi organ failure.
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Shock Mechanisms:
• Compensatory mechanisms:
– Adrenaline  cold, clammy skin
• Complications: Ischemic damage.
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Shock Management:
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Position, clothing – vital organs….!
Airway
Stimulants – ammonia inhalation.
Fluids, electrolytes, Blood pressure
Treat the cause.
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Disorders of Growth
• Understand Growth disorders.
• Difference between Neoplastic & Non
neoplastic growths.
• Classification of growth disorders.
• Characters of tumors – Biology of tumors
• Diagnosis & management of tumors.
(Basic)
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New Cancer Statistics – USA
1996
Prostate
Breast
Lung
Colon-rectum
Lung
Colon-rectum
317,000
184,000
112,000
82,000
78,000
68,000
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Introduction:
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•
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Inflammatory, Degenerative & Neoplastic
Tumor – Swelling / new growth / mass
Two types of growth disorders:
Non-Neoplastic
– Secondary / adaptation due to other cause.
• Neoplastic.
– Primary growth abnormality.
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Non-Neoplastic Proliferation:
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•
•
•
*Controlled & Reversible
Hypertrophy – Size
Hyperplasia – Number
Metaplasia – Change
Dysplasia – Disordered
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Neoplastic Proliferation:
Uncontrolled & Irreversible*
• Benign
– Localized, non-invasive.
• Malignant (Cancer)
– Spreading, Invasive.
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Pathogenesis – Smoke - Lung Dis.
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Mechanism of Growth Disorders
Normal
Adaptation
Benign
Malignant
Polyclonal
Monoclonal
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Nomenclature:
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Cell of origin + Suffix
(Oma, Carcinoma & Sarcoma)
Fibroma - Fibrosarcoma
Osteoma - Osteosarcoma
Adenoma - Adencarcinoma
Papilloma - Squamous cell carcinoma
Chondroma – Chondrosarcoma
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Diagnosis:
• History of Clinical examination
• Radiographic analysis – X-Ray, US, CT,
MRI
• Laboratory analysis – Tumor markers
• Cytology –Pap smear, FNAB
• Biopsy - Histopathology, markers.
• Autopsy – Research, learning & teaching
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Biology of Tumor
• Grading – Differentiation
• Staging – Progression
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TNM: Staging of tumor:
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TNM: Staging of tumor:
• T1N1M0 – Means primary tumor is within
the organ but cancer cells have spread to
local lymphnodes, there is no metastasis.
• T3N0Mo - Means tumor has spread
beyond primary organ but has not spread
to lymphnodes or other sites.
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Immune Disorders
• Humoral Immunity
–B lymphocytes - Antibody
• Cell mediated Immunity
–T lymphocytes – Macrophages
• Non-Specific immunity
–Neutrophils, Macrophages
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Introduction:
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Immunity is not inherited.
Antigen / Antibody
Active / Passive immunity.
Vaccine, Toxoid, Live/Killed
Primary response – slow, weak.
–Learning period, memory cells.
• Secondary response – rapid,
strong
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Immune Disorders:
• Immunodeficiency disorders
–AIDS, antibody deficiency
• Hypersensitivity Disorders
(allergy)
–Type-I (IgE), II-IgG, IIIImmunecomplex, IV-Cell mediated.
• Autoimmune disorders
–SLE, Rhematoid, Rheumatic fever.
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Rheumatic fever:
• Autoimmune disorder.
• Group A, streptococcal pharyngitis.
• Antibody cross react with connective
tissue in - susceptible individuals*
• 2-3 weeks – Autoimmune reaction.
• Inflammation - T lymphocytes,
macrophages.
• Heart, skin, brain & joints.
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Morphology:
• Acute Rheumatic Fever
–
–
–
–
–
–
Acute Inflammatory Phase
Heart – Pancarditis
Skin – Erythema Marginatum
CNS – Sydenham Chorea
Migratory polyarthritis
• Chronic Rheumatic
Fever
– Deforming fibrotic valvular
disease.
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What is Asthma?
• Hypersensitivity – Allergy , Type I
• of airways of lungs - Bronchi
• Allergens – in the air, mast cell - IgE
ab.
• Inflammation of airways –
Bronchitis.
• Genetic, Environmental, Race, Age.
• High in industrial cities 4-19%, Fiji <
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1%
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Pathogenesis - Atopic Asthma:
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Asthma
Mechanism:
• Allergy
• Inflammation Of
Bronchi
• Obstruction
• Mucous Plugs
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INFLAMMATION
INDUCERS
Allergens,pollutants
Airway
Hyperresponsiveness
Genetic*
Airflow Limitation
TRIGGERS
Exercise
Cold Air, diseases,
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Asthma - Bronchial morphology
• inflammation
• Eosinophils
• Gland
hyperplasia
• Mucous plug in
lumen
• Hypertrophy of
muscle layer
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Autoimmune Disorders
• Immune response against self antigen
resulting in Tissue damage.
• Single organ or systemic multi organ.
• Common in females.
• Normally immune system is tolerant to self
antigens (learns during fetal development).
• Autoimmune disorders result from
Defective tolerance, cross reacting
antibodies or antigenic mimicry.
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Immunodeficiency
& AIDS
• Serious, persistent, unusual, recurrent
Opportunistic infections.
• Secondary causes more common.
• Antibody deficiency – Bacterial inf.
• Cell Mediated imm def. – viral / fungal
• AIDS – infection by HIV virus –
destruction of T helper cells –
deficiency of humoral & CM immunity.
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Introduction:
• Specific Immune System
– Humoral
– Cell medicated
• Non-Specific Immune System
– Phagocytes
– Complements
• Single or multiple component deficiency.
• Susceptibility - Opportunistic infections.
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Classification:
• Primary Deficiencies (Inherited)
– B cell defects – Ig def. Bacterial infections.
– T cell defects – T cells. – Viral & fungal infect.
– Combined defects – T & B
• Secondary Deficiencies –(Acquired) – T*
– Malnutrition – Protein
– Immunosuppressive therapy, drugs.
– Infections – viral, chronic bacterial, malaria.
– Chronic diseases – Diabetes*, Malignancy.
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History
• 1979 – Increased Kaposi sarcoma and
Pneumocystis carinii infections in
homosexuals noted in Africa.
• 1981 – First case in California.
• > 30 million in world – 1999 – increasing
• 0.01% incidence in Australasia
• 67% in Sub-Saharan Africa…!
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Pathogenesis
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HIV
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Retrovirus Replication:
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Immune Response to HIV
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Genetic Disorders
Congenital Disorders
• Non Genetic:
– Developmental defects – Malformations
• Genetic Disorders
– Chromosomal
– Gene - Mendelian
• Multifactorial
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Mutations:
• Genome: whole set – Polyploidy 4n, 8n
etc.
• Chromosomal: change in chromosome.
– Number: Trisomy, monosomy
– Structure: Deletion, Translocation etc.
• Gene: Submicroscopic.
– Point mutation – single base sequence
– Deletions – Insertions
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Cell
Cycle
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Mitosis
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Meiosis
• Reduction Division (4n-2n)
–
–
–
–
Prophase-1(Synapsis, g.rec)
Metaphase-1
Anaphase-1
Telophase-1
• Equatorial Division (2n-n)
–
–
–
–
Prophase-2
Metaphase-2
Anaphase-2
Telophase-2
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Cytogenetic Abnormalities:
• Abnormal number of chromosomes:
– Non-disjunction - Down’s Syndrome
– Anaphase lag - Turner’s xxx
• Abnormal Structure: (normal no)
– Deletion of short arm 5q- Cri-du-chat
syndrome
– Inversion – Translocation - Ph Chromosome - t(9:22)
CML,
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Non-disjunction:
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Downs
Sy.
Trisomy
-21
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Downs Syndrome:
•
•
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Mental retardation
Neck folds
Epicanthic folds
Flat facial profile
Simian crease
Hypotonia
Umbilical hernia
Leukemia
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Anatomy of Heart
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Circulation
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Coronary Arteries
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Major Disorders of CVS
•Atherosclerosis
•Hypertension
•Myocardial Infarction (MI)
•Stroke
•IHD - Ischemic Heart Disease
•VHD - Valvular Heart Disease
•RHD – Rheumatic Heart Disease
•CHD - Congenital Heart Disease
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Atherosclerosis:
“Chronic inflammatory disorder of
intima of large blood vessels
characterised by formation of
fibrofatty plaques called atheroma”.
Hardening of arteries - Arteriosclerosis
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Introduction:
•
•
•
•
•
Large elastic arteries – Starts in Intima
Fat deposits, Hardening and destruction.
Major cause of IHD, MI & Stroke.
Incidence is decreasing since 1995
Better understanding & Change in life
style.
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Risk Factors:
• Non modifiable
• Age – middle to late.
• Sex – Males,
complications
• Genetic - Hyperchol.
• Family history.
• Potentially Modifiable
• Hyperlipidemia –
HDL/LDL ratio.
• Hypertension.
• Smoking.
• Diabetes
• Life style, diet,
excercise
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Pathogenesis:
• Unknown etiology – Hyperlipidemia, life
style, hypertension, smoking, genetic etc.
• Starts with Initial intimal injury,
inflammation, necrosis, Lipid accumulation,
Fibrosis - Atheroma.
• Leads to Obstruction or destruction of
vessel
• Organ damage due to ischemia.
• Complications - Thrombosis, embolism,
aneurism, dissection & rupture.
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Common Sites:
•
•
•
•
•
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Aorta, Carotid & Iliac. (large vessels)
Major Vessels - Heart, Brain & Kidney.
Coronary
Renal
Abdominal
Limbs
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Morphology:
•
•
•
•
•
Fatty Dots
Fatty Streaks
Atheromatous – Soft Plaque
Fibrofatty – Hard Plaque
Complications
– Ulceration, Rupture,Hemorrhage, Thrombosis
– Atheroemboli or cholesterol emboli.
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Complications:
•
•
•
•
•
•
•
Heart attack – Myocardial infarction.
Stroke – Cerebral infarction
Gangrene – tissue infarction.
Kidney failure – Kidney infarction.
Aneurysms
Rupture
Thromboembolism.
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Hyperlipidemia:
•
•
•
•
Hypercholesterolemia – Risk
Hypertriglyceridemia - less significant
LDL – Increased risk
HDL – lowers the risk – Reverse transport
– Mobilises the cholesterol from tissues to liver.
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Good Fats:
• Mono unsaturated fats
• Poly unsaturated fats
• Omega-3 fatty acids (Fish)
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Lipoprotiens - LDL & HDL
• Good and Bad Fats?
• Lower LDL, Increase HDL
• Mono unsaturated fats
• Poly unsaturated fats
• Omega-3 fatty acids (Fish)
• LDL indicate Positive lipid
balance, HDL – negative.
• No Cholesterol in any
vegetable oil…?
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Ischaemic Heart Disease
•
•
•
•
•
Common Health problem.
High Mortality & Morbidity.
Etiology – common Atherosclerosis
Two major types Angina & MI.
Risk factors –
–
–
–
–
Hypertension
Hypercholesterolemia
Diabetes
Smoking, Life style, Diet, Genetic.
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Patterns of CHD:
• Angina Pectoris:
• Acute Myocardial Infarction:
• Sudden cardiac death:
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Pathogenesis:
• Obstruction to blood flow.
– Atheroma, Thrombosis Embolism
• Diminished coronary perfusion.
• Ischemia – Angina
• Infarction – Necrosis
– Inflammation
– Granulation tissue
– Fibrous scarring.
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Myocardial Infarction-MI
• “Death of heart tissue due to lack of blood
supply”
• Atherosclerosis is the common cause.
• Coagulative necrosis – intact cell shape.
• Severe chest pain, breathlessness &
sweating
• Complications –cardiogenic shock, Death or
Cardiac failure.
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Myocardial Infarction-MI
Gross - Morphology - Micro
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•
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•
•
1-18h – none
24h – Pale, edema
3-4D – Hemorrhage
1-3W – Thin, yellow
3-6W – Tough white
•
•
•
•
•
None
Edema, inflammation
Necrosis, granulation
Granulation tissue
Dense Fibrosis
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Complications:
 Cardiogenic shock, death
 Arrhythmias and conduction defects,
 Congestive heart failure (pul edema)
 Mural thrombosis, - embolization
 Myocardial wall rupture, tamponade
 Ventricular aneurysm
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Laboratory Diagnosis
• LDH - 1-5 (1 - 2 flip)
• CK- Isoenzymes (Fractions)
– MM - Muscles
– MB - Cardiac muscle.
– BB - Brain
• Troponins
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Management:
•
1.
2.
3.
Aimed to prevent complications.
Rest & sedation*
Supportive mesures
Thrombolytic agents - Streptokinase
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HEMATOLOGY:
RBC Disorders
C.B.C
• Haemoglobin - 15±2.5, 14 ±2.5 - g/dl
• PCV - 0.47 ±0.07, 0.42 ±0.05 - l/l (%)
– Haematocrit, effective RBC volume - better
• RBC count - 5.5 ±1, 4.8 ± 1 x1012/l
• MCHC - Hb/PCV - 30-36 - g/dl
– Hb synthesis within RBC
• MCH - Hb/RBC - 29.5 ± 2.5 pg/l
– Average Hb in RBC
• MCV - PCV/RBC 85 ± 8 - fl
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RBC disorders (Anemias) :
“Anemia is decreased red cell mass
affecting tissue oxygenation”
* Low Hb <13.5 (males), <11.5 (females)
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RBC disorders :
• Decreased Production:
– Aplastic, Hypoplastic anemias - drugs
– Deficiency anemias Iron, B12, Folate etc.
• Increased loss/destruction:
– Blood loss anemias - parasites, bleeding
– Hemolytic anemias – Immune,
mechanical, drugs & toxins.
– Congenital disorders – Sickle cell,
thalassemia
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Iron Deficiency Anemia:
• Most abundant metal, common
deficiency..!
• Limited absorption and no excretory mech.
• Recycling of iron – dead cells to new cells
• 1mg/day  3-6G body  1mg/day
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Microcytic Anemia (IDA)
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Iron Metabolism
• 10% of the 10 to 20 mg of dietary iron is
absorbed each day to balance the 1 to 2
mg daily loss.
• Iron is absorbed in Jejunum.
• Stored as Ferritin & Hemosiderin.
• Laboratory tests:
• Serum iron(1mg/l)
• Serum iron binding capacity (3mg)
• Serum ferritin (>20ug)
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Causes of Iron deficiency Anemia
1. Chronic Blood loss – parasites,
ulcers, hernia, drugs (NSAID),
Carcinoma, colitis, diverticulosis etc.
Rarely hematuria.
2. Increased need – Pregnancy, children
3. Malabsorption – gastrectomy, coeliac
disease.
4. Poor diet – Contributory but rarely the
sole cause.
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Clinical Features:
•
•
•
•
Anemia
Pallor, Weakness, Lethargy
Breathlessness on exertion
Palpitations may lead to heart failure edema
• IDA:
• Angular cheilosis, atrophic glossitis,
• dysphagia, koilonychia, gastric atrophy.
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Megaloblastic anemia:
• Vitamin B12/Folic acid deficiency
• Low DNA – less division – more cell
size
• Megaloblasts, Abnormal – destruction
– pan-cytopenia
• Multi System disease – All organs with
increased cell division.
• Macrocytic anemia, pancytopenia.
• Pernicious anaemia –
– autoimmune, Gastric atrophy, VitB12 def. 123
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Macrocytic Anemia (Meg.):
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Blood Loss anemias
• All have Polychromasia (Marrow
response)
• Acute blood loss
• Hemolytic anemias (+ Jaundice)
–Immune – Auto immune & Allo
immune
–Mechanical - Valve, DIC
–Hereditary – Sickle, Thalassemia
–Infection Clostridia, malaria.
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Hemolytic anemias
•
•
•
•
•
•
Laboratory evaluation
Blood smear – Morphology very important
CBC, Bilirubin levels
Direct and indirect Coombs test (antibody)
Hemoglobin electrophoresis – abnormal Hb.
Tests for parasites.
• Kidney & Liver function tests important*
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SHOCK
Introduction
Definition:
SHOCK is an acute circulatory failure, characterized
by dysfunction of the microcirculation , inadequate
blood flow to vital organs and inability of the body cell
mass to metabolize the nutrients normally.
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Different kind of Reason
Inadequate Blood Flow
Circulatory Failure
Metabolic Disturbances
Special Clinical Syndrome
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SHOCK
Etiology and Classification of Shock
1. Classification of Shock by Causes
(1) Hypovolemic shock
Hemorrhagic shock
Traumatic shock
(2) Cardiogenic shock
(3) Neurogenic shock
(4) Anaphylactic shock
(5) Infectious shock
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2. Classification of Shock according to hemodynamic
changes:
⑴Hypodynamic Shock:
Cardiac Output ,
Vascular Resistace,
Cold Skin;
⑵ Hyperdynamic Shock: Cardiac Output ,
Vascular Resistace ,
Worm Skin;
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SHOCK
Pathophysiologic process of Shock by severity
⑴ Stage Ⅰ— Early reversible shock (compensated shock);
⑵ Stage Ⅱ — Late reversible shock (decompensated shock);
⑶ Stage Ⅲ — Refractory shock;
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SHOCK
Systemic pathophysiologic responces of Shock
1. Initial changes of shock
⑴ Reduction of blood volume: volume and rate;
⑵ Decrease in myocardial contractility: infarction;
⑶ Increased vascular-bed volume;
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Systemic pathophysiologic responces of Shock
Redistribution of blood flow
Low blood flow
Skin,fat,skeletal
muscls,kidney,intestines
Heart,brain
normal or
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Systemic pathophysiologic responces of Shock
2. Changes of Microcirculation
⑴ Neurogenic mechanisms : carotid, aortic sympathetic NS,
BP (50mmHg)  CNS;
⑵ Cellular mechanisms: Polymorphonuclear leukocytes,
⑶ Humoral mechanisms: ① Noradrenaline and adrenaline;
② Renin and angiotensin;
③ Vasopressin (posterior pituitary);
④ Histamine and serotonin;
⑤ Kinin;
⑥ Neuropeptides;
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SHOCK
Systemic pathophysiologic responces of Shock
1. Stage of Vasoconstriction (Ischemic Anoxia)
 Changing in the microcirculation : catecholamine ;
 Maintenance of blood pressure, shift of fluid, redistribution of
of blood supply, conservation of sodium and water;
 Clinical aspects: pale, cool limbs, clammy skin,
fast and weak impulse, decreased urine output, BP n;
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SHOCK
Systemic pathophysiologic responces of Shock
2. Stage of Vasodilation (Stagnant Anoxia)
 Changing in the microcirculation : acidosis, histamine ,
endotoxin;
 Blood in the liver, intestine, lung ↑; venous return ↓;
shift of fluid, blood concentrated; BP↓; no urine;
 Clinical aspects: BP ↓, poor heart beat, unconscious,
less to no urine, cynosis;
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SHOCK
Systemic pathophysiologic responces of Shock
3. Stage of Vasofailure :
 DIC
 MOF septa
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SHOCK
Responses of specific organ systems of shock
1. Disturbance of cell metabolism :
a. Hypoxia, anaerobic metabolism ↑;
b. Disturbance of Na+-Ka+ pump, cell swelling ;
c. Local acidosis; ↓
2. Effects on kidneys : (shock kidney), oliguria , hyperkalemia,
acidosis;
a. Functional renal failure;
b. Parenchymal renal failure;
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SHOCK
Responses of specific organ systems of shock
5. Effects on Gastrointestinal tract and Liver: peptic ulcer,
acidosis and sepsis;
6. Effects on brain: restless, lassitude and coma;
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Clinical manifestation of shock
Skin system
Pale of the skin,
Cool and wet limbs
Kidney
Oliguria;
Heart
Weak and Fast Impulse;
BP
Lung
Rapid and Deep rest
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Monitoring of shock
1.Phsychologic
States
General monitoring
Heart rate
Breathing
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Monitoring of shock
2．Colour and temprature
of skin
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Monitoring of shock
3．BP
Systolic Pressure was
lower than 12kPa(90mmHg)
4. Urina
Oliguria
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Monitoring of shock
Special monitoring
1.CVP
5-10cmH2O
CVP<5cmH2O
Inadequecy of blood volume
CVP>12cmH2O
Cardiac dysfunction
2.Lung arterial pressure
3.Cardiac output
4.Blood gas
PO2 75-100mmHg
Pco2 40mmHg
PH 7.35—7.45
5.Coagulation test
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SHOCK
Treatment of the shock
Fundamental principle
1.Emergency care;
2.Restore of the blood volume;
3.Correction of the acidosis;
4.Application of vasoactive drugs;
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Treatment of the shock
Pulmonary dysfunction
1.Recognition of ventilatory insufficiency
2.Establishment of airway
3.Oxygenation and ventilation
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Treatment of the shock
Establishment of Airway
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Treatment of the shock
Other Emergency Care
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Treatment of the shock
Position of Body
30。
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Treatment of the shock
Keep the body worm
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Treatment of the shock
Control the bleeding
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Treatment of the shock
Common Reason
1. Big vascular rupture
2. Organ rupture
3. Intestinal bleeding
4. Bone fracture
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