cellular injury & ageing

1Shashi Mar-03

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.

2Shashi Mar-03

Cellular Injury & Adaptation:

• Normal cell is in a steady state “Homeostasis”

• Change in Homeostasis due to stimuli - Injury

• Injury - Reversible / Irreversible

• Adaptation / cell death

3Shashi Mar-03

Response to Injury:

• Adaptations (reversible)– Hydropic degeneration– Hypertrophy– Hyperplasia– Atrophy– Accumulations - hyaline, fat, etc.

• Necrosis (irreversible) – cell death.

4Shashi Mar-03

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.

5Shashi Mar-03

Types of Necrosis:

• Coagulative – Eg. Infarction

• Liquifactive - Brain, abscess

• Caseous - Bacterial / Tuberculosis

• Gangrene - With infection

6Shashi Mar-03

Sequels of Necrosis:

• Cell Death

• Necrosis

• Autolysis

• Phagocytosis

• Organization & fibrous repair.

7Shashi Mar-03

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.

8Shashi Mar-03

Factors affecting Ageing:

• Genetic – Clock genes, (fibroblasts)

• Diet – malnutrition, obesity etc.

• Social conditions -

• Diseases – Atherosclerosis, diabetes etc.

• Werner’s syndrome.

9Shashi Mar-03

Cellular mechanisms of ageing

• Cross linking proteins & DNA.

• Accumulation of toxic by-products.

• Ageing genes.• Loss of repair

mechanism.• Free radicle injury• Telomerase shortening.

10Shashi Mar-03

Telomerase in ageing:

GermCells

SomaticCells

11Shashi Mar-03

Ageing –changes:

• 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.

12Shashi Mar-03

Pathology of elderly

13Shashi Mar-03

Factors affecting ageing:

• Stress• Infections• Diseases• Malnutrition• Accidents

• Diminished stress response.

• Diminished immune response.

• Good health.

14Shashi Mar-03

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

15Shashi Mar-03

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.

16Shashi Mar-03

Lewis Triple Response:

• FlushFlush:: capillary dilatation.

• FlareFlare:: arteriolar dilatation.

• WealWeal:: exudation, edema.

17Shashi Mar-03

Red, Warm & Swollen(Flare, Flush & Weal – Lewis)

Triple response

18Shashi Mar-03

Cardinal Signs of Inflammation

• RuborRubor : : Redness – Hyperaemia.

• CalorCalor : : Warm – Hyperaemia.

• DolorDolor : : Pain – Nerve, Chemical med.

• TumorTumor:: Swelling – Exudation

• LossLoss ofof FunctionFunction: :

19Shashi Mar-03

Inflammation - Mechanism

1. Vaso dilatation

2. Exudation - Edema

3. Emigration of cells

4. Chemotaxis

20Shashi Mar-03

Mechanism of Inflammation:

21Shashi Mar-03

22Shashi Mar-03

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.

23Shashi Mar-03

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.

24Shashi Mar-03

Inflammation Outcome

Acute Inflammation

Resolution

Chronic Inflammation

Abscess

SinusFistula

Fibrosis/Scar

Ulcer

Injury

FungusVirusCancersT.B. etc.

25Shashi Mar-03

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

• Neo-vascularisation

• No/less exudation• Prominent fibrosis

26Shashi Mar-03

Stages of Healing:

• Hemorrhage

• Inflammation

• Granulation tissue (soft callus)

• Scar – Fibrosis (hard callus)

• Remodeling & Wound strength

27Shashi Mar-03

Repair

• Regeneration of injured tissue by parenchymal cells of the same type

• Replacement by connective tissue

• In other words– Regeneration– Scar

28Shashi Mar-03

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

29Shashi Mar-03

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

30Shashi Mar-03

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

31Shashi Mar-03

Components of the processof 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

32Shashi Mar-03

Wound healing

• Induction of acute inflammatory response by an initial injury

• Parenchymal cell regeneration

• Migration and proliferation of parenchymal and connective tissue cells

33Shashi Mar-03

Wound healing (cont’d)

• Synthesis of ECM proteins

• Remodeling of parenchymal elements to restore tissue function

• Remodeling of connective tissue to achieve wound strength

34Shashi Mar-03

Healing byFirst Intention

Focal Disruption of Basement Membrane and loss of only a few

epithelial cellse.g. Surgical Incision

35Shashi Mar-03

Healing by Second Intention

Larger injury, abscess, infarction

Process is similar butResults in much larger

Scar and then CONTRACTION

36Shashi Mar-03

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)

37Shashi Mar-03

Factors affecting Healing:

SystemicSystemic

• Age

• Nutrition

• Vitamin def.

• Immune status

• Other diseases

LocalLocal

• Infection

• Size or extent.

• apposition

• Blood supply

• Mobility

• Foreign body

38Shashi Mar-03

Summary:

• 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

39Shashi Mar-03

Circulatory disorders:

• BV - Narrowing, rupture, aneurism.

• Thrombosis

• Embolism

• Venous congestion

• Edema

• Shock

40Shashi Mar-03

Thrombosis:• 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

41Shashi Mar-03

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

42Shashi Mar-03

Sequels of Block

• Collateral circulation:

• Ischemia,

• Infarction, Gangrene

• Haemorrhage

43Shashi Mar-03

Common Sites of B.V block:

44Shashi Mar-03

Edema & Shock….!

45Shashi Mar-03

Normal Microcirculation

Capillary Arterial VenousHydrostatic Pressure + 36 + 16Oncotic Pressure - 26 - 26Net filtration Pressure + 10 mmHg - 9 mm Hg

(leak-out) (Reabsorb)

46Shashi Mar-03

Edema:• Increased interstitial fluid volume

• Two major types

• Local - inflammation

• Generalised - anasarca - Systemic causes.

47Shashi Mar-03

Edema mechanism:• Leaky vessels – inflammation.

• Increased capillary hydrostatic pressure– Venous obstructions– Cardiac failure

• Decreased Osmotic pressure – Hypoproteinemia – liver disease, anemia.

• Lymphatic obstruction– Elephantiasis

48Shashi Mar-03

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.

49Shashi Mar-03

Shock Featurs:

• Hypotension

• Tachycardia

• Cold clammy skin

• Rapid shallow respiration.

• Drowsiness, confusion, irritability

• Multi organ failure.

50Shashi Mar-03

Shock Mechanisms:

• Compensatory mechanisms: – Adrenaline cold, clammy skin

• Complications: Ischemic damage.

51Shashi Mar-03

Shock Management:

• Position, clothing – vital organs….!

• Airway

• Stimulants – ammonia inhalation.

• Fluids, electrolytes, Blood pressure

• Treat the cause.

52Shashi Mar-03

Disorders of GrowthDisorders 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)

53Shashi Mar-03

New Cancer Statistics – USA 1996

Prostate 317,000 Breast 184,000 Lung 112,000 Colon-rectum 82,000 Lung 78,000 Colon-rectum 68,000

54Shashi Mar-03

Introduction:

• 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.

55Shashi Mar-03

Non-Neoplastic Proliferation:

*Controlled & Reversible• Hypertrophy – Size• Hyperplasia – Number• Metaplasia – Change• Dysplasia – Disordered

56Shashi Mar-03

Neoplastic Proliferation:

Uncontrolled & Irreversible*• Benign

– Localized, non-invasive.• Malignant (Cancer)

– Spreading, Invasive.

57Shashi Mar-03

Pathogenesis – Smoke - Lung Dis.

58Shashi Mar-03

Polyclonal Monoclonal

Normal Adaptation Benign

Malignant

Mechanism of Growth Disorders

59Shashi Mar-03

Nomenclature:

Cell of origin + Suffix

(Oma, Carcinoma & Sarcoma)

• Fibroma - Fibrosarcoma

• Osteoma - Osteosarcoma

• Adenoma - Adencarcinoma

• Papilloma - Squamous cell carcinoma

• Chondroma – Chondrosarcoma

60Shashi Mar-03

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

61Shashi Mar-03

Biology of Tumor

• Grading – Differentiation

• Staging – Progression

62Shashi Mar-03

TNM: Staging of tumor:

63Shashi Mar-03

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.

64Shashi Mar-03

Immune Disorders

• Humoral Immunity–B lymphocytes - Antibody

• Cell mediated Immunity–T lymphocytes – Macrophages

• Non-Specific immunity–Neutrophils, Macrophages

65Shashi Mar-03

Introduction:

• 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

66Shashi Mar-03

Immune Disorders:

• Immunodeficiency disorders–AIDS, antibody deficiency

• Hypersensitivity Disorders (allergy)–Type-I (IgE), II-IgG, III-

Immunecomplex, IV-Cell mediated.

• Autoimmune disorders–SLE, Rhematoid, Rheumatic fever.

67Shashi Mar-03

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.

68Shashi Mar-03

Morphology:• Acute Rheumatic Fever

– – Acute Inflammatory Phase– Heart – Pancarditis– Skin – Erythema Marginatum– CNS – Sydenham Chorea– Migratory polyarthritis

• Chronic Rheumatic Fever – Deforming fibrotic valvular

disease.

69Shashi Mar-03

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 < 1% • Increasing incidence …!

70Shashi Mar-03

Pathogenesis - Atopic Asthma:

71Shashi Mar-03

Asthma Mechanism:

• AllergyAllergy• Inflammation Of Inflammation Of

BronchiBronchi• ObstructionObstruction• Mucous PlugsMucous Plugs

72Shashi Mar-03

INFLAMMATIONINFLAMMATION

TRIGGERSExercise

Cold Air, diseases,

AirwayHyperresponsiveness

Genetic*

INDUCERSAllergens,pollutants

Airflow Limitation

73Shashi Mar-03

Asthma - Bronchial morphology

• inflammation • Eosinophils• Gland

hyperplasia• Mucous plug in

lumen• Hypertrophy of

muscle layer

74Shashi Mar-03

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.

75Shashi Mar-03

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.

76Shashi Mar-03

Introduction:

• Specific Immune System – Humoral– Cell medicated

• Non-Specific Immune System– Phagocytes– Complements

• Single or multiple component deficiency.• Susceptibility - Opportunistic infections.

77Shashi Mar-03

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.

78Shashi Mar-03

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…!

79Shashi Mar-03

Pathogenesis

80Shashi Mar-03

HIV

81Shashi Mar-03

Retrovirus Replication:

82Shashi Mar-03

Immune Response to HIV

83Shashi Mar-03

Genetic DisordersGenetic Disorders Congenital Disorders

• Non Genetic:– Developmental defects – Malformations

• Genetic Disorders– Chromosomal– Gene - Mendelian

• Multifactorial

84Shashi Mar-03

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

85Shashi Mar-03

Cell Cycle

86Shashi Mar-03

Mitosis

87Shashi Mar-03

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

88Shashi Mar-03

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,

89Shashi Mar-03

Non-disjunction:

90Shashi Mar-03

Downs Sy.

Trisomy-21

91Shashi Mar-03

Downs Syndrome:

• Mental retardation• Neck folds• Epicanthic folds• Flat facial profile• Simian crease• Hypotonia• Umbilical hernia• Leukemia

92Shashi Mar-03

Anatomy of Heart

93Shashi Mar-03

Circulation

94Shashi Mar-03

Coronary Arteries

95Shashi Mar-03

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

96Shashi Mar-03

Atherosclerosis:

“Chronic inflammatory disorder of intima of large blood vessels characterised by formation of

fibrofatty plaques called atheroma”.

Hardening of arteries - Arteriosclerosis

97Shashi Mar-03

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.

98Shashi Mar-03

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

99Shashi Mar-03

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.

100Shashi Mar-03

Common Sites:

• Aorta, Carotid & Iliac. (large vessels)

• Major Vessels - Heart, Brain & Kidney.

• Coronary

• Renal

• Abdominal

• Limbs

101Shashi Mar-03

Morphology:

• Fatty Dots

• Fatty Streaks

• Atheromatous – Soft Plaque

• Fibrofatty – Hard Plaque

• Complications– Ulceration, Rupture,Hemorrhage, Thrombosis– Atheroemboli or cholesterol emboli.

102Shashi Mar-03

Complications:

• Heart attack – Myocardial infarction.

• Stroke – Cerebral infarction

• Gangrene – tissue infarction.

• Kidney failure – Kidney infarction.

• Aneurysms

• Rupture

• Thromboembolism.

103Shashi Mar-03

104Shashi Mar-03

Hyperlipidemia:

• Hypercholesterolemia – Risk

• Hypertriglyceridemia - less significant

• LDLLDL – Increased risk

• HDLHDL – lowers the risk – Reverse transport– Mobilises the cholesterol from tissues to liver.

105Shashi Mar-03

Good Fats:

• Mono unsaturated fats

• Poly unsaturated fats

• Omega-3 fatty acids (Fish)

106Shashi Mar-03

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…?

Shashi Mar-03

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.

Shashi Mar-03

Patterns of CHD:• Angina Pectoris:

• Acute Myocardial Infarction:

• Sudden cardiac death:

Shashi Mar-03

Pathogenesis:

• Obstruction to blood flow.– Atheroma, Thrombosis Embolism

• Diminished coronary perfusion.

• Ischemia – Angina

• Infarction – Necrosis– Inflammation– Granulation tissue– Fibrous scarring.

Shashi Mar-03

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.

Shashi Mar-03

Gross - Morphology - Micro

• 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

Myocardial Infarction-MI

112Shashi Mar-03

Complications:

Cardiogenic shock, death Arrhythmias and conduction defects, Congestive heart failure (pul edema) Mural thrombosis, - embolization Myocardial wall rupture, tamponade Ventricular aneurysm

113Shashi Mar-03

Laboratory Diagnosis

• LDH - 1-5 (1 - 2 flip)

• CK- Isoenzymes (Fractions)– MM - Muscles– MB - Cardiac muscle.– BB - Brain

• Troponins

114Shashi Mar-03

Management:• Aimed to prevent complications.

1. Rest & sedation*

2. Supportive mesures

3. Thrombolytic agents - Streptokinase

115Shashi Mar-03

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

116Shashi Mar-03

RBC disorders (Anemias) :

““Anemia is decreased red cell mass Anemia is decreased red cell mass affecting tissue oxygenation”affecting tissue oxygenation”

* Low Hb <13.5 (males), <11.5 (females)* Low Hb <13.5 (males), <11.5 (females)

117Shashi Mar-03

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

118Shashi Mar-03

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

119Shashi Mar-03

Microcytic Anemia (IDA)

120Shashi Mar-03

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)

121Shashi Mar-03

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.

122Shashi Mar-03

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.

123Shashi Mar-03

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.

124Shashi Mar-03

Macrocytic Anemia (Meg.):

125Shashi Mar-03

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.

126Shashi Mar-03

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*

127Shashi Mar-03

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.

128Shashi Mar-03

Metabolic Disturbances

Inadequate Blood Flow

Circulatory Failure

Different kind of Reason

Special Clinical Syndrome

129Shashi Mar-03

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

130Shashi Mar-03

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;

131Shashi Mar-03

SHOCK

Pathophysiologic process of Shock by severity

⑴ Stage — Early reversible shock (compensated shock);Ⅰ ⑵ Stage — Late reversible shock (decompensated shock);Ⅱ ⑶ Stage — Refractory shock; Ⅲ

132Shashi Mar-03

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;

133Shashi Mar-03

Low blood flow

Skin,fat,skeletal

muscls,kidney,intestines

Heart,brain normal or


Redistribution of blood flow

134Shashi Mar-03

2. Changes of Microcirculation

⑴ Neurogenic mechanisms : carotid, aortic sympathetic NS, BP (50mmHg) CNS;

⑵ Cellular mechanisms: Polymorphonuclear leukocytes, ⑶ Humoral mechanisms: Noradrenaline and adrenaline;①

② Renin and angiotensin; ③ Vasopressin (posterior pituitary); ④ Histamine and serotonin; ⑤ Kinin; ⑥ Neuropeptides;


135Shashi Mar-03

136Shashi Mar-03

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;


137Shashi Mar-03

2. Stage of Vasodilation (Stagnant Anoxia)

Changing in the microcirculation : acidosis, histamine , endotoxin;

Clinical aspects: BP ↓, poor heart beat, unconscious, less to no urine, cynosis;

Blood in the liver, intestine, lung ↑; venous return ↓; shift of fluid, blood concentrated; BP↓; no urine;

SHOCK


138Shashi Mar-03

3. Stage of Vasofailure :

DIC

MOF septa

SHOCK


139Shashi Mar-03

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;

140Shashi Mar-03

141Shashi Mar-03

SHOCK

5. Effects on Gastrointestinal tract and Liver: peptic ulcer, acidosis and sepsis; 6. Effects on brain: restless, lassitude and coma;

Responses of specific organ systems of shock

142Shashi Mar-03

Skin system Pale of the skin, Cool and wet limbs

Kidney Oliguria;

Heart Weak and Fast Impulse; BP

Lung Rapid and Deep rest

Clinical manifestation of shock

143Shashi Mar-03

Monitoring of shock

1.Phsychologic 1.Phsychologic StatesStates

General monitoring

Heart rateBreathing

144Shashi Mar-03

Monitoring of shock

22 ．． Colour and Colour and temprature of skin temprature of skin

145Shashi Mar-03

Monitoring of shock

3 ． BP Systolic Pressure was

lower than 12kPa(90mmHg)

4. Urina

Oliguria

146Shashi Mar-03

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

Monitoring of shock

147Shashi Mar-03

SHOCK

Treatment of the shock

1.Emergency care;

2.Restore of the blood volume;

3.Correction of the acidosis;

4.Application of vasoactive drugs;

Fundamental principleFundamental principle

148Shashi Mar-03

1.Recognition of ventilatory insufficiency

2.Establishment of airway

3.Oxygenation and ventilation


Pulmonary dysfunction

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Establishment of Airway

150Shashi Mar-03


Other Emergency Care

151Shashi Mar-03

Treatment of the shockPosition of Body 30 。

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Keep the body worm

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Control the bleeding

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156Shashi Mar-03


Common Reason

1. Big vascular rupture

2. Organ rupture

3. Intestinal bleeding

4. Bone fracture

cellular injury & ageing

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