Exam 3 Pathophysiology

Acute inflammation leads to

chronic inflammation

Stages of acute inflammation

1. Vasoconstriction

2. Exudate formation

3. Vasodilation (leads to resolution and healing)

Exudate (2nd stage of acute inflammation)

• serous (burn) “watery”, decrease protein content, decrease cells

• fibrinous= fibrin, clotting

• purulent= pus, WBC invasion (neutrophils)

• hemorrhagic= extravascular RBC

Function of exudates

• dilute toxins and dilute cellular debris

  • carried away through the lymph

  • deliver plasma proteins, WBC

3 components of acute inflammation

1. Mast cell degranulation

2. Plasma system

3. Cellular components

Mast cell (basophil) is degranulated by

• complement

• physical injury

• chemical injury

What does the mast cell release after degranulation

• Heparin

• Histamine (H1, H2, H3, H4)

• Leukotrienes

• Prostaglandin E

H1 (histamine)

• allergic responses

• alter vascular system

• form exudate

• caused WBC to come (neutrophils)→ neutrophil chemotaxis

H2 (histamine)

• gastric lining

• immune system→ temper reactions

H3 (histamine)

neurotransmission

H4 (histamine)

• immunomodulation

• chemotaxis

H1 and H2 system

1. vasoconstrict (increase resistance)

2. WBC ICAM

3. Diapedesis: WBC squeeze between cells to get into tissue

4. Squeeze through epithelium and form exudates in tissue

• H1: vasoconstricted, contracted epithelium, neutrophil chemotaxis

• H2: few, decrease other mast cell degranulation, suppress other WBC 

Leukotrine

same as histamine but longer half life (use lipo-oxygenase)

• pain potentiates

Prostaglandin E (PGE)

use cyclo-oxygenase

• potentiate pain

(-) FB mast cell degranulation

1. vasoconstrict

2. back pressure: push fluid out and form exudate

Other factors involved with mast cell degranulation

• neutrophils chemotactic factor

• eosinophils chemotactic factor

  • major basic protein break down roundworm cuticle

Plasma clotting system includes

clot, anti-clot, complement, kallikrein system

Extrinsic plasma activating system

lipoprotein, thromboplastin

Intrinsic plasma activating system

initiated by Hageman Factor a

Plasma activating system steps

1. Extrinsic activator: lipoprotein, thromboplastin

or

2. Intrinsic activator: Hageman Factor a

3. Activates Stuart Factor

4. Stuart factor activates prothrombin to thrombin enzyme

5. The thrombin enzyme makes fibrinogen into fibrin a

Brick and cement

brick- platelets

fibrin- cement

Platelets release

thromboxane and serotonin (vasoconstrictors)

Plasmin ——> plasminogen

TPA- tissue plasminogen activator

1. Other pathways to activate plasmin are

   1. Hageman factor

   2. thrombin

   3. Kallikrein

What activates complement

1. Plasmin

2. Hageman factor

3. Kallikrein

Functions of complement

• activate mast cell

• increase vascular permeability

• endothelium contraction

• chemotactic

Stuart factor- antithrombin 3

when heparin binds, it is irreversible and shuts down the clotting cascade

Cell components 

• macrophage (antigen present)

• granulocytes

  • neutrophils

  • eosinophils

  • basophils

Neutrophils

• O2 radical

• H2O2

• Interaction with Cl-: make hypoxy-cholride and hydrolytic enzymes

Eosinophils

• janitors

• clean up after immunologic problems

• get rid of roundworms

Basophils

• mast cells

• acute inflammation

Hematopoietic pulri-potential stem cell

erythropoetin→ erythrocyte

• red marrow= flat bone (cranium, rib, hip)

• white marrow= fat

PP stem cell lymphoid cell

1. Thymus T-cells → cell mediated

2. Bursa equivalent→ B-cell/plasma cells (Humoral Immunity)

PP stem cell non-lymphoid

1. RBC- erythrocyte

2. Megakaryocytes

3. Monocytes → macrophages

4. Granulocytes

Reticular dysgenesis

(block) cannot make blood cells

• blocks right at HPP SC

Reticular dysgenesis SCIDS (severe combined immuno deficient syndrome)

• Bare lymphocytes

• Wiscott-Aldrich (x-linked)

Blocks after lymphoid cell line

Reticular dysgenesis that blocks after thymus

• DiGeorge’s

• Nezlof’s 

Reticular dysgenesis that stops cell mediated immunity

chronic mucocutaneous candidas

Reticular dysgenesis that stops the bursa equivalent

Hypogammaglobulinemia 

• Burton’s (X-linked)

• Transient (2-4, late bloomer)

Reticular dysgenesis that stops humoral immunity

Hypogammaglobulinemia

• Common variable (IgM, IgG, IgD, IgA)

  • Selective IgA deficiency 

Non-lymphoid line Neutropenia

• decrease in 2 weeks for process

• turnover

• bacterial infection

• autoimmunity

• complement

Chronic Granulomatous Disease

• cannot make O2 radicals (disarms neutrophils)

• Job’s syndrome (neutrophils cannot undergo chemotaxis)

Non-lymphoid line

Eosinopenia

1. Allergic response: act hypersensitivity I

2. Parasitic infection

Basophils→ mast cells→ cause inflammation 

Monocytes→ macrophages

1. Aplastic anemia

2. Hairy cells

3. Myelocytic anemias

Infectious mononucleosis (mono) 

self-limiting, Epstein Barr virus

• B-cells surface protein→ lymphoid tissue (tonsil) and lymph nodes 

• IgM and IgG

• Transform B-cells with virus: react, stimulate cytotoxic T-cells and T-suppressors

  • Proliferate→ lymph node swelling and liver/spleen swelling (hepatosplenomegaly)

Leukemia

• increase WBC→ increase viscosity of blood→ cardiac workload

• Leukopenia, panleukopenia (red and white blood cell is pancytopenia), crowd out other normal blast cells

• Megakaryocyte→ platelets (crowd out, decrease platelets, thrombopenia)

• Leukemia→ lysis, hyperkalemia

Acute leukemia lymphocytic/genous

• pre-B, pre-T cells

• 2-4 in young children (80% of cancers); brain infiltrated

Acute leukemia myelocytic/genous

• common secondary cancer

• chromosomal disorders (Down’s, Kleinfelter’s, Turner’s)

Chronic leukemia lymphocytic/genous

• 50 yo or older

• degree of anaplasia

• B-cell typical cell lines 

  • if convert to hairy cells- severe malignancy, very spiculated

Chronic leukemia myelocytic/genous

• 30-50 yo

• translocation of chromosome 22 to 9

• proto-oncogene 22→ 9

• Philadelphia chromosome: inappropriately move during mitosis 

Multiple myeloma

• transformed plasma cells= cancerous 

• increase production of IgA and IgG

  • aby fragments= Bence Tone proteins (increase PP, BO, reabsorption, blood volume, BP)

• Il-6: increase cell division of plasma cells→ crowd out and replace RBC lineage (cause anemia)

• Il-13: activate osteoclasts

  • Cranium: golf-ball with divots

  • Erode flat bone: hip fracture

Hodgkin’s Lymphoma

• Reed-Sternberg cells

• multi-nucleated monocytes 

• originate in single node and passed through node chain

• supra-diaphragmatic nodes 

Non-Hodgkin’s Lymphoma

• without Reed Sternberg cells

• originate in any lymph nodes

• associated with retro virus (RNA): Epstein Barr, HIV, Human T-lymphocyte

• low grade= well differentiated

• high grade= less differentiated (more cancerous)

Rhinovirus

• ICAM-1

• mucous membrane

• nasal and pharyngeal passages

• release interferons (IL) chemotactic and call in immune cells (eosinophils, T-cells, neutrophils, macrophages)

Influenza

• Neurimidase: cleave sialic acid→ break apart mucus and get into cell

• Hemaglutin: binds to sialic acid→ cell surface

• M-protein: uncoat virus

• 3 Types

  • A: epidemic and pandemic

  • B: epidemic, no pandemic (only humans)

  • C: neither epidemic or pandemic

Multiple mutations of the flu virus are required to

jump from species to species

Influenza affects

• all organs, lung is the most affected

• Inflammation in respiratory tract  (increase mucus)

• can progress to pneumonia 

Corona virus 

• retro-virus, RNA, reverse transcriptase

• outer coat M protein and spike protein

  • lung, heart, kidney, ACE

• Use up T-cells→ lymphopenia

• interleukin storms→ TL6 and TL8: increase chemotaxis of neutrophils and T-cells

• CD4 and CD8 exhaustion 

Legionella pneumophilia

• infect→ amoeboid cells propagate

• AC of large buildings

• spread when breathed in

• infect alveolar macrophages (amoeboid cell)→ survive, divide, and release

Mycobacterium Tuberculosis (TB)

• mycolic acid: survive alveolar macrophage and divide in the lung

• Ghonfocus is the primary infection and goes into the blood stream

  • hi O2, hi metabolism

  • kidney

  • retina

  • brain

  • Simon focus: secondary infection

  • caseous necrosis 

Not complaint with TB meds leads to 

antibiotic strain

Histoplasmosis capsulatam

• fungal spores (bird and bat feces)

• picked up by wind and breathed in

• environment (when dried): mycelium forum 

• body temp→ free cellular yeast phase

  • go to macs and survive and get released to lymph nodes

Pneumonia

• red hepatization→ infiltrate with WBC→ grey hepatization

• congesting capillaries with RBC

  • extravascular; fill alveolar spaces

• lobes→ lobules→ alveolar sacs

• lobar, broncho (bedridden), interstitial

Cystic fibrosis

• mutation in the CFTR gene (in GI tract)

• Columnar pseudostratified squamous epithelium

• airway=conducting system

• cAMP activates

  • Cl- 

  • Na+

  • H2O 

CFTR in GI tracts

1. cAMP Cl- out and in

2. HCO3-

• Neutralize gastric acid for enzymatic function in GI tract

• pancreatic duct, biliary duct system, small intestinal lining

CF in airways

• increase resistance to airflow

• mucus plug, increase resistance

• airway walls thicken

• prone to bacterial infections; induces inflammation

CF organs

• Lungs: increase airway resistance, thick viscous mucus, bacterial infect

• Pancreas: decrease HCO3-, cannot buffer GI tract→ enzymes

  • polymers→ monomers

  • Diarrhea (osmotic disease)

• Liver: thick and viscous mucus, block areas

Obstruct biliary ducts (scar): biliary duct cirrhosis

Backup enzymes: pancreatitis→ DM

Respiratory distress syndrome

• Type 1 pneumocytes: promote gas exchange

• Type 2: surfactant 

• Lungs partially collapse because of no type 2 pneumocytes

• Surface tension: 60 mmHg

RDS adult

• Pneumonia, aspiration gastric contents, near drowning, pulmonary edema (lung transplant, heart failure, PE)

RDS infant (premature infants)

• deficient in surfactant (increase in surface tension, lungs are very elastic)

• decrease in compliance= moves

• Suvanta: surfactant from cow lungs so they can develop their own

Pneumothorax 

• 1 way valve, increase air in space

• Tension pneumo= positive pressure

  • mediastinal shift hi→ lo

• Visceral and parietal pleura

Visceral pleura pneumothorax

closed pneumothorax, bleb (weaken visceral pleura and pop)

Parietal pleura pneumothorax

open pneumothorax, open chest wound

EKG lead 2

• 60 degree axis, heart is at a 59 degree axis

• isolate lead 2 to check for heart movement

Extrinsic asthma

• atopic, alllergic→ IgE mediated by mast cells

• eosinophilic chemotactic factor

  • major basic proteins (damage airways)

• inflammation causes bronchoconstriction/asthma, very destructive

Intrinsic asthma

• non-atopic/non-allergic

• (-) skin test, normal IgE levels

• irritant or irritating stimulant 

• hyper-reaction (decrease threshold, stimulating parasympathetic vagal response)

• causes bronchoconstriction

COPD vital capacity

FEV1, sec 80%

Obstructive disorder spirometry

FEV1, sec decreased

FVC normal

Restrictive disorder spirometry

FEV1, sec decreased

FVC decreased

Chronic bronchitis

• chronic inflammation, forms mucus plugs

• increase resistance, thicken walls and increased mucus

• hyperplasia/hypertrophy

• trapped air in lung (increased CO2 and decreased O2)→ vasoconstrict

• decreased O2=hypoxic (blue bloater)

Chronic bronchitis heart

• Right heart is weaker→ right heart failure= Cor Pulmonale 

• increase resistance= back pressure from the lung all the way down to the IVC and the liver

  • causes liver HTN, increased BH, and edema (ascites)

Emphysema (pink puffer)

• alpha antitrypsin (from liver)→ goes into blood

• trypsin protease→ anti trypsin is inhibitor of protease

• decrease surface area: decrease systemic O2 and increase CO2= vasodilate (pink appearance)

• Inhale= expand, exhale= collapse

• puff/purse lips, hyperventilate (thin because use so much metabolic energy)

Panlobar emphysema (mutation)

• non-smokers, genetic

• mutated alpha-antitrypsin

• collapses airways

Central lobar emphysema

• smokers

• inflammation, recruit neutrophils (release proteases)

• central lobar empty spaces

Restrictive disorders

• chest wall

• kypophysis 

Anterior pituitary gland (adeno)

• endocrine, endoderm

• Gi tract, lungs, glands

Hypothalamus

• GH-RH- somatotrope GH

• Thyrotropic RH- thyrotrope TSH

• Corticotropic RH- corticotrope ACTH
  

Adenoma (benign cancer)

• can crush the cells- resolved by hormone replacement therapy

• panhypopituarism: not going to get the RH

Achondroplasia

decrease in somatostatin, decrease in GH-RH

Anterior pituitary gland somatotrope

1. GH to the liver

   1. induces hyperglycemia

   2. glyconeolysis glycogen→ glucose

   3. gluconeogensis→ makes glucose 

2. somatomedin comes out of the liver for bone growth

Puberty

1. Gigantism

2. Acromegaly 

   1. 30 yo→ diagnosed 40 yo

   2. increase protein synthesis, enlarged organs

   3. GH→ hyperglycemic state (burns out the beta cells)

   4. Beta cell→ insulin  (type I diabetes)

   5. Thickening of irregular bones (facial and vertebral stenosis)

   6. Short bones hands and feet

GH deficiency child onset

• congenital

• idiopathic

• genetic

• embryonic defect

GH deficiency adult onset

• head trauma

• tumors

GH excessive

1. Adenoma of somatotropes

   1. increase GH

2. Extrapituitary GH

   1. ex. pancreatic cancer- Isles of Langerhan

   2. lymphoma (increase GH)

3. Increase GH-RH- cancer