Introduction to Pathophysiology

Physical constants of homeostasis

Physical constants of homeostasis

temp + atmospheric pressure

chemical constants of homeostasis

O2,H20,nutrients

idiopathic

exact cause of disease not identified

nozocomial

diseases due to hospital conditions

sequela

complication during/after illness, from illness or treatment

primary, secondary and tertiary prophylaxes

primary - prevent of risks secondary - prevention of disease worsening tertiary - prevents of complications of disease

Evolution of disease

etiology (cause) - pathogenesis - cell abnormalities - symptoms

predominantly endogenous etiological factor

diseases caused by the alteration of the genome, but which only manifest under certain environmental conditions

ionizing radiation has effects on

DNA - cell death, teratogenesis, carcinogenesis

Marasmus vs. Kwashiorkor

Marasmus-low in both calories and protein Kwashiorkor-severe protein deficiency

Hypoxia vs anoxia

Hypoxia- Low Oxygen. Anoxia- No Oxygen.

Evolution of cell death

reversible injury - irreversible - necrosis or apoptosis

stress response involes activation of _______ or __________ or ________

heat shock proteins (Hsp) or stress proteins or chaperone proteins

ATP depletion (cell mechanism)

in hypoxia or chem aggression, leads to reduction of membrane pump activity (- lysis) + protein synthesis, alterations in energy metabolism, Ca2+ accumulation

Mitochondrial affection (cell mechanism)

in excess Ca2+ and Reactive O2 Species (ROS), protein apoptosis in intermembrane space + cytochrome C release creates intrinsic pathway apoptosis

Calcium influx + loss of calcium homeostasis (cell mechanism)

in ischemia, causes affection of membrane + its proteins, DNA damage, depletion of ATP

Oxidative stress (cell mechanism)

free radicals - chem unstable, in patho + physio conditions, causes

when is ROS produced

• leukocytes activated in inflammation

• enzymatic metabolism of exo. chemicals

• transition metals

ROS removal is due to

antioxidants (liposoluble vitamins + Fe + Cu, enzymes that decompose H202 and 02)

Patho effects of ROS

• perioxidation of membrane lipids (- lesions)

• oxidative changes of proteins (misfolding)

• DNA loss + oxidation

• triggers cell death

Defects in plasma membrane permeability (cell mechanism)

• ROS

• decreased membrane phospholipid synthesis

• cytoskeletal abnormalities

• mitochondrial + + lysosome + cell membrane damage

DNA and protein affection (cell mechanism)

if lesions are too severe causes apoptosis - death receptors, cytochrom c, caspases

disease associated w/ decreased apoptosis and increased cellular growth

cancer, autoimmune diseases

diseases associated w/ increased apoptosis and low cellular survival

neurodegenerative, myocardial infarction, destruction of viral infected cells

2 phenomena that characterize irreversible cell injury

• inability to correct mitochondrial dysfunction to make ATP + ox phospho

• deep plasma/lysosomal membrane alterations

Cell biomarkers in cardiac muscle fibers

Creatine Kinase + Troponin contractile protein

Cell biomarkers in hepatocytes

transaminases, Alkaline phosphatase

In ______, anaerobic glycolysis is still possible

hypoxia

In ischemia, anaerobic glycolysis is inhibited by

depletion of glucose sources or accumulation of toxins

reperfusion

reestablishment of blood flow, rescues ischemic cells

free radicals after ischemia + reperfusion injuries are made by

parenchymal, endothelial cells and leukocytes

activation of complement system is important for

immune defense + ischemic tissue

big amounts of cytokines are produced + adhesion molecules recruit neutrophils at _____________

reperfusion tissue

which organ is most affected by toxic chemical lesions

liver

direct cytopathogenic effect

cyanides affect mitochondria, mercuric chloride affects proteins, antibiotics, antineoplastic drugs

effects of toxic active metabolites

in ROS formation, lipid peroxidation, P450 cytochrome in ER of liver, CCl4, acetaminophen

Circadian variation rate is lower in _______ and higher in ______--

morning (3am), evening (18pm)

Thermoregulation is regulated by

neuro-endocrine feedback control mechanisms

Internal temperature is a balance between

thermogenesis and thermolis

poikilothermic vs homeothermic organisms

poiki - body temp close to envir homoeothermic - body temp constant

how does calorie consumption affect thermoregulation?

increases body temp

High temperatures in ______ or _______, low temperatures in __________, ____________ or _____________

viscera or skeletal muscles upper face skin, extremities, airways

neuro-humoral control mechanisms and self-regulation affect

thermoregulation

Thermogenesis

heat production during redox rxns

main sources of energy for thermogenesis

redox reactions and activity of internal organs

internal organ thermogenesis is controlled by hormonal mechanisms that stimulates

catabolism by VNS (rapid adaptation) and thyroid (slow adaptation)

Most of energy from thermogenesis is from?

skeletal muscle effort

Voluntary muscle contraction is _______ movements, involuntary muscle contraction is __________

warming, shivering (muscle rigidity)

Conduction

exchange of heat bw body and enviro from direct contact w/ enviro

Convection

permanently changing warm air from direct contact with skin

the higher the ___________ the higher the thermolysis

air velocity

Irradiation

main way of losing body heat, human body absorbs caloric radiations from heated body

Losses are performed according to

the thermal transfer gradient and the body surface area

nervous reflex

1. thermo receptors

2. afferent nerve pathways

3. nerve reflex center

4. efferent somatic, vegetative + endocrine nerve pathways

5. effectors

Types of afferent pathways

• somatic specific afferent nerve pathway

• nonspecific pathways

• afferent vegetative

Anterior HTH

thermolysis center, activated by increased blood temp

Posterior HTH

thermogenesis center, activated by low blood temp

vegetative pathway in relation to thermoregulation

vns modulation + thermolysis

somatic effectors of thermoregulation

skeletal muscles + sweat glands

visceral effectors of thermoregulation

blood vessels from skin or organs

___________ increase base metabolism and glucocorticoids by catabolic effects

thyroid hormones (effector of thermoregulation)

Piloerection

reduces heat loss to the surface of the skin

Hypothermia

Decreased central body temperature at or below 35°C

risk factors for hypothermia

extreme age, alcoholics, mental diseases, neuroleptic meds, sleeping disorders

Hypothermia - what happens if inadequate thermogenesis?

decreased cell metabolism, alteration in thermoregulation, toxins (drug-induced)

endogenic hypothermia

defect in thermoregulation (tumors, hypoglycemia, drugs, no chills)

Pathogenesis of hypothermia comprises three evolutionary phases:

1. excitation

2. inhibition or exhaustion

3. criticism or paralysis

Phase of excitation of hypothermia

in mild hypothermia (32-35), inhibited thermolysis, vasoconstriction (more O2 consumption)

Phase of inhibition or exhaustion of hypothermia

in moderate hypothermia (28-32), less movements, muscles rigid, resp. depression, less CNS activity , no consciousness

Critical or paralytic phase of hypothermia

in severe hypothermia (<28), fixed mydriasis, ventricular issues, apnea

Cold effects on cells

cell + vessel lesions from crystals, hydroelectrolitic eq changes, microthrombi

lesions that occur if reheating is done too suddenly are similar to those of

ischemia and reperfusion

which types of hypothermia are active?

moderate and severe

severe hypothermia causes

cardio-respiratory arrest

grade I frostbite

pallor + loss of sensitivity, pain after reheating

grade II frostbite

after 12-24hrs of exposure, healing w/ postvesicular scars

grade III frostbite

after days/weeks of exposure, necrosis, heals w/ sequelae

Hyperthermia

increase in internal temp but regulation threshold of hypothalamic centers unchanged, over 37

how does hyperthermia affect skeletal muscles

low muscle tone, then complete relaxation

exogenous hyperthermia

high ambient temp, cramps, exhaustion, syncope then shock

endogenic hyperthermia

malignant hyperthermia, normal ambient temp, defects in thermogenesis, tumors, hypoglycemia, drugs

thermic mialgia

hyperthermal cramp, under physical effort, excess water and mineral loss w/ only water restoration (no salt)

thermic collapse

peripheral vasodilation w/ hypovolemia + less CO, less BP

thermic syncope

episodes of loss of consciousness, <40 + sweat, from physical effort

what is seen in \ thermic syncope

hemoconcentration, ionic imbalances, tachycardia, hypotension

in heat shock, internal temp is _______, thermoregulation no functional

40-43

malignant hyperthermia

hereditary, rapid internal temp increase, triggered by anesthetics

Pathogenesis of malignant hyperthermia

SR defect, massive ca2+ release, muscle contractions

treatment of malignant hyperthermia

removal of anesthetics, body cooling, dantrolene sodium

sunstroke causes

cerebral hyperthermia, can cause cerebral edema + serous meningitis

grade I burn

edema + erythema

grade II burn

vesicular-bulbous lesions

grade III burn

necrosis

febrile reaction

nonspecific mechanism triggered by pyrogenic factors

in case of fever, the hypothalamic thermostat's set point is __________ , and the feedback mechanisms are ________ and will keep the temperature at a high level.

increased, normal

endogenous pyrogens

cytokines, most potent is IL-1 and TNF-a

central effects of pyrogens

arachidonic acid cascaded activated, release of lipid-pge2 mediators, increase in set point of thermoregulatory center

peripheral effects of pyrogens

increase in mediator release of lipid origin + inflammatory rnx + hepatic synthesis of acute phase proteins, activation of phagocytosis in micro+macrophages,

Phases of febrile rxn

1. prodromal phase

2. temp rise (thermolysis decreases, active thermogenesis thru chills)

3. fever phase (thermolysis/thermogenesis balance, vasodilation)

4. temp normal

fever increases non-specific defense ability of body against infections by

decreases metals (stimulate bacteria) stimulates immune system fxn lysosomal membrane destruction pro-inflammatory factors